A nanofluidic spiking synapse.

Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.

Thin-film lithium niobate circulator-free dispersion compensator in a time-lens system for femtosecond-pulse generation.

We demonstrate a circulator-free thin-film lithium niobate (TFLN) dispersion compensator based on the cascading 2 × 2 multimode interferometer (MMI) and two identical chirped Bragg gratings (CBGs). The cascaded MMI-CBG structure provides a dispersion value of 920 ps/nm/m over a 20 nm bandwidth covering 1537 to 1557 nm, featuring a compact footprint of 1 mm × 0.7 mm. Utilizing this device within a TFLN electro-optic time-lens system, we successfully generate 863-fs pulses at a 37 GHz repetition rate. Our compact, scalable, low-loss, and circulator-free dispersion compensator is the building block for the efficient generation of high-peak-power femtosecond laser pulses.

Spatial and mode selective switch for orbital angular momentum mode division multiplexing.

In analogy to a wavelength selective switch in wavelength-division multiplexing (WDM) optical fiber communication systems, a spatial and optical mode selective switch (SMSS) would be an important component in future ultrahigh capacity optical fiber communication systems based on space and mode division multiplexing. In this work, a free-space SMSS for orbital angular momentum (OAM) mode-division multiplexing (MDM) is proposed and experimentally demonstrated. The SMSS consists of a separating part for transforming OAM modes to spatial modes and a recombining part for selecting and recombining the modes to any spatial channel. The SMSS is able to implement strictly non-blocking switching between a total of 36 SDM/MDM channels configured as four spatial channels each supporting nine OAM mode channels.

Low-loss silicon waveguide and an ultrahigh-Q silicon microring resonator in the 2†µm wave band.

Silicon photonic-integrated circuits (PICs) operating in the 2 µm wave band are of great interest for spectroscopic sensing, nonlinear optics, and optical communication applications. However, the performance of silicon PICs in this wave band lags far behind the conventional optical communication band (1310/1550 nm). Here we report the realization of a low-loss waveguide and an ultrahigh-Q microring resonator in the 2 µm wave band on a standard 200 mm silicon photonic platform. The single-mode strip waveguide fabricated on a 220 nm-thick silicon device layer has a record-low propagation loss ∼0.2 dB/cm. Based on the low-loss waveguide, we demonstrate an ultrahigh-Q microring resonator with a measured loaded Q-factor as high as 1.1 × 106 and intrinsic Q-factor of 2 × 106, one order of magnitude higher than prior silicon resonators operating in the same wave band. The extinction ratio of the resonator is higher than 22 dB. These high-performance silicon photonic components pave the way for on-chip sensing applications and nonlinear optics in the 2 µm wave band.

Immune responses and reinfection of SARS-CoV-2 Omicron variant in patients with lung cancer.

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre-Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies including total antibodies, anti-receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS-CoV-2 wild type (WT) and BA.4/5 variant. T cell responses against SARS-CoV-2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron-infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long-lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p < .05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/106 PBMCs, p = .0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non-reinfected patients (all p < .05), and those patients of unvaccinated at late stage receiving anti-cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection.

Morroniside promotes skin wound re-epithelialization by facilitating epidermal stem cell proliferation through GLP-1R-mediated upregulation of ß-catenin expression.

Epidermal stem cells (EpSCs) play a vital role in skin wound healing through re-epithelialization. Identifying chemicals that can promote EpSC proliferation is helpful for treating skin wounds. This study investigates the effect of morroniside on cutaneous wound healing in mice and explores the underlying mechanisms. Application of 10‒50 µg/mL of morroniside to the skin wound promotes wound healing in mice. In vitro studies demonstrate that morroniside stimulates the proliferation of mouse and human EpSCs in a time- and dose-dependent manner. Mechanistic studies reveal that morroniside promotes the proliferation of EpSCs by facilitating the cell cycle transition from the G1 to S phase. Morroniside increases the expression of ß-catenin via the glucagon-like peptide-1 receptor (GLP-1R)-mediated PKA, PKA/PI3K/AKT and PKA/ERK signaling pathways, resulting in an increase in cyclin D1 and cyclin E1 expression, either directly or by upregulating c-Myc expression. This process ultimately leads to EpSC proliferation. Administration of morroniside to mouse skin wounds increases the phosphorylation of AKT and ERK, the expressions of ß-catenin, c-Myc, cyclin D1, and cyclin E1, as well as the proliferation of EpSCs, in periwound skin tissue, and accelerates wound re-epithelialization. These effects of morroniside are mediated by the GLP-1R. Overall, these results indicate that morroniside promotes skin wound healing by stimulating the proliferation of EpSCs via increasing ß-catenin expression and subsequently upregulating c-Myc, cyclin D1, and cyclin E1 expressions through GLP-1R signaling pathways. Morroniside has clinical potential for treating skin wounds.

Anesthesia modality in endovascular treatment for distal medium vessel occlusion stroke: intention-to-treat propensity score-matched analysis.

BACKGROUND: The optimal anesthesia modality during endovascular treatment (EVT) for distal medium vessel occlusion (DMVO) stroke is uncertain. We aimed to evaluate the association of the anesthesia modality with procedural and clinical outcomes following EVT for DMVO stroke. METHODS: This is a multicenter retrospective analysis of a prospectively collected database. Patients were included if they had DMVO involving the middle cerebral artery-M3/4, anterior cerebral artery-A2/3, or posterior cerebral artery-P1/P2-3, and underwent EVT. The cohort was divided into two groups, general anesthesia (GA) and non-general anesthesia (non-GA), and compared based on the intention-to-treat principle as primary analysis. We used propensity scores to balance the two groups. The primary outcome was the shift in the degree of disability as measured by the 90-day modified Rankin Scale (mRS). Secondary outcomes included successful reperfusion, as well as excellent (mRS 0-1) and good (mRS 0-2) clinical outcomes at 90 days. Safety measures included procedural complications, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: Among 366 DMVO thrombectomies, 61 matched pairs were eligible for analysis. Median age and National Institutes of Health Stroke Scale score as well as other baseline demographic and clinical characteristics were balanced between both groups. The GA group had no difference in the overall degree of disability (common OR 1.19, 95% CI 0.52 to 2.86, P=0.67) compared with the non-GA arm. Likewise, the GA group had comparable rates of successful reperfusion (OR 2.38, 95% CI 0.80 to 7.07, P=0.12), good/excellent clinical outcomes (OR 1.14, 95% CI 0.44 to 2.96, P=0.79/(OR 0.65, 95% CI 0.24 to 1.81, P=0.41), procedural complications (OR 1.00, 95% CI 0.19 to 5.16, P>0.99), sICH (OR 3.24, 95% CI 0.83 to 12.68, P=0.09), and 90-day mortality (OR 1.43, 95% CI 0.48 to 4.27, P=0.52) compared with the non-GA group. CONCLUSIONS: In patients with DMVO, our study showed that GA and non-GA groups had similar procedural and clinical outcomes, as well as safety measures. Further larger controlled studies are warranted.

Key Roles of Gli1 and Ihh Signaling in Craniofacial Development.

The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ). Losing Ihh results in cranial bone malformation and decreased ossification and affects the formation of cranial base cartilage unions, TMJ condyles, and joint discs. Gli1 is predominantly expressed during early craniofacial development, and Gli1+ cells are identified as the primary mesenchymal stem cells (MSCs) for craniofacial bones, crucial for cell differentiation and morphogenesis. In addition, a complex mutual regulatory mechanism exists between Gli1 and Ihh, ensuring the normal function of the Hh signaling pathway by directly or indirectly regulating each other's expression levels. And the interaction between Ihh and Gli1 significantly impacts the normal development of craniofacial tissues. This review summarizes the pivotal roles of Gli1 and Ihh in the intricate landscape of mammalian craniofacial development and outlines the molecular regulatory mechanisms and intricate interactions governing the growth of bone and cartilage exhibited by Gli1 and Ihh, which provides new insights into potential therapeutic strategies for related diseases or researches of tissue regeneration.

Orchestrated Codelivery of Peptide Antigen and Adjuvant to Antigen-Presenting Cells by Using an Engineered Chimeric Peptide Enhances Antitumor T-Cell Immunity.

The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens (Ag) and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. In this study, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of Ags and cytosine-guanosine oligodeoxynucleotide (CpG) to modulate vaccine efficacy via translating an engineered chimeric peptide, eTAT, as an intramolecular adjuvant. Linking Ags to eTAT enhanced cytosolic delivery of the Ags. This, in turn, led to improved activation and lymph node-trafficking of Ag-presenting cells and Ag cross-presentation, thus promoting Ag-specific T-cell immune responses. Simple mixing of eTAT-linked Ags and CpG significantly enhanced codelivery of Ags and CpG to the Ag-presenting cells, and this substantially augmented the adjuvant effect of CpG, maximized vaccine immunogenicity, and elicited robust and durable CD8+ T-cell responses. Vaccination with this formulation altered the tumor microenvironment and exhibited potent antitumor effects, with generally further enhanced therapeutic efficacy when used in combination with anti-PD1. Altogether, the engineered chimeric peptide-based orchestrated codelivery of Ag and adjuvant may serve as a promising but simple strategy to improve the efficacy of peptide-based cancer vaccines.

A non-viral DNA delivery system consisting of multifunctional chimeric peptide fused with zinc-finger protein.

Non-viral gene delivery systems have received sustained attention as a promising alternative to viral vectors for disease treatment and prevention in recent years. Numerous methods have been developed to enhance gene uptake and delivery in the cytoplasm; however, due to technical difficulties and delivery efficiency, these systems still face challenges in a range of biological applications, especially in vivo. To alleviate this challenge, we devised a novel system for gene delivery based on a recombinant protein eTAT-ZF9-NLS, which consisted of a multifunctional chimeric peptide and a zinc-finger protein with sequence-specific DNA-binding activity. High transfection efficiency was observed in several mammalian cells after intracellular delivery of plasmid containing ZF9-binding sites mediated by eTAT-ZF9-NLS. Our new approach provides a novel transfection strategy and the transfection efficiency was confirmed both in vitro and in vivo, making it a preferential transfection reagent for possible gene therapy.

Lower Melatonin Indicates Poor Short-term Prognosis in Patients with Acute Ischemic Stroke.

AIMS: We evaluated endogenous melatonin levels in the acute phase of cerebral infarction and explored the impact of possible changes in melatonin levels on the prognosis of patients. METHODS: This study recruited acute ischemic stroke (AIS) patients from the Department of the Second Affiliated Hospital of Soochow University between December 2019 and June 2021, along with healthy control subjects. Salivary melatonin samples were collected from each participant between 7 pm and 10 pm, and fasting plasma was collected the following morning to measure the levels of inflammatory markers. The prognosis was assessed through follow-up three months after discharge. The relationship between melatonin levels and plasma inflammatory markers was assessed, followed by an analysis of the effect of melatonin levels on patient prognosis. RESULTS: The study enrolled a total of 160 participants, including 120 AIS patients aged 50 years or older (61.7% male) and 40 age-matched controls (55.0% male). The AIS group exhibited lower salivary melatonin levels at 19 (P = 0.002), 20 (P < 0.001), 21 (P < 0.001), and 22 (P < 0.001) o'clock, and the average melatonin level was also lower (P < 0.001). Logistic regression analysis models indicated an association between low melatonin levels and poor prognosis. Salivary melatonin levels demonstrated good predictive ability for the prognosis of AIS patients. CONCLUSION: Melatonin levels were lower in AIS patients compared to controls. In addition, lower melatonin levels were associated with a poorer prognosis among AIS patients.

Focusing Micromechanical Polaritons in Topologically Nontrivial Hyperbolic Metasurfaces.

Vertically stacked multiple atomically thin layers have recently widened the landscape of rich optical structures thanks to these quantum metamaterials or van der Waals (vdW) materials, featuring hyperbolic polaritons with unprecedented avenues for light. Despite their far-reaching implications, most of their properties rest entirely on a trivial band topological origin. Here, a 2D approach is adopted toward a micromechanical vdW analogue that, as a result of engineered chiral and mirror symmetries, provides topologically resilient hyperbolic radiation of mechanical vibrations in the ultrasonic regime. By applying laser vibrometry of the micrometer-sized metasurface, we are able to exhibit the exotic fingerprints of robust hyperbolic radiation spanning several frequencies, which beyond their physical relevance, may enable ultrasonic technologies.

Monolithic Strong Coupling of Topological Surface Acoustic Wave Resonators on Lithium Niobate.

Coherent phonon transfer via high-quality factor (Q) mechanical resonator strong coupling has garnered significant interest. Yet, the practical applications of these strongly coupled resonator devices are largely constrained by their vulnerability to fabrication defects. In this study, topological strong coupling of gigahertz frequency surface acoustic wave (SAW) resonators with lithium niobate is achieved. The nanoscale grooves are etched onto the lithium niobate surface to establish robust SAW topological interface states (TISs). By constructing phononic crystal (PnC) heterostructures, a strong coupling of two SAW TISs, achieving a maximum Rabi splitting of 22 MHz and frequency quality factor product fQm of ≈1.2 × 1013 Hz, is realized. This coupling can be tuned by adjusting geometric parameters and a distinct spectral anticrossing is experimentally observed. Furthermore, a dense wavelength division multiplexing device based on the coupling of multiple TISs is demonstrated. These findings open new avenues for the development of practical topological acoustic devices for on-chip sensing, filtering, phonon entanglement, and beyond.

Single photon emitter deterministically coupled to a topological corner state.

Incorporating topological physics into the realm of quantum photonics holds the promise of developing quantum light emitters with inherent topological robustness and immunity to backscattering. Nonetheless, the deterministic interaction of quantum emitters with topologically nontrivial resonances remains largely unexplored. Here we present a single photon emitter that utilizes a single semiconductor quantum dot, deterministically coupled to a second-order topological corner state in a photonic crystal cavity. By investigating the Purcell enhancement of both single photon count and emission rate within this topological cavity, we achieve an experimental Purcell factor of Fp = 3.7. Furthermore, we demonstrate the on-demand emission of polarized single photons, with a second-order autocorrelation function g(2)(0) as low as 0.024 ± 0.103. Our approach facilitates the customization of light-matter interactions in topologically nontrivial environments, thereby offering promising applications in the field of quantum photonics.

Tunable quantum dots in monolithic Fabry-Perot microcavities for high-performance single-photon sources.

Cavity-enhanced single quantum dots (QDs) are the main approach towards ultra-high-performance solid-state quantum light sources for scalable photonic quantum technologies. Nevertheless, harnessing the Purcell effect requires precise spectral and spatial alignment of the QDs' emission with the cavity mode, which is challenging for most cavities. Here we have successfully integrated miniaturized Fabry-Perot microcavities with a piezoelectric actuator, and demonstrated a bright single-photon source derived from a deterministically coupled QD within this microcavity. Leveraging the cavity-membrane structures, we have achieved large spectral tunability via strain tuning. On resonance, a high Purcell factor of ~9 is attained. The source delivers single photons with simultaneous high extraction efficiency of 0.58, high purity of 0.956(2) and high indistinguishability of 0.922(4). Together with its compact footprint, our scheme facilitates the scalable integration of indistinguishable quantum light sources on-chip, therefore removing a major barrier to the development of solid-state quantum information platforms based on QDs.

Preparation of PMMA-Based Temperature/pH Responsive Nanoparticles Encapsulating 5-Fluorouracil and Methotrexate In Situ by One-Pot Dispersion Photopolymerization.

In order to achieve long-term and controllable release of anti-tumor drugs at specific sites, temperature/pH responsive nanoparticles encapsulating 5-fluorouracil and methotrexate in situ are prepared through dispersion photopolymerization under green LED irradiation. The physicochemical properties of nanoparticles are characterized by scanning electron microscopy, Fourier transform infrared, dynamic light scattering, thermogravimetric/differential scanning calorimetry, and X-ray diffraction. In vitro drug release at different temperatures and pH values is examined to ascertain the release pattern of two drugs, which can be well described by Korsmeyer-Peppas kinetic model. The cytotoxicity evaluation illustrates that the tumor cells could be more effectively killed by the drug-loaded nanoparticles, and the improved therapeutic effect is attributed to the controllable and sustainable drug release as well as the enhanced cellular uptake. The blood safety and good biocompatibility of nanoparticles are further confirmed by hemolysis assay, indicating the prepared nanoparticles are potential candidates for effective tumor treatment.

Circadian Rhythm Disturbance in Acute Ischemic Stroke Patients and Its Effect on Prognosis.

INTRODUCTION: Poststroke sleep disturbances are common and can affect stroke outcomes, but the clinical studies mainly focus on breathing-related sleep disorders, while the bidirectional impact of circadian rhythm dysfunction in ischemic stroke remains unknown. This study observed the characteristics of melatonin secretion in acute ischemic stroke patients and evaluated whether melatonin rhythm impacts the prognosis after stroke by assessing the neurological function, cognition, emotion, and quality of life 3 months after stroke. METHODS: Acute ischemic stroke patients were selected from the Department of Neurology Inpatients of the Second Hospital affiliated with Soochow University from October 2019 to July 2021. Healthy control subjects were recruited at the same time. Demographic and clinical data were collected, and relevant scale scores (including neurological function, cognition, emotion, and sleep) were assessed within 2 weeks of onset and followed up 3 months later. All participants collected salivary melatonin samples on the 4th day of hospitalization and dim light melatonin onset (DLMO) was calculated according to melatonin concentration. Stroke patients were then divided into three groups based on their DLMO values. RESULTS: A total of 74 stroke patients and 33 control subjects were included in this analysis. Compared with healthy controls, stroke patients exhibited a delayed melatonin rhythm during the acute phase of stroke (21:36 vs. 20:38, p = 0.004). Stroke patients were then divided into three groups, namely normal (n = 36), delayed (n = 28), or advanced DLMO (n = 10), based on their DLMO values. A χ2 test showed that there were significant differences in the rate of poor prognosis (p = 0.011) and depression tendency (p = 0.028) among the three groups. A further pairwise comparison revealed that stroke patients with delayed DLMO were more likely to experience poor short-term outcomes than normal DLMO group (p = 0.003). The average melatonin concentration of stroke patients at 5 time points was significantly lower than that of the control group (3.145 vs. 7.065 pg/mL, p < 0.001). Accordingly, we split stroke patients into three groups, namely low melatonin level (n = 14), normal melatonin level (n = 54), or high melatonin level (n = 6). Unfortunately, there were no great differences in the clinical characteristics, cognition, emotion, sleep quality, and short-term outcome among groups. CONCLUSIONS: This is a preliminary study, and our results indicate that changes in melatonin secretion phase of stroke patients may have effect on their short-term prognosis.

High-Precision Single-Cell microRNA Therapy by a Functional Nanopipette with Sensitive Photoelectrochemical Feedback.

This work proposes the concept of single-cell microRNA (miR) therapy and proof-of-concept by engineering a nanopipette for high-precision miR-21-targeted therapy in a single HeLa cell with sensitive photoelectrochemical (PEC) feedback. Targeting the representative oncogenic miR-21, the as-functionalized nanopipette permits direct intracellular drug administration with precisely controllable dosages, and the corresponding therapeutic effects can be sensitively transduced by a PEC sensing interface that selectively responds to the indicator level of cytosolic caspase-3. The experimental results reveal that injection of ca. 4.4 × 10-20 mol miR-21 inhibitor, i.e., 26488 copies, can cause the obvious therapeutic action in the targeted cell. This work features a solution to obtain the accurate knowledge of how a certain miR-drug with specific dosages treats the cells and thus provides an insight into futuristic high-precision clinical miR therapy using personalized medicine, provided that the prerequisite single-cell experiments are courses of personalized customization.

Laser beam steering of 532†nm using a power-efficient focal plane array.

Laser beam steering is important for classical and quantum information processing. On-chip beam steering is a major motivation for developing large-scale photonic integrated circuits such as optical phased arrays. A major challenge for such arrays is to simultaneously control a large number of on-chip phase shifters, which requires a complicated analog control algorithm and rapidly increasing power consumption. We report a green light (532 nm) 1 × 16 focal plane array photonic integrated circuit with simple control and low power consumption. Fabricated on a silicon nitride platform, the focal plane array achieves angular beam steering over a 10° field of view, with ultra-low electrical power consumption (4 × 3.1 mW).