Type VII secretion system extracellular protein B targets STING to evade host anti-Staphylococcus aureus immunity.

Staphylococcus aureus (S. aureus) can evade antibiotics and host immune defenses by persisting within infected cells. Here, we demonstrate that in infected host cells, S. aureus type VII secretion system (T7SS) extracellular protein B (EsxB) interacts with the stimulator of interferon genes (STING) protein and suppresses the inflammatory defense mechanism of macrophages during early infection. The binding of EsxB with STING disrupts the K48-linked ubiquitination of EsxB at lysine 33, thereby preventing EsxB degradation. Furthermore, EsxB-STING binding appears to interrupt the interaction of 2 vital regulatory proteins with STING: aspartate-histidine-histidine-cysteine domain-containing protein 3 (DHHC3) and TNF receptor-associated factor 6. This persistent dual suppression of STING interactions deregulates intracellular proinflammatory pathways in macrophages, inhibiting STING's palmitoylation at cysteine 91 and its K63-linked ubiquitination at lysine 83. These findings uncover an immune-evasion mechanism by S. aureus T7SS during intracellular macrophage infection, which has implications for developing effective immunomodulators to combat S. aureus infections.

Entanglement of two quantum memories via fibres over dozens of kilometres.

A quantum internet that connects remote quantum processors1,2 should enable a number of revolutionary applications such as distributed quantum computing. Its realization will rely on entanglement of remote quantum memories over long distances. Despite enormous progress3-12, at present the maximal physical separation achieved between two nodes is 1.3 kilometres10, and challenges for longer distances remain. Here we demonstrate entanglement of two atomic ensembles in one laboratory via photon transmission through city-scale optical fibres. The atomic ensembles function as quantum memories that store quantum states. We use cavity enhancement to efficiently create atom-photon entanglement13-15 and we use quantum frequency conversion16 to shift the atomic wavelength to telecommunications wavelengths. We realize entanglement over 22 kilometres of field-deployed fibres via two-photon interference17,18 and entanglement over 50 kilometres of coiled fibres via single-photon interference19. Our experiment could be extended to nodes physically separated by similar distances, which would thus form a functional segment of the atomic quantum network, paving the way towards establishing atomic entanglement over many nodes and over much longer distances.

Asymmetrically Coordinated Mn-S1 N3 Configuration Induces Localized Electric Field-Driven Peroxymonosulfate Activation for Remarkably Efficient Generation of 1 O2.

Singlet oxygen (1 O2 ) species generated in peroxymonosulfate (PMS)-based advanced oxidation processes offer opportunities to overcome the low efficiency and secondary pollution limitations of existing AOPs, but efficient production of 1 O2 via tuning the coordination environment of metal active sites remains challenging due to insufficient understanding of their catalytic mechanisms. Herein, an asymmetrical configuration characterized by a manganese single atom coordinated is established with one S atom and three N atoms (denoted as Mn-S1 N3 ), which offer a strong local electric field to promote the cleavage of O─H and S─O bonds, serving as the crucial driver of its high 1 O2 production. Strikingly, an enhanced the local electric field caused by the dynamic inter-transformation of the Mn coordination structure (Mn-S1 N3 ↔ Mn-N3 ) can further downshift the 1 O2 production energy barrier. Mn-S1 N3 demonstrates 100% selective product 1 O2 by activation of PMS at unprecedented utilization efficiency, and efficiently oxidize electron-rich pollutants. This work provides an atomic-level understanding of the catalytic selectivity and is expected to guide the design of smart 1 O2 -AOPs catalysts for more selective and efficient decontamination applications.

KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3ß/ß-catenin signaling pathway.

Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-ß-catenin and phospho-GSK3ß (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3ß/ß-catenin signaling pathway.

MFG-E8 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells through GSK3ß/ß-catenin signaling pathway.

Fracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG-E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. We investigated the osteogenic effect of MFG-E8 in vitro and in vivo. The CCK-8 assay was used to assess the effect of recombinant human MFG-E8 (rhMFG-E8) on the viability of hBMSCs. Osteogenesis was investigated using RT-PCR, Western blotting, and immunofluorescence. Alkaline phosphatase (ALP) and Alizarin red staining were used to evaluate ALP activity and mineralization, respectively. An enzyme-linked immunosorbent assay was conducted to evaluate the secretory MFG-E8 concentration. Knockdown and overexpression of MFG-E8 in hBMSCs were established via siRNA and lentivirus vector transfection, respectively. Exogenous rhMFG-E8 was used to verify the in vivo therapeutic effect in a tibia bone defect model based on radiographic analysis and histological evaluation. Endogenous and secretory MFG-E8 levels increased significantly during the early osteogenic differentiation of hBMSCs. Knockdown of MFG-E8 inhibited the osteogenic differentiation of hBMSCs. Overexpression of MFG-E8 and rhMFG-E8 protein increased the expression of osteogenesis-related genes and proteins and enhanced calcium deposition. The active ß-catenin to total ß-catenin ratio and the p-GSK3ß protein level were increased by MFG-E8. The MFG-E8-induced enhanced osteogenic differentiation of hBMSCs was partially attenuated by a GSK3ß/ß-catenin signaling inhibitor. Recombinant MFG-E8 accelerated bone healing in a rat tibial-defect model. In conclusion, MFG-E8 promotes the osteogenic differentiation of hBMSCs by regulating the GSK3ß/ß-catenin signaling pathway and so, is a potential therapeutic target.

Photochemical Transformation of Dissolved Organic Matter in Surface Water Augmented the Formation of Disinfection Byproducts.

Sunlight may lead to changes in disinfection byproducts (DBPs) formation potentials of source water via transforming dissolved organic matter (DOM); however, the underlying mechanisms behind these changes remain unclear. This work systematically investigated the effect of photochemical transformation of DOM from reservoir water (DOMRe) and micropolluted river water (DOMRi) after 36 h of simulated sunlight irradiation (equivalent to one month under natural sunlight) on DBPs formation. Upon irradiation, high molecular weight (MW) and aromatic molecules tended to be mineralized or converted into low-MW and highly oxidized (O/C > 0.5) ones which might react with chlorine to generate high levels of DBPs, resulting in an elevation in the yields (µg DBP/mg C) of almost all the measured DBPs and the quantities of unknown DBPs in both DOM samples after chlorination. Additionally, DOMRi contained more aromatic molecules susceptible to photooxidation than DOMRe. Consequently, irradiated DOMRi exhibited a greater increase in the formation potentials of haloacetonitriles, halonitromethanes, and specific regulated DBPs, with nitrogenous DBPs being responsible for the overall rise in the calculated cytotoxicity following chlorination. This work emphasized the importance of a comprehensive removal of phototransformation products that may serve as DBPs precursors from source waters, especially from micropolluted source waters.

Binding Strengths and Orientations in CO2 Adsorption on Cationic Scandium Oxides: Governing Factor Revealed by a Combined Infrared Spectroscopy and Theoretical Study.

Carbon dioxide (CO2) adsorption is a critical step to curbing carbon emissions from fossil fuel combustion. Among various options, transition metal oxides have received extensive attention as promising CO2 adsorbents due to their affordability and sustainability for large-scale use. Here, the nature of binding interactions between CO2 molecules and cationic scandium oxides of different sizes, i.e., ScO+, Sc2O2+, and Sc3O4+, is investigated by mass-selective infrared photodissociation spectroscopy combined with quantum chemical calculations. The well-accepted electrostatic considerations failed to provide explanations for the trend in the binding strengths and variations in the binding orientations between CO2 and metal sites of cationic scandium oxides. The importance of orbital interactions in the driving forces for CO2 adsorption on cationic scandium oxides was revealed by energy decomposition analyses. A molecular surface property, known as the local electron attachment energy, is introduced to elucidate the binding affinity and orientation-specific reactivity of cationic scandium oxides upon the CO2 attachment. This study not only reveals the governing factor in the binding behaviors of CO2 adsorption on cationic scandium oxides but also serves as an archetype for predicting and rationalizing favorable binding sites and orientations in extended surface-adsorbate systems.

Device-independent quantum random-number generation.

Randomness is important for many information processing applications, including numerical modelling and cryptography1,2. Device-independent quantum random-number generation (DIQRNG)3,4 based on the loophole-free violation of a Bell inequality produces genuine, unpredictable randomness without requiring any assumptions about the inner workings of the devices, and is therefore an ultimate goal in the field of quantum information science5-7. Previously reported experimental demonstrations of DIQRNG8,9 were not provably secure against the most general adversaries or did not close the 'locality' loophole of the Bell test. Here we present DIQRNG that is secure against quantum and classical adversaries10-12. We use state-of-the-art quantum optical technology to create, modulate and detect entangled photon pairs, achieving an efficiency of more than 78 per cent from creation to detection at a distance of about 200 metres that greatly exceeds the threshold for closing the 'detection' loophole of the Bell test. By independently and randomly choosing the base settings for measuring the entangled photon pairs and by ensuring space-like separation between the measurement events, we also satisfy the no-signalling condition and close the 'locality' loophole of the Bell test, thus enabling the realization of the loophole-free violation of a Bell inequality. This, along with a high-voltage, high-repetition-rate Pockels cell modulation set-up, allows us to accumulate sufficient data in the experimental time to extract genuine quantum randomness that is secure against the most general adversaries. By applying a large (137.90 gigabits × 62.469 megabits) Toeplitz-matrix hashing technique, we obtain 6.2469 × 107 quantum-certified random bits in 96 hours with a total failure probability (of producing a random number that is not guaranteed to be perfectly secure) of less than 10-5. Our demonstration is a crucial step towards transforming DIQRNG from a concept to a key aspect of practical applications that require high levels of security and thus genuine randomness7. Our work may also help to improve our understanding of the origin of randomness from a fundamental perspective.

Free-space coupled, large-active-area superconducting microstrip single-photon detector for photon-counting time-of-flight imaging.

Numerous applications at the photon-starved regime require a free-space coupling single-photon detector with a large active area, low dark count rate (DCR), and superior time resolutions. Here, we developed a superconducting microstrip single-photon detector (SMSPD), with a large active area of 260 µm in diameter, a DCR of ∼5k c p s, and a low time jitter of ∼171p s, operated at a near-infrared of 1550 nm and a temperature of ∼2.0K. As a demonstration, we applied the detector to a single-pixel galvanometer scanning system and successfully reconstructed the object information in depth and intensity using a time-correlated photon counting technology.

Peptidoglycan-associated lipoprotein contributes to the virulence of Acinetobacter baumannii and serves as a vaccine candidate.

The role of peptidoglycan-associated lipoprotein (Pal) in A. baumannii pathogenesis remains unclear. Here, we illustrated its role by constructing a pal deficient A. baumannii mutant and its complementary strain.Transcriptome analysis of the WT and pal mutant revealed a total of 596 differentially expressed genes. Gene Ontology analysis revealed that pal deficiency caused the downregulation of genes related to material transport and metabolic processes. The pal mutant showed a slower growth and was sensitive to detergent and serum killing compared to WT strain, whereas, the complemented pal mutant showed rescued phenotype. The pal mutant caused decreased mortality in mice pneumonia infection compared to WT strain, while the complemented pal mutant showed increased mortality. Mice immunized with recombinant Pal showed 40% protection against A. baumannii-mediated pneumonia. Collectively, these data indicate Pal is a virulence factor of A. baumannii and may serve as a potential target for preventive or therapeutic interventions.

Regional distribution prevalence of heterotopic ossification in the elbow joint: a 3D study of patients after surgery for traumatic elbow injury.

BACKGROUND: Heterotopic ossification (HO) is a common complication after elbow fracture surgery and can lead to severe upper extremity disability. The radiographic localization of postoperative HO has been reported previously. However, there is no literature examining the distribution of postoperative HO at the three-dimensional (3D) level. This study aimed to investigate 1) the distribution characteristics of postoperative HO and 2) the possible risk factors affecting the severity of postoperative HO at a 3D level. METHODS: A retrospective review was conducted of patients who presented to our institution with HO secondary to elbow fracture between 13 January 2020 and 16 February 2023. Computed tomography scans of 56 elbows before elbow release surgery were reconstructed in 3D. HO was identified using density thresholds combined with manual identification and segmentation. The elbow joint and HO were divided into six regions according to three planes: the transepicondylar plane, the lateral ridge of the trochlear plane, and the radiocapitellar joint and coronoid facet plane. The differences in the volume of regional HO associated with different initial injuries were analyzed. RESULTS: Postoperative HO was predominantly present in the medial aspect of the capsule in 52 patients (93%), in the lateral aspect of the capsule in 45 patients (80%), in the medial supracondylar in 32 patients (57%), and in the lateral supracondylar, radial head, and ulnar region in the same number of 28 patients (50%). The median and interquartile range volume of total postoperative HO was 1683 (777-4894) mm3. The median and interquartile range volume of regional postoperative HO were: 584 (121-1454) mm3 at medial aspect of capsule, 207 (5-568) mm3 at lateral aspect of capsule, 25 (0-449) mm3 at medial supracondylar, 1 (0-288) at lateral supracondylar, 2 (0-478) at proximal radius and 7 (0-203) mm3 at the proximal ulna. In the subgroups with Injury Severity Score > or = 16, Gustilo-Anderson II, normal uric acid levels, elevated alkaline phosphatase, and body mass index > or = 24, the median HO volume exceeds that of the respective control groups. CONCLUSION: The medial aspect of the capsule was the area with the highest frequency and median volume of postoperative HO among all initial elbow injury types. Patients with higher Gustilo-Anderson grade, Injury Severity Score, alkaline phosphatase or Body Mass Index had higher median volume of postoperative HO.

The TaGW2-TaSPL14 module regulates the trade-off between tiller number and grain weight in wheat.

IDEAL PLANT ARCHITECTURE1 (IPA1) is a pivotal gene controlling plant architecture and grain yield. However, little is known about the effects of Triticum aestivum SQUAMOSA PROMOTER-BINDING-LIKE 14 (TaSPL14), an IPA1 ortholog in wheat, on balancing yield traits and its regulatory mechanism in wheat (T. aestivum L.). Here, we determined that the T. aestivum GRAIN WIDTH2 (TaGW2)-TaSPL14 module influences the balance between tiller number and grain weight in wheat. Overexpression of TaSPL14 resulted in a reduced tiller number and increased grain weight, whereas its knockout had the opposite effect, indicating that TaSPL14 negatively regulates tillering while positively regulating grain weight. We further identified TaGW2 as a novel interacting protein of TaSPL14 and confirmed its ability to mediate the ubiquitination and degradation of TaSPL14. Based on our genetic evidence, TaGW2 acts as a positive regulator of tiller number, in addition to its known role as a negative regulator of grain weight, which is opposite to TaSPL14. Moreover, combinations of TaSPL14-7A and TaGW2-6A haplotypes exhibit significantly additive effects on tiller number and grain weight in wheat breeding. Our findings provide insight into how the TaGW2-TaSPL14 module regulates the trade-off between tiller number and grain weight and its potential application in improving wheat yield.

Analysis of mandibular asymmetry in adolescent and adult patients with unilateral posterior crossbite on cone-beam computed tomography.

INTRODUCTION: This study aimed to evaluate mandibular asymmetry in unilateral posterior crossbite (UPXB) patients and compare the asymmetry between adolescents and adults with UPXB. METHODS: This study included and analyzed cone-beam computed tomography scans of 125 subjects. The subjects were divided into a UPXB group and a control group according to the presence or absence of UPXB, and each group included adolescent patients (aged 10-15 years) and adult patients (aged 20-40 years). Linear, angular, and volumetric measurements were obtained to evaluate the asymmetries of the mandibles. RESULTS: Both adolescent and adult patients in the UPXB group presented asymmetries in condylar unit length, ramal height, body length, and mediolateral ramal inclination (P <0.05). Adult patients with UPXB showed greater asymmetries than adolescents. Differences with condylar unit length, condylar unit width, ramal height, condylar unit volume, and hemimandibular volume were significantly greater in adult UPXB patients than adolescent UPXB patients (P <0.05). CONCLUSIONS: The worsening of mandibular asymmetries in UPXB adults suggests that asymmetry in UPXB patients may progress over time; therefore, early treatment should be considered for UPXB adolescent patients. Further studies are still needed to evaluate the effectiveness of early treatment.

rFSAV promotes Staphylococcus aureus-infected bone defect healing via IL-13- mediated M2 macrophage polarization.

Staphylococcus aureus (S. aureus) contamination commonly occurs in orthopedic internal fixation operations, leading to a delayed healing of the defected bone tissue. However, antibiotic treatments are ineffective in dealing with S. aureus bone infections due to the rise in multiple antimicrobial resistances. Here, we reported the protective effects of a recombinant five-antigen S. aureus vaccine (rFSAV) in an S. aureus infected bone defect model. In this study, we found the number of M2 macrophages markedly increased in the defect site and played a critical role in the healing of defected bone mediated by rFSAV. Mechanistically, rFSAV mediated increased level of IL-13 in bone defect site predominant M2 macrophage polarization. In summary, our study reveals a key role of M2 macrophage polarization in the bone regeneration process in S. aureus infection induced bone defect, which provide a promising application of rFSAV for the treatment of bone infection for orthopedic applications.

An artificial-intelligence-based age-specific template construction framework for brain structural analysis using magnetic resonance images.

It is an essential task to construct brain templates and analyze their anatomical structures in neurological and cognitive science. Generally, templates constructed from magnetic resonance imaging (MRI) of a group of subjects can provide a standard reference space for analyzing the structural and functional characteristics of the group. With recent development of artificial intelligence (AI) techniques, it is desirable to explore AI registration methods for quantifying age-specific brain variations and tendencies across different ages. In this article, we present an AI-based age-specific template construction (called ASTC) framework for longitudinal structural brain analysis using T1-weighted MRIs of 646 subjects from 18 to 82 years old collected from four medical centers. Altogether, 13 longitudinal templates were constructed at a 5-year age interval using ASTC, and tissue segmentation and substructure parcellation were performed for analysis across different age groups. The results indicated consistent changes in brain structures along with aging and demonstrated the capability of ASTC for longitudinal neuroimaging study.

High band-width mid-infrared frequency-modulated Faraday rotation spectrometer for time resolved measurement of the OH radical.

We present a novel mid-infrared frequency-modulated Faraday rotation spectrometer (FM-FRS) for highly sensitive and high bandwidth detection of OH radicals in a photolysis reactor. High frequency modulation (up to 150 MHz) of the probe laser using an electro-optical modulator (EOM) was used to produce a modulation sideband on the laser output. An axial magnetic field was applied to the multi-pass Herriott cell, causing the linearly polarized light to undergo Faraday rotation. OH radicals were generated in the cell by photolyzing a mixture of ozone (O3) and water (H2O) with a UV laser pulse. The detection limit of OH reaches 6.8 × 108 molecule/cm3 (1σ, 0.2 ms) after 3 and falling to 8.0 × 107 molecule/cm3 after 100 event integrations. Relying on HITRAN absorption cross section and line shape data, this corresponds to minimum detectable fractional absorption (Amin) of 1.9 × 10-5 and 2.2 × 10-6, respectively. A higher signal-to-noise ratio and better long-term stability was achieved than with conventional FMS because the approach was immune to interference from diamagnetic species and residual amplitude modulation noise. To our knowledge, this work reports the first detection of OH in a photolysis reactor by FM-FRS in the mid-infrared region, a technique that will provide a new and alternative spectroscopic approach for the kinetic study of OH and other intermediate radicals.

Unmanned-aerial-vehicle-borne cavity enhanced albedometer: a powerful tool for simultaneous in-situ measurement of aerosol light scattering and absorption vertical profiles.

Vertical profiles of aerosol light scattering (bscat), absorption (babs), as well as the single scattering albedo (SSA, ω), play an important role in the effects of aerosols on climate, air quality, and local photochemistry. High-precision in-situ measurements of the vertical profiles of these properties are challenging and therefore uncommon. We report here the development of a portable cavity-enhanced albedometer operating at λ = 532 nm for use aboard an unmanned aerial vehicle (UAV). Multi-optical parameters, bscat, babs, extinction coefficient bext, and ω, can be measured simultaneously in the same sample volume. The achieved detection precisions in laboratory were 0.38, 0.21, and 0.43 Mm-1 for bext, bscat, and babs, respectively, for a 1 s data acquisition time. The albedometer was installed on an hexacopter UAV and simultaneous in-situ measurements of the vertical distributions of bext, bscat, babs, and ω were realized for the first time. Here we report a representative vertical profile up to a maximum height of 702 m with a vertical resolution of better than 2 m. The UAV platform and the albedometer demonstrate good performance and will be a valuable and powerful tool for atmospheric boundary layer research.

Millimeter-scale active area superconducting microstrip single-photon detector fabricated by ultraviolet photolithography.

The effective and convenient detection of single photons via advanced detectors with a large active area is becoming significant for quantum and classical applications. This work demonstrates the fabrication of a superconducting microstrip single-photon detector (SMSPD) with a millimeter-scale active area via the use of ultraviolet (UV) photolithography. The performances of NbN SMSPDs with different active areas and strip widths are characterized. SMSPDs fabricated by UV photolithography and electron beam lithography with small active areas are also compared from the aspects of the switching current density and line edge roughness. Furthermore, an SMSPD with an active area of 1 mm × 1 mm is obtained via UV photolithography, and during operation at 0.85 K, it exhibits near-saturated internal detection efficiency at wavelengths up to 800 nm. At a wavelength of 1550 nm, the detector exhibits a system detection efficiency of ∼5% (7%) and a timing jitter of 102 (144) ps, when illuminated with a light spot of ∼18 (600) µm in diameter, respectively.

Experimental Twin-Field Quantum Key Distribution over 1000 km Fiber Distance.

Quantum key distribution (QKD) aims to generate secure private keys shared by two remote parties. With its security being protected by principles of quantum mechanics, some technology challenges remain towards practical application of QKD. The major one is the distance limit, which is caused by the fact that a quantum signal cannot be amplified while the channel loss is exponential with the distance for photon transmission in optical fiber. Here using the 3-intensity sending-or-not-sending protocol with the actively-odd-parity-pairing method, we demonstrate a fiber-based twin-field QKD over 1002 km. In our experiment, we developed a dual-band phase estimation and ultra-low noise superconducting nanowire single-photon detectors to suppress the system noise to around 0.02 Hz. The secure key rate is 9.53×10^{-12} per pulse through 1002 km fiber in the asymptotic regime, and 8.75×10^{-12} per pulse at 952 km considering the finite size effect. Our work constitutes a critical step towards the future large-scale quantum network.

Solving Graph Problems Using Gaussian Boson Sampling.

Gaussian boson sampling (GBS) is not only a feasible protocol for demonstrating quantum computational advantage, but also mathematically associated with certain graph-related and quantum chemistry problems. In particular, it is proposed that the generated samples from the GBS could be harnessed to enhance the classical stochastic algorithms in searching some graph features. Here, we use Jiǔzhang, a noisy intermediate-scale quantum computer, to solve graph problems. The samples are generated from a 144-mode fully connected photonic processor, with photon click up to 80 in the quantum computational advantage regime. We investigate the open question of whether the GBS enhancement over the classical stochastic algorithms persists-and how it scales-with an increasing system size on noisy quantum devices in the computationally interesting regime. We experimentally observe the presence of GBS enhancement with a large photon-click number and a robustness of the enhancement under certain noise. Our work is a step toward testing real-world problems using the existing noisy intermediate-scale quantum computers and hopes to stimulate the development of more efficient classical and quantum-inspired algorithms.