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Achieving accurate characterization of protein structures in the gas phase continues to be a formidable challenge. To tackle this issue, the present study employs Molecular Dynamics (MD) simulations in tandem with enhanced sampling techniques (methods designed to efficiently explore protein conformations). The objective is to identify suitable structures of proteins by contrasting their calculated Collision Cross-Section (CCS) with those observed experimentally. Significant discrepancies were observed between the initial MD-simulated and experimentally measured CCS values through Ion Mobility-Mass Spectrometry (IMS-MS). To bridge this gap, we employed two distinct enhanced sampling methods, Harmonic Biasing Potential and Adaptive Biasing Force, which help the proteins overcome energy barriers to adopt more compact configurations. These techniques leverage the radius of gyration as a reaction coordinate (guiding parameter), guiding the system toward compressed states that potentially match experimental configurations more closely. The guiding forces are only employed to overcome existing barriers and are removed to allow the protein to naturally arrive at a potential gas phase configuration. The results demonstrated close alignment (within ∼4%) between simulated and experimental CCS values despite using different strengths and/or methods, validating their efficacy. This work lays the groundwork for future studies aimed at optimizing biasing methods and expanding the collective variables used for more accurate gas-phase structural predictions.

Phthalates (PAEs) are synthetic chemicals widely used in industrial and personal consumer products as adhesives or plasticizers. PAEs have been demonstrated to have toxic effects on the human body. However, biological monitoring data for the internal PAE exposure levels of Chinese rural residents are still limited. The present study investigated the exposure levels of ten phthalate metabolites (mPAEs) of rural residents in Northwest China. The results showed that mPAEs were wildly prevalent in urine and the geometric mean concentration of Σ 10 mPAEs was 957.02 ng mL -1 (adjusted by specific gravity). Mono- n -butyl phthalate (MBP) and metabolites of di(2-ethylhexyl)-phthalate (DEHP) were the most dominant mPAEs in urine, with specific gravity adjusted median concentrations of 174.67 and 156.30 ng mL -1 , respectively. Urinary concentrations of mPAEs were significantly associated with age, body mass index and economic level ( p < 0.05). By calculating the percentage and relative conversion rate of DEHP metabolites, it was found that the degree of oxidative metabolism of DEHP in children was significantly higher than that in adults ( p < 0.05), indicating that the pathway and degree of DEHP oxidation were age-related. The risk assessment showed that 59.12% of rural residents may have a noncancer risk from PAE exposure. This study provides important basis for assessing the occurrence and exposure of urinary phthalate metabolites among rural residents in China., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, and American Chemical Society.)

Polycyclic aromatic hydrocarbon (PAH) exposure is suspected to be linked to oxidative damage. Herein, ten PAH human exposure biomarkers [hydroxylated PAH metabolites (OH-PAHs)] and five oxidative stress biomarkers (OSBs) were detected in urine samples collected from participants living in a rural area ( n = 181) in Northwestern China. The median molar concentration of ΣOH-PAHs in urine was 47.0 pmol mL -1 . The 2-hydroxynaphthalene (2-OHNap; median: 2.21 ng mL -1 ) was the dominant OH-PAH. The risk assessment of PAH exposure found that hazard index (HI) values were <1, indicating that the PAH exposure of rural people in Jingyuan would not generate significant cumulative risks. Smokers (median: 0.033) obtained higher HI values than nonsmokers (median: 0.015, p < 0.01), suggesting that smokers face a higher health risk from PAH exposure than nonsmokers. Pearson correlation and multivariate linear regression analysis revealed that ΣOH-PAH concentrations were significant factors in increasing the oxidative damage to deoxyribonucleic acid (DNA) (8-hydroxy-2'-deoxyguanosine, 8-OHdG), ribonucleic acid (RNA) (8-oxo-7,8-dihydroguanine, 8-oxoGua), and protein ( o , o '-dityrosine, diY) ( p < 0.05). Among all PAH metabolites, only 1-hydroxypyrene (1-OHPyr) could positively affect the expression of all five OSBs ( p < 0.05), suggesting that urinary 1-OHPyr might be a reliable biomarker for PAH exposure and a useful indicator for assessing the impacts of PAH exposure on oxidative stress. This study is focused on the relation between PAH exposure and oxidative damage and lays a foundation for the study of the health effect mechanism of PAHs.

Zearalenone (ZEN) is a mycotoxin that is harmful to humans and animals. In this study, female and male rats were exposed to ZEN, and the results showed that ZEN reduced the farnesoid X receptor (FXR) expression levels in the liver and disrupted the enterohepatic circulation of bile acids (BAs). A decrease in food intake induced by ZEN was negatively correlated with an increase in the level of total BAs. BA-targeted metabolomics revealed that ZEN increased glycochenodeoxycholic acid levels and decreased the ratio of conjugated BAs to unconjugated BAs, which further increased the hypothalamic FXR expression levels. Preventing the increase in total BA levels induced by ZEN via Lactobacillus rhamnosus GG intervention restored the appetite. In conclusion, ZEN disrupted the enterohepatic circulation of BAs to decrease the level of food intake. This study reveals a possible mechanism by which ZEN affects food intake and provides a new approach to decrease the toxic effects of ZEN.

Vacuum ultraviolet photoionization (VUV-PI) is a soft ionization technique that operates under pressures ranging from vacuum to ambient pressure. VUV-PI has played an essential role in direct sampling mass spectrometry. In this study, new ionization processes initiated by photoelectrons have been studied through the inclusion of a radio frequency (RF) electric field at different pressures. After deducting the contribution of single photoionization (SPI), the signal intensity of 1 ppmv toluene (C 7 H 8 + ) in Ar was approximately 5-fold higher than that in N 2 . Mixed gases with different ionization energies (IEs) and excitation energies (EEs) were further investigated to reveal that metastable species were involved in the enhancement process. Reactant ions were produced by photoelectron impact ionization (PEI), which further triggered ion-molecule reactions, i.e., chemical ionization (CI). Metastable species were produced by photoelectron impact excitation (PEE), which further triggered Penning ionization (PenI). Analytes with IEs above 10.6 eV, such as CO 2 (IE = 13.78 eV) and CHCl 3 (IE = 11.37 eV), could be sensitively ionized by PenI with a sensitivity comparable to SPI. Except for the contribution of SPI, the dominant ionization process was switched from PEI-CI to PenI when the pressure was elevated from 50 to 500 Pa, as the electron energy gradually decreased and was only able to produce metastable states based on the kinetic energy balance equation of electrons. The conversion processes and conditions from PEI-CI to PenI will provide novel insights to develop new selective and sensitive VUV-PI sources and understand the ionization mechanism in other discharge ionization sources.

Surface waves are known for their mechanical role in coastal processes that influence the weather and climate. However, their chemical impact, particularly on the transformation of pyrogenic carbon, is poorly understood. Pyrogenic carbon is generally assumed to show negligible postformational alteration of its stable carbon isotope composition. Here we present an electrochemical interaction of pyrogenic carbon with the sprayed seawater microdroplets resulting from wave breaking, driven by the galvanic coupling between the microdroplet water-carbon interfaces and the microdroplet water-vapor interfaces. This enables refractory pyrogenic carbon to rapidly degrade via the oxygenation and mineralization reaction, which makes it ∼2.6‰ enriched in 13 C, far exceeding the generally assumed postformation alteration values (<0.5‰) of pyrogenic carbon. The unique chemical dynamics of seawater microdroplets provide new insights into the discrepancy in carbon isotope signatures between riverine and marine black carbon, emphasizing the potential of coastal oceans for carbon sequestration in the global carbon cycle.

Efficient and accurate acquisition of cellular biomolecular information is crucial for exploring cell fate, achieving early diagnosis, and the effective treatment of various diseases. However, current DNA biosensors are mostly limited to single-target detection, with few complex logic circuits for comprehensive analysis of three or more targets. Herein, we designed a sea anemone-like DNA nanomachine based on DNA strand displacement composed of three logic gates (YES-AND-YES) and delivered into the cells using gold nano bipyramid carriers. The AND gate activation depends on the trigger chain released by upstream DNA strand displacement reactions, while the output signal relies on the downstream DNAzyme structure. Under the influence of diverse inputs (including enzymes, miRNA, and metal ions), the interconnected logic gates simultaneously perform logical analysis on multiple targets, generating a unique output signal in the YES/NO format. This sensor can successfully distinguish healthy cells from tumor cells and can be further used for the diagnosis of different tumor cells, providing a promising platform for accurate cell-type identification.

The accurate quantification of cancer-derived exosomes, which are emerging as promising noninvasive biomarkers for liquid biopsies in the early diagnosis of cancer, is becoming increasingly imperative. In our work, we developed a magnetically controlled photothermal, colorimetric, and fluorescence trimode aptasensor for human gastric cancer cell (SGC-7901)-derived exosomes. This sensor relied on CP/Mn-PBA DSNBs nanocomposites, created by decorating copper peroxide (CP) nanodots on polyethyleneimine-modified manganese-containing Prussian blue analogues double-shelled nanoboxes (PEI-Mn-PBA DSNBs). Through self-assembly, we attached CD63 aptamer-labeled CP/Mn-PBA DSNBs (Apt-CP/Mn-PBA DSNBs) to complementary DNA-labeled magnetic beads (cDNA-MB). During exosome incubation, these aptamers preferentially formed complexes with exosomes, and we efficiently removed the released CP/Mn-PBA DSNBs by using magnetic separation. The CP/Mn-PBA DSNBs exhibited high photoreactivity and photothermal conversion efficiency under near-infrared (NIR) light, leading to temperature variations under 808 nm irradiation, correlating with different exosome concentrations. Additionally, colorimetric detection was achieved by monitoring the color change in a 3,3',5,5'-tetramethylbenzidine (TMB) system, facilitated by PEI modification, NIR-enhanced peroxidase-like activity of CP/Mn-PBA DSNBs and their capacity to generate Cu 2+ and H 2 O 2 under acidic conditions. Moreover, in the presence of Cu 2+ and ascorbic acid (AA), DNA sequences could form dsDNA-templated copper nanoparticles (CuNPs), which emitted strong fluorescence at around 575 nm. Increasing exosome concentrations correlated with decreases in temperature, absorbance, and fluorescence intensity. This trimode biosensor demonstrated satisfactory ability in differentiating gastric cancer patients from healthy individuals using human serum samples.

Tumor-associated macrophages (TAMs) are among the most abundant infiltrating leukocytes in the tumor microenvironment (TME). Reprogramming TAMs from protumor M2 to antitumor M1 phenotype is a promising strategy for remodeling the TME and promoting antitumor immunity; however, the development of an efficient strategy remains challenging. Here, a genetically modified bacterial biomimetic vesicle (BBV) with IFN-γ exposed on the surface in a nanoassembling membrane pore structure was constructed. The engineered IFN-γ BBV featured a nanoscale structure of protein and lipid vesicle, the existence of rich pattern-associated molecular patterns (PAMPs), and the costimulation of introduced IFN-γ molecules. In vitro , IFN-γ BBV reprogrammed M2 macrophages to M1, possibly through NF-κB and JAK-STAT signaling pathways, releasing nitric oxide (NO) and inflammatory cytokines IL-1β, IL-6, and TNF-α and increasing the expression of IL-12 and iNOS. In tumor-bearing mice, IFN-γ BBV demonstrated a targeted enrichment in tumors and successfully reprogrammed TAMs into the M1 phenotype; notably, the response of antigen-specific cytotoxic T lymphocyte (CTL) in TME was promoted while the immunosuppressive myeloid-derived suppressor cell (MDSC) was suppressed. The tumor growth was found to be significantly inhibited in both a TC-1 tumor and a CT26 tumor. It was indicated that the antitumor effects of IFN-γ BBV were macrophage-dependent. Further, the modulation of TME by IFN-γ BBV produced synergistic effects against tumor growth and metastasis with an immune checkpoint inhibitor in an orthotopic 4T1 breast cancer model which was insensitive to anti-PD-1 mAb alone. In conclusion, IFN-γ-modified BBV demonstrated a strong capability of efficiently targeting tumor and tuning a cold tumor hot through reprogramming TAMs, providing a potent approach for tumor immunotherapy.

Nanoporous adsorbents can mechanically swell or shrink once upon the accumulation of guest fluid molecules at their internal surfaces or in their cavities. Existing theories in this field attribute such sorption-induced swelling to a tensile force, while shrinkage is always associated with a contractive force. In this study, however, we propose that the sorption-induced deformation of a porous architecture is not solely dictated by the stress conditions but can also be largely influenced by its mechanical anisotropy. In more detail, the sorption-induced deformation of a polymeric slab is investigated using a hybrid molecular dynamics and Monte Carlo algorithm. When subjected to water loading, the slab is found to swell along its normal direction and display an overall positive volumetric strain. Moreover, the surface roughness is enhanced as a response to the surface energy decrease induced by the water covering the slab external surface. Unexpectedly, the in-plane deformation of the slab material seems to be highly constrained, so that it is far below its normal counterpart. This anisotropy is enhanced when the slab thickness decreases. With a thickness of around 1.35 nm, an in-plane shrinkage is observed throughout the entire hygroscopic range. A theoretical analysis based on a poromechanical model suggests that the anisotropic mechanical properties, which are common for a slab material, are the essence of the constrained in-plane swelling or even shrinkage under the isotropic sorption-induced tensile forces. This study, unveiling overlooked mechanisms of sorption-induced shrinkage in mechanically anisotropic materials, provides new insights into this field.

Although protonated polyoxometalates (POMs) are promising hole-transporting layer (HTL) materials for optoelectronic devices owing to their excellent hole collection/injection property, pH neutrality, and noncorrosiveness, POMs are seldom used as high-performance HTL materials. Herein, we designed and synthesized a series of mixed-additive POMs with pH-neutral counterions (NH 4 + , K + , and Na + ) as HTL materials. X-ray photoelectron spectroscopy and single-crystal X-ray analyses indicated that the use of the lacunary heteropolyanion [P 2 W 15 O 56 ] 12- as an intermediate ensured successful incorporation of the counterions into the mixed-addenda POMs without causing deterioration of the POM frameworks. The hole-transporting layer performance of POM-NH 4 , which was characterized by a high work function and good conductivity and could be prepared using a low-cost method surpassed those of its protonated counterpart POM-4 and many classic HTL materials. An organic solar cell (OSC) modified with POM-NH 4 delivered a power conversion efficiency of 18.0%, which was the highest photovoltaic efficiency achieved by POM-based OSCs to date. Moreover, an HTL material based on POM-NH 4 reduced the turn-on voltage of an organic light-emitting diode from 4.2 to 3.2 V. The results of this study suggest that POMs are promising alternatives to the classic HTL materials owing to their excellent hole-collection ability, low costs, neutral nature, and high-chemical stability.

Constructing high-performance solution-processed organic light-emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) conjugated polymers remains a challenging issue. The electron-withdrawing ability of acceptors in TADF units significantly affects the TADF properties of the conjugated polymers. Herein, we have designed three TADF conjugated polymers, in which phenoxazine donors and anthracen-9(10H)-one acceptors are incorporated into the polymeric backbones and side chains, respectively, and the carbazole derivative is copolymerized as the host. By incorporating different heteroatoms, such as nitrogen, oxygen, or sulfur, with slightly different electronegativities into anthracen-9(10H)-one, the effect of the electron-withdrawing ability of the acceptor on the performance of conjugated TADF polymer-based OLEDs is thus systematically studied. It is found that the introduction of a nitrogen atom can enhance the spin-orbital coupling and RISC process due to the modulated energy levels and nature of the excited states. As a result, the solution-processed OLEDs based on the prepared polymer p-PXZ-XN display an excellent comprehensive performance with an EQE max of 17.6%, a low turn-on voltage of 2.8 V, and a maximum brightness of 14750 cd m -2 . Notably, the efficiency roll-off is quite low, maintaining 15.1% at 1000 cd m -2 , 12.1% at 3000 cd m -2 , and 6.1% at 10000 cd m -2 , which ranks in the first tier among the reported TADF conjugated polymers. This work provides a guideline for constructing high-efficiency TADF polymers.

Antimicrobial peptides have been extensively studied as potential alternatives to antibiotics. Porcine angiogenin 4 (pANG4) is a novel antimicrobial peptide in the angiogenin (ANG) family, which may have a regulatory effect on intestinal microflora. The object of present study is obtained pANG4 protein by heterologous expression, so as to explore the biological function of recombinant pANG4 (rpANG4). The pANG4 was expressed in Pichia pastoris ( P. pastoris ) and anti-inflammatory effects were investigated in intestinal porcine epithelial cell line-J2 (IPEC-J2) and mice. Purified rpANG4 had bacteriostatic activity and did not cause hemolysis or cytotoxicity at concentrations below 128 μg/mL. Purified rpANG4 increased the activity of IPEC-J2 and reduced apoptosis in vitro . rpANG4 reduced the pro-inflammatory gene expression and upregulated tight junction protein gene expression during inflammation. rpANG4 alleviated lipopolysaccharide (LPS)-induced liver and spleen damage, intestinal inflammation, jejunal apoptosis genes' expression, and improved immune function in an in vivo mice model. rpANG4 increased tight junction protein gene expression in jejunum, thereby improving the jejunum intestinal barrier function. In conclusion, rpANG4 had antibacterial activity, inhibited intestinal inflammation, improved intestinal barrier function, and alleviated liver and spleen damage. The current study contributes to the development of antibiotic substitutes and the improvement of animal health.

Heterojunctions featuring a type II band alignment play a crucial role in a wide range of devices, particularly in the realm of solar cells. However, the design of such heterojunctions with a specific type of band alignment poses a substantial challenge due to the immense number of potential combinations of bulk semiconductors and their relative orientations. In this study, we propose an efficient, high-throughput computational screening method tailored for heterojunctions. Our approach, using the ideal vacuum level as a reference energy, eliminates the need for explicit electronic structure calculations for junctions. Through this protocol, we identify 1041 type II heterojunctions out of 2692 structures constructed from 86 selected inorganic compounds with appropriate band gaps sourced from the Inorganic Crystal Structure Database. For potential application in solar cells, we assess these heterojunctions, and remarkably, 58 of them exhibit a power conversion efficiency (PCE) exceeding 15%, with 13 surpassing the 20% threshold. Test calculations with expensive interface models confirm the reliability of PCE predictions based on ideal vacuums. These predictions will be of benefit in assessing the material applicability for solar cell applications. Furthermore, the versatility of our proposed screening method extends beyond solar cells, making it a valuable theoretical design tool that can be applied to a wide range of heterojunction devices.

Based on the tetraphenylsilane skeleton, a new class of thermally activated delayed fluorescence (TADF) molecules have been designed and synthesized. Benefiting from the unique tetrahedron architecture of tetraphenylsilane, the intermolecular distance between TADF units can be enlarged and thus weakened the aggregation-induced quenching of triplet excitons. By adjusting the numbers of TADF subunits, the spin-orbit coupling processes can be controlled, leading to efficient up-conversion processes. The related OLEDs are fabricated through the solution processing technology, and pure-blue and green electroluminescence were observed with maximum external quantum efficiencies (EQ E ) of 6.6 and 13.8% as well as Commission Internationale de l'Eclairage coordinates of (0.14, 0.15) and (0.25, 0.45), respectively. This study provides a new idea for designing color-tunable TADF emitters through spatial structure regulation.max ) of 6.6 and 13.8% as well as Commission Internationale de l'Eclairage coordinates of (0.14, 0.15) and (0.25, 0.45), respectively. This study provides a new idea for designing color-tunable TADF emitters through spatial structure regulation.

Oils are hydrophobic, but their degradation is frequently found to be accelerated in the presence of water microdroplets. The direct chemical consequences of water-oil contact have long been overlooked. We show that aqueous microdroplets in emulsified water-hexadecane (C 16 H 34 ) mixtures can spontaneously produce CO 2 , •H, H 2 , and short-chain hydrocarbons (mainly C 1 and C 2 ) as detected by gas chromatography, electron paramagnetic resonance spectroscopy, and mass spectrometry. This reaction results from contact electrification at the water-oil microdroplet interface, in which reactive oxygen species are produced, such as hydrated hydroxyl radicals and hydrogen peroxide. We also find that the H 2 originates from the water microdroplet and not the hydrocarbon it contacts. These observations highlight the potential of interfacial contact electrification to produce new chemistry.

The ion conversion processes in CH 2 Cl 2 -enhanced vacuum ultraviolet photoionization of oxygenated volatile organic compounds (OVOCs) have been systematically studied by regulating the pressure, humidity, and reaction time in the ionization source of a time-of-flight mass spectrometer. As the ionization source pressure increased from 100 to 1100 Pa, the main characteristic ions changed from CH 2 Cl + to CH 2 Cl + (H 2 O), CH 2 OH + , and C 2 H 4 OH + and then to the hydrated hydronium ions H 3 O + (H 2 O) n ( n = 1, 2, 3). The total ion current (TIC) almost remained unchanged even if the humidity increased from 44 to 3120 ppmv, indicating interconversion between ions through ion-molecule reactions. The intensity of protonated methanol/ethanol (sample S) ion was almost linearly correlated with the intensity of H 3 O + (H 2 O) n , which pointed to the proton transfer reaction (PTR) mechanism. The reaction time was regulated by the electric field strength in the ionization region. The intensity variation trends of different ions with the reaction time indicated that a series of step-by-step ion-molecule reactions occurred in the ionization source, i.e., the primary ion CH 2 Cl + reacted with H 2 O and converted to the intermediate product ions CH 2 OH + and C 2 H 4 OH + , which then further reacted with H 2 O and led to the production of H 3 O + , and finally, the protonated sample ion SH + was obtained through PTR with H 3 O + , as the ion-molecule reactions progressed. This study provides valuable insights into understanding the formation mechanism of some unexpected intermediate product ions and hydrated hydronium ions in dopant-enhanced VUV photoionization and also helps to optimize experimental conditions to enhance the sensitivity of OVOCs.

Development of fluorescence polarization (FP) assays, especially in a competitive manner, is a potent and mature tool for measuring the binding affinities of small molecules. This approach is suitable for high-throughput screening (HTS) for initial ligands and is also applicable for further study of the structure-activity relationships (SARs) of candidate compounds for drug discovery. Buffer and tracer, especially rational design of the tracer, play a vital role in an FP assay system. In this perspective, we provided different kinds of approaches for tracer design based on successful cases in recent years. We classified these tracers by different types of ligands in tracers, including peptide, nucleic acid, natural product, and small molecule. To make this technology accessible for more targets, we briefly described the basic theory and workflow, followed by highlighting the design and application of typical FP tracers from a perspective of medicinal chemistry.

Prevailing absorbents like wood-derived porous scaffolds or polymeric aerogels are normally featured with hierarchical porous structures. In former molecular simulation studies, sorption, deformation, and coupled sorption-deformation have been studied for single-scale materials, but scarcely for materials where micropores (<2 nm) and mesopores (2-50 nm) coexist. The present work, dealing with a mesoscopic slit pore between two slabs of microporous amorphous cellulose (AC), aims at modeling sorption-deformation interplay in hierarchical porous cellulosic structures inspired by polymeric modern adsorbents. Specifically, the atomic system is modeled by a hybrid workflow combining molecular dynamics (MD) and grand canonical Monte Carlo (GCMC) simulations. The results clarify the multiple sorption/deformation mechanisms in porous materials with different slit-pore sizes, including water filling in micropores, surface covering at the solid-air interface, and subsequent capillary condensation in mesopores. In particular, before the onset of capillary condensation, the sorption behavior of the AC matrix in the hybrid system is almost the same as that of bulk AC, in which sorption and deformation enhance each other through sorption-induced swelling and additional sorption in the newly created voids. Upon capillary condensation, the interaction between the micropores and the mesopore emerges. Water molecules in the mesopore exert a negative hydrostatic pressure perpendicular to the slab surface on the matrices, resulting in an increase in porosity and water content, a decrease in distance between the centers of mass (COMs) of the slabs, and thus a thinning of the slit pore. As described by Bangham's Law, the surface area of the rough slit-pore slab increases proportionally to the surface energy variation during surface covering. For a system composed of a compliant polymer like AC, however, the surface area enlargement does not result in an in-plane swelling as expected but instead in an in-plane shrinkage along with an increase in local roughness or irregularity (an accordion effect).

Polarization sensitivity, which shows great potential in photoelectric detection, is expected to be significantly improved by the ferroelectric anomalous photovoltaic (APV) effect. However, it is challenging to explore new APV-active ferroelectrics due to severe polarization fatigue induced by the leakage current of photoexcited carriers. For the first time, we report a strong APV effect in a 2D hybrid perovskite ferroelectric assembled by alloying mixed organic cations, (HA) 2 (EA) 2 Pb 3 Br 10 ( 1 , where HA + is n -hexylammonium and EA + is ethylammonium), which has a large spontaneous polarization ∼3.8 μC/cm 2 and high a Curie temperature ∼378 K. Its ferroelectricity allows a strong APV effect with an above-bandgap photovoltage up to 7.4 V, which exceeds its bandgap (∼2.7 eV). Most strikingly, based on the dependence on polarized-light angle, this strong APV effect renders the highest level of polarization sensitivity with a giant current ratio of ∼25, far beyond other 2D single-phase materials. This study sheds light on the exploration of APV-active ferroelectrics and inspires their future high-performance optoelectronic device applications.

Toward greater separation techniques for ions, a differential mobility analyzer (DMA) has been coupled with field asymmetric waveform ion mobility spectrometry (FAIMS) to take advantage of two mobility-related but different methods of separation. The filtering effect of the DMA allows ions to be selected individually based on low-field mobility and studied in FAIMS at variable electric field, yielding mobility separations in two dimensions. Because spectra fully describe ion mobility at variable field strength, results are then compared with a two-temperature theory-predicted mobility up to the fourth-order approximation. The comparison yields excellent results up to at least 100 Td, beyond which the theory deviates from experiments. This is attributed to two effects, the enlargement of the structure due to ion heating and the inelasticity of the collisions with the nitrogen bath gas. The corrected mobility can then be used to predict the dispersion plot through a newly developed implicit equation that circumvents the possible issues related to the more elaborate Buryakov equation. Our results simultaneously show that the DMA-FAIMS coupling yields complete information on ion mobility versus the field-strength to gas-density ratio and works toward predicting such spectra from ion structures and gas properties.

There is a growing urgent need for point-of-care testing (POCT) devices that integrate sample pretreatment and nucleic acid detection in a rapid, economical, and non-labor-intensive way. Here, we have developed an automated, portable nucleic acid detection system employing microfluidic chips integrating rotary valve-assisted sample pretreatment and recombinase polymerase amplification (RPA)-T7-Cas13a into one-step nucleic acid detection. The RPA and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a were integrated into a single-chamber reaction. As a validation model, we used this method to detect Group B streptococci ( GBS ) DNA and achieved a detection sensitivity of 8 copies/reaction, which is 6 times more sensitive than gold-standard polymerase chain reactions (PCRs). Dual specific recognition of RPA with CRISPR/Cas13a makes our method ultraspecific, with correct detection of Group B streptococci from 8 kinds of pathogenic bacteria. For the 16 positive and 24 negative clinical GBS samples, our assay achieved 100% accuracy compared to the PCR technique. The whole procedure can be automatically completed within 30 min, providing a more robust, sensitive, and accurate molecular diagnostic tool for POCT.

Hydrogen cyanide (HCN) is a well-known toxic compound in many fields. The trace amount of endogenous HCN in human exhalation has been associated with the presence of Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) patients. Online monitoring of HCN profile is promising to screen PA infection rapidly and accurately. In this study, a gas flow-assisted negative photoionization (NPI) mass spectrometry method was developed for monitoring the single-exhalation HCN profile. The sensitivity could be optimized by introducing helium to eliminate the humidity influence and reduce the low mass cutoff effect, with improvements of a factor 150 observed. By employing a purging gas procedure and minimizing the length of the sample line, the residual and response time were greatly reduced. The limit of detection (LOD) of 0.3 ppbv and time resolution of 0.5 s were achieved. HCN profiles of exhalations from different volunteers before or after gargling with water were detected to show the performance of the method. All profiles showed a sharp peak and a stable end-tidal plateau, representing the concentration of oral cavity and end-tidal gas, respectively. The HCN concentration based on the plateau of the profile showed better reproducibility and accuracy, which indicates this method has potential application in the detection of PA infection in CF patients.

Ethyl carbamate (EC), a carcinogenic compound, is naturally produced in fermented foods and alcoholic beverages. Rapid and accurate measurement of EC is necessary and important for quality control and safety evaluation of Chinese liquor, a traditionally distilled spirit with the highest consumption in China, but it remains a great challenge. In this work, a direct injection mass spectrometry (DIMS) with time-resolved flash-thermal-vaporization (TRFTV) and acetone-assisted high-pressure photoionization (HPPI) strategy has been developed. EC was rapidly separated from the main matrix components, ethyl acetate (EA) and ethanol, by the TRFTV sampling strategy due to the retention time difference of these three compounds with large boiling point differences on the inner wall of a poly(tetrafluoroethylene) (PTFE) tube. Therefore, the matrix effect of EA and ethanol was effectively eliminated. The acetone-assisted HPPI source was developed for efficient ionization of EC through a photoionization-induced proton transfer reaction between EC molecules and protonated acetone ions. The accurate quantitative analysis of EC in liquor was achieved by introducing an internal standard method (ISM) using deuterated EC ( d -EC). As a result, the limit of detection (LOD) for EC was 8.88 μg/L with the analysis time of only 2 min, and the recoveries ranged from 92.3 to 113.1%. Finally, the prominent capability of the developed system was demonstrated by rapid determination of trace EC in Chinese liquors with different flavor types, exhibiting wide potential applications in online quality control and safety evaluation of not only Chinese liquors but also other liquor and alcoholic beverages.5 -EC). As a result, the limit of detection (LOD) for EC was 8.88 μg/L with the analysis time of only 2 min, and the recoveries ranged from 92.3 to 113.1%. Finally, the prominent capability of the developed system was demonstrated by rapid determination of trace EC in Chinese liquors with different flavor types, exhibiting wide potential applications in online quality control and safety evaluation of not only Chinese liquors but also other liquor and alcoholic beverages.

The photodissociation and photoionization behaviors of haloalkanes in the VUV regime are important to fully understand the mechanism of ozone depletion in the stratosphere. The ionization of dichloromethane (CH 2 Cl 2 ) under the irradiation of 10.0 and 10.6 eV light was investigated. CH 2 Cl + was observed at 10 Pa, while both CH 2 Cl + and CHCl 2 + were observed at higher pressure. The production efficiency of CH 2 Cl + decreased with the increasing number density of CH 2 Cl 2 , while that of CHCl 2 + increased. A kinetic model was successfully derived to quantitatively describe the variation trends of CH 2 Cl + and CHCl 2 + , in which the competition between photoinduced ion-pair and photodissociation-assisted photoionization (PD-PI) were included. The ion-pair channel was quenched efficiently at higher pressure or concentration, which reduced its contribution. Our study proposed new insights into the complicated photoexcitation behaviors of CH 2 Cl 2 in the VUV regime and revealed the important role of photodissociation in photoionization at low photon flux.

Thermal gas jet probes, including post-plasma desorption/ionization sources, have not been studied using computational fluid dynamics (CFD) models, as have other ambient mass spectrometry sampling techniques. Two systems were constructed: a heated nitrogen jet probe to establish practical bounds for a sampling/transmission experiment and a CFD model to study trajectories of particles desorbed from a surface through optimization of streamlines and temperatures. The physical model configuration as tested using CFD revealed large losses, transmitting less than 10% of desorbed particles. Different distances between the desorption probe and the transport tube and from the sample surface were studied. The transmission improved when the system was very close to the sample, because the gas jet otherwise creates a region of low pressure that guides the streamlines below the inlet. A baffle positioned to increase pressure in the sample region improves collection efficiency. A Lagrangian particle tracking approach confirms the optimal design leading to a transmission of almost 100%.

A normal phosphorylation state is essential for the function of proteins. Biased regulation frequently results in morbidity, especially for the hyperphosphorylation of oncoproteins. The hyperphosphorylation of ASK1 at Thr838 leads to a persistently high activity state, which accelerates the course of gastric cancer. Under normal conditions, PP5 specifically dephosphorylates p-ASK1 T838 in cells, thereby weakening ASK1 to a low-basal activity state. However, in tumor types, PP5 shows low activity with a self-inhibition mechanism, making p-ASK1 T838 remain at a high level. Thus, we aim to design phosphatase recruitment chimeras (PHORCs) through a proximity-mediated effect for specifically accelerating the dephosphorylation of p-ASK1 T838 . Herein, we describe DDO3711 as the first PP5-recruiting PHORC, which is formed by connecting a small molecular ASK1 inhibitor to a PP5 activator through a chemical linker, to effectively decrease the level of p-ASK1 T838 in vitro and in vivo. DDO3711 shows preferable antiproliferative activity (IC 50 = 0.5 μM) against MKN45 cells through a direct binding and proximity-mediated mechanism, while the ASK1 inhibitor and the PP5 activator, used alone or in combination, exhibit no effect on MKN45 cells. Using DDO3711 , PHORCs are identified as effective tools to accelerate the dephosphorylation of POIs and provide important evidence to achieve precise phosphorylation regulation, which will promote confidence in the further regulation of abnormally phosphorylated oncoproteins.

Achieving ultraviolet and narrowband emission simultaneously in nondoped organic light-emitting diodes (OLEDs) remains a tremendous challenge. Here, a "space-crowded donor-acceptor-donor" molecular design strategy is proposed for developing ultraviolet pure organic fluorophores by the nearby substituted positions at the phenyl linker between carbazole and pyridine units. Benefitting from the large steric hindrance effect, multiple intramolecular interactions, and low-frequency vibronic coupling dominated excited state property, all the emitters exhibit excellent fluorescence efficiencies at the solid state as well as the narrow full width at half maximums (FWHMs). Moreover, the effect of different substitution positions of pyridine on the structure-property relationship is also revealed. Consequently, the nondoped OLEDs exhibit an electroluminescence emission peak of 397 nm with FWHMs of 17 and 22 nm. Due to the high-lying reverse intersystem crossing process, external quantum and exciton utilization efficiencies of 3.6 and 54.55%, respectively, have been achieved based on the emitter with para -linkage. These findings may pave an avenue for the development of high-performance narrowband ultraviolet materials and OLEDs.

Molecular ferroelectric films (MFFs) offer a good platform for miniaturized electronic devices, which are inseparable from their multiaxial nature. Despite great studies, soft MFFs with broadband photo-electroactivity still remain a huge blank as the photoexcited leakage current will severely deteriorate ferroelectricity, hindering their optoelectronic applications. Here, we constructed the multiaxial MFF of HA 2 EA 2 Pb 3 I 10 ( 1 , where EA = ethylammonium and HA = n -hexylammonium) in 2D multilayered perovskites. Eight equivalent polarization directions were observed in 1 , as verified by its symmetry breaking ( i.e ., 4/ mmm F m species), which is the maximum among 2D multilayered perovskites and even more than that of classic ceramic BaTiO 3 . Specially, spin-coated flexible MFFs of 1 are approximately orientated parallel to layered perovskite frameworks, exhibiting in-plane spontaneous polarization ( P s = 1.8 μC/cm 2 ) and broadband absorption (∼1.83 eV). In addition, self-powered broadband detection (∼0.55 μA/cm 2 at 637 nm illumination) was achieved on the soft films, revealing their potential for flexible and wearable electronic devices. Our result sheds light on the design of flexible photoelectronic devices and provides an effective way to expand the applications of 2D molecular ferroelectric materials.

NLRP3 inflammasome activation plays a critical role in inflammation-related disorders. More small-molecule entities are needed to study the mechanism of NLRP3 inflammasome activation and to validate the efficacy and safety of the NLRP3 pathway. Herein, we report the discovery of an orally bioavailable proteasome inhibitor NIC-0102 ( 27 ) that specifically prevents NLRP3 inflammasome activation but has no effect on NLRC4 or AIM2 inflammasomes. In vitro studies revealed that NIC-0102 induced the polyubiquitination of NLRP3, interfered with the NLRP3-ASC interaction, and blocked ASC oligomerization, thereby resulting in the inhibition of NLRP3 inflammasome activation. In addition, NIC-0102 also inhibited the production of pro-IL-1β. Importantly, NIC-0102 showed potent anti-inflammatory effects on DSS-induced ulcerative colitis model in vivo. As a result of these studies, a potential small molecule is identified to demonstrate the possible link between the proteasome and NLRP3 pathway, which supports further exploration of potentially druggable nodes to modulate NLRP3 inflammasome activation.

The present study investigated the mechanism underlying the impact of hesperidin (HES) on nonalcoholic fatty liver (NAFLD). C57BL/6J male mice were administered a low-fat diet, high-fat diet (HFD), or HFD plus 0.2% (wt/wt) HES (HFD + HES) diet. After 16 weeks of intervention, the mice in the HFD+HES group showed a lower final body weight and liver weight and improved serum lipid profiles when compared with the HFD group. Alleviation of liver dysfunction induced by HFD was observed in HES-fed mice, and the expression of genes involved in lipid metabolism was also altered. Moreover, HES changed the composition of the intestinal microbiota and enriched specific genera such as Bacteroidota . Liver metabolomics analysis indicated that HES enhanced the abundance of metabolites in arginine-related as well as mitochondrial oxidation-related pathways, and these metabolites were predicted to be positively correlated with the gut genera enriched by HES. Together, these results indicate that HFD-fed mice supplemented with HES showed a markedly regulated hepatic metabolism concurrent with shifts in specific gut bacteria.

In recent years, with the successful development of proteolysis-targeting chimeric molecules (PROTACs), the potential of heterobifunctional molecules to contribute to reenvisioning drug design, especially small-molecule drugs, has been increasingly recognized. Inspired by PROTACs, diverse heterobifunctional molecules have been reported to simultaneously bind two or more molecules and bring them into proximity to interaction, such as ribonuclease-recruiting, autophagy-recruiting, lysosome-recruiting, kinase-recruiting, phosphatase-recruiting, glycosyltransferase-recruiting, and acetyltransferase-recruiting chimeras. On the basis of the heterobifunctional principle, more opportunities for advancing drug design by linking potential effectors to a protein of interest (POI) have emerged. Herein, we introduce heterobifunctional molecules other than PROTACs, summarize the limitations of existing molecules, list the main challenges, and propose perspectives for future research directions, providing insight into alternative design strategies based on substrate-proximity-based targeting.

High-pressure photoionization time-of-flight mass spectrometry (HPPI-TOFMS) combined with dynamic headspace sampling was developed for rapid identification of adulteration in extra virgin olive oil (EVOO). The volatile organic compound (VOC) fingerprints of EVOO, refined rapeseed oil (r-RO), peanut oil (PO), corn oil (CO), fragrant rapeseed oil (f-RO), and sunflower oil (SO) were obtained in just 1.5 min, which enabled satisfactory classification of different edible oils. 1,4-Bis(methylene)cyclohexane and dimethyl disulfide were unique VOCs in r-RO and f-RO, respectively, while 2,5-dimethylpyrazine and 2-methylpyrazine were distinctive VOCs in PO. Percentages as low as 3% r-RO, 1% PO, and 1% f-RO in r-RO-EVOO, PO-EVOO, and f-RO-EVOO mixtures, respectively, were successfully identified based on the characteristic VOCs. Linear regression equations of these VOCs were established and utilized for predicting the adulteration proportions. The good agreements between the actual adulteration proportions and the predicted ones demonstrated that HPPI-TOFMS was reliable for the quantification of EVOO adulteration.

Nanocomposite conductive fiber has been newly developed as a lightweight material with high flexibility and strong weavability, which can meet the requirements of flexible wearable devices. Herein, lightweight porous aramid nanofibers (ANF) and carbon nanotube (CNT) aerogel fibers coated with polypyrrole (PPy) layers are prepared by a wet spinning method for motion detection and information transmission. The ANF/CNT/PPy aerogel fiber with low density (56.3 mg/cm 3 ), conductivity (6.43 S/m), and tensile strength (2.88 MPa) were used as motion sensors with high sensitivity (0.12) and long life (1000 cycles). At the same time, the differential conductivity of aerogel fibers is utilized to reduce the information transmission time (up to 46%). High- and low-temperature-resistant (-196 to 100 °C) aerogel fibers are also available as a quick heater and ionic solution detector. In summary, the prepared ANF/CNT/PPy aerogel fiber can be used as a multifunctional sensor for human-health detection and motion monitoring.

A linearly decreasing electric field has been previously proven to be effective for diffusional correction of ions in a varying field drift tube (VFDT) system, leading to higher resolving powers compared to a conventional drift tube due to its capacity to narrow distributions midflight. However, the theoretical predictions in resolving power of the VFDT were much higher than what was observed experimentally. The reason behind this discrepancy has been identified as the difference between the theoretically calculated resolving power (spatial) and the experimental one (time). To match the high spatial resolving power experimentally, a secondary high voltage pulse (HVP) at a properly adjusted time is used to provide the ions with enough momentum to increase their drift velocity and hence their time-resolving power. A series of systematic numerical simulations and experimental tests have been designed to corroborate our theoretical findings. The HVP-VFDT atmospheric pressure portable system improves the resolving power from the maximum expected of 60-80 for a regular drift tube to 250 in just 21 cm in length and 7kV, an unprecedent accomplishment.

Adequate dietary fiber intake during gestation is critical for maternal-fetal health. This experiment aims to uncover the impacts of maternal long-term intake of inulin on fetal development and its underlying mechanism. Eighty female Sprague-Dawley rats were randomly assigned to two groups receiving either a fiber-free diet or an inulin diet (inulin) for three parities. On the 19 th day of pregnancy in the third parity, blood, intestinal, placental, and colonic digesta samples were collected. Results showed that maternal intake of inulin significantly decreased the within-litter birth weight variation in parities 2 and 3. Inulin intake modified the gut microbiome profiles and elevated the colonic contents of short chain fatty acids (propionate and butyrate). Inulin decreased the serotonin (5-HT) concentration in the colon, whereas it increased the 5-HT concentrations in serum and placenta and the number of 5-HT + enterochromaffin cells in the colon. The protein expression of melatonin-synthesizing enzyme (arylalkylamine N -acetyltransferase) and the melatonin concentration in the placenta were also increased by inulin. Inulin improved the placental redox status and nutrient transport. These findings indicated that maternal long-term intake of inulin improves fetal development by altering the intestinal microbiota and related metabolites in rats.

The aim of this study is to investigate mRNA expression profiling by RNA sequencing (RNA-seq) in patients with coronary artery disease (CAD) and validate differentially expressed genes (DEGs) as novel biomarkers for CAD. Transcriptome-wide mRNA expression analysis of peripheral blood mononuclear cells was performed in five CAD patients and five controls. Functional enrichment analyses, protein-protein interaction network construction, and hub gene selection were further conducted. Relative expression levels of hub genes were validated by quantitative reverse transcription PCR in larger cohorts. Spearman correlation test and multiple linear regression analysis were applied to examine the relationship between confounding factors with severity of coronary artery atherosclerosis. Receiver operating characteristic (ROC) curve analysis was adopted to identify potentially diagnostic biomarkers for CAD. A total of 527 upregulated and 653 downregulated mRNAs were identified as DEGs in CAD patients. The relative expression levels of beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), F-box and leucine-rich repeat protein 4 (FBXL4), ubiquitin conjugating enzyme E2 D2 (UBE2D2), and ankyrin repeat and SOCS box containing 1 (ASB1) were significantly different between two groups (all p ≤ 0.05). The severity of coronary artery atherosclerosis was negatively associated with the BTRC gene relative expression level ( r = -0.323, p < 0.001) and positively with UBE2D2 ( r = 0.285, p < 0.001). ROC analysis of BTRC and UBE2D2 genes showed that the areas under the curve were 0.782 (95% CI: 0.720-0.845, p < 0.001) and 0.753 (95% CI: 0.681-0.824, p < 0.001), respectively. We described the characteristics of mRNA expression in the peripheral blood of CAD patients and controls by RNA-seq. Combined with Spearman correlation analysis and ROC analyses, BTRC and UBE2D2 genes had significantly diagnostic values, which may have potential to act as novel diagnostic biomarkers and therapeutic targets for CAD., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.