Strong Response Research Articles

Diffeomorphism invariance and quantum mechanical paradoxes

Paradoxes in gravitational physics, such as grandfather paradoxes with closed timelike curves or the AMPS paradox, are often constructed in a weak gravity regime but upon further examination engender strong gravitational responses such as unstable Cauchy horizons or firewalls. In contrast, some proposed paradoxes in nonrelativistic quantum mechanics ignore gravity completely. Such nonrelativistic proposed paradoxes are often not gauge invariant — they use local operators which should be forbidden by diffeomorphism-invariant quantum gravity. Ignoring this complication is reasonable if there is a consistent weak gravity regime where the paradox can be formulated with gauge invariant observables up to some order in Newton’s constant. We show that this approach remains inconsistent due to a lack of analyticity of the necessary solutions. As a consequence, there is no consistent weak gravity, diffeomorphism invariant embedding of such paradoxes—just as in other gravitational paradoxes they generate a strong gravitational response and are in principle sensitive to quantum gravity.

Music-Evoked Autobiographical Memories are Associated with Negative Affect in Younger and Older Adults

ABSTRACT BACKGROUND Music evokes strong and persistent emotional responses. However, the mechanisms underlying the emotional effects of music, particularly in older adults, are largely unknown. One purported mechanism by which music evokes emotions is through memory – that is, music evokes personal, autobiographical memories that then lead to emotional responses. METHOD Here, we investigated whether memory-evoking music induces stronger and longer-lasting emotional responses than non-memory-evoking music, and whether these emotional responses differ between younger and older adults. Older (N = 30) and younger adults (N =30) listened to two blocks of self-selected music (one block of memory-evoking music and one block of familiar but non-memory-evoking music). Participants reported their emotions prior to and at three timepoints post-listening. RESULTS Older adults reported higher levels of positive affect than younger adults. For both groups, positive affect increased after listening to both memory-evoking and non-memory-evoking music. However, negative affect only increased after listening to memory-evoking music. CONCLUSIONS These results suggest that both memory-evoking and non-memory-evoking music generate strong emotions in younger and older adults, but music that conjures personal memories is more likely to elicit mixed emotions. Our results have important clinical implications when designing music-based interventions for mood and affect, particularly in older adult populations.

Epitope screening and vaccine molecule design of PRRSV GP3 and GP5 protein based on immunoinformatics.

Porcine reproductive and respiratory syndrome (PRRS) is a respiratory disease in pigs that causes severe economic losses. Currently, live PRRSV vaccines are commonly used but fail to prevent PRRS outbreaks and reinfection. Inactivated PRRSV vaccines have poor immunogenicity, making PRRSV a significant threat to swine health globally. Therefore, there is an urgent need to develop an effective PRRSV vaccine. This study used immunoinformatics to predict, screen, design and construct a candidate vaccine that fused B-cell epitopes, CTL- and HTL-dominant protective epitopes of PRRSV strain's GP3 and GP5 proteins. The study identified 12 B-cell epitopes, 6 CTL epitopes and 5 HTL epitopes of GP3 and GP5 proteins. The candidate vaccine was constructed with 50S ribosomal protein L7/L1 molecular adjuvant, which has antigenicity, solubility, stability, non-allergenicity and a high affinity for its target receptor, TLR-3. The C-ImmSim immunostimulation results showed significant increases in cellular and humoral responses (B cells and T cells) and production of TGF-β, IL-2, IL-10, IFN-γ and IL-12. The constructed vaccine was stable and immunogenic, and it can effectively induce strong T-cell and B-cell immune responses against PRRSV. Therefore, it is a promising candidate vaccine for controlling and preventing PRRSV outbreaks.

Impacts of Extreme Precipitation and Diurnal Temperature Events on Grassland Productivity at Different Elevations on the Plateau

The impact of extreme climate events on vegetation growth and ecosystem function has garnered widespread attention, particularly in plateau regions, which are facing increasingly severe environmental pressures. This study employs the Events Coincidence Analysis (ECA) method to examine the impacts of extreme climate events on the Net Primary Productivity (NPP) of vegetation in plateau regions. Specifically, we focus on the unique phenomenon of asymmetric daytime and nighttime warming and evaluate the compounding effect of extreme precipitation with extreme temperature events. The results indicate that grassland NPP has higher overall sensitivity and Coincidence Rates (CR) to extreme precipitation events compared to extreme temperature events. Specifically, extreme drought events significantly negatively impact grassland NPP, and the sensitivity of NPP increases with the severity of extreme drought events. In lower elevations (<3200 m), grassland NPP shows a strong response to extreme precipitation events, with sensitivity decreasing with increasing elevation, especially for alpine meadows. Extreme high-temperature events contributed significantly to NPP in mid to high elevations (3000–5000 m). Compound extreme climate events amplify the average coincidence degree with NPP anomalies, with extreme precipitation events playing a major role in compound effects. The CR of compound climate events can reach above 0.6, reflected in the anomaly increase of NPP in temperate grasslands at higher elevations caused by compound events of extremely wet and extremely high temperatures.

Highly deformable and strongly magnetic semi-interpenetrating hydrogels based on alginate or cellulose

The effective implementation of many of the applications of magnetic hydrogels requires the development of innovative systems capable of withstanding a substantial load of magnetic particles to ensure exceptional responsiveness, without compromising their reliability and stability. To address this challenge, double-network hydrogels have emerged as a promising foundation, thanks to their extraordinary mechanical deformability and toughness. Here, we report a semi-interpenetrating polymer networks (SIPNs) approach to create diverse magnetic SIPNs hydrogels based on alginate or cellulose, exhibiting remarkable deformability under certain stresses. Achieving strong responsiveness to magnetic fields is a key objective, and this characteristic is realized by the incorporation of highly magnetic iron microparticles at moderately large concentrations into the polymer network. Remarkably, the SIPNs hydrogels developed in this research accommodate high loadings of magnetic particles without significantly compromising their physical properties. This feature is essential for their use in applications that demand robust responsiveness to applied magnetic fields and overall stability, such as a hydrogel luminescent oxygen sensor controlled by magnetic fields that we designed and tested as proof-of-concept. These findings underscore the potential and versatility of magnetic SIPNs hydrogels based on carbohydrate biopolymers as fundamental components in driving the progress of advanced hydrogels for diverse practical implementations.

Genome-based prediction of cross-protective, HLA-DR-presented epitopes as putative vaccine antigens for multiple Bordetella species.

Pertussis, caused by Bordetella pertussis, can cause debilitating respiratory symptoms, so whole-cell pertussis vaccines (wPVs) were introduced in the 1940s. However, reactogenicity of wPV necessitated the development of acellular pertussis vaccines (aPVs) that were introduced in the 1990s. Since then, until the COVID-19 pandemic began, reported pertussis incidence was increasing, suggesting that aPVs do not induce long-lasting immunity and may not effectively prevent transmission. Additionally, aPVs do not provide protection against other Bordetella species that are observed during outbreaks. The significance of this work is in determining potential new vaccine antigens for multiple Bordetella species that are predicted to elicit long-term immune responses. Genome-based approaches have aided the development of novel vaccines; here, these methods identified Bordetella vaccine candidates that may be cross-protective and predicted to induce strong memory responses. These targets can lead to an improved vaccine with a strong safety profile while also strengthening the longevity of the immune response.

In Situ Chiral Template Approach to Synthesize Homochiral Lead Iodides for Second‐Harmonic Generation

AbstractHomochiral halide perovskites have gained increasing attention because of their fascinating optoelectronic properties and prospective applications in laser technologies. However, the limited choice of chiral organic templates severely restricts their structural diversity and second‐harmonic generation (SHG) effects. Here, we present an in situ chiral template approach for the synthesis of one‐dimensional (1D) homochiral lead iodides. A chiral imine (L‐ipp) template was generated in situ by reacting L‐proline (L‐pro) and acetone under ambient conditions. Notably, L‐ipp can cooperate with L‐pro to direct the formation of a homochiral lead iodide with dual chiral templates, which is unprecedented in crystalline metal halides. The homochiral lead iodide containing both L‐ipp and L‐pro shows a strong SHG response of 8.0 times that of KH2PO4 (8.0×KDP). The SHG efficiency is one of the largest values reported to date for any homochiral lead halides under 1064 nm laser irradiation. A comparative study shows that homochiral 1D lead iodides containing either L‐ipp or L‐pro exhibit relatively weak SHG responses (≤1.0×KDP). This work demonstrates the advantage of using two different chiral templates over a single chiral template in enhancing the SHG responses of halide materials.

Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine

Malaria, caused by Plasmodium parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts to lower morbidity and mortality. Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a single Plasmodium falciparum (Pf) pre-erythrocytic (PE) sporozoite (spz) surface protein known as circumsporozoite (CS). These vaccines induce humoral immunity but fail to elicit CD8 + T-cell responses sufficient for long-term protection. In contrast, whole-organism (WO) vaccines, such as Radiation Attenuated Sporozoites (RAS), achieved sterile protection but require a series of intravenous doses administered in multiple clinic visits. Moreover, these WO vaccines must be produced in mosquitos, a burdensome process that severely limits their availability. To reduce reliance on WO while maintaining protection via both antibodies and Trm responses, we have developed an accelerated vaccination regimen that combines two distinct agents in a prime-and-trap strategy. The priming dose is a single dose of self-replicating RNA encoding the full-length P. yoelii CS protein, delivered via an advanced cationic nanocarrier (LIONTM). The trapping dose consists of one dose of WO RAS. Our vaccine induces a strong immune response when administered in an accelerated regimen, i.e., either 5-day or same-day immunization. Additionally, mice after same-day immunization showed a 2-day delay of blood patency with 90% sterile protection against a 3-week spz challenge. The same-day regimen also induced durable 70% sterile protection against a 2-month spz challenge. Our approach presents a clear path to late-stage preclinical and clinical testing of dose-sparing, same-day regimens that can confer sterilizing protection against malaria.

In Situ Chiral Template Approach to Synthesize Homochiral Lead Iodides for Second-Harmonic Generation.

Homochiral halide perovskites have gained increasing attention because of their fascinating optoelectronic properties and prospective applications in laser technologies. However, the limited choice of chiral organic templates severely restricts their structural diversity and second-harmonic generation (SHG) effects. Here, we present an in situ chiral template approach for the synthesis of one-dimensional (1D) homochiral lead iodides. A chiral imine (L-ipp) template was generated in situ by reacting L-proline (L-pro) and acetone under ambient conditions. Notably, L-ipp can cooperate with L-pro to direct the formation of a homochiral lead iodide with dual chiral templates, which is unprecedented in crystalline metal halides. The homochiral lead iodide containing both L-ipp and L-pro shows a strong SHG response of 8.0 times that of KH2 PO4 (8.0×KDP). The SHG efficiency is one of the largest values reported to date for any homochiral lead halides under 1064 nm laser irradiation. A comparative study shows that homochiral 1D lead iodides containing either L-ipp or L-pro exhibit relatively weak SHG responses (≤1.0×KDP). This work demonstrates the advantage of using two different chiral templates over a single chiral template in enhancing the SHG responses of halide materials.

Assessing the Precision of Radon Measurements from Beta-Attenuation Monitors

Atmospheric radon measurements assist in many aspects of climate and meteorological research, notably as an airmass tracer and for modelling boundary layer development, mixing heights and stability. Daughter products from radon decay are sometimes incorporated into the particle pollution measurements of commercially available beta-attenuation monitors (BAM). BAMs incorporating radon measurements are used in air quality monitoring networks and can supplement traditional radon measurements. Here we compare in-situ radon measurements from Thermo Fisher Scientific (Franklin, MA, USA) BAM instruments (Thermo Scientific 5014i, Thermo Scientific 5030 SHARP, Thermo Anderson FH62C14) at two air quality monitoring stations in New South Wales, Australia. Between systems we find strong correlations for hourly measurements (r = 0.97–0.99); daily means (r = 0.97–0.99); hour of the day (r = 0.84–0.98); and month (r = 0.82–0.98). The regression analysis for radon measurements between systems showed strong linear responses, although there are some variations in the slopes of the regressions. This implies that with correction BAM measurements can be comparable to standard measurement techniques, for example, from the Australian Nuclear Science and Technology Organisation (ANSTO) dual flow loop monitors. Our findings imply that BAM derived radon measurements are precise, although their accuracy varies. BAM radon measurements can support studies on boundary layer development or where radon is used as an atmospheric transport tracer.

A candidate glycoconjugate vaccine induces protective antibodies in the serum and intestinal secretions, antibody recall response and memory T cells and protects against both typhoidal and non-typhoidal Salmonella serovars.

Human Salmonella infections pose significant public health challenges globally, primarily due to low diagnostic yield of systemic infections, emerging and expanding antibiotic resistance of both the typhoidal and non-typhoidal Salmonella strains and the development of asymptomatic carrier state that functions as a reservoir of infection in the community. The limited long-term efficacy of the currently licensed typhoid vaccines, especially in smaller children and non-availability of vaccines against other Salmonella serovars necessitate active research towards developing a multivalent vaccine with wider coverage of protection against pathogenic Salmonella serovars. We had earlier reported immunogenicity and protective efficacy of a subunit vaccine containing a recombinant outer membrane protein (T2544) of Salmonella Typhi in a mouse model. This was achieved through the robust induction of serum IgG, mucosal secretory IgA and Salmonella-specific cytotoxic T cells as well as memory B and T cell response. Here, we report the development of a glycoconjugate vaccine, containing high molecular weight complexes of Salmonella Typhimurium O-specific polysaccharide (OSP) and recombinant T2544 that conferred simultaneous protection against S. Typhi, S. Paratyphi, S. Typhimurium and cross-protection against S. enteritidis in mice. Our findings corroborate with the published studies that suggested the potential of Salmonella OSP as a vaccine antigen. The role of serum antibodies in vaccine-mediated protection is suggested by rapid seroconversion with high titers of serum IgG and IgA, persistently elevated titers after primary immunization along with a strong antibody recall response with higher avidity serum IgG against both OSP and T2544 and significantly raised SBA titers of both primary and secondary antibodies against different Salmonella serovars. Elevated intestinal secretory IgA and bacterial motility inhibition by the secretory antibodies supported their role as well in vaccine-induced protection. Finally, robust induction of T effector memory response indicates long term efficacy of the candidate vaccine. The above findings coupled with protection of vaccinated animals against multiple clinical isolates confirm the suitability of OSP-rT2544 as a broad-spectrum candidate subunit vaccine against human infection due to typhoidal and non-typhoidal Salmonella serovars.

A {P6Mo18}-type heteropolyblue modified NiO-based carbon nanofibers for bifunctional biosensors

Non-enzymatic electrochemical biosensors have great application value in the identification and detection of organic biological small molecules, especially in biomedical detection. In this paper, a carbon-based sensing material consisting of basket-type polyoxometallates (POMs) modified with synergistic multicomponent active centers was prepared. A novel POMs with heteropolyblue properties, {Co(phen)3}3[{Co(H2O)2}{Co(H2O)3}4}{Sr ⊂ P6MoVI16MoV2O73}2]·8H2O (CoP6Mo18), was modified on NiO-loaded carbon nanofibers (NiO-CNFs) to construct novel nanocomposites CoP6Mo18@NiO-CNFs. Differential pulse voltammetry (DPV) tests show that the nanocomposite electrode had a strong response to L-tryptophan (L-Trp) and dopamine (DA) with lower detection limit of 22.2 nM and 27.8 nM (S/N = 3) in the linear range of 66.7 nM-478 μM and 83.3 nM-437 μM, respectively. The results demonstrated that the modified electrode can quickly and efficiently detect DA and L-Trp alone or together due to catalytic synergy between CoP6Mo18 and NiO-CNFs. The combination of the two materials not only enhances the current response signals of the electrodes to the analytes DA and L-Trp, but also effectively improves the selectivity and stability of the sensor. Importantly, the prepared sensor can be used for trace detection of DA and L-Trp in pre-treated human serum samples in practical applications, and the recovery rate is as high as 98.9 %, which suggests that the CoP6Mo18@NiO-CNFs/GCE sensor has potential application value in biology and medical fields.

Strong plastic responses in aerenchyma formation in F1 hybrids of Imperata cylindrica under different soil moisture conditions.

Hybrids can express traits plastically, enabling them to occupy environments that differ from parental environments. However, there is insufficient evidence demonstrating how phenotypic plasticity in specific traits mediates hybrid performance. Two parental ecotypes of Imperata cylindrica produce F1 hybrids. The E-type in wet habitats has larger internal aerenchyma than the C-type in dry habitats. This study evaluated relationships between habitat utilisation, aerenchyma plasticity, and growth of I. cylindrica accessions. We hypothesize that plasticity in expressing parental traits explains hybrid establishment in habitats with various soil moisture conditions. Aerenchyma formation was examined in the leaf midribs, rhizomes and roots of two parental ecotypes and their F1 hybrids in their natural habitats. In common garden experiments, we examined plastic aerenchyma formation in leaf midribs, rhizomes and roots of natural and artificial F1 hybrids and parental ecotypes and quantified vegetative growth performance. In the natural habitats where soil moisture content varied widely, the F1 hybrids showed larger variation in aerenchyma formation in rhizomes than their parental ecotypes. In the common garden experiments, F1 hybrids showed high plasticity of aerenchyma formation in rhizomes, and their growth was similar to that of C-type and E-type under drained and flooded conditions, respectively. The results demonstrate that F1 hybrids of I. cylindrica exhibit plasticity in aerenchyma development in response to varying local soil moisture content. This characteristic allows the hybrids to thrive in diverse soil moisture conditions.

Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice

Compulsive behaviors are observed in a range of psychiatric disorders, however the neural substrates underlying the behaviors are not clearly defined. Here we show that the basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to the manifestation of compulsive-like behaviors. We revealed that the BLA neurons projecting to the DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with the neuronal population that responds to aversive predator stress, a widely used anxiogenic stressor. Specific optogenetic activation of the BLA-DMS circuit induced a strong anxiety response followed by compulsive grooming. Furthermore, we developed a mouse model for compulsivity displaying a wide spectrum of compulsive-like behaviors by chronically activating the BLA-DMS circuit. In these mice, persistent molecular changes at the BLA-DMS synapses observed were causally related to the compulsive-like phenotypes. Together, our study demonstrates the involvement of the BLA-DMS circuit in the emergence of enduring compulsive-like behaviors via its persistent synaptic changes.

Blue-light-enhanced avalanche photodiode with amulti-finger grating structure for fluorescence detection.

The responsiveness of the photodetectors is critical to the accuracy of the fluorescent fiber optical temperature sensor. However, the current gain and signal-to-noise ratio (SNR) of traditional photodiodes (PDs) is low, which makes it difficult to meet the high-precision detection requirements of the system. In response to the above problems, this paper achieves a novel, to the best of our knowledge, multi-finger grating (MFG) avalanche photodiode (APD). The device combines the polysilicon gate and the space charge region formed by P+/N-Well to detect photon signals. The conversion capability of the photodetector can be significantly enhanced by the MFG structure. The principle of the device is simulated and verified by technology-computer-aided design (TCAD). The standard grating APD (SG-APD), 2-finger grating APD (2FG-APD), 3-finger grating APD (3FG-APD), and 4-finger grating APD (4FG-APD) are fabricated based on 0.18µm CMOS process. The optoelectronic detection characteristics of these devices are analyzed by establishing an optoelectronic test platform. At 480nm, the responsivity of 2FG-APD, 3FG-APD, and 4FG-APD increases by 79.3%, 96.9%, and 70.2%, respectively, compared to SG-APD (4.021A/W). The test results indicate that 3FG-APD exhibits a strong photon response in the blue light range. The device has broad application prospects in the field of fluorescence detection.

Predicting Two-Photon Absorption Spectra of Octupolar Molecules: A Deep-Learning Approach Based Exclusively on Molecular Structures.

Octupolar molecules possessing a strong two-photon response are vital for numerous advanced applications. However, accurately predicting their two-photon absorption (TPA) spectra requires high-precision quantum chemical calculations, which are computationally expensive due to repeated simulations of molecular excited-state properties. To address this challenge, we introduce a deep learning approach capable of rapidly and accurately forecasting TPA spectra for octupolar molecules. By leveraging the geometric structure as an initial descriptor, we employ a graph neural network to predict the maximum two-photon transition wavelength and cross-section. Our model demonstrates a mean absolute percentage error of less than 4% compared to time-dependent density-functional theory calculations, effectively reproducing experimental observations. Notably, this deep learning technique is nearly 100 000 times faster than comparable quantum calculations, making it an efficient and cost-effective tool for simulating TPA properties of octupolar molecules. Furthermore, this method holds great promise for the high-throughput screening of exceptional TPA materials.

Cryptosporidium infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus

ABSTRACT Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen C. hominis and absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system for C. hominis using human enterocytes differentiated under air-liquid interface (ALI) conditions. Human ALI cultures supported robust growth and complete development of C. hominis in vitro including all life cycle stages. Cryptosporidium infection induced a strong interferon response from enterocytes, possibly driven, in part, by an endogenous dsRNA virus in the parasite. Prior infection with Cryptosporidium induced type III IFN secretion and consequently blunted infection with Rotavirus, including live attenuated vaccine strains. The development of hALI provides a platform for further studies on human-specific pathogens, including clinically important coinfections that may alter vaccine efficacy.

Comparison of the Efficacy of Different Schemes for Using Recombinant Vector Vaccines against Ebola Fever, Based on Vaccinia Virus, MVA Strain

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.

CRISPR/Cas12a cleavage-mediated isothermal amplification lights up the dimeric G-quadruplex signal unit for ultrasensitive and label-free detection of circulating tumor DNA

Circulating tumor DNA (ctDNA) is a valuable and potential cancer biomarker for real-time monitoring, and plays a vital role in cancer early diagnosis. In this work, we developed an ultrasensitive and label-free fluorescent biosensor for ctDNA detection. A well-designed RNA-DNA chimeric primer (RD) with phosphate groups modified at the 3-terminal was cleaved by target-initiated CRISPR/Cas12a, and then the subsequent exponential amplification reaction (EXPAR) was started to produce numerous G-rich sequences, which could be assembled with Thioflavin T to form a dimeric G-quadruplex (dimer-G4/ThT) and significantly enhance the fluorescence. Due to the innovative combination of the specificity of CRISPR/Cas12a and RD primers, the high amplification efficiency of EXPAR, and the strong fluorescence response of dimer-G4/ThT, this strategy demonstrated excellent sensitivity at the aM level. In addition, the sensing system showed satisfactory anti-interference ability and reliable accuracy in complex serum environment and tumor cell lysate. More importantly, this strategy avoided the complicated and expensive labeling process of traditional signal probes, making the construction of fluorescent biosensor simpler and more practical, offering practical insights for molecular diagnostics and clinical applications.

Montmorillonite nanosheets as an adjuvant eliciting potent cellular immunity

The experience of fighting COVID-19 shows the growing importance of vaccine-induced cellular immunity, whereas aluminum adjuvants fail to meet this medical requirement. Herein, with very simple processing, we prepared a narrow lateral size of monolayer clay nanosheets from montmorillonite, a FDA-approved generally recognized as safe (GARS) material. The nanosheets adsorbed antigen ovalbumin (OVA) through hydrophilic and electrostatic interactions, while utilizing nanosheets to expose more octahedral Al-OH and tetrahedral Si-OH residues to complete the adsorption of mannose (Man) targeting antigen presentation cells, leading to the production of nanosheet vaccines. In additional, the lyophilization process did not significantly affect the loading of OVA and Man on the nanosheets. The obtained nanosheet vaccines induced a strong cellular immune response in addition to a potent humoral immune response. Inspired by the results, the prophylactic nanosheet adjuvant vaccine against Epstein-Barr virus (EBV) was developed, which induced a 13-fold increase in EBV-neutralizing antibody titers compared to aluminum adjuvant vaccine, and efficiently blocked EBV infection of target cells. Based on the simple formulation process, remarkable immune response effect and excellent safety profile, montmorillonite nanosheets have the potential to replace aluminum adjuvant as a vaccine platform for inducing effective immune responses.