Circular RNAs: Potential biomarkers and therapeutic targets for autoimmune diseases.

The outcomes and prognosis of autoimmune diseases depend on early diagnosis and effective treatments. However, symptoms of early autoimmune diseases are often remarkably similar to many inflammatory diseases, leading to difficulty in precise diagnosis. Circular RNAs (circRNAs) belong to a novel class of endogenous RNAs, functioning as microRNA (miRNA) sponges or participating in protein coding. It has been shown in many studies that patients with autoimmune diseases have aberrant circRNA expression in liquid biopsy samples (such as plasma, saliva, and urine). Thus, circRNAs are potential biomarkers for the diagnosis and prognosis of autoimmune diseases. Moreover, overexpression and depletion of target circRNAs can be utilized as possible therapeutic approaches for treating autoimmune diseases. In this review, we summarized recent progress in the roles of circRNAs in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. We also discussed their potential as biomarkers and therapeutic targets.

Pollution Status and Associated Risk Assessment of Heavy Metals in Sewage Sludge in the Yangtze River Delta, China.

The risk assessment of heavy metals (HMs) in sewage sludge (SS) is essential before land application. Six HMs in nineteen SS collected in the Yangtze River Delta were analyzed to assess risks to environment, ecosystem, and human health. HMs concentrations were ranked in the order of Zn > Cu > Cr > Ni > Pb > Cd, with Cu, Zn, and Ni in a total of 16% of samples exceeding the legal standard. Zn showed greatest extractability according to EDTA-extractable concentrations. HMs in 16% of SS samples posed heavy contamination to the environment with Zn as the major pollutant. HMs in 26% of samples posed ecological risk to the ecosystem and Cd was the highest risky HM. The probabilistic health risk assessment revealed that HMs posed carcinogenic risks to all populations, but non-carcinogenic risks only to children. This work will provide fundamental information for land application of SS in this area.

Phase separation of Ddx3xb helicase regulates maternal-to-zygotic transition in zebrafish.

Vertebrate embryogenesis involves a conserved and fundamental process, called the maternal-to-zygotic transition (MZT), which marks the switch from a maternal factors-dominated state to a zygotic factors-driven state. Yet the precise mechanism underlying MZT remains largely unknown. Here we report that the RNA helicase Ddx3xb in zebrafish undergoes liquid-liquid phase separation (LLPS) via its N-terminal intrinsically disordered region (IDR), and an increase in ATP content promotes the condensation of Ddx3xb during MZT. Mutant form of Ddx3xb losing LLPS ability fails to rescue the developmental defect of Ddx3xb-deficient embryos. Interestingly, the IDR of either FUS or hnRNPA1 can functionally replace the N-terminal IDR in Ddx3xb. Phase separation of Ddx3xb facilitates the unwinding of 5' UTR structures of maternal mRNAs to enhance their translation. Our study reveals an unprecedent mechanism whereby the Ddx3xb phase separation regulates MZT by promoting maternal mRNA translation.

Two-Step Dielectric Responsive Organic-Inorganic Hybrid Material with Mid-Band Light Emission.

Hybrid organic-inorganic perovskite (HOIP) have received tremendous scientific attention because of the phase transition and photovoltaic properties. However, achieving the special perovskite structure with both two-step dielectric response and luminescence characteristics is rarely reported. Herein, we report an organic-inorganic hybrid perovskite, [(BA)2 ⋅ PbI4 ] (Compound 1, BA=n-butylamine) by introducing flexible organic cations (HBA+ ), with direct mid-band gap as 2.28 eV. Interestingly, this material exhibits two-step reversible dielectric response at 350 K and 460 K (in heating process), respectively. Besides, the photoluminescence was found: it emits charming green light under 365 nm lamp (Photoluminescence quantum yield is 9.52 %). The outstanding two-step dielectric response and luminescence characteristics of this compound might pave the way for the application of dielectric and ferroelectric functional materials in temperature sensors and mechanical switches.

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation.

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

Two-step nonlinear optical switch in a hydrogen-bonded perovskite-type crystal.

Switchable nonlinear optical (NLO) materials have aroused broad interest on account of their captivating optical and electronic properties. We demonstrate a novel perovskite-type crystal with exceptional hydrogen bond interactions that are associated with the onset of reorientational motions of organic cations and thus induce the occurrence of two successive phase transitions to be a two-step NLO switch. This finding affords an alternative approach for the design and assembly of switchable NLO materials.

Genome-wide identification, characterization and functional analysis of the chitianse and chitinase-like gene family in Diaphorina citri.

BACKGROUND: Insect chitinases play vital roles in postembryonic development, especially during the molting process, and are potential targets for the RNA interference (RNAi)-based insecticidal strategy. Systematic functional analyses of chitinase genes have already been conducted on numerous insect pests, but similar analyses have not been carried out on Diaphorina citri. RESULTS: Eleven chitinase/chitinase-like genes and one endo-ß-N-acetylglucosaminidase (ENGase) gene were identified in the Diaphorina citri genome using various bioinformatic tools. Transcriptomes of the integument and midgut from fifth-instar nymphs and freshly-emerged adults of Diaphorina citri were generated and sequenced. Potential functions of 12 chitinase/chitinase-like genes were examined during nymph-adult transitions. Four chitinase genes, including DcCht5, DcCht7, DcCht10-1 and DcCht10-2, were mainly expressed in the integument of fifth-instar nymphs. These four genes were also up-regulated significantly under 20-hydroxyecdysone (20E) treatments. RNAi-mediated knockdown of these four genes suggests that they are essential for nymph-adult transition. CONCLUSION: Our results demonstrated essential roles of the chitinase/chitinase-like genes during the nymph-adult transition in Diaphorina citri, which are potentially useful targets for controlling the Diaphorina citri pest. © 2022 Society of Chemical Industry.

The Transcriptome Characteristics of Severe Asthma From the Prospect of Co-Expressed Gene Modules.

Rationale: Severe asthma is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of asthmatic bronchial epithelial cells have provided biological insights and underscored possible pathological mechanisms; however, the molecular basis in severe asthma is still poorly understood. Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype. Methods: The k-means clustering and differentially expressed genes (DEGs) were performed in 129 asthma individuals in the Severe Asthma Research Program. The DEG profiles were analyzed by weighted gene co-expression network analysis (WGCNA), and the expression value of each gene module in each individual was annotated by gene set variation analysis (GSVA). Results: Expression analysis defined five stable asthma subtype (AS): 1) Phagocytosis-Th2, 2) Normal-like, 3) Neutrophils, 4) Mucin-Th2, and 5) Interferon-Th1 and 15 co-expressed gene modules. "Phagocytosis-Th2" enriched for receptor-mediated endocytosis, upregulation of Toll-like receptor signal, and myeloid leukocyte activation. "Normal-like" is most similar to normal samples. "Mucin-Th2" preferentially expressed genes involved in O-glycan biosynthesis and unfolded protein response. "Interferon-Th1" displayed upregulation of genes that regulate networks involved in cell cycle, IFN gamma response, and CD8 TCR. The dysregulation of neural signal, REDOX, apoptosis, and O-glycan process were related to the severity of asthma. In non-TH2 subtype (Neutrophils and Interferon-Th1) with severe asthma individuals, the neural signals and IL26-related co-expression module were dysregulated more significantly compared to that in non-severe asthma. These data infer differences in the molecular evolution of asthma subtypes and identify opportunities for therapeutic development. Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.

Unique Design Strategy for Dual Phase Transition That Successfully Validates Dual Switch Implementation in the Dielectric Material.

Dual phase transition/switch materials are a critical cornerstone of information storage and sensing. However, they are difficult to design successfully, and compared with materials showing single-switchable phase transitions, the dual ones retain many challenges by far. Therefore, the significance of a general strategy is far greater than an accidental success. Here, an efficient strategy combining branchlike Et3R and trunklike benzylamine analogues successfully validates dual-switch implementation in the dielectric materials. This inevitable success is based on our treelike analogue mentioned above in which amines with multiple branches can achieve a temperature-induced phase change. Exactly, (BCDA)2ZnBr4 [BCDA = benzyl-(2-chloroethyl)dimethylammonium] proves the regularity and undergoes two reversible phase transitions at 295.4 and 340.8 K, respectively. Variable-temperature single-crystal X-ray diffraction revealed that the generation of double phase transitions is caused by progressive changes of treelike BCDA+ as the temperature rises. Because the permittivity ε' of (BCDA)2ZnBr4 abruptly changed near the phase-transition temperatures, such physical properties make it have latent applicability. In short, the success of our strategy will inspire researches to discover more interesting dual phase transition/switch materials.

Enantiomorphic Perovskite Ferroelectrics with Circularly Polarized Luminescence.

Materials with circularly polarized luminescence (CPL) activity have immense potential applications in molecular switches, optical sensors, information storage, asymmetric photosynthesis, 3D optical displays, biological probe, and spintronic devices. However, the achiral architectures of most of the luminophores severely limit their practical needs. Within this context, molecular ferroelectrics with striking chemical variability and structure-property flexibility bring light to the assembly of CPL-active ferroelectric materials. Herein, we report organic-inorganic perovskite enantiomorphic ferroelectrics, (R)- and (S)-3-(fluoropyrrolidinium)MnBr3, undergoing a 222F2-type ferroelectric phase transition at 273 K. Their mirror relationships are verified by both single-crystal X-ray diffraction and vibrational circular dichroism (VCD). Furthermore, the corresponding Cotton effect for two chiral crystals was captured by mirror CPL activity. This may be assigned to the inducing interaction between the achiral luminescent perovskite framework and chiral organic components. As far as we know, this is the first molecular ferroelectric with CPL activity. Accordingly, this will inspire intriguing research in molecular ferroelectrics with CPL activity and holds great potential for the development of new optoelectronic devices.

Three-Dimensional Metal-Free Molecular Perovskite with a Thermally Induced Switchable Dielectric Response.

Temperature-responsive materials with switching physical properties have been widely researched. Among them, the switchable dielectric perovskite materials show potential applications in the electrical and electronic industries and even the intelligence industries. However, perovskite oxides and hybrid organic-inorganic perovskites, as the most representative switchable dielectric materials, are limited by bad biocompatibility. Herein, we report temperature-dielectric-responsive metal-free perovskite (H2dabco)(NH4)[BF4]3 constructed by the strategy of substituting the B site in the general formula ABX3 (doubly protonated 1,4-diazabicyclo[2.2.2]octane = H2dabco). Meanwhile, structurally similar hybrid material (H2dabco)Rb[BF4]3 was designed as a control. They exhibit similar phase-transition characteristics and dielectric response behaviors around 333 K. More interestingly, the ordered-disordered transformation of their organic "spherical" cations (H2dabco) was deemed to produce their phase transitions and dielectric response switching. Given its ability to generate a dielectric response, (H2dabco)(NH4)[BF4]3 will show the potential application of metal-free perovskite in a future thermal sensing device.

Two-Dimensional Layered Perovskite Ferroelectric with Giant Piezoelectric Voltage Coefficient.

Piezoelectric sensors that can work under various conditions with superior performance are highly desirable with the arrival of the Internet of Things. For practical applications, a large piezoelectric voltage coefficient g and a high Curie temperature Tc are critical to the performance of piezoelectric sensors. Here, we report a two-dimensional perovskite ferroelectric (4-aminotetrahydropyran)2PbBr4 [(ATHP)2PbBr4] with a saturated polarization of 5.6 µC cm-2, high Tc of 503 K [above that of BaTiO3 (BTO, 393 K)], and extremely large g33 of 660.3 × 10-3 V m N-1 [much beyond that of Pb(Zr,Ti)O3 (PZT) ceramics (20 to 40 × 10-3 V m N-1), more than 2 times higher than that of poly(vinylidene fluoride) (PVDF, about 286.7 × 10-3 V m N-1)]. Combined with the advantages of molecular ferroelectrics, such as light weight, easy and environmentally friendly processing, and mechanical flexibility, (ATHP)2PbBr4 would be a competitive candidate for next-generation smart piezoelectric sensors in flexible devices, soft robotics, and biomedical devices.

Anion-Regulated Molecular Rotor Crystal: The First Case of a Stator-Rotator Double Switch with Relaxation Behavior.

Molecular rotational motion is crucial in artificial molecular machines and is expected to be very significant for the development of an electronic information molecular machine as mentioned in the 2016 Nobel Prize. However, controlling multiple motor modes is a huge challenge. Here, we report a case in which the structural phase transition effectively triggers multiple motor modes by regulating the rotational speed of the cation and/or anion. A novel switchable crystalline supramolecular rotor, [(cyclohexylammonium)(18-crown-6)] FSO3 (1), exhibits prominent temperature-dependent double switching behavior at 157.9 and 389.1 K induced by the variation of the rotational speed of the FSO3- anion (which acts as a super miniature rotator) in response to temperature. Moreover, it exhibits significant relaxation behavior and excellent pyroelectric switch characteristics. To the best of our knowledge, this might be the first discovery of the stator-rotator double switch with a relaxation effect, which could be a promising candidate for a slow/fast responsive double switch over a wide temperature range.

Nonselective uptake of silver and gold nanoparticles by wheat.

Metallic nanoparticles (NPs) show unique reactivity to crop plants, but the uptake mechanisms remain unclear. We quantitatively evaluated the phytoavailability of particles to wheat (Triticum aestivum L.) in hydroponics upon exposure to AgNPs (15 nm) or AuNPs (13 and 33 nm). Particles were physically separated from the released Ag ions by a dialysis membrane, under which particle-specific uptake of AgNPs could be discerned. Plants did not differentiate AgNPs and AuNPs during particle uptake, with uptake rate constants of 1.1 ± 0.1, 1.2 ± 0.3, and 1.2 ± 0.1 L kg-1 h-1 for AgNPs, AuNPs (13 nm), and AuNPs (33 nm), respectively. We found little effect of particle size (13 or 33 nm AuNPs) or core composition (Ag or Au) on particle bioavailability. Plants stimulated the subsequent uptake of Evans blue stain and showed cell damage in root tips. These results imply similar physiological processes involved in particle-specific uptake of AgNPs and AuNPs. The internalization of particles was further confirmed by single particle inductively coupled plasma mass spectrometry (spICP-MS) and transmission electron microscope-energy dispersive spectrometer (TEM-EDS) analysis. The work here builds the knowledge base for the nature of particle-specific uptake of different NP types by crop plants.

Higher-Temperature Dielectric Molecular Motor Induced by Unusual Chair-to-Rotator Motion.

With regard to the artificial molecular motor that was recognized with the 2016 Nobel Prize, this success proves the great scientific significance of rotary motor-type motion at the molecular level, which has been expected to play an invaluable role in the development of electronic information molecular materials. However, designing electronic information-critical high-temperature molecular motors has always been a huge challenge. Since we discovered [(CH3)3NCH2Cl]MnCl3, this cation rotation pattern with a motor-type motion structure has continued to attract our attention. Considering a strategy that combines molecular machines with dielectric theory, ( N, N-dimethylpiperidinium)CdCl3, the new dielectric molecular motor material that exhibits superior physical properties, could be considered to be an excellent dielectric switch based on its electric field and temperature. Crystal structure analyses reveal that the reversible phase transition is mainly induced by the unusual chair-to-rotator motion of cations. Because of the unprecedented leaping structural transition from P63/ mmc to P21/ c and the rotating motor-type motion structure, the material exhibits remarkable anisotropy and outstanding dielectric switching characteristics. These findings open a new avenue for the design and assembly of novel molecular motor materials in the field of electronic information.

High local coordination symmetry around the spin center and the alignment between magnetic and symmetric axes together play a crucial role in single-molecule magnet performance.

A tetradentate 8-hydroxyquinoline-based acyl hydrazone ligand (HL1 = 8-hydroxyquinoline-2-carboxaldehyde-(aminourea)hydrochloride) was elaborately used to construct a mononuclear dysprosium complex DyCl3HL1·CH3OH (1) with a nearly ideal pentagonal bipyramid coordination geometry (D5h) surrounding the Dy(iii) ion to achieve the significant performance of single-molecule magnets (SMMs). Meanwhile, the isolated high local symmetry center was successfully kept intact and further bridged to a series of double bipyramid systems by two phenolic oxygen atoms of the acyl hydrazone ligands (HL1 and HL2 = 8-hydroxyquinoline-2-carboxaldehyde-(benzoyl)hydrazine), with the formulae [Dy2Cl4(L1)2(CH3OH)2]·4C5H5N (2) and [Dy2Cl4(L2)2]·2CH3CN (3). In addition, the monodentate co-ligand anion was replaced by a larger sterically hindered ligand and a bidentate monovalent ß-diketonate anion to generate [Dy2(tfo)4(L2)2(EtOH)2] (4), [Dy2(tta)4(L2)2(EtOH)2]·2(EtOH) (5) and [Dy2(dbm)4(L2)2(EtOH)2] (6) (tfo = trifluoromethanesulfonic acid, dbm = dibenzoylmethane, tta = 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione) with eight-coordinate geometry. Strikingly, the dynamic magnetic measurements revealed that complexes 1-3 did not display the expected significant SMM performance albeit they had high local symmetry. In combination with ab initio calculation, the alignment of the coordination symmetric axis and the magnetic easy axis dominates the molecular magnetic anisotropy, and the magnetic easy axis could be modulated by the distribution of coordination atoms with different electrostatic properties.

Switchable Dielectric Phase Transition Triggered by Pendulum-Like Motion in an Ionic Co-crystal.

Molecular-based ionic co-crystals, which have the merits of low-cost/easy fabrication processes and flexible structure and functionality, have already exhibited tremendous potential in molecular memory switches and other electric devices. However, dipole (ON/OFF switching) triggering is a huge challenge. Here, we introduce a pendulum-like dynamic strategy to induce the order-disorder transition of a co-crystal [C5 H7 N3 Cl]3 [Sb2 Br9 ] (compound 1). Here, the anion and cation act as a stator and a pendulum-like rotor (the source of the dielectric switch), respectively. The temperature-dependent dielectric and differential scanning calorimetry (DSC) analyses reveal that 1 undergoes a reversible phase transition, which stems from the order-disorder transition of the cations. The thermal ON/OFF switchable motions make 1 a promising candidate to promote the development of bulk crystals as artificial intelligent dielectric materials. In addition, the pendulum-like molecular dynamics and distinct arrangements of two coexisting ions with a notable offset effect promotes/hinders dipolar reorientation after dielectric transition and provides a rarely observed but fairly useful and feasible strategy for understanding and modulating the dipole motion in crystalline electrically polarizable materials.

Reversible Thermal Dielectric Switch Triggered by Blooming-Flower Structural Phase Transition in Ionic Crystal without Metal.

Due to having excellent properties of sensitive switchable physical and/or chemical response, simple preparation, and environmentally friendly processing, bistable switches (electric switching between "on" and "off" bistable states) have gradually developed into an ideal class of highly smart materials. However, most of them contain metals, especially heavy metals, which are highly toxic to the environment, and metal-free switch materials are rarely reported. Based on this issue, we successfully designed and synthesized organic ion crystals and realized thermal dielectric switching characteristics. Differential scanning calorimetry and dielectric measurements show that the large-size crystal (F-TEDA)(BF4)2 (1) can be regarded as an sensitive dielectric bistable switching between high (switch on) and low (switch off) dielectric states. Variable-temperature single crystal structure reveals one-half of the BF4- anions in the crystal undergoes order-disorder transition around 200 K, similar to the transition between flower buds and blooming flowers. This flower-style transition of BF(1)4-/BF(0.5)8- triggered the rapid switching performance; those properties establish the basis of their applications in excellent temperature-responsive electrical switches, especially lightweight devices.

An evaluation of impact of social support and care-giving on medication adherence of people living with HIV/AIDS: A nonrandomized community intervention study.

To evaluate the effect of the social support on adherence of highly active antiretroviral therapy (HAART) of people living with human immunodeficiency virus/acquired immune deficiency syndrome (PLWHA). Participants of PLWHA at Beijing, China were intervened by 1-year social support program intervention. Difference of social support scale and medication adherence scale before and after the intervention were evaluated. Our results showed that there were statistically significant difference for total score and subjective score, medication adherence between before and after intervention (t = -3.62, -2.81, 5.75, P < .05), and there were statistically significant correlation between the difference of total social support score and that of social support utilization score, and the difference of medication adherence score (r = 0.14, 0.12, all P < .05). Multifactor linear regression showed that the medication adherence score was influenced by the insurance status, the residential status, and the difference in the social support utilization score (ß = -0.14, 0.17, 0.16, all P < .05). Social support and care-giving can exert some influence and facilitate PLWHAs adherence of HAART.

Tunable dielectric transitions in layered organic-inorganic hybrid perovskite-type compounds: [NH3(CH2)2Cl]2[CdCl4-4xBr4x] (x = 0, 1/4, 1).

Molecular bistable dielectric switches represent a class of highly desirable intelligent materials due to their sensitive switchable responses, simple and environmentally friendly processing, light weights, and mechanical flexibility. However, most of these switches can only work at a very low temperature, extremely limiting their potential applications. Herein, three layered organic-inorganic hybrid perovskite-type compounds of the general formula A2BX4, [NH3(CH2)2Cl]2[CdCl3Br] (1), [NH3(CH2)2Cl]2[CdCl4] (2) and [NH3(CH2)2Cl]2[CdBr4] (3), which display sensitive dielectric switching reversibility and remarkable switching anti-fatigue, have been successfully designed. Differential scanning calorimetry and dielectric measurements for 1 confirm its reversible phase transition at around 166 K. Through anion modulation, the phase transition temperatures of 2 and 3 can be greatly improved up to 237 K and 254 K, respectively. Structural analysis discloses that the phase transition temperature's shifts may result from the differences among the inorganic frameworks. Moreover, due to the significant order-disorder transitions of ammonium cations, the permittivities of 1, 2 and 3 change abruptly at around the phase transition points, making them excellent stimuli-responsive electrical switches. Such an anion-modulated method will open up new possibilities of highly efficiently tuning the phase transition temperature of molecular bistable dielectric switches.