Novel transcription and replication-competent virus-like particles system modelling the Nipah virus life cycle.

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.

Silicon or Calcium Doping Coordinates the Immunostimulatory Effects of Aluminum Oxyhydroxide Nanoadjuvants in Prophylactic Vaccines.

Aluminum salts still remain as the most popular adjuvants in marketed human prophylactic vaccines due to their capability to trigger humoral immune responses with a good safety record. However, insufficient induction of cellular immune responses limits their further applications. In this study, we prepare a library of silicon (Si)- or calcium (Ca)-doped aluminum oxyhydroxide (AlOOH) nanoadjuvants. They exhibit well-controlled physicochemical properties, and the dopants are homogeneously distributed in nanoadjuvants. By using Hepatitis B surface antigen (HBsAg) as the model antigen, doped AlOOH nanoadjuvants mediate higher antigen uptake and promote lysosome escape of HBsAg through lysosomal rupture induced by the dissolution of the dopant in the lysosomes in bone marrow-derived dendritic cells (BMDCs). Additionally, doped nanoadjuvants trigger higher antigen accumulation and immune cell activation in draining lymph nodes. In HBsAg and varicella-zoster virus glycoprotein E (gE) vaccination models, doped nanoadjuvants induce high IgG titer, activations of CD4+ and CD8+ T cells, cytotoxic T lymphocytes, and generations of effector memory T cells. Doping of aluminum salt-based adjuvants with biological safety profiles and immunostimulating capability is a potential strategy to mediate robust humoral and cellular immunity. It potentiates the applications of engineered adjuvants in the development of vaccines with coordinated immune responses.

Air pollution exposure, accelerated biological aging, and increased thyroid dysfunction risk: Evidence from a nationwide prospective study.

BACKGROUND: Long-term air pollution exposure is a major health concern, yet its associations with thyroid dysfunction (hyperthyroidism and hypothyroidism) and biological aging remain unclear. We aimed to determine the association of long-term air pollution exposure with thyroid dysfunction and to investigate the potential roles of biological aging. METHODS: A prospective cohort study was conducted on 432,340 participants with available data on air pollutants including particulate matter (PM2.5, PM10, and PM2.5-10), nitrogen dioxide (NO2), and nitric oxide (NO) from the UK Biobank. An air pollution score was calculated using principal component analysis to reflect joint exposure to these pollutants. Biological aging was assessed using the Klemera-Doubal method biological age and the phenotypic age algorithms. The associations of individual and joint air pollutants with thyroid dysfunction were estimated using the Cox proportional hazards regression model. The roles of biological aging were explored using interaction and mediation analyses. RESULTS: During a median follow-up of 12.41 years, 1,721 (0.40 %) and 9,296 (2.15 %) participants developed hyperthyroidism and hypothyroidism, respectively. All air pollutants were observed to be significantly associated with an increased risk of incident hypothyroidism, while PM2.5, PM10, and NO2 were observed to be significantly associated with an increased risk of incident hyperthyroidism. The hazard ratios (HRs) for hyperthyroidism and hypothyroidism were 1.15 (95 % confidence interval: 1.00-1.32) and 1.15 (1.08-1.22) for individuals in the highest quartile compared with those in the lowest quartile of air pollution score, respectively. Additionally, we noticed that individuals with higher pollutant levels and biologically older generally had a higher risk of incident thyroid dysfunction. Moreover, accelerated biological aging partially mediated 1.9 %-9.4 % of air pollution-associated thyroid dysfunction. CONCLUSIONS: Despite the possible underestimation of incident thyroid dysfunction, long-term air pollution exposure may increase the risk of incident thyroid dysfunction, particularly in biologically older participants, with biological aging potentially involved in the mechanisms.

Applying improved ddPCR to reliable quantification of MPXV in clinical settings.

Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/µL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV. IMPORTANCE: The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

[Assessment of auditory perception of children with single-sided deafness after cochlear implantation].

Unilateral deafness will lead to the decline of children's speech recognition rate, language development retardation and spatial positioning ability, which will have many adverse effects on children's life and study. Cochlear implantation can help children rebuild binaural hearing, and systematic audiological evaluation after operation is particularly important for clinicians to evaluate the hearing recovery of children. In this study, a variety of commonly used audiological evaluation, testing processes and methods after cochlear implantation in children with unilateral deafness are described in detail, and the related research status and results are summarized.

RNA binding motif 4 inhibits the replication of ebolavirus by directly targeting 3'-leader region of genomic RNA.

Ebola virus (EBOV) belongs to Filoviridae family possessing single-stranded negative-sense RNA genome, which is a serious threat to human health. Nowadays, no therapeutics have been proven to be successful in efficiently decreasing the mortality rate. RNA binding proteins (RBPs) are reported to participate in maintaining cell integrity and regulation of viral replication. However, little is known about whether and how RBPs participate in regulating the life cycle of EBOV. In our study, we found that RNA binding motif protein 4 (RBM4) inhibited the replication of EBOV in HEK293T and Huh-7 cells by suppressing viral mRNA production. Such inhibition resulted from the direct interaction between the RRM1 domain of RBM4 and the "CU" enrichment elements located in the PE1 and TSS of the 3'-leader region within the viral genome. Simultaneously, RBM4 could upregulate the expression of some cytokines involved in the host innate immune responses to synergistically exert its antiviral function. The findings therefore suggest that RBM4 might serve as a novel target of anti-EBOV strategy.

A Polymer Acceptor with Grafted Small Molecule Acceptor Unit for Efficient All Polymer Organic Solar Cells.

A polymer acceptor, named PX-1, is  designed and synthesized using a polymerization strategy with grafted small molecule acceptors. This design approach allows for the freedom of end groups while maintaining efficient terminal packing, enhancing π-π interactions, and facilitating charge transport. All-polymer organic solar cells based on PM6: PX-1 demonstrate a promising efficiency of 13.55%. The result presents an alternative pathway for the design of high-efficiency polymer acceptors through the careful regulation of small molecule acceptor monomers and linker units.

Fabrication of a micro/nanocomposite structure on the surface of high oxygen concentration titanium to promote bone formation.

This study investigated the properties of the micro/nano composite structure on the surface of high oxygen concentration titanium (HOC-Ti) after anodic oxidation modification (HOC-NT) and evaluated its biocompatibility as a dental implant material in vitro and in vivo. HOC-Ti was produced by titanium powders and rutile powders using the powder metallurgy method. Its surface was modified by anodic oxidation. After detecting the electrochemical characteristics, the surface properties of HOC-NT were investigated. MC3T3 and MLO-Y4 cells were employed to evaluate the biocompatibility of HOC-NT and cocultured to study the effects of the changes in osteocytes induced by HOC-NT on osteoblasts. While, its possible mechanism was investigated. In addition, osseointegration around the HOC-NT implant was investigated through in vivo experiments. The results showed that a unique micronano composite structure on the HOC-Ti surface with excellent hydrophilicity and suitable surface roughness was created after anodic oxidation promoted by its electrochemical characteristics. The YAP protein may play an important role in regulating bone remodeling by ß-catenin and Rankl/OPG Signaling Pathways. An in vivo study also revealed an accelerated formation rate of new bone and more stable osseointegration around the HOC-NT implant. In view of all experimental results, it could be concluded that the unique morphology of HOC-NT has enhanced physicochemical and biological properties. The promotion of bone formation around implants indicated the feasibility of HOC-NT for applications in oral implants.

Effect of High Jugular Bulb on the Hearing Loss Characteristics in Patients With LVAS: A Pilot Study.

OBJECTIVE: Both large vestibular aqueduct syndrome (LVAS) and high jugular bulb (HJB) are regarded as abnormalities commonly seen on the temporal bone CT. High jugular bulb has been found to erode the vestibular aqueduct, and there are several studies on jugular bulb vestibular aqueduct dehiscence. However, there is no study that specifically reports LVAS with concurrent HJB and its hearing loss relatedness. This study presents the pure tone audiometry differences between LVAS with HJB, and LVAS without HJB. METHODS: This was a case control study involving 36 bilateral LVAS with concurrent unilateral HJB patients, total of 72 ears. Intra-person comparison was done, by dividing ears into two groups: the case group, 36 ears (LVAS with HJB); and the control group, 36 ears (LVAS without HJB). Air conduction thresholds (250-4000 Hz), bone conduction thresholds (250-1000 Hz), and air bone gap (250-1000 Hz) were analyzed and compared between groups. RESULT: There were statistically significant differences in AC thresholds at 250, 500, 2000, and 4000 Hz between the groups, p < 0.05. But there was no statistical significant difference at 1000 Hz, p > 0.05. There were statistical significant differences in BC thresholds at 250 and 500 Hz, p < 0.05, but there was no statistical difference at 1000 Hz. There were no significant differences in air bone gap at 250, 500, and 1000 Hz between the two groups. CONCLUSION: LVAS with concurrent HJB was found to have higher air conduction thresholds, especially at 250, 500, 2000, and 4000 Hz. Bone conduction thresholds were higher at 250 and 500 Hz. Air bone gap at 250, 500, and 1000 Hz, were not significantly higher in LVAS with concurrent HJB.

Rh(III)-Catalyzed Chemoselective C-H Alkenylation and [5 + 1] Annulation with Gem-Difluoromethylene Enabled by the Distinctive Fluorine Effect.

The efficient couplings of diverse N-arylureas and gem-difluoromethylene alkynes have been realized via Rh(III)-catalyzed chemoselective C-H alkenylation and [5 + 1] annulation, which were induced by the distinctive fluorine effect to provide the different coordination mode of the Rh(III) catalyst binding to the directing group, thereby giving the direct access to difluorinated 2-alkenyl arylureas and 3,4-dihydroquinazolin-2(1H)-ones bearing both an α-quaternary carbon center and a monofluoroalkenyl moiety with broad substrate compatibility and good functional group tolerance. The synthetic application in C-H alkenylation of the N-pyridylaniline, the late-stage [3 + 2] annulation, and the derivation of the obtained products has been also demonstrated to further strengthen the synthetic utility of the chemodivergent transformations.

[Outcome of otolith organ function after treatment of sudden sensorineural hearing loss].

Objective:This study aimed to assess the clinical practice value of ocular vestibular evoked myogenic potential（oVEMP） and cervical vestibular evoked myogenic potential（cVEMP） in monitoring the rehabilitation of vestibular function in patients with suddensen sorineural hearing loss（SSHL）. Method:Twenty-four patients with SSHL were retrospectively enrolled， showing no VEMP response on the affected side but exhibiting VEMP responses after therapies We analyzed the improvement and the restoration of hearing and the parameters of VEMP response. Result:After treatment, seven patients showed VEMP recovery, including three cases with both oVEMP and cVEMP recovery, three cases with oVEMP recovery, and one case with cVEMP recovery. Between VEMP recoved group and VEMP unrecoved group, before treatment, no significant difference was found in the thresholds of pure-tone audiometry（PTA）. However, after treatment, VEMP recoved group exhibited lower PTA thresholds and better PTA shift （P<0.01）. Multivariate analysis revealed that recovery of VEMP was the independent risk factor for the therapeutic effect of SSHL. Conclusion:The Combination of oVEMP and cVEMP is an objective tool for assessing vestibular otolithic end organ function during dynamic functional recovery in SSHL and the recovery of VEMP could predict the auditory improvement.

Mechanical properties and biocompatibility of titanium with a high oxygen concentration for dental implants.

In order to improve the strength of commercially pure Ti (CP-Ti) for oral implants, the high oxygen content Ti (HOC-Ti) was prepared via powder metallurgy. Its composition and mechanical properties were then characterized. After surface treatment by sandblasting and acid etching (SLA), the surface morphology, wettability and roughness of the HOC-Ti and CP-Ti sample were examined. In an in vitro test that followed an evaluation of the protein adsorption capacity of HOC-Ti, the mouse preosteoblast cells were inoculated onto the specimens to evaluate their biocompatibility, in comparison with those of CP-Ti. The oxygen concentration of the HOC-Ti increased to 0.62 wt%, which is higher than the 0.26 wt% of the CP-Ti, while their compositions and microstructures were very similar. The tensile and compressive yield strength of the HOC-Ti (800 MPa) was improved significantly in comparison to that of the CP-Ti (530 MPa). After surface treatment, a unique structure of micropores with a diameter of 380 nm was observed on the entire surface of the HOC-Ti that facilitates cell adhesion and proliferation. The wettability of the HOC-Ti was obviously superior (p < 0.05). The in vitro study showed that the MC3T3-E1 cells inoculated on the surface of HOC-Ti exhibited a homogeneous microstructure, and the viability was higher than that of the control group on days 4 and 7 (p < 0.05). In addition, the number and differentiation activity of cells that adhered to the surface of the HOC-Ti increased significantly on day 7 (p < 0.05). The experimental results showed that, in view of its mechanical properties and biocompatibility, HOC-Ti is superior to CP-Ti and is promising for oral implant applications.

A 4-N,N-dimethylaminoaniline salicylaldehyde Schiff-base solution-solid dual emissive fluorophore: An aggregation-induced turquoise emission characteristics in liquid as a fluorescent probe for Zn2+ response; a strong near-infrared emission in solid state and application for optical data storage.

A new Schiff-base 1 based on 4-N,N-dimethylaminoaniline salicylaldehyde is developed. It possesses unique solution-solid dual emission behaviour with emission color: an aggregation-induced bright turquoise emission in liquid and strong near-infrared emission in the solid state. Interestingly, on the one hand, compound 1 is promising a ratiometric fluorescent probe for Zn2+ ions detection in the aqueous solution with high sensitivity, selectivity, and relatively low detection limit. On the other hand, based on its inner stimuli-responsive nature, outstanding thermostability and photostability, 1 should be a very promising candidate for the write-once read-many optical data storage medium.

A through-bond energy transfer-based ratiometric fluorescent pH probe: For extreme acidity and extreme alkaline detection with large emission shifts.

A ratiometric fluorescence pH probe 1 based on through-bond energy transfer (TBET) with a 2-(2-hydroxyphenyl)benzoxazole (HBO) as donor and a Rhodamine derivative as acceptor is developed through simple condensation reaction. The probe exhibits a ratiometric fluorescence emission (I593/I422) characteristics and linear response to extreme acidity range of 5.00-2.88, and a ratiometric fluorescence emission (I555/I422) characteristics and linear response to extreme alkaline range of 10.00-13.78, respectively. Moreover, 1 possesses highly selective response to pH over metal ions, good reversibility and excellent photostability. Probe 1 is cellpermeable and can distinguish near pH 5.55 fluctuations in Hela cells. Furthermore, 1 can be immobilized on a test paper, which shows a rapid and reversible colorimetric response to HCl/NH3 vapor by the naked-eye.

Chemodivergent Couplings of N-Arylureas and Methyleneoxetanones via Rh(III)-Catalyzed and Solvent-Controlled C-H Activation.

The efficient couplings of diverse N-arylureas and methyleneoxetanones have been realized via Rh(III)-catalyzed and solvent-controlled chemoselective C-H functionalization, which involved the tunable ß-H elimination and ß-O elimination processes, thereby giving divergent access to quinolin-2(1 H)-ones and ortho-allylated N-arylureas with broad substrate compatibility and good functional group tolerance. the divergent synthetic utilities of the transformations have also been exemplified by subsequently tandem C-H allylation, unsymmetrical C-H functionalization, alternative reaction mode, as well as removal of the carbamoyl group.