A positively tuned voltage indicator for extended electrical recordings in the brain.

Genetically encoded voltage indicators (GEVIs) enable optical recording of electrical signals in the brain, providing subthreshold sensitivity and temporal resolution not possible with calcium indicators. However, one- and two-photon voltage imaging over prolonged periods with the same GEVI has not yet been demonstrated. Here, we report engineering of ASAP family GEVIs to enhance photostability by inversion of the fluorescence-voltage relationship. Two of the resulting GEVIs, ASAP4b and ASAP4e, respond to 100-mV depolarizations with ≥180% fluorescence increases, compared with the 50% fluorescence decrease of the parental ASAP3. With standard microscopy equipment, ASAP4e enables single-trial detection of spikes in mice over the course of minutes. Unlike GEVIs previously used for one-photon voltage recordings, ASAP4b and ASAP4e also perform well under two-photon illumination. By imaging voltage and calcium simultaneously, we show that ASAP4b and ASAP4e can identify place cells and detect voltage spikes with better temporal resolution than commonly used calcium indicators. Thus, ASAP4b and ASAP4e extend the capabilities of voltage imaging to standard one- and two-photon microscopes while improving the duration of voltage recordings.

A Type I Photosensitizer-Polymersome Boosts Reactive Oxygen Species Generation by Forcing H-Aggregation for Amplifying STING Immunotherapy.

Activation of the innate immune Stimulator of Interferon Genes (STING) pathway potentiates antitumor immunity. However, delivering STING agonists systemically to tumors presents a formidable challenge, and resistance to STING monotherapy has emerged in clinical trials with diminishing natural killer (NK) cell proliferation. Here, we encapsulated the STING agonist diABZI within polymersomes containing a Type I photosensitizer (NBS), creating a nanoagonist (PNBS/diABZI) for highly responsive tumor immunotherapy. This structure promoted H-aggregation and intersystem crossing of NBS, resulting in a ∼ 3-fold amplification in superoxide anion and singlet oxygen generation. The photodynamic therapy directly damaged hypoxia tumor cells and stimulated the proliferation of NK cells and cytotoxic T lymphocytes, thereby sensitizing STING immunotherapy. A single systemic intravenous administration of PNBS/diABZI eradicated orthotopic mammary tumors in murine models, achieving long-term antitumor immune memory to inhibit tumor recurrence and metastasis and significantly improving long-term tumor-free survival. This work provides a design rule for boosting reactive oxygen species production by promoting the intersystem crossing process, highlighting the potential of Type I photosensitizer-polymer vehicles for augmenting STING immunotherapy.

Conversion of Photoluminescence Blinking Types in Single Colloidal Quantum Dots.

Almost all colloidal quantum dots (QDs) exhibit undesired photoluminescence (PL) blinking, which poses a significant obstacle to their use in numerous luminescence applications. An in-depth study of the blinking behavior, along with the associated mechanisms, can provide critical opportunities for fabricating high-quality QDs for diverse applications. Here the blinking of a large series of colloidal QDs is investigated with different surface ligands, particle sizes, shell thicknesses, and compositions. It is found that the blinking behavior of single alloyed CdSe/ZnS QDs with a shell thickness of up to 2 nm undergoes an irreversible conversion from Auger-blinking to band-edge carrier blinking (BC-blinking). Contrastingly, single perovskite QDs with particle sizes smaller than their Bohr diameters exhibit reversible conversion between BC-blinking and more pronounced Auger-blinking. Changes in the effective trapping sites under different excitation conditions are found to be responsible for the blinking type conversions. Additionally, changes in shell thickness and particle size of QDs have a significant effect on the blinking type conversions due to altered wavefunction overlap between excitons and effective trapping sites. This study elucidates the discrepancies in the blinking behavior of various QD samples observed in previous reports and provides deeper understanding of the mechanisms underlying diverse types of blinking.

Multi-view fringe projection profilometry for surfaces with intricate structures and high dynamic range.

Fringe projection profilometry plays an important role for quality control in production line. However, it is facing challenges in the measurement of objects with intricate structures and high dynamic range that involved in precision manufacturing and semiconductor packaging. In this paper, a multi-view fringe projection profilometry system, which deploys a vertical telecentric projector and four oblique tilt-shift cameras, is presented to address the "blind spots" caused by shadowing, occlusion and local specular reflection. A flexible and accurate system calibration method is proposed, in which the corrected pinhole imaging model is used to calibrate the telecentric projection, and the unified calibration is performed by bundle adjustment. Experimental results show that the 3D repeated measurement error and standard deviation are no more than 10 µm within a measurable volume of 70 × 40 × 20 mm3. Furthermore, a group of experiments prove that the developed system can achieve complete and accurate 3D measurement for high dynamic range surfaces with complex structures.

Three-dimensional quantum imaging of dynamic targets using quantum compressed sensing.

Quantum imaging based on entangled light sources exhibits enhanced background resistance compared to conventional imaging techniques in low-light conditions. However, direct imaging of dynamic targets remains challenging due to the limited count rate of entangled photons. In this paper, we propose a quantum imaging method based on quantum compressed sensing that leverages the strong correlation characteristics of entangled photons and the randomness inherent in photon pair generation and detection. This approach enables the construction of a compressed sensing system capable of directly imaging high-speed dynamic targets. The results demonstrate that our system successfully achieves imaging of a target rotating at a frequency of 10 kHz, while maintaining an impressive data compression rate of 10-6. This proposed method introduces a pioneering approach for the practical implementation of quantum imaging in real-world scenarios.

Anomalous layer-dependent photoluminescence spectra of supertwisted spiral WS2.

Twisted stacking of two-dimensional materials with broken inversion symmetry, such as spiral MoTe2 nanopyramids and supertwisted spiral WS2, emerge extremely strong second- and third-harmonic generation. Unlike well-studied nonlinear optical effects in these newly synthesized layered materials, photoluminescence (PL) spectra and exciton information involving their optoelectronic applications remain unknown. Here, we report layer- and power-dependent PL spectra of the supertwisted spiral WS2. The anomalous layer-dependent PL evolutions that PL intensity almost linearly increases with the rise of layer thickness have been determined. Furthermore, from the power-dependent spectra, we find the power exponents of the supertwisted spiral WS2 are smaller than 1, while those of the conventional multilayer WS2 are bigger than 1. These two abnormal phenomena indicate the enlarged interlayer spacing and the decoupling interlayer interaction in the supertwisted spiral WS2. These observations provide insight into PL features in the supertwisted spiral materials and may pave the way for further optoelectronic devices based on the twisted stacking materials.

Enhanced detection limit in an exceptional surface-based fiber resonator by manipulating Fano interference.

An exceptional surface (ES) has advantages in improving sensing robustness and enhancing frequency splitting. Typically, the eigenvalue splitting must exceed the mode linewidth in order to be clearly visible in the spectrum, which limits the precision of the ES-based sensing structure. In this paper, a strategy for manipulating spectral line shape in an ES-based structure is experimentally realized. In addition, the limit of the minimum detectable displacement can be further reduced by monitoring the peak intensity of the Fano interference line shape. The demonstration of Fano interference in an ES-based system opens the way for a new class of ultrasensitive optical sensors.

The change in thyroid function categories with time in patients with subclinical hypothyroidism: a systematic review and meta-analysis.

BACKGROUND: Subclinical hypothyroidism (SCH) is characterized by elevated levels of thyroid hormone (TSH) and normal levels of free thyroxine (FT4). The outcomes of SCH patients are crucial for determining treatment plans; therefore, our aim is to summarize the existing prospective studies to understand the changes in thyroid function over time in SCH patients and the factors influencing these changes, providing references for clinical diagnosis and treatment. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science for prospective follow-up studies on natural outcomes of SCH published until September 2024. Results are presented as the overall risk ratio (RR) and 95% confidence intervals (CI). RESULTS: We reviewed 8 prospective follow-up studies involving 1,859 individuals and extracted data from them for a meta-analysis. We found that when TSH levels are ≥ 10 mU/L, patients with SCH are more likely to progress to overt hypothyroidism (OH) (RR11.38, 95%CI 4.98-26.03, P<0.001) and were less likely to return to normal TSH levels (RR 0.20, 95%CI 0.09-0.42, P<0.001) compared to patients with TSH between 4.5 and 9.9 mU/L. In addition, patients who test positive for thyroid peroxidase antibodies (TPOAb) are more likely to progress to OH (RR 2.53, 95% CI 1.86-3.44, P < 0.001) and less likely to return to euthyroidism (RR 0.68, 95% CI 0.60-0.76, P < 0.001) compared to TPOAb-negative patients. CONCLUSION: The results indicated that a large proportion of patients diagnosed with SCH will return to normal TSH levels or maintain SCH. Additionally, patients with TSH levels ≥ 10 mU/L or positive for TPOAb are more likely to experience progression and should be closely monitored. However, we did not find any gender differences in the natural outcome of SCH.

Global, Regional, and National Burdens of Otitis Media From 1990 to 2019: A Population Based Study.

OBJECTIVES: Otitis media is one of the most important causes of hearing loss at an early age. Effective vaccination with the routine 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in 2000. It has been gradually replaced by the pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine or the higher-valent 13-valent PCV (PCV-13) since 2010. Data on the change in otitis media burden in recent years are sparse at the global, regional, and national levels. DESIGN: The Global Burden of Disease 2019 study was used to evaluate the prevalence, incidence, mortality, disability-adjusted life year (DALY) rates, and the average annual percentage changes (AAPCs) in otitis media in geographic populations worldwide from 1990 to 2019. These global trends were further analyzed by subgroup (age, sex, and sociodemographic index [SDI]). RESULTS: Globally, the all-age rate of prevalence (AAPC = -0.7, 95% confidence interval [CI] = -0.7 to -0.8), DALYs (AAPC = -1.0, 95% CI = -1.1 to -1.0), and mortality (AAPC = -6.8, 95% CI = -7.3 to -6.4) from otitis media decreased constantly between 1990 and 2019. The all-age rate of incidence decreased sharply between 2000 and 2009 with an AAPC of -1.2 (95% CI = -1.4 to -0.9) and continued the downward trend between 2010 and 2019 (AAPC = -0.2, 95% CI = -0.3 to -0.1). In 2019, children aged 1 to 4 years old had the highest incidence at 29,127.3 per 100,000 population, while young adults under 30 years old accounted for 91.3% of the incident cases. Individuals living in middle-SDI countries had the largest increase in the incidence of otitis media, with an AAPC of 0.3 (95% CI = 0.3 to 0.3) between 1990 and 2019. The incidence and DALYs from otitis media decreased with increasing SDI. Regionally, the largest increase in incidence was observed in high-income Asia Pacific, Eastern Europe, and Western Sub-Saharan Africa between 1990 and 2019. Nationally, the largest increase in the incidence of otitis media was observed in the Republic of Korea, with an AAPC of 0.8 (95% CI = 0.6 to 1.1) in the same time period. CONCLUSIONS: There have been successful previous endeavors to reduce DALYs and mortality attributed to otitis media on a global scale. The worldwide incidence of otitis media experienced a sharp decline following the introduction of PCV-7 in 2000, and this downward trend persisted in subsequent years with the adoption of PCV-13/pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine. Continual epidemiological surveillance of otitis media's global trends, pathogen distribution, and resistance patterns remains imperative.

Size-dependent photoluminescence blinking mechanisms and volume scaling of biexciton Auger recombination in single CsPbI3 perovskite quantum dots.

Determining the correlation between the size of a single quantum dot (QD) and its photoluminescence (PL) properties is a challenging task. In the study, we determine the size of each QD by measuring its absorption cross section, which allows for accurate investigation of size-dependent PL blinking mechanisms and volume scaling of the biexciton Auger recombination at the single-particle level. A significant correlation between the blinking mechanism and QD size is observed under low excitation conditions. When the QD size is smaller than their Bohr diameter, single CsPbI3 perovskite QDs tend to exhibit BC-blinking, whereas they tend to exhibit Auger-blinking when the QD size exceeds their Bohr diameter. In addition, by extracting bright-state photons from the PL intensity trajectories, the effects of QD charging and surface defects on the biexcitons are effectively reduced. This allows for a more accurate measurement of the volume scaling of biexciton Auger recombination in weakly confined CsPbI3 perovskite QDs at the single-dot level, revealing a superlinear volume scaling (τXX,Auger ∝ σ1.96).

Quality Evaluation of Asparagus officinalis by Profile of Amino Acids and Mineral Elements in Different Parts Combined with Chemometrics Methods.

Asparagus officinalis has a homologous value in medicine and vegetables. Its immature stem, commonly called asparagus, is a central edible part. Asparagus skin and leaf also contain rich nutrients. However, these parts are often discarded. This study investigated amino acid and mineral elements in immature stem, skinless asparagus, asparagus skin, and leaf. Their quality was further evaluated by chemometrics methods such as principal component analysis and neural network analysis. The results showed amino acid content was high in immature stem and skinless asparagus and low in leaf, whereas the mineral elements were in four parts. Quality evaluation results showed four parts were divided into three grades. Immature stem and skinless asparagus were grouped into cluster 1 with the best quality as high-quality raw materials in food and health-care products. Meanwhile, three AA (Cys, His, Arg) and two mineral elements (Na, Cr) were identified as quality evaluation iconic substances.

Intelligent Sensing of Thermal Error of CNC Machine Tool Spindle Based on Multi-Source Information Fusion.

Aiming at the shortcomings of single-sensor sensing information characterization ability, which is easily interfered with by external environmental factors, a method of intelligent perception is proposed in this paper. This method integrates multi-source and multi-level information, including spindle temperature field, spindle thermal deformation, operating parameters, and motor current. Firstly, the internal and external thermal-error-related signals of the spindle system are collected by sensors, and the feature parameters are extracted; then, the radial basis function (RBF) neural network is utilized to realize the preliminary integration of the feature parameters because of the advantages of the RBF neural network, which offers strong multi-dimensional solid nonlinear mapping ability and generalization ability. Thermal-error decision values are then generated by a weighted fusion of different pieces of evidence by considering uncertain information from multiple sources. The spindle thermal-error sensing experiment was based on the spindle system of the VMC850 (Yunnan Machine Tool Group Co., LTD, Yunnan, China) vertical machining center of the Yunnan Machine Tool Factory. Experiments were designed for thermal-error sensing of the spindle under constant speed (2000 r/min and 4000 r/min), standard variable speed, and stepped variable speed conditions. The experiment's results show that the prediction accuracy of the intelligent-sensing model with multi-source information fusion can reach 98.1%, 99.3%, 98.6%, and 98.8% under the above working conditions, respectively. The intelligent-perception model proposed in this paper has higher accuracy and lower residual error than the traditional BP neural network perception and wavelet neural network models. The research in this paper provides a theoretical basis for the operation, maintenance management, and performance optimization of machine tool spindle systems.

High-Density Energetic Materials with Low Mechanical Sensitivity and Twinning Derived from Nitroimidazole Fused Ring.

The innovative synthesis of 3,8-dibromo-2,9-dinitro-5,6-dihydrodiimidazo [1,2-a:2',1'-c]pyrazine and 3,9-dibromo-2,10-dinitro-6,7-dihydro-5H-diimidazo [1,2-a:2',1'-c][1,4]diazepine is described in this study. The tricyclic fused molecular structures are formed by the respective amalgamation of piperazine and homopiperazine with the imidazole ring containing nitro. Compound 1 and 2 possess excellent high-density physical properties (ρ1 = 2.49 g/cm3, ρ2 = 2.35 g/cm3) due to the presence of a fused ring structure and Br atom. In addition to their high density, they have high decomposition temperatures (Td > 290 °C) which means that they have excellent thermal stability and can be used as potential heat-resistant explosives. Low mechanical sensitivities (IS > 40 J, FS > 360 N) are observed. The twinning structure of 2 was resolved by X-ray diffraction. Non-covalent interaction analysis, Hirshfeld surfaces, 2D fingerprint plot, and Electrostatic potential analysis were used to understand the intramolecular interactions in relation to physicochemical properties. The unique structures of this type of compound provide new potential for the evolution of energetic materials.

Enrichment and Evaluation of Antitumor Properties of Total Flavonoids from Juglans mandshurica Maxim.

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Study on the Stability of Complex Networks in the Stock Markets of Key Industries in China.

Investigating the significant "roles" within financial complex networks and their stability is of great importance for preventing financial risks. On one hand, this paper initially constructs a complex network model of the stock market based on mutual information theory and threshold methods, combined with the closing price returns of stocks. It then analyzes the basic topological characteristics of this network and examines its stability under random and targeted attacks by varying the threshold values. On the other hand, using systemic risk entropy as a metric to quantify the stability of the stock market, this paper validates the impact of the COVID-19 pandemic as a widespread, unexpected event on network stability. The research results indicate that this complex network exhibits small-world characteristics but cannot be strictly classified as a scale-free network. In this network, key roles are played by the industrial sector, media and information services, pharmaceuticals and healthcare, transportation, and utilities. Upon reducing the threshold, the network's resilience to random attacks is correspondingly strengthened. Dynamically, from 2000 to 2022, systemic risk in significant industrial share markets significantly increased. From a static perspective, the period around 2019, affected by the COVID-19 pandemic, experienced the most drastic fluctuations. Compared to the year 2000, systemic risk entropy in 2022 increased nearly sixtyfold, further indicating an increasing instability within this complex network.

Anoctamin 8 tethers endoplasmic reticulum and plasma membrane for assembly of Ca2+ signaling complexes at the ER/PM compartment.

Communication and material transfer between membranes and organelles take place at membrane contact sites (MCSs). MCSs between the ER and PM, the ER/PM junctions, are the sites where the ER Ca2+ sensor STIM1 and the PM Ca2+ influx channel Orai1 cluster. MCSs are formed by tether proteins that bridge the opposing membranes, but the identity and role of these tethers in receptor-evoked Ca2+ signaling is not well understood. Here, we identified Anoctamin 8 (ANO8) as a key tether in the formation of the ER/PM junctions that is essential for STIM1-STIM1 interaction and STIM1-Orai1 interaction and channel activation at a ER/PM PI(4,5)P2-rich compartment. Moreover, ANO8 assembles all core Ca2+ signaling proteins: Orai1, PMCA, STIM1, IP3 receptors, and SERCA2 at the ER/PM junctions to mediate a novel form of Orai1 channel inactivation by markedly facilitating SERCA2-mediated Ca2+ influx into the ER. This controls the efficiency of receptor-stimulated Ca2+ signaling, Ca2+ oscillations, and duration of Orai1 activity to prevent Ca2+ toxicity. These findings reveal the central role of MCSs in determining efficiency and fidelity of cell signaling.

Accurate and flexible calibration method for a 3D microscopic structured light system with telecentric imaging and Scheimpflug projection.

3D imaging and metrology of complex micro-structures is a critical task for precision manufacturing and inspection. In this paper, an accurate and flexible calibration method for 3D microscopic structured light system with telecentric imaging and Scheimpflug projector is proposed. Firstly, a fringe projection 3D microscopy (FP-3DM) system consisting of a telecentric camera and a Scheimpflug projector is developed, which can take full advantage of the depth of field (DOF) and increase the measurement depth range. Secondly, an accurate and flexible joint calibration method is proposed to calibrate the developed system, which utilizes the established pinhole imaging model and Scheimpflug distortion model to calibrate telecentric imaging, and fully considers the correction and error optimization of the Scheimpflug projection model. Meanwhile, the optimized local homography is calculated to obtain more accurate sub-pixel correspondence between the camera and the projector, and the perspective-n-point (PnP) method make the 3D coordinate estimation of the feature point more accurate. Finally, a prototype and a dedicated calibration program are developed to realize high-resolution and high-precision 3D imaging. The experimental results demonstrate that the re-projection error is less than 1µm, and the 3D repeated measurement error based on feature fitting is less than 4µm, within the calibrated volume of 10(H)mm × 50(W)mm × 40(D)mm.

High frequency near-infrared up-conversion single-photon imaging based on the quantum compressed sensing.

Infrared up-conversion single-photon imaging has potential applications in remote sensing, biological imaging, and night vision imaging. However, the used photon counting technology has the problem of long integration time and sensitivity to background photons, which limit its application in real-world scenarios. In this paper, a novel passive up-conversion single-photon imaging method is proposed, in which the high frequency scintillation information of a near infrared target is captured by using the quantum compressed sensing. Through the frequency domain characteristic imaging of the infrared target, the imaging signal-to-noise ratio is significantly improved with strong background noise. In the experiment, the target with flicker frequency on the order of GHz is measured, and the signal-to-background ratio of the imaging reaches up to 1:100. Our proposal greatly improved the robustness of near-infrared up-conversion single-photon imaging and will promote its practical application.

Charge and energy transfer dynamics in single colloidal quantum dots/monolayer MoS2 heterostructures.

The charge and energy transfer dynamics in colloidal CdSeTe/ZnS quantum dots (QDs)/monolayer molybdenum disulfide (MoS2) heterostructures have been investigated by time-resolved single-dot photoluminescence (PL) spectroscopy. A time-gated method is used to separate the PL photons of single QDs from the PL photons of monolayer MoS2, which are impossible to be separated by the spectral filter due to their spectral overlap. It is found that the energy transfer from MoS2 to single QDs increases the exciton generation of the QDs by 37.5% and the energy transfer from single QDs to MoS2 decreases the PL quantum yield of the QDs by 66.9%. In addition, it is found that MoS2 increases the discharging rate of single QDs by 59%, while the charging rate remains unchanged. This investigation not only provides valuable insight into the exciton generation and recombination at the single-dot level across such hybrid 0D-2D interfaces but also promotes the application of the hybrid system in various optoelectronic devices.

Nutritional Composition Profiles and Quality Evaluation of Different Cultivars of Asparagus Officinalis with Potential as Functional Foods and Health-Care Products.

Asparagus officinalis is a health-care vegetable with homology value of medicine and food. The quality of A. officinalis is greatly different from various cultivars. It is essential to reveal the relationship between the variety and quality. This study investigated six nutritional compositions in ten A. officinalis cultivars, including amino acid, mineral substance, carbohydrate, vitamin C, protein and total sugar. Five chemometrics methods were further employed to evaluate their quality. The results consistently showed that ten varieties were divided into three grades as nutritional composition differences. HuaMiaoF1, JinGuan and FeiCuiMingZhu were grouped into cluster3 with the best quality, and Atlas and Jersey Giant were grouped into cluster1 with the lowest quality. Therefore, HuaMiaoF1, JinGuan and FeiCuiMingZhu can be suggested as good raw materials for medicine, food and health-care products industries. Meanwhile, the comprehensive application of five chemometrics methods was confirmed as a reliable methodology for quality evaluation of A. officinalis.