Topological defect-mediated morphodynamics of active-active interfaces.

Physical interfaces widely exist in nature and engineering. Although the formation of passive interfaces is well elucidated, the physical principles governing active interfaces remain largely unknown. Here, we combine simulation, theory, and cell-based experiment to investigate the evolution of an active-active interface. We adopt a biphasic framework of active nematic liquid crystals. We find that long-lived topological defects mechanically energized by activity display unanticipated dynamics nearby the interface, where defects perform "U-turns" to keep away from the interface, push the interface to develop local fingers, or penetrate the interface to enter the opposite phase, driving interfacial morphogenesis and cross-interface defect transport. We identify that the emergent interfacial morphodynamics stems from the instability of the interface and is further driven by the activity-dependent defect-interface interactions. Experiments of interacting multicellular monolayers with extensile and contractile differences in cell activity have confirmed our predictions. These findings reveal a crucial role of topological defects in active-active interfaces during, for example, boundary formation and tissue competition that underlie organogenesis and clinically relevant disorders.

Three-Dimensional Chiral Morphogenesis of Active Fluids.

Chirality is an essential nature of biological systems. However, it remains obscure how the handedness at the microscale is translated into chiral morphogenesis at the tissue level. Here, we investigate three-dimensional (3D) tissue morphogenesis using an active fluid theory invoking chirality. We show that the coordination of achiral and chiral stresses, arising from microscopic interactions and energy input of individual cells, can engender the self-organization of 3D papillary and helical structures. The achiral active stress drives the nucleation of asterlike topological defects, which initiate 3D out-of-plane budding, followed by rodlike elongation. The chiral active stress excites vortexlike topological defects, which favor the tip spheroidization and twisting of the elongated rod. These results unravel the chiral morphogenesis observed in our experiments of 3D organoids generated by human embryonic stem cells.

Benzoselenadiazole-Functionalized H-Bonded Arylamide Foldamers: Solvent-Responsive Properties and Helix Self-Assembly Directed by Chalcogen Bonding in Solid State.

In this study, a series of H-bonded arylamide foldamers bearing benzoselenadiazole ends with solvent-responsive properties have been synthesized. In dichloromethane or dimethyl sulfoxide solvents, the molecules exhibit meniscus or linear structures, respectively, which can be attributed to the unique intramolecular hydrogen bonding behavior evidenced by 1D 1H NMR and 2D NOESY spectra. UV-vis spectroscopy experiments show that the absorption wavelength of H-bonded arylamide foldamers are significantly red-shifted due to the presence of benzoselenadiazole group. In addition, the crystal structures reveal that effective intermolecular dual Se ⋅ ⋅ ⋅ N interactions between benzoselenadiazole groups induce further assembly of the monomers. Remarkably, supramolecular linear and double helices structures are constructed under the synergistic induction of intramolecular hydrogen bonding and intermolecular chalcogen bonding. Additionally, 2D DOSY diffusion spectra and theoretical modelling based on density functional theory (DFT) are performed to explore the persistence of intermolecular Se ⋅ ⋅ ⋅ N interactions beyond the crystalline state.

In vivo transgenic studies confirm the critical acylation function of LeBAHD56 for shikonin in Lithospermum erythrorhizon.

KEY MESSAGE: LeBAHD56 is preferentially expressed in tissues where shikonin and its derivatives are biosynthesized, and it confers shikonin acylation in vivo. Two WRKY transcriptional factors might regulate LeBAHD56's expression. Shikonin and its derivatives, found in the roots of Lithospermum erythrorhizon, have extensive application in the field of medicine, cosmetics, and other industries. Prior research has demonstrated that LeBAHD1(LeSAT1) is responsible for the biochemical process of shikonin acylation both in vitro and in vivo. However, with the exception of its documented in vitro biochemical function, there is no in vivo genetic evidence supporting the acylation function of the highly homologous gene of LeSAT1, LeBAHD56(LeSAT2), apart from its reported role. Here, we validated the critical acylation function of LeBAHD56 for shikonin using overexpression (OE) and CRISPR/Cas9-based knockout (KO) strategies. The results showed that the OE lines had a significantly higher ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than the control. In contrast, the KO lines had a significantly lower ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than controls. As for its detailed expression patterns, we found that LeBAHD56 is preferentially expressed in roots and callus cells, which are the biosynthesis sites for shikonin and its derivatives. In addition, we anticipated that a wide range of putative transcription factors might control its transcription and verified the direct binding of two crucial WRKY members to the LeBAHD56 promoter's W-box. Our results not only confirmed the in vivo function of LeBAHD56 in shikonin acylation, but also shed light on its transcriptional regulation.

Development and validation of a urinary microRNA biomarker panel as a tool for early detection of prostate cancer in a Chinese population.

INTRODUCTION: Urinary microRNAs (miRNAs) may serve as promising biomarkers for non-invasive early detection of prostate cancer (PCa). We aimed to identify multi-miRNA urinary biomarker panel for early detection of PCa. METHODS: Urine samples from 83 PCa patients and 88 healthy control subjects in a Chinese population were collected for miRNA profiling. The absolute expression of 360 unique miRNAs were measured in each sample using a highly sensitive and robust RT-qPCR workflow. Candidate urinary miRNA biomarkers were identified based on differential expression between PCa patients and healthy controls. Multi-miRNA biomarker panels were optimised for detection of PCa using three regression algorithms (Lasso, Stepwise, Exhaustive) to identify an optimal biomarker panel with best detection performance and least number of miRNAs. RESULTS: A total of 312 miRNAs were detected in urine samples, 10 candidate urinary miRNA biomarkers differentially expressed between PCa and healthy samples were identified. A panel comprising these 10 miRNAs detected PCa with an area under the curve (AUC) of 0.738. Optimization of multi-miRNA panels resulted in a 6-miRNA biomarker panel (hsa-miR-375, hsa-miR-520d-5p, hsa-miR-199b-5p, hsa-miR-518e-5p, hsa-miR-31-3p and hsa-miR-4306) that had an AUC of 0.750. CONCLUSION: We identified a urinary miRNA biomarker panel for early detection of PCa in a Chinese population.

Azide Ionic Liquids for Safe, Green, and Highly-Efficient Azidation Reactions to Produce Azide Polymers.

Azide compounds are widely used and especially, polymers bearing pendant azide groups are highly desired in numerous fields. However, harsh reaction conditions are always mandatory to achieve full azidation, causing severe side reactions and degradation of the polymers. Herein, we report the design and preparation of two azide ionic liquids (AILs) with azide anion and triethylene glycol (E3 )-containing cation, [P444E3 ][N3 ] and [MIME3 ][N3 ]. Compared with the traditional sodium azide (NaN3 ) approach, both AILs showed much higher reaction rates and functional-group tolerance. More importantly, they could act as both reagents and solvents for the quantitative azidation of various polymeric precursors under mild conditions. Theoretical simulations suggested that the outstanding performance of AILs originated from the existence of ion pairs during the reaction, and the E3 moieties played a crucial role. Lastly, after the reaction, the AILs could be easily regenerated, presenting a safer, greener, and highly efficient synthesis route for azide polymers.

Exosomes derived from myeloid-derived suppressor cells facilitate castration-resistant prostate cancer progression via S100A9/circMID1/miR-506-3p/MID1.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is a major cause of recurrence and mortality among prostate cancer (PCa) patients. Myeloid-derived suppressor cells (MDSCs) regulate castration resistance in PCa. Previously, it was shown that intercellular communication was efficiently mediated by exosomes (Exos), but the role and the mechanism of MDSC-derived Exos in CRPC progression was unclear. METHODS: In this study, the circRNA expression profiles in PC3 cells treated with MDSC-Exo and control cells were investigated using a circRNA microarray. RESULTS: The data showed that circMID1 (hsa_circ_0007718) expression was elevated in PC3 cells treated with MDSC-Exo. Moreover, high circMID1 expression was found in PCa compared with benign prostatic hyperplasia (BPH) tissues and in CRPC patients compared with hormone sensitive prostate cancer (HSPC) patients. Further studies showed that MDSC-Exo accelerated PCa cell proliferation, migration, and invasion, while circMID1 deficiency inhibited MDSC-Exo-regulated CRPC progression in vitro and in vivo. Mechanistically, MDSC-derived exosomal S100A9 increased circMID1 expression to sponge miR-506-3p, leading to increased MID1 expression and accelerated tumor progression. CONCLUSION: Together, our results showed that a S100A9/circMID1/miR-506-3p/MID1 axis existed in MDSC-Exo-regulated CRPC progression, which provided novel insights into MDSC-Exo regulatory mechanisms in CRPC progression.

Spontaneous organization and phase separation of skyrmions in chiral active matter.

Skyrmions are topologically protected vortex-like excitations that hold promise for applications such as information processing and electron manipulation. Here we combine theoretical analysis and numerical simulations to show that skyrmions can spontaneously emerge in chiral active matter without external confinements or regulation. Strikingly, these activity-driven skyrmions can either self-organize into a periodic, stable square lattice consisting of half Néel skyrmions and antiskyrmions, where the in-plane flows display an antiferromagnetic vortex array, or undergo phase separation between skyrmions with different topological numbers. We identify that the emerging skyrmion dynamics stems from the competition between the chiral and polar coherence length scales dictated by the interplay of intrinsic chirality, polarity, and elasticity in the system. Our results reveal unanticipated topological excitations, self-organization, and phase separation in non-equilibrium systems and also suggest a potential way towards engineering complicated bespoke skyrmionic structures through manipulating active matter.

CRISPR/Cas13a combined with hybridization chain reaction for visual detection of influenza A (H1N1) virus.

This study provides proof of concept of a colorimetric biosensor for influenza H1N1 virus assay based on the CRISPR/Cas13a system and hybridization chain reaction (HCR). Target RNA of influenza H1N1 virus activated the trans-cleavage activity of Cas13a, which cleaved the special RNA sequence (-UUU-) of the probe, further initiating HCR to copiously generate G-rich DNA. Abundant G-quadruplex/hemin was formed in the presence of hemin, thus catalyzing a colorimetric reaction. The colorimetric biosensor exhibited a linear relationship from 10 pM to 100 nM. The detection limit was 0.152 pM. The biosensor specificity was excellent. This new and sensitive detection method for influenza virus is a promising rapid influenza diagnostic test.

Influence of genetic polymorphisms in P2Y12 receptor signaling pathway on antiplatelet response to clopidogrel in coronary heart disease.

BACKGROUNDS: Remarkable interindividual variability in clopidogrel response is observed, genetic polymorphisms in P2RY12 and its signal pathway is supposed to affect clopidogrel response in CHD patients. METHODS: 539 CHD patients treated with clopidogrel were recruited. The platelet reaction index (PRI) indicated by VASP-P level were detected in 12-24 h after clopidogrel loading dose or within 5-7 days after initiation of maintain dose clopidogrel. A total of 13 SNPs in relevant genes were genotyped in sample A (239 CHD patients). The SNPs which have significant differences in PRI will be validated in another sample (sample B, 300 CHD patients). RESULTS: CYP2C19*2 increased the risk of clopidogrel resistance significantly. When CYP2C19*2 and CYP2C19*3 were considered, CYP2C19 loss of function (LOF) alleles were associated with more obviously increased the risk of clopidogrel resistance; P2RY12 rs6809699C > A polymorphism was also associated with increased risk of clopidogrel resistance (AA vs CC: P = 0.0398). This difference still existed after stratification by CYP2C19 genotypes. It was also validated in sample B. The association was also still significant even in the case of stratification by CYP2C19 genotypes in all patients (sample A + B). CONCLUSION: Our data suggest that P2RY12 rs6809699 is associated with clopidogrel resistance in CHD patients. Meanwhile, the rs6809699 AA genotype can increase on-treatment platelet activity independent of CYP2C19 LOF polymorphisms.

The relationship between urologic cancer outcomes and national Human Development Index: trend in recent years.

OBJECTIVES: To describe the influence of the socioeconomic development on worldwide age-standardized incidence and mortality rates, as well as mortality-to-incidence ratio (MIR) and 5-year net survival of urologic cancer patients in recent years. METHODS: The Human Development Index (HDI) values were obtained from the United Nations Development Programme, data on age-standardized incidence/mortality rates of prostate, bladder and kidney cancer were retrieved from the GLOBOCAN database, 5-year net survival was provided by the CONCORD-3 program. We then evaluated the association between incidence/MIR/survival and HDI, with a focus on geographic variability as well as temporal patterns during the last 6 years. RESULTS: Urologic cancer incidence rates were positively correlated with HDIs, and MIRs were negatively correlated with HDIs. Prostate cancer survival also correlated positively with HDIs, solidly confirming the interrelation among cancer indicators and socioeconomic factors. Most countries experienced incidence decline over the most recent 6 years, and a substantial reduction in MIR was observed. Survival rates of prostate cancer have simultaneously improved. CONCLUSION: Development has a prominent influence on urologic cancer outcomes. HDI values are significantly correlated with cancer incidence, MIR and survival rates. HDI values have risen along with increased incidence and improved outcomes of urologic caner in recent years.

Broadband silicon nitride nanophotonic phased arrays for wide-angle beam steering.

In this Letter, the broadband operation in wavelengths from 520 nm to 980 nm is demonstrated on silicon nitride nanophotonic phased arrays. The widest beam steering angle of 65° on a silicon nitride phased array is achieved. The optical radiation efficiency of the main grating lobe in a broad wavelength range is measured and analyzed theoretically. The optical spots radiated from the phased array chip are studied at different wavelengths of lasers. The nanophotonic phased array is excited by a supercontinuum laser source for a wide range of beam steering for the first time to the best of our knowledge. It paves the way to tune the wavelength from visible to near infrared range for silicon nitride nanophotonic phased arrays.

An electrochemical biosensor for the detection of pathogenic bacteria based on dual signal amplification of Cu3(PO4)2-mediated click chemistry and DNAzymes.

A novel electrochemical biosensor for detecting pathogenic bacteria was designed based on specific magnetic separation and highly sensitive click chemistry. Instead of enzyme-antibody conjugates, organic-inorganic hybrid nanoflowers [concanavalin A (Con A)-Cu3(PO4)2] were used as the signal probe of the sandwich structure. The inorganic component, the copper ions of hybrid nanoflowers, was first used to amplify signal transduction for enzyme-free detection. Sodium ascorbate could dissolve Cu3(PO4)2 of the signal probe to produce Cu2+, which was subsequently converted to Cu+, triggering the Cu+-catalyzed alkyne-azide cycloaddition (CuAAC) reaction between azide-functionalized ssDNA (a fragment of the DNAzyme-containing sequence) and alkyne-functionalized ssDNA immobilized onto the electrode surface. As a result, the DNAzyme was immobilized onto the gold electrode, which produced a positive and stable electrical signal. An exceptional linear relationship was observed between the electrical signal and the concentration of Salmonella typhimurium (101-107 CFU mL-1) with a detection limit of 10 CFU mL-1. The developed electrochemical biosensor based on dual signal amplification of Cu3(PO4)2-mediated click chemistry and DNAzymes exhibited good results in detecting S. typhimurium in milk samples.

16S rRNA-functionalized multi-HCR concatemers in a signal amplification nanostructure for visual detection of Salmonella.

To prevent foodborne diseases and minimize their impacts, it is extremely important to develop a cost-effective and efficient bacterial detection assay for diagnostics, particularly in resource-poor settings. In this study, 16S rRNA from foodborne Salmonella was coupled with multiple HCR (hybridization chain reaction) concatemers and functionalized in a signal structure for lateral flow nucleic acid biosensor (LFNAB) detection. The 16S rRNA was incubated with two specific capture probes and multiple helper probes carrying the same initiator, to unwind its secondary structure and form an "initiators-on-a-string" complex. Through use of the initiators, each target 16S rRNA yielded multiple HCR concatemers tethered to numerous biotins, and numerous streptavidin-labeled gold nanoparticles were introduced on the LFNAB. The limit of detection was 53.65 CFU/mL for Salmonella. Notably, this method has high specificity and applicability for the detection of Salmonella in food and water samples.

A five-gene methylation signature predicts overall survival of patients with clear cell renal cell carcinoma.

BACKGROUND: In this study, we aimed to screen methylation signatures associated with the prognosis of patients with clear cell renal cell carcinoma (ccRCC). METHODS: Gene expression and methylation profiles of ccRCC patients were downloaded from publicly available databases, and differentially expressed genes (DEGs)-differentially methylated genes (DMGs) were obtained. Subsequently, gene set enrichment and transcription factor (TF) regulatory network analyses were performed. In addition, a prognostic model was constructed and the relationship between disease progression and immunity was analyzed. RESULTS: A total of 23 common DEGs-DMGs were analyzed, among which 14 DEGs-DMGs were obtained with a cutoff value of PCC < 0 and p < 0.05. The enrichment analysis showed that the 14 DEGs-DMGs were enriched in three GO terms and three KEGG pathways. In addition, a total of six TFs were shown to be associated with the 14 DEGs-DMGs, including RP58, SOX9, NF-κB65, ATF6, OCT, and IK2. A prognostic model using five optimized DEGs-DMGs which efficiently predicted survival was constructed and validated using the GSE105288 dataset. Additionally, four types of immune cells (NK cells, macrophages, neutrophils, and cancer-associated fibroblasts), as well as ESTIMATE, immune, and stromal scores were found to be significantly correlated with ccRCC progression (normal, primary, and metastasis) in addition to the five optimized DEGs-DMGs. CONCLUSION: A five-gene methylation signature with the predictive ability for ccRCC prognosis was investigated in this study, consisting of CCNB2, CDKN1C, CTSH, E2F2, and ERMP1. In addition, potential targets for methylation-mediated immunotherapy were highlighted.

A metal template for preparing guiding planes for removable partial dentures.

Precise preparation of guiding planes is essential for removable partial dentures (RPDs). This report introduces a metal template fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM) to help prepare guiding planes for RPDs.

Over 10 attenuation length gigabits per second underwater wireless optical communication using a silicon photomultiplier (SiPM) based receiver.

Underwater wireless optical communication (UWOC) will play an important role in the underwater environment exploration and marine resource development due to its advantages of high data rate and good mobility. However, the significant signal power attenuation in the underwater channel limits the transmission distance of UWOC. Attenuation length (AL) is widely used as an indicator for evaluating the UWOC system's long-distance transmission capability. At present, Gbps UWOC is limited within 7AL. Using a SiPM based receiver can dramatically increase the AL that UWOC can support. In this paper, a novel UWOC receiver built from an off-the-shelf SiPM has been demonstrated. The finite pulse width and limited bandwidth of SiPM limit the SiPM based UWOC system's data rate. To boost the system's data rate, an optimum method to process the SiPM's signal has therefore been investigated. Based on these methods, the communication capabilities of the SiPM based UWOC have been investigated experimentally. Results show that the SiPM based receiver can support 11.6AL without turbulence and 9.28AL within weak turbulence (scintillation index = 0.0447) at 1 Gbps.

Pattern Formation and Defect Ordering in Active Chiral Nematics.

Many biological systems display intriguing chiral patterns and dynamics. Here, we present an active nematic theory accounting for individual spin to explore the collective handedness in chiral rod-shaped aggregations. We show that coordinated individual spin and motility can engender a vortex-array pattern with chirality and drive ordering of topological defects. During this chiral process, the stationary trefoil-like defects self-organize into a periodic, hexagon-dominated polygonal network, which segregates persistently rotating cometlike defects in pairs within each polygon, leading to a translation symmetry at the global scale while a broken reflection symmetry at the local scale. Such defect ordering agrees exactly with the Voronoi tiling of two-dimensional space and the emergence of the hexagonal symmetry is deciphered in analogy with topological charge neutralization. We calculate energy barriers to the topological transition of the defect ordering and explain the existing metastable states with nonhexagonal polygons. Our findings shed light on the chiral morphodynamics in life processes and also suggest a potential route towards tuning self-organization in active materials.

The impact of the indica rice SSIIa allele on the apparent high amylose starch from rice grain with downregulated japonica SBEIIb.

KEY MESSAGE: Catalytically active indica SSIIa allele in high amylose rice with down-regulated japonica SBEIIb can increase starch content and modify the starch structure and properties without changing its amylose content. Rice (Oryza sativa) genotypes with inactive starch synthase IIa (SSIIa) with recessive variants of starch branching enzyme IIb (SBEIIb) exhibit a range of alterations in grain phenotype, starch granule morphology, starch granule bound proteins, starch structure, and functional properties. However, the interactions between the two enzymes have not been thoroughly investigated yet. We analysed recombinant rice lines having down-regulated SBEIIb expression (SBEIIbDR) with either indica or japonica type SSIIa (SSIIaind or SSIIajap). In SBEIIbDR rice starch granules, the increased abundance of two protein bands (SSI and SSIIa) was found with eight additional protein bands not generally associated with starch granules. The amount of SSIIa was higher in SSIIaindSBEIIbDR than SSIIajapSBEIIbDR, which indicated that indica type SSIIa, possibly in the monomer form, was extensively involved in starch biosynthesis in the SBEIIbDR endosperm. Furthermore, SSIIaindSBEIIbDR grains had higher total starch content and higher starch swelling power than SSIIajapSBEIIbDR lines, but the amylopectin gelatinization temperatures and enthalpy and the apparent amylose content remained similar. In summary, this work suggests that SSIIaind can partly compensate for the alteration of starch synthesis resulting from the SBEIIb down-regulation in japonica background without reducing its amylose content. The study provides insight into the starch structural and textural improvements of high amylose starch.

The production of wheat - Aegilops sharonensis 1Ssh chromosome substitution lines harboring alien novel high-molecular-weight glutenin subunits.

In our previous work, a novel high-molecular-weight glutenin subunit (HMW-GS) with an extremely large molecular weight from Aegilops sharonensis was identified that may contribute to excellent wheat (Triticum aestivum) processing quality and increased dough strength, and we further generated HMW-GS homozygous lines by crossing. In this study, we crossed the HMW-GS homozygous line 66-17-52 with 'Chinese Spring' Ph1 mutant CS ph1b to induce chromosome recombination between wheat and Ae. sharonensis. SDS-PAGE was used to identify 19 derived F2 lines with the HMW-GSs of Ae sharonensis. The results of non-denaturing fluorescence in situ hybridization (ND-FISH) indicated that lines 6-1 and 6-7 possessed a substitution of both 5D chromosomes by a pair of 1Ssh chromosomes. Further verification by newly developed 1Ssh-specific chromosome markers showed that these two lines amplified the expected fragment. Thus, it was concluded that lines 6-1 and 6-7 are 1Ssh(5D) chromosome substitution lines. The 1Ssh(5D) chromosome substitution lines, possessing alien subunits with satisfactory quality-associated structural features of large repetitive domains and increased number of subunits, may have great potential in strengthening the viscosity and elasticity of dough made from wheat flour. Therefore, these substitution lines can be used for wheat quality improvement and further production of 1Ssh translocation lines.