Electrochemiluminescence resonance energy transfer detection of HBsAg based on Co doped 3D porous luminol-based conjugates and quencher UiO-66-NH2@Au.

An electrochemiluminescence (ECL) biosensor based on ECL resonance energy transfer (ECL-RET) was designed to sensitively detect hepatitis B virus surface antigen (HBsAg). In this ECL-RET system, luminol was employed as ECL donor, and gold nanoparticles functionalized zirconium organoskeleton (UiO-66-NH2@Au) was prepared and served as ECL acceptor. The UiO-66-NH2@Au possessed an ultraviolet-visible (UV-vis) absorption between 400 nm and 500 nm, and the absorption spectra overlapped with the ECL spectrum of luminol. Furthermore, Graphene oxide-poly(aniline-luminol)-cobalt nanoparticles conjugates (GO-PALu-Co) was prepared to optimize the ECL behavior through the catalysis of Cobalt nanoparticles and served as a stable 3D porous film to load capture probe primary antibody (Ab1). Based on the ECL-RET biosensing method, the UiO-66-NH2@Au-labeled Ab2 and target HBsAg could pair with primary antibody Ab1 to form sandwich-type structure, and the ECL signal of GO-PALu-Co was quenched. Under optimized experimental conditions, the ECL-RET analytical method represented eminent analytical performance for HBsAg detection with a wide linear relationship from 2.2 × 10-13 to 2.2 × 10-5 mg/mL, and a detection limit of 9 × 10-14 mg/mL (S/N = 3), with spiked sample recoveries ranging from 97.27 % to 102.73 %. The constructed sensor has good stability, reproducibility, and specificity. It can be used to detect HBsAg in human serum and has the potential to be used for the sensitive detection of other disease biomarkers.

Advances in large viewing angle and achromatic 3D holography.

Optical holography is a promising technique to achieve a naked-eye 3D display. However, the narrow viewing angle and chromatic aberration are the two key issues that usually limit the holographic display performance. A recent work proposes a novel way to circumvent these constraints by introducing a color liquid crystal grating into a time-sequenced holography system.

Twist-Angle-Controlled Nonlinear Circular Dichroism on Gold-Crystal Hybrid Metasurfaces.

Optical chirality, which plays important roles in liquid crystal display and biological and chemical detection, has been attracting scientists' attention due to its potential applications in optical information processing. Usually, the chiral optical response of natural molecules is very weak. However, the emergence of metasurfaces offers a promising solution to solve this issue. By judiciously designing the geometry of meta-atoms, we have realized strong optical circular dichroism (CD) in both linear and nonlinear optical regimes. However, tuning of the CD with a metasurface remains challenging. Here, we propose the twist-angle-controlled nonlinear CD effect by using the second-harmonic generation process on a gold-crystal hybrid metasurface. The CD effect of the second-harmonic waves can be tuned well by controlling the twist angle between the two constituent materials. The proposed hybrid metasurface may open new avenues for developing ultracompact and multifunctional nonlinear optical devices.

Spin Unlocked Vortex Beam Generation on Nonlinear Chiroptical Metasurfaces.

Optical vortices with spin and orbital angular momentum (SAM and OAM) states offer multiple degrees of freedom for manipulating optical fields and thus enable great potentials in optical information processing. Recently, the optical metasurface has become an important platform for vortex beam generation and steering. However, the strong spin-orbit interaction on such metasurfaces usually leads to spin locked OAM generation, which limits the complete control of the angular momentum state of light. Here, we propose to solve this constraint using geometric phase controlled nonlinear chiroptical metasurfaces. The metasurface consists of two types of plasmonic meta-atoms which have opposite handedness and exhibit a strong spin-dependent circular dichroism effect. By encoding specific phase singularities and phase gradients to different channels, we experimentally demonstrate the spin unlocked second harmonic beam steering. The proposed nonlinear chiroptical metasurfaces may have important applications in developing multifunctional nonlinear optical devices.

Time-Dependent Ultrafast Quadratic Nonlinearity in an Epsilon-Near-Zero Platform.

Ultrafast nonlinearity, which results in modulation of the linear optical response, is a basis for the development of time-varying media, in particular those operating in the epsilon-near-zero (ENZ) regime. Here, we demonstrate that the intraband excitation of hot electrons in the ENZ film results in a second-harmonic resonance shift of ∼10 THz (40 nm) and second-harmonic generation (SHG) intensity changes of >100% with only minor (<1%) changes in linear transmission. The modulation is 10-fold enhanced by a plasmonic metasurface coupled to a film, allowing for ultrafast modulation of circularly polarized SHG. The effect is described by the plasma frequency renormalization in the ENZ material and the modification of the electron damping, with a possible influence of the hot-electron dynamics on the quadratic susceptibility. The results elucidate the nature of the second-order nonlinearity in ENZ materials and pave the way to the rational engineering of active nonlinear metamaterials and metasurfaces for time-varying applications.

Precore mutation enhances viral replication to facilitate persistent infection especially in HBeAg-negative patients.

Naturally occurred precore (PC, G1896A) and/or basal core promoter (BCP, A1762T/G1764A) mutations are prevalent in chronic HBV-infected patients, especially those under HBeAg-negative status. However, the replicative capacity of HBV with PC/BCP mutations remains ambiguous. Herein, meta-analysis showed that, only under HBeAg-negative status, the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the mutation. Both PC mutation alone and BCP â€‹+ â€‹PC mutations promoted HBV replication in cell and hydrodynamic injection mouse models. In human hepatocyte chimeric mouse model, BCP â€‹+ â€‹PC mutations led to elevated replicative capacity and intrahepatic core protein accumulation. Mechanistically, preC RNA harboring PC mutation could serve as mRNA to express core and P proteins, and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative status. Additionally, BCP â€‹+ â€‹PC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric mice. This study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.

All-optical ultrafast polarization switching with nonlinear plasmonic metasurfaces.

Optical switching has important applications in optical information processing, optical computing, and optical communications. The long-term pursuit of optical switch is to achieve short switching time and large modulation depth. Among various mechanisms, all-optical switching based on Kerr effect represents a promising solution. However, it is usually difficult to compromise both switching time and modulation depth of a Kerr-type optical switch. To circumvent this constraint, symmetry selective polarization switching via second-harmonic generation (SHG) in nonlinear crystals has been attracting scientists' attention. Here, we demonstrate SHG-based all-optical ultrafast polarization switching by using geometric phase controlled nonlinear plasmonic metasurfaces. A switching time of hundreds of femtoseconds and a modulation depth of 97% were experimentally demonstrated. The function of dual-channel all-optical switching was also demonstrated on a metasurface, which consists of spatially variant meta-atoms. The nonlinear metasurface proposed here represents an important platform for developing all-optical ultrafast switches and would benefit the area of optical information processing.

Cephalopod-inspired polymer composites with mechanically tunable infrared properties.

Cephalopods have evolved an all-soft skin that can rapidly display colors for protection, predation, or communication. Development of synthetic analogs to mimic such color-changing abilities in the infrared (IR) region is pivotal to a variety of technologies ranging from soft robotics, flexible displays, dynamic thermoregulatory systems, to adaptive IR disguise platforms. However, the integration of tissue-like mechanical properties and rapid IR modulation ability into smart materials remains challenging. Here, by drawing inspiration from cephalopod skin, we develop an all-soft adaptive IR composite that can dynamically change its IR appearance upon equiaxial stretching. The biomimetic composite is built entirely from soft materials of liquid metal droplets and elastic elastomer, which are analogs of chromatophores and dermal layer of cephalopod skin, respectively. Driven by externally applied strains, the liquid metal inclusions transition between a contracted droplet state with corrugated surface and an expanded platelet state with relatively smooth surface, enabling dynamic variations in the IR reflectance/emissivity of the composite and ultimately resulting in reversible IR adaption. Strain-actuated flexible IR displays and pneumatically-driven soft devices that can dynamically manipulate their IR appearance are demonstrated as examples of the applicability of this material in emerging adaptive soft electronics.

Significant Enhancement of Circular Polarization in Light Emission through Controlling Helical Pitches of Semiconductor Nanohelices.

Circularly polarized light emission (CPLE) can be potentially applied to three-dimensional displays, information storage, and biometry. However, these applications are practically limited by a low purity of circular polarization, i.e., the small optical dissymmetry factor gCPLE. Herein, glancing angle deposition (GLAD) is performed to produce inorganic nanohelices (NHs) to generate CPLE with large gCPLE values. CdSe NHs emit red CPLE with gCPLE = 0.15 at a helical pitch (P) ≈ 570 nm, having a 40-fold amplification of gCPLE compared to that at P ≈ 160 nm. Ceria NHs emit ultraviolet-blue CPLE with gCPLE ≈ 0.06 at P ≈ 830 nm, with a 103-fold amplification compared to that at P ≈ 110 nm. Both the photoluminescence and scattering among the close-packed NHs complicatedly account for the large gCPLE values, as revealed by the numerical simulations. The GLAD-based NH-fabrication platform is devised to generate CPLE with engineerable color and large gCPLE = 10-2-10-1, shedding light on the commercialization of CPLE devices.

The A1762T/G1764A mutations enhance HBV replication by alternating viral transcriptome.

The A1762T/G1764A mutations, one of the most common mutations in the hepatitis B virus basal core promoter, are associated with the progression of chronic HBV infection. However, effects of these mutations on HBV replication remains controversial. This study aimed to systematically investigate the effect of the mutations on HBV replication and its underlying mechanisms. Using the prcccDNA/pCMV-Cre recombinant plasmid system, a prcccDNA-A1762T/G1764A mutant plasmid was constructed. Compared with wild-type HBV, A1762T/G1764A mutant HBV showed enhanced replication ability with higher secreted HBV DNA and RNA levels, while Southern and Northern blot indicated higher intracellular levels of relaxed circular DNA, single-stranded DNA, and 3.5 kb RNA. Meanwhile, the mutations increased expression of intracellular core protein and decreased the production of HBeAg and HBsAg. In vitro infection based on HepG2-NTCP cells and mice hydrodynamic injection experiment also proved that these mutations promote HBV replication. 5'-RACE assays showed that these mutations upregulated transcription of pregenomic RNA (pgRNA) while downregulating that of preC RNA, which was further confirmed by full-length transcriptome sequencing. Moreover, a proportion of sub-pgRNAs with the potential to express polymerase were also upregulated by these mutations. The ChIP-qPCR assay showed that A1762T/G1764A mutations created a functional HNF1α binding site in the BCP region, and its overexpression enhanced the effect of A1762T/G1764A mutations on HBV. Our findings revealed the mechanism and importance of A1762T/G1764A mutations as an indicator for management of CHB patients, and provided HNF1α as a new target for curing HBV-infected patients.

Holographic THz Beam Generation by Nonlinear Plasmonic Metasurface Emitters.

The advancement of terahertz (THz) technology hinges on the progress made in the development of efficient sources capable of generating and shaping the THz emission. However, the currently available THz sources provide limited control over the generated field. Here, we use near-field interactions in nonlinear Pancharatnam-Berry phase plasmonic metasurfaces to achieve deep subwavelength, precise, and continuous control over the local amplitude of the emitted field. We show that this new ability can be used for holographic THz beam generation. Specifically, we demonstrate the generation of precisely shaped Hermite-Gauss, Top-Hat, and triangular beams. We show that using this method, higher-order modes are completely suppressed, indicating optimal nonlinear diffraction efficiency. In addition, we demonstrate the application of the generated structured beams for obtaining enhanced imaging resolution and contrast. These demonstrations hold immense potential to address challenges associated with a broad range of new applications employing THz technology.

Microbiome predators in changing soils.

Microbiome predators shape the soil microbiome and thereby soil functions. However, this knowledge has been obtained from small-scale observations in fundamental rather than applied settings and has focused on a few species under ambient conditions. Therefore, there are several unaddressed questions on soil microbiome predators: (1) What is the role of microbiome predators in soil functioning? (2) How does global change affect microbiome predators and their functions? (3) How can microbiome predators be applied in agriculture? We show that there is sufficient evidence for the vital role of microbiome predators in soils and stress that global changes impact their functions, something that urgently needs to be addressed to better understand soil functioning as a whole. We are convinced that there is a potential for the application of microbiome predators in agricultural settings, as they may help to sustainably increase plant growth. Therefore, we plea for more applied research on microbiome predators.

Cuproptosis-related gene SERPINE1 is a prognostic biomarker and correlated with immune infiltrates in gastric cancer.

PURPOSE: The serine protease inhibitor clade E member 1 (SERPINE1) has been studied as a potential biomarker in a variety of cancers, but poorly studied in gastric cancer (GC). The purpose of this study was to explore the prognostic value of SERPINE1 in GC and primarily analyze its functions. METHODS: We analyzed the the prognostic value of SERPINE1 and studied the relationship with clinicopathologic biomarkers in gastric cancer. The expression of SERPINE1 was analyzed by GEO and TCGA databases. Moreover, we validated the results by immunohistochemistry. Next, the correlation analysis between SERPINE1 and the cuproptosis-related genes was analyzed by the "Spearman" method. CIBERSORT and TIMER algorithms were used to analyze the correlation of SERPINE1 with immune infiltration. Furthermore, GO and KEGG gene enrichment analyses were used to study the functions and pathways that SERPINE1 might be involved in. Then, drug sensitivity analysis was performed using CellMiner database. Finally, a cuproptosis-immune-related prognostic model was constructed using genes related to immune and cuproptosis, and verified against external datasets. RESULTS: SERPINE1 was up-regulated in gastric cancer tissues, which tends toward poor prognosis. Using immunohistochemistry experiment, the expression and prognostic value of SERPINE1 were verified. Then, we found that SERPINE1 was negatively correlated with cuproptosis-related genes FDX1, LIAS, LIPT1, and PDHA1. On the contrary, SERPINE1 was positively correlated with APOE. This indicates the effect of SERPINE1 on the cuproptosis process. Furthermore, by conducting immune-related analyses, it was revealed that SERPINE1 may promote the inhibitory immune microenvironment. The infiltration level of resting NK cells, neutrophils, activated mast cells, and macrophages M2 was positively correlated with SERPINE1. However, B cell memory and plasma cells were negatively correlated with SERPINE1. Functional analysis showed that SERPINE1 was closely related to angiogenesis, apoptosis, and ECM degradation. The KEGG pathway analysis showed that SERPINE1 may be associated with P53, Pi3k/Akt, TGF-ß, and other signaling pathways. Drug sensitivity analysis showed that SERPINE1 could be also seen as a potential treatment target. The risk model based on SERPINE1 co-expression genes could better predict the survival of GC patients than SERPINE1 alone. We also verified the prognostic value of the risk score by GEO external datasets. CONCLUSION: SERPINE1 is highly expressed in gastric cancer and related to poor prognosis. SERPINE1 may regulate cuproptosis and the immune microenvironment by a series of pathways. Therefore, SERPINE1 as a prognostic biomarker and potential therapeutic target deserves further study.

Nematode biomass changes along an elevational gradient are trophic group dependent but independent of body size.

Aboveground, large and higher trophic-level organisms often respond more strongly to environmental changes than small and lower trophic-level organisms. However, whether this trophic or size-dependent sensitivity also applies to the most abundant animals, microscopic soil-borne nematodes, remains largely unknown. Here, we sampled an altitudinal transect across the Tibetan Plateau and applied a community-weighted mean (CWM) approach to test how differences in climatic and edaphic properties affect nematode CWM biomass at the level of community, trophic group and taxon mean biomass within trophic groups. We found that climatic and edaphic properties, particularly soil water-related properties, positively affected nematode CWM biomass, with no overall impact of altitude on nematode CWM biomass. Higher trophic-level omnivorous and predatory nematodes responded more strongly to climatic and edaphic properties, particularly to temperature, soil pH, and soil water content than lower trophic-level bacterivorous and fungivorous nematodes. However, these differences were likely not (only) driven by size, as we did not observe significant interactions between climatic and edaphic properties and mean biomasses within trophic groups. Together, our research implies a stronger, size-independent trophic sensitivity of higher trophic-level nematodes compared with lower trophic-level ones. Therefore, our findings provide new insights into the mechanisms underlying nematode body size structure in alpine grasslands and highlight that traits independent of size need to be found to explain increased sensitivity of higher trophic-level nematodes to climatic and edaphic properties, which might affect soil functioning.

A Centimeter-Scale Dielectric Metasurface for the Generation of Cold Atoms.

The single-beam magneto-optical trap (MOT) based on the diffractive optical element offers a new route to develop compact cold atom sources. However, the optical efficiency in the previous single-beam MOT systems is usually low and unbalanced, which will affect the quality of the trapped atoms. To solve this issue, we developed a centimeter-scale dielectric metasurface optical chip with dynamic phase distributions, which was used to split a single incident laser beam into five separate ones with well-defined polarization states and uniform energy distributions. The measured diffraction efficiency of the metasurface is up to 47%. A single-beam MOT integrated with the metasurface optical chip was then used to trap the 87Rb atoms with numbers ∼1.4 × 108 and temperatures ∼7.0 µK. The proposed concept in this work may provide a promising solution for developing ultracompact cold atom sources.

Cationic Gelatin Cross-Linked with Transglutaminase and Its Electrospinning in Aqueous Solution.

Gelatin (GE) is a renewable biopolymer with abundant active groups that are beneficial for manufacturing functional biomaterials via GE modification. An antibacterial fibrous GE film was prepared by electrospinning the modified GE in an aqueous solution. The original GE was modified by reacting it with N,N-dimethyl epoxypropyl octadecyl ammonium chloride (QAS), and then it was cross-linked with transglutaminase (TGase). FTIR analysis illustrated that QAS was grafted onto GE through the epoxy ring-opening reaction, and the modification did not influence the main GE skeleton structure. The investigation of the solution properties showed that the grafted cationic QAS group was the main factor that decreased the surface tension of the solution, increased the electrical conductivity of the solution, and endowed GE with antibacterial activity. TGase cross-linking clearly influenced the rheological properties such that the flow pattern of the spinning solution varied from Newton-type to shear thinning, and the aqueous solution of GE-QAS-TGs transformed from liquid-like to solid-like and even induced gelatinization with increasing TGase content. A satisfactory fibrous morphology of 200-500 nm diameter was obtained using a homemade instrument under the optimized electrospinning conditions of a temperature of 35 °C, a distance between electrodes of 12 cm, and a voltage of 15 kV. The study of film properties showed that the antibacterial activity of the fibrous GE film depended only on the grafted quaternary ammonium, whereas the thermostability, wettability, and permeability were greatly influenced by both the TGase cross-linking and film-forming methods. Cytotoxicity was tested using the CCK-8 and live/dead kit staining methods in vitro, which showed that the modified GE had good biocompatibility.

[Analysis on quality value transmitting of Qinggusan reference sample of classical prescription based on quantitative fingerprint technology].

Qinggusan is the 69th prescription in the first batch of "Catalogue of Ancient Chinese Classic Formulas". In modern clinical practice， Qinggusan is mainly used to treat noninfectious fever. However， because few studies on Qinggusan reference samples and their quality value transfer are available， the development and promotion of its compound preparations are restricted. Therefore， establishing an accurate and comprehensive quality control method to clarify the critical quality attributes of Qinggusan reference samples is of great importance. In this study， 15 batches of Qinggusan reference samples were processed to determine the range of their dry extract ratios. Quantitative high-performance liquid chromatography （HPLC） fingerprint analysis was performed using a Waters Symmetry Shield RP18 column （250 mm×4.6 mm， 5 µm） with acetonitrile-0.1% （v/v） formic acid aqueous solution as the mobile phase in gradient elution mode. The flow rate was 1.0 mL/min， the column temperature was 30 ℃， and the detection wavelength was 254 nm. The HPLC fingerprints of the Qinggusan reference samples were established under these conditions to evaluate their similarity. The established method was systematically validated and found to demonstrate good precision， repeatability， and sample stability. Subsequently， characteristic peaks were identified and attributed by HPLC-quadrupole-time-of-flight-mass spectrometry （HPLC-Q-TOF-MS） analysis. MS was performed in electrospray ionization mode， the data were collected in both positive- and negative-ion modes， and the detection range was m/z 50-2000. The contents and transfer rate ranges of the index components， namely， gentiopicrin， mangiferin， picroside Ⅱ， picroside Ⅰ， and glycyrrhizic acid， were determined to analyze the quality value transfer of the samples. The results demonstrated that the dry extract rate of the 15 batches of Qinggusan reference samples ranged from 24.10% to 26.88% and that their fingerprint similarities were generally greater than 0.95. Twelve common peaks were identified by reference identification， literature comparison， and high-resolution MS analysis. Twelve compounds， including six iridoid glycosides， two flavonoids， one alkaloid， one triterpenoid saponin， and two others. Among them， L-picein， androsin， picroside Ⅳ， picroside Ⅱ and picroside Ⅰ were from Picrorhizae Rhizoma， loganin acid， swertiamarin and gentiopicrin were from Gentianae Macrophyllae Radix， neomangiferin and mangiferin were from Anemarrhenae Rhizoma， dichotomine B was from Stellariae Radix， and glycyrrhizic acid was from Glycyrrhizae Radix et Rhizoma. The five key components presented good linear relationships in their respective linear ranges， and all correlation coefficients were higher than 0.999. The relative standard deviations （RSDs） of precision， stability， and repeatability were less than 1.3%. The average recoveries varied between 95.92% and 102.5%， with RSDs less than 3.9%； these values meet the requirements defined in the 2020 edition of the Chinese Pharmacopoeia. The contents of gentiopicrin， mangiferin， picroside Ⅱ， picroside Ⅰ， and glycyrrhizic acid in the 15 batches of reference samples were in the range of 17.92-27.55， 1.83-4.42， 23.08-36.44， 8.43-15.04， and 0.94-2.39 mg/g， respectively， and their transfer rates from the decoction pieces to the reference samples were 47.91%-63.95%， 22.96%-59.39%， 60.82%-77.82%， 64.25%-99.53%， and 15.30%-39.30%， respectively. In this study， the chemical components of Qinggusan reference samples were comprehensively identified and their quality value transfer was studied through the combination of HPLC fingerprinting and MS. Clarification of the critical quality attributes of Qinggusan reference samples could provide a basis for the quality control of Qinggusan compound preparations.

Large-scale achromatic flat lens by light frequency-domain coherence optimization.

Flat lenses, including metalens and diffractive lens, have attracted increasing attention due to their ability to miniaturize the imaging devices. However, realizing a large scale achromatic flat lens with high performance still remains a big challenge. Here, we developed a new framework in designing achromatic multi-level diffractive lenses by light coherence optimization, which enables the implementation of large-scale flat lenses under non-ideal conditions. As results, a series achromatic polymer lenses with diameter from 1 to 10 mm are successfully designed and fabricated. The subsequent optical characterizations substantially validate our theoretical framework and show relatively good performance of the centimeter-scale achromatic multi-level diffractive lenses with a super broad bandwidth in optical wavelengths (400-1100 nm). After comparing with conventional refractive lens, this achromatic lens shows significant advantages in white-light imaging performance, implying a new strategy in developing practical planar optical devices.

Double exceptional points in grating coupled metal-insulator-metal heterostructure.

In this work we theoretically study the exceptional points and reflection spectra characteristics of a grating coupled metal-insulator-metal heterostructure, which is a non-Hermitian system. Our results show that by selecting suitable geometrical parameters with grating periodicity @150 nm, that satisfy zero reflection condition, double exceptional points appear in a mode bifurcation regime. Furthermore, the thickness of partition metal layer between two cavities plays an important role in controlling the reflection properties of the heterostructure. There is a clear mode splitting when the partition layer allows strong coupling between the two cavity modes. Conversely, in weak coupling regime the mode splitting becomes too close to be distinguished. Moreover, the vanishing of reflection leads to unidirectional reflectionless propagation, which is also known as unidirectional invisibility. With grating periodicity ≥400nm, the transmissions for forward and backward incident directions are no longer the same due to the generation of diffraction. High contrast ratio (≈1) between the two incident directions leads to asymmetric transmission. This work lays the basis for designing double exceptional points and asymmetric transmission in coupled non-Hermitian photonics system. The proposed heterostructure can be a good candidate for new generation optical communications, optical sensing, photo-detection, and nano-photonic devices.