Reticular Ratchets for Directing Electrochemiluminescence.

Electrochemiluminescence (ECL) involves charge transfer between electrochemical redox intermediates to produce an excited state for light emission. Ensuring precise control of charge transfer is essential for decoding ECL fundamentals, yet guidelines on how to achieve this for conventional emitters remain unexplored. Molecular ratchets offer a potential solution, as they enable the directional transfer of energy or chemicals while impeding the reverse movement. Herein, we designed 10 pairs of imine-based covalent organic frameworks as reticular ratchets to delicately manipulate the intrareticular charge transfer for directing ECL transduction from electric and chemical energies. Aligning the donor and acceptor (D-A) directions with the imine dipole effectively facilitates charge migration, whereas reversing the D-A direction impedes it. Notably, the ratchet effect of charge transfer directionality intensified with increasing D-A contrast, resulting in a remarkable 680-fold improvement in the ECL efficiency. Furthermore, dipole-controlled exciton binding energy, electron/hole decay kinetics, and femtosecond transient absorption spectra identified the electron transfer tendency from the N-end toward the C-end of reticular ratchets during ECL transduction. An exponential correlation between the ECL efficiency and the dipole difference was discovered. Our work provides a general approach to manipulate charge transfer and design next-generation electrochemical devices.

Mitigation Measures Could Aggravate Unbalanced Nitrogen and Phosphorus Emissions from Land-Use Activities.

Socioeconomic factors and mitigation potentials are essential drivers of the dynamics of nutrient emissions, yet these drivers are rarely examined at broad spatiotemporal scales. Here, we combine material flow analysis and geospatial analysis to examine the past and future changes of nitrogen and phosphorus emissions in China. Results show that anthropogenic nitrogen and phosphorus emissions increased by 17% and 32% during 2000-2019, respectively. Meanwhile, many regions witnessed decreasing nitrogen emissions but rising phosphorus discharged to waterbody, leading to a 20% decrease in the nitrogen/phosphorus ratio. In addition to many prominent factors like fertilizer use, the increasing impervious land area around cities is a notable factor driving the emissions, indicating the urgency to limit building expansion, especially in North China Plain and other less-developed regions. Improving land-use efficiency and consuming behaviors could reduce nitrogen and phosphorus emissions by 65-77% in 2030, but the nitrogen/phosphorus ratio will increase unintendedly due to larger reduction potentials for phosphorus, which may deteriorate the aquatic ecosystem. We highlight that nitrogen and phosphorus emissions should be reduced with coordinated but differentiated measures by prioritizing nitrogen reduction through cropland and food-system management.

3-(Methylthio)Propionic Acid from Bacillus thuringiensis Berliner Exhibits High Nematicidal Activity against the Root Knot Nematode Meloidogyne incognita (Kofoid and White) Chitwood.

Root knot nematodes cause serious damage to global agricultural production annually. Given that traditional chemical fumigant nematicides are harmful to non-target organisms and the environment, the development of biocontrol strategies has attracted significant attention in recent years. In this study, it was found that the Bacillus thuringiensis Berliner strain NBIN-863 exhibits strong fumigant nematicidal activity and has a high attraction effect on Meloidogyne incognita (Kofoid and White) Chitwood. Four volatile organic compounds (VOCs) produced by NBIN-863 were identified using solid-phase microextraction and gas chromatography-mass spectrometry. The nematicidal activity of four VOCs, namely, N-methylformamide, propenamide, 3-(methylthio)propionic acid, and phenylmalonic acid, was detected. Among these compounds, 3-(methylthio)propionic acid exhibited the highest direct contact nematicidal activity against M. incognita, with an LC50 value of 6.27 µg/mL at 24 h. In the fumigant bioassay, the mortality rate of M. incognita treated with 1 mg/mL of 3-(methylthio)propionic acid for 24 h increased to 69.93%. Furthermore, 3-(methylthio)propionic acid also exhibited an inhibitory effect on the egg-hatching of M. incognita. Using chemotaxis assays, it was determined that 3-(methylthio)propionic acid was highly attractive to M. incognita. In pot experiments, the application of 3-(methylthio)propionic acid resulted in a reduction in gall numbers, decreasing the number of galls per gram of tomato root from 97.58 to 6.97. Additionally, the root length and plant height of the treated plants showed significant increases in comparison with the control group. The current study suggests that 3-(methylthio)propionic acid is a novel nematicidal virulence factor of B. thuringiensis. Our research provides evidence for the potential use of NBIN-863 or its VOCs in biocontrol against root knot nematodes.

Antidepressants as Autophagy Modulators for Cancer Therapy.

Cancer is a major global public health problem with high morbidity. Depression is known to be a high-frequency complication of cancer diseases that decreases patients' life quality and increases the mortality rate. Therefore, antidepressants are often used as a complementary treatment during cancer therapy. During recent decades, various studies have shown that the combination of antidepressants and anticancer drugs increases treatment efficiency. In recent years, further emerging evidence has suggested that the modulation of autophagy serves as one of the primary anticancer mechanisms for antidepressants to suppress tumor growth. In this review, we introduce the anticancer potential of antidepressants, including tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). In particular, we focus on their autophagy-modulating mechanisms for regulating autophagosome formation and lysosomal degradation. We also discuss the prospect of repurposing antidepressants as anticancer agents. It is promising to repurpose antidepressants for cancer therapy in the future.

Silencing of RHEB inhibits cell proliferation and promotes apoptosis in colorectal cancer cells via inhibition of the mTOR signaling pathway.

Colorectal cancer (CRC) is commonly known as one of the most prominent reasons for cancer-related death in China. Ras homolog enriched in brain (RHEB) and the mammalian target activity of rapamycin (mTOR) signaling pathway were found correlated with CRC, but their specific interaction in CRC was still to be investigated. Therefore, we explored whether RHEB gene silencing affected the cell proliferation, differentiation, and apoptosis by directly targeting the mTOR signaling pathway in cells previously harvested from CRC patients. A microarray analysis was subsequently conducted to investigate the relationship between RHEB and mTOR. Eighty-three adjacent normal tissues and CRC tissues were selected. Immunohistochemistry was carried out to detect the positive expression rates of RHEB and Ki-67 in the CRC tissues. Cells were then transfected with different siRNAs to investigate the potential effects RHEB would have on CRC progression. The expressions of RHEB, 4EBP1, ribosomal protein S6 kinase (p70S6K), proliferating cell nuclear antigen (PCNA), B cell lymphoma 2 (bcl-2), and bcl-2-associated X protein (bax) were determined and then the cell cycle, cell proliferation, and apoptotic rate were also measured. We identified RHEB and mTOR as upregulated genes in CRC. Cells treated with RHEB silencing showed a decreased extent of mTOR, p70S6K, 4EBP1 phosphorylation and expression of RHEB, Ki-67, mTOR, p70S6K, 4EBP1, bcl-2, and PCNA as well as decreased activity of cell proliferation and differentiation; although, the expression of bax was evidently higher. Collectively, our data propose the idea that RHEB gene silencing might repress cell proliferation and differentiation while accelerating apoptosis via inactivating the mTOR signaling pathway.

Performance evaluation of regression splines for propensity score adjustment in post-market safety analysis with multiple treatments.

Observational studies provide a core resource in assessing post-market drug safety and effectiveness. Propensity scores are a predominant method for confounding adjustment to achieve unbiased estimation of average treatment effects in observational data. However, the use of propensity score methods has been limited to comparing two treatment groups, while medical situations frequently present with multiple treatment options. Inverse probability of treatment weighting (IPTW) is a popular propensity score adjustment method, but its performance degrades with decreased positivity leading to extreme weights, a problem that can be amplified with multiple treatment groups. Meanwhile, regression on a spline of the propensity score has shown favorable performance compared to other propensity score methods in recent studies involving two treatments. This project utilizes a simulation study to compare IPTW and propensity score splines as adjustment methods in a three-treatment setting. We test a variety of spline methods, including natural cubic splines with varying numbers of interior knots, and thin-plate regression splines. We vary several parameters across simulations, including the degree of propensity score overlap among treatment groups, treatment prevalence, outcome prevalence, and true marginal relative risk. We assess methods based on their bias, root mean squared error, and coverage of the true marginal relative risk across simulations. We find that all methods perform similarly well when there is good propensity score distribution overlap. However, with even moderate decrease in overlap or low outcome prevalence, IPTW produces more biased estimates and higher variance than propensity score splines. Low treatment prevalence or unequal treatment prevalences across groups also worsens IPTW performance. Overall, a natural cubic spline with a relatively small number of interior knots provides good performance across a range of simulations.

Hydrophosphonodifluoromethylation of Alkenes via Thiyl-Radical/Photoredox Catalysis.

Visible-light-induced catalytic hydrophosphonodifluoromethylation of mono- and disubstituted alkenes using bromodifluoromethanephosphonate with a Hantzsch ester as the terminal reductant is reported. The combination of thiyl-radical catalysis with photoredox catalysis is important for achieving good chemoselectivity and high yields.

Photo-induced dual passivation via Usanovich acid-base on surface defects of methylammonium lead triiodide perovskite.

Post-fabrication defect passivation of organometal halide perovskites has become an efficient way to improve their photophysical properties, but the underlying mechanisms are still in debate. In this work, we used p-benzoquinone (p-BQ) to generate surface defects on methylammonium lead triiodide perovskite (MAPbI3), and found that a Usanovich acid-base (O2, acetone or acetonitrile) treatment can effectively passivate those defects and lead to photoluminescence (PL) enhancement. The passivation effect arose from partial neutralization of defect charges via electron transfer between passivation reagents and relevant defects. O2 accepted photo-generated electrons, formed negatively charged oxygen species and attached to the I vacancy site to reduce its PL quenching efficiency by neutralising the defects positive charge. Likewise, acetone accepted photo-generated holes, formed positively charged species and partially neutralised the defects negative charge. The reduced trapping ability of defects caused PL enhancement. In addition, the observed photo-catalysed oxidation of acetone by O2 on the crystal surface supported the single electron transfer mechanism, and showed the potential of MAPbI3 as a photo-catalyst.

Light and oxygen induce chain scission of conjugated polymers in solution.

Conjugated polymers have been widely studied as flexible, versatile semiconductors in organic electronics. However, the material stability is one of the problems limiting their applications. Thus, understanding the degradation process of conjugated polymers is crucial. In this work, we monitored the chain scission of the model polymer MEH-PPV in chloroform solutions under different conditions by assessing its molecular weight using gel permeation chromatography and optical spectral measurements. We showed that changes in the UV-VIS spectrum can be seen only when the degradation has already progressed substantially. The fluorescence spectrum was found to be almost totally insensitive to the degradation stage of the polymers. We demonstrate that chain scission in solutions happens even in the dark leading to a 15% decrease of the molecular weight after just one day of storage. If exposed to room light, the chain length decreases by about 10 times over one day of exposure. Using stronger light intensity or enriching the solution with oxygen accelerates the degradation process dramatically. The rate of the reaction follows approximately a square root dependence with light intensity and oxygen concentration. We conclude that some extent of polymer degradation is difficult to avoid in common laboratory practices since to prevent it, one needs to work in an oxygen-free atmosphere in the dark. Preparation of polymer films from partially degraded solutions might lead not only to losing the connection between the molecular weight and the opto-electronic properties but also to unintentional doping of the semiconductor by products of chain scission reactions.

Absorption and Quantum Yield of Single Conjugated Polymer Poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) Molecules.

We simultaneously measured the absorption and emission of single conjugated polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) molecules in a poly(methyl methacrylate) (PMMA) matrix using near-critical xenon to enhance the photothermal contrast for direct absorption measurements. We directly measured the number of monomers and the quantum yield of single conjugated polymer molecules. Simultaneous absorption and emission measurements provided new insight into the photophysics of single conjugated polymers under optical excitation: quenching in larger molecules is more efficient than in smaller ones. Photoinduced traps and defects formed under prolonged illumination lead to decrease of both polymer fluorescence and absorption signals with the latter declining slower.

Aggregation-induced visible light absorption makes reactant 1,2-diisocyanoarenes act as photosensitizers in double radical isocyanide insertions.

The joint computational and experimental efforts reveal that the organic molecule 1,2-diisocyano-4,5-dimethylbenzene (1) acts as both a reactant and a photosensitizer (PS) in a metal-free reaction with perfluoroalkylhalide (2) to produce 2-perfluoroalkyl quinoxalines (3) under visible light. Both the π-π stacking aggregation in crystals and the solvation in various solvents of PS 1 exhibited visible-light absorption at 466 nm in spite of its smaller coefficient than that of the ultraviolet-light absorption. Such an aggregation-assisted visible-light absorption phenomenon is rationalized by theoretical calculations of the condensed-phase properties with the consideration of the explicit polarization effect from the neighboring molecules. Upon irradiation with different wavelengths, the emission colors changed from navy to bright yellow. Fluorescence lifetime measurements show that the emission of 1 comes from its singlet excited state. The aggregation induced emission when excited at 420 nm has a shorter lifetime (0.45 ns) than that of the emission from isolated molecules (2.71 ns) when excited at 381 nm. It is conceived that the aggregation assisted visible light absorption properties may be general in other photo-reactive molecules, such as 1,4-diisocyano-2,5-dimethylbenzene (4), 1,4-dicyanobenzene (5), and 1,4-diisocyanobenzene (6), which are widely used in many photochemical reactions in the absence of any external photosensitizer.

The roles of mitochondria in radiation-induced autophagic cell death in cervical cancer cells.

Mitochondria as the critical powerhouse of eukaryotic cells play important roles in regulating cell survival or cell death. Under numerous stimuli, impaired mitochondria will generate massive reactive oxygen species (ROS) which participate in the regulation of vital signals and could even determine the fate of cancer cells. While the roles of mitochondria in radiation-induced autophagic cell death still need to be elucidated. Human cervical cancer cell line, Hela, was used, and the SOD2 silencing model (SOD2-Ri) was established by gene engineering. Cell viability was detected by methyl thiazolyl tetrazolium (MTT) assays, MitoTracker Green staining was used to detect mitochondrial mass, Western blot was used to detect protein expression, and the level of ROS, autophagy, and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. Ionizing radiation (IR) could induce the increase of MAPLC3-II/MAPLC3-I ratio, Beclin1 expression, and ROS generation but decrease the MMP in a time-dependent manner. After SOD2 silencing, the IR-induced changes of ROS and the MMP were significantly enhanced. Moreover, both the radio sensitivity and autophagy increased in SOD2-Ri cells. Whereas, compared with SOD2-Ri, the opposite results were obtained by NAC, an antioxidant. After the treatment with the inhibitor of mitochondrial electron-transport chain complex II, thenoyltrifluoroacetone (TTFA), the rate of autophagy, ROS, and the total cell death induced by IR increased. In addition, the decrease of MMP was more obvious. However, these results were reversed by cyclosporine A (CsA). IR could induce ROS generation and mitochondrial damage which lead to autophagic cell death in Hela cells.

Hsp90 regulates autophagy and plays a role in cancer therapy.

Nowadays, heat shock protein 90 (Hsp90), a highly conserved molecular chaperone, has become the target of antitumor drugs as a result of its close relationship with the occurrence and development, biological behavior, and prognosis of a tumor. Autophagy has attracted big attention recently for its paradoxical roles in cell survival and cell death, especially in the pathogenesis and treatment of cancer. Moreover, it has been verified that Hsp90 plays a role in autophagy via regulating the stability and activity of signaling proteins, and some Hsp90 inhibitors can induce autophagy. However, the underlying mechanisms for these important processes have not been clarified so far. In this study, we focus on the roles of Hsp90 in the regulation of autophagy, such as toll-like receptor (TLR)-mediated autophagy, Ulk1-mediated mitophagy, and chaperone-mediated autophagy (CMA). The roles of Hsp90 inhibitors in cancer therapy will also be elucidated.

Excited state and charge-carrier dynamics in perovskite solar cell materials.

Organo-metal halide perovskites (OMHPs) have attracted enormous interest in recent years as materials for application in optoelectronics and solar energy conversion. These hybrid semiconductors seem to have the potential to challenge traditional silicon technology. In this review we will give an account of the recent development in the understanding of the fundamental light-induced processes in OMHPs from charge-photo generation, migration of charge carries through the materials and finally their recombination. Our and other literature reports on time-resolved conductivity, transient absorption and photoluminescence properties are used to paint a picture of how we currently see the fundamental excited state and charge-carrier dynamics. We will also show that there is still no fully coherent picture of the processes in OMHPs and we will indicate the problems to be solved by future research.

Giant photoluminescence blinking of perovskite nanocrystals reveals single-trap control of luminescence.

Fluorescence super-resolution microscopy showed correlated fluctuations of photoluminescence intensity and spatial localization of individual perovskite (CH3NH3PbI3) nanocrystals of size ∼200 × 30 × 30 nm(3). The photoluminescence blinking amplitude caused by a single quencher was a hundred thousand times larger than that of a typical dye molecule at the same excitation power density. The quencher is proposed to be a chemical or structural defect that traps free charges leading to nonradiative recombination. These trapping sites can be activated and deactivated by light.

Combination of miRNA and RNA functions as potential biomarkers for gastric cancer.

Gastric cancer (GC) is the second leading cause of cancer-related death in the world. The optimal treatment regimens for GC depend on tumor stage, histopathological subtype, and other factors. The detection of tumor biomarkers is a quick way to get information of the tumor state. In this study, new biomarkers are detected for GC diagnostic and prognostic purposes. A total of 305 cases of diagnosed gastric adenocarcinoma were enrolled, microRNAs (miRNAs) and their transcriptome sequencing data were obtained from the "The Cancer Genome Atlas." Blood samples were collected from GC patients before surgery and therapy. The miRNA levels and the expression of RNA were detected by real-time RT-PCR. Receiver operating characteristic analysis was used to evaluate the sensitivity and specificity of biomarkers. The combining predictors were established with the logistic regression analysis. Hundreds of miRNA were with higher area under curve (AUC) than 0.5; among them, nine miRNAs were with the highest AUC more than 0.90 and displayed strong diagnostic value. Moreover, the mir-17 level was correlated with tumor stage (p = 0.029), while mir-133b, mir-133a-2, and mir-1-2 levels were significantly correlated with race, tumor pathologic, and tumor stage (p < 0.05). The combination biomarker (mir-181a-1/KAT2B with a sensitivity of 95.83 % and specificity of 94.12 %) could be used as an independent diagnostic indicator for GC patients. For GC patients, mir-17, mir-133b, mir-133a-2, and mir-1-2 appear to be a potential novel predictor of tumor stage and preoperative and intraoperative diagnosis. The combination of miRNA and mRNA such as mir-181a-1/KAT2B (with a sensitivity of 95.83 % and specificity of 94.12 %) showed significant improvement in the diagnostic accuracy.

Mechanistic insights into perovskite photoluminescence enhancement: light curing with oxygen can boost yield thousandfold.

A light-induced photoluminescence (PL) enhancement in surface-deposited methylammonium lead iodide (CH3NH3PbI3) perovskites was investigated in detail using time-resolved luminescence microscopy. We found the PL intensity to increase up to three orders of magnitude upon light illumination with an excitation power density of 0.01-1 W cm(-2). The PL enhancement is accompanied by an increase of the PL lifetime from several nanoseconds to several hundred nanoseconds and also by an increase of the initial amplitude of the PL decay. The latter suggests excited state quenching at the subpicosecond timescale. We propose a model where the trapping sites responsible for non-radiative charge recombination can be de-activated by a photochemical reaction involving oxygen. The reaction zone is spatially limited by the excitation light-penetration depth and diffusion length of the charge carriers. The latter increases in the course of the light-curing process making the reaction zone spreading from the surface towards the interior of the crystal. The PL enhancement can be reversed by switching on/off the excitation light or switching the atmosphere between oxygen and nitrogen. Slow diffusion of the reactants and products and equilibrium between the active and "cured" trapping sites are proposed to be the reasons for peculiar responses of PL to such varied experimental conditions.

Single molecule as a local acoustic detector for mechanical oscillators.

A single molecule can serve as a nanometer-sized detector of acoustic strain. Such a nanomicrophone has the great advantage that it can be placed very close to acoustic signal sources and high sensitivities can be achieved. We demonstrate this scheme by monitoring the fluorescence intensity of a single dibenzoterrylene molecule in an anthracene crystal attached to an oscillating tuning fork. The characterization of the vibration amplitude and of the detection sensitivity is a first step towards detection and control of nanomechanical oscillators through optical detection and feedback.

Stable single-molecule lines of terrylene in polycrystalline para-dichlorobenzene at 1.5 K.

The spectroscopic properties of single terrylene (Tr) molecules are studied in a polycrystalline matrix of para-dichlorobenzene (p-DCB) at 1.5 K. Samples grown in a glass capillary show a very strong site at 597 nm, which is redshifted by more than 700 cm(-1) from the observed transition energy for Tr in p-DCB prepared as a film on a coverslip (572 nm). Each of these two sites is characterized by measuring their single-molecule spectroscopic parameters at 1.5 K. Lifetime-limited linewidths of 45±5 MHz are found for both sites. Fluorescence detection rates reach 8×10(4) count s(-1) at saturation. The spectral trails of the majority of single molecules show no spectral jumps, indicating an absence of interacting two-level systems; however, the small distribution of linewidths may indicate weak interactions with low-frequency modes. Frequency jumps are observed for 10 % of the molecules. The complete emission spectra from two different single molecules at the center of each of the two sites is presented. Debye-Waller factors of αDW=0.33±0.05 for the normal site (572 nm) and αDW=0.30±0.05 for the red site (597 nm) are reported. This new host-guest system provides a quick and easy way to obtain lifetime-limited single-molecule lines.

Cyclodextrin insulation prevents static quenching of conjugated polymer fluorescence at the single molecule level.

Conjugated polymers (CPs) are promising materials for fluorescence imaging application. However, a significant problem in this field is the unexplained abnormally low fluorescence brightness (or number of fluorescence photons detected per one excitation photon) exhibited by most of CP single chains in solid polymer hosts. Here it is shown that this detrimental effect can be fully avoided for short chains of polyfluorene-bis-vinylphenylene (PFBV) embedded in a host polymer matrix of PMMA, if the conjugated backbone is insulated by cyclodextrin rings to form a polyrotaxane (PFBV-Rtx). Fluorescence kinetics and quantum yields are measured for the polymers in liquid solutions, pristine films, and solid PMMA blends. The fluorescence brightness of PFBV-Rtx single chains dispersed in a solid PMMA is very close to that expected for a chain with 100% fluorescence quantum yield, while the unprotected PFBV chains of the same length possess 4 times lower brightness. Despite this, the fluorescence decay kinetics are the same for both polymers, suggesting the presence of static or ultrafast fluorescence quenching in the unprotected polymer. About 80% of an unprotected PFBV chain is estimated to be completely quenched. The hypothesis is that the cyclodextrin rings prevent the quenching by working as 'bumpers' reducing the mechanical forces applied by the host polymer to the conjugated backbone and help retaining its conformational freedom. While providing a recipe for making CP fluorescence bright at the single-molecule level, these results identify a lack of fundamental understanding in the community of the influence of the environment on excited states in conjugated materials.