Ultra-compact and fabrication-tolerant multimode photonic jumpers based on dual Bezier curves.

Compact routing of multimode bus waveguides is of great significance for on-chip mode-division multiplexing (MDM) systems to realize high integration density and flexible layout. In this Letter, we propose and experimentally demonstrate a novel, to the best of our knowledge, multimode photonic jumper (MPJ) on a standard silicon-on-insulator (SOI) platform. It enables an ultra-compact connection between two parallel multimode waveguides (MWGs) with an arbitrary displacement. As a proof of concept, we describe two MPJs with displacements of 5.9 µm and 0.6 µm, each supporting three modes and featuring a longitudinal distance of around 14 µm. For both MPJs, the experimental results show insertion losses (ILs) below 0.086 dB and inter-modal cross talk (CT) below -17.6 dB over the wide wavelength range of 1525-1600 nm for all three modes.

Positron Emission Tomography Imaging of Synaptic Dysfunction in Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases with a complex pathogenesis. Aggregations formed by abnormal deposition of alpha-synuclein (αSyn) lead to synapse dysfunction of the dopamine and non-dopamine systems. The loss of dopaminergic neurons and concomitant alterations in non-dopaminergic function in PD constitute its primary pathological manifestation. Positron emission tomography (PET), as a representative molecular imaging technique, enables the non-invasive visualization, characterization, and quantification of biological processes at cellular and molecular levels. Imaging synaptic function with PET would provide insights into the mechanisms underlying PD and facilitate the optimization of clinical management. In this review, we focus on the synaptic dysfunction associated with the αSyn pathology of PD, summarize various related targets and radiopharmaceuticals, and discuss applications and perspectives of PET imaging of synaptic dysfunction in PD.

Cellular senescence imaging and senolysis monitoring in cancer therapy based on a ß-galactosidase-activated aggregation-induced emission luminogen.

Cellular senescence is a permanent state of cell cycle arrest characterized by increased activity of senescence associated ß-galactosidase (SA-ß-gal). Notably, cancer cells have been also observed to exhibit the senescence response and are being considered for sequential treatment with pro-senescence therapy followed by senolytic therapy. However, there is currently no effective agent targeting ß-galactosidase (ß-Gal) for imaging cellular senescence and monitoring senolysis in cancer therapy. Aggregation-induced emission luminogen (AIEgen) demonstrates strong fluorescence, good photostability, and biocompatibility, making it a potential candidate for imaging cellular senescence and monitoring senolysis in cancer therapy when endowed with ß-Gal-responsive capabilities. In this study, we introduced a ß-Gal-activated AIEgen named QM-ß-gal for cellular senescence imaging and senolysis monitoring in cancer therapy. QM-ß-gal exhibited good amphiphilic properties and formed aggregates that emitted a fluorescence signal upon ß-Gal activation. It showed high specificity towards the activity of ß-Gal in lysosomes and successfully visualized DOX-induced senescent cancer cells with intense fluorescence both in vitro and in vivo. Encouragingly, QM-ß-gal could image senescent cancer cells in vivo for over 14 days with excellent biocompatibility. Moreover, it allowed for the monitoring of senescent cancer cell clearance during senolytic therapy with ABT263. This investigation indicated the potential of the ß-Gal-activated AIEgen, QM-ß-gal, as an in vivo approach for imaging cellular senescence and monitoring senolysis in cancer therapy via highly specific and long-term fluorescence imaging. STATEMENT OF SIGNIFICANCE: This work reported a ß-galactosidase-activated AIEgen called QM-ß-gal, which effectively imaged DOX-induced senescent cancer cells both in vitro and in vivo. QM-ß-gal specifically targeted the increased expression and activity of ß-galactosidase in senescent cancer cells, localized within lysosomes. It was cleared rapidly before activation but maintained stability after activation in the DOX-induced senescent tumor. The AIEgen exhibited a remarkable long-term imaging capability for senescent cancer cells, lasting over 14 days and enabled monitoring of senescent cancer cell clearance through ABT263-induced apoptosis. This approach held promise for researchers seeking to achieve prolonged imaging of senescent cells in vivo.

The effects of brightness and prominent colors on outdoor thermal perception in Chongqing, China.

Outdoor thermal comfort has become an important factor affecting human mental and physical health due to rapid urbanization. This study aimed to investigate the influence of brightness and prominent colors on thermal perception in hot summer and cold winter regions. Meteorological measurements were conducted accompanied by subjective thermal and visual questionnaires (n = 2020) during summer and winter. The physiological equivalent temperature (PET) was applied as thermal indices to evaluate the influence of visual conditions on thermal perception. The results showed that (1) the neutral PET is 20.2 °C with a range of 14.8 ~ 25.7 °C in Chongqing and neutral illumination range is 0 ~ 8663 lx. (2) Thermal sensitivity is most great in neutral brightness than bright and too bright groups. The influence of outdoor prominent colors in winter supports hue-heat hypothesis. However, in summer, result only supports the hypothesis under low thermal stress. Both cool and warm colors can reduce the thermal sensitivity of visitors compared to neutral colors (gray and white). (3) The interactions between colors and brightness are more obvious under low thermal stress levels. (4) Thermal perceptions of females are more greatly affected by brightness and prominent colors compared with males. These results could help landscape designers better understand the correlation between the thermal and visual environments and provide a reference for comprehensive designs of urban open spaces.

Time and Space Dual-Blockade Strategy for Highly Invasive Nature of Triple-Negative Breast Cancer in Enhanced Sonodynamic Therapy Based on Fe-MOF Nanoplatforms.

Triple-negative breast cancer (TNBC), due to its high malignant degree and strong invasion ability, leads to poor prognosis and easy recurrence, so effectively curbing the invasion of TNBC is the key to obtaining the ideal therapeutic effect. Herein, a therapeutic strategy is developed that curbs high invasions of TNBC by inhibiting cell physiological activity and disrupting tumor cell structural function to achieve the time and space dual-blockade. The time blockade is caused by the breakthrough of the tumor-reducing blockade based on the ferroptosis process and the oxidation-toxic free radicals generated by enhanced sonodynamic therapy (SDT). Meanwhile, alkyl radicals from 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) and 1O2 attacked the organelles of tumor cells under ultrasound (US), reducing the physiological activity of the cells. The attack of free radicals on the cytoskeleton, especially on the proteins of F-actin and its assembly pathway, achieves precise space blockade of TNBC. The damage to the cytoskeleton and the suppression of the repair process leads to a significant decline in the ability of tumor cells to metastasize and invade other organs. In summary, the FTM@AM nanoplatforms have a highly effective killing and invasion inhibition effect on invasive TNBC mediated by ultrasound, showcasing promising clinical transformation potential.

Isolation and characterization of seven neovibsane-type diterpenoids from Viburnum odoratissimum and their neuroblastoma cell protective effects.

Seven undescribed neovibsane-type diterpenoids (1-7) were isolated from the leaves of Viburnum odoratissimum. Their planar structures and relative configurations were elucidated based on a combination of 1D and 2D NMR analysis. The absolute configurations were confirmed by Rh2(OCOCF3)4-induced ECD analysis and comparison of experimental and TDDFT-calculated ECD spectrum. Based on the empirical results of the ECD of in situ formed Rh-complexes, rapid determination of the absolute configuration of C-14 within vibsane-type diterpenoids was proposed. In addition, 3 exhibited a high neuroblastoma cell protective effect of 81.8 % at 50 µM (the control group showed a neuroblastoma cell protective effect of 56.2 % at 50 µM).

A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high mortality and poor prognosis. WBDC-1 is a novel highly oxidized germacranolide from the Elephantopus tomentosus in our previous work, which has excellent anti-HCC activity, but the detailed mechanism is still unclear. In this study, we found that WBDC-1 was able to inhibit the proliferation and colony formation of Hep3B and HepG2 cells, as well as the cell migration ability and EMT. In addition, WBDC-1 showed no obvious toxicity to normal liver epithelial cells L-02. The potential targets of WBDC-1 were predicted by network pharmacology, and the following verified experiments showed that WBDC-1 exerted anti-HCC effect by targeting EGFR. Mechanismly, subsequent biological analysis showed that WBDC-1 can inhibit EGFR and its downstream RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways. Overexpression of EGFR reversed the anticancer properties of WBDC-1. Consistent with in vitro experiments, WBDC-1 was able to inhibit tumor growth and was non-toxic in xenograft tumor models. In summary, this study revealed a potential tumor suppressive mechanism of WBDC-1 and provided a novel strategy for HCC treatment. It also laid a foundation for further research on the anti-tumor effect of highly oxidized germacranolides.

A Fully Elastic Wearable Electrochemical Sweat Detection System of Tree-Bionic Microfluidic Structure for Real-Time Monitoring.

Fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body. However, existing wearable sweat detection systems face challenges in efficiently collecting and detecting fresh sweat in real-time. Additionally, they often lack the necessary deformation capabilities, resulting in discomfort for the wearer. Here, a fully elastic wearable electrochemical sweat detection system is developed that integrates a sweat-collecting microfluidic chip, a multi-parameter electrochemical sensor, a micro-heater, and a sweat detection elastic circuit board system. The unique tree-bionic structure of the microfluidic chip significantly enhances the efficiency of fresh sweat collection and discharge, enabling real-time detection by the electrochemical sensors. The sweat multi-parameter electrochemical sensor offers high-precision and high-sensitivity measurements of sodium ions, potassium ions, lactate, and glucose. The electronic system is built on an elastic circuit board that matches perfectly to wrinkled skin, ensuring improved wearing comfort and enabling multi-channel data sampling, processing, and wireless transmission. This state-of-the-art system represents a significant advancement in the field of elastic wearable sweat detection and holds promising potential for extending its capabilities to the detection of other sweat markers or various wearable applications.

Active polarization controller based on micro-ring resonators.

On-chip polarization handling is of great significance for optical interconnects to overcome polarization sensitivity. In this Letter, we propose and experimentally demonstrate a novel, to the best of our knowledge, on-chip polarization controller (PC) on a 220 nm silicon-on-insulator (SOI) platform. It is the first demonstration of a PC based on micro-ring resonators. Any input polarization states can be actively converted to the standard transverse-electric (TE) mode under the phase manipulation. Experimental results show that the insertion loss is less than 0.8 dB and the polarization dependent loss (PDL) is around 0.5 dB. The proposed device also exhibits excellent performances in wavelength tunability over the C band and 35 Gbps data transmission.

Stereochemical insights into structurally diverse lignanamides from the herbs of Solanum lyratum Thunb.

A chemical investigation of Solanum lyratum Thunb. (Solanaceae) afforded six pairs of enantiomeric lignanamides consisting of twelve undescribed compounds, along with two undescribed racemic mixtures, and the separations of the enantiomers were accomplished by chiral-phase HPLC. The structures of these undescribed compounds were elucidated by the analysis of spectroscopic data, NMR and electronic circular dichroism calculations. All isolated compounds were assessed for neuroprotective activities in H2O2-induced human neuroblastoma SH-SY5Y cells, and acetylcholinesterase (AChE) inhibitory activities. Among tested isolates, some enantiomeric lignanamides exhibited conspicuous neuroprotective effects and AChE inhibitory effect.

Four Pairs of Neuroprotective Aryldihydronaphthalene-Type Lignanamide Enantiomers from the Herbs of Solanum lyratum.

Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50 µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40 µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.

Biomass-Derived Bifunctional Cathode Electrocatalyst and Multiadaptive Gel Electrolyte for High-Performance Flexible Zn-Air Batteries in Wide Temperature Range.

High-efficiency and low-cost bifunctional electrocatalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), as well as gel electrolytes with high thermal and mechanical adaptability are required for the development of flexible batteries. Herein, abundant Setaria Viridis (SV) biomass is selected as the precursor to prepare porous N-doped carbon tubes with high specific surface area and the 900 °C calcination product of SV (SV-900) shows the optimum ORR/OER activities with a small EOER -EORR of 0.734 V. Meanwhile, a new multifunctional gel electrolyte named C20E2G5 is prepared using cellulose extracted from another widely distributed biomass named flax as the skeleton, epichlorohydrin as the cross-linker and glycerol as the antifreezing agent. C20E2G5 possesses high ionic conductivity from -40 to + 60 °C, excellent tensile and compressive resistance, high adhesion, strong freezing and heat resistance. Moreover, the symmetrical cell assembled with C20E2G5 can significantly inhibit Zn dendrite growth. Finally, flexible solid-state Zn-air batteries assembled with SV-900 and C20E2G5 show high open circuit voltage, large energy density, and long-term operation stability between -40 and + 60 °C. This biomass-based approach is generic and can be used for the development of diverse next-generation electrochemical energy conversion and storage devices.

Preparation of "Co-Nx Carbon Net" Protected CoFe Alloy on Carbon Nanotubes as an Efficient Bifunctional Electrocatalyst in Zn-Air Batteries.

Herein, Co/Fe bimetallic hydroxide nanosheets (Co3Fe2 BMHs) were densely deposited on polypyrrole nanotubes (PPy NTs), followed by the successive coating of polydopamine (PDA) and zeolitic imidazolate frameworks (ZIF)-67 to form a composite catalyst precursor. Then, Co3Fe2 BMHs, PPy NTs, and ZIF-67/PDA in this precursor were calcined into Co2Fe alloy nanoparticles, nitrogen-doped carbon NTs (NCNTs), and a Co-Nx activated carbon net, respectively, which constituted a novel composite catalyst. In this composite catalyst, the high-density Co2Fe alloy nanoparticles are highly dispersed on the NCNT and coated by the Co-Nx activated carbon net. The Co-Nx activated carbon net protects the alloy particles from agglomerating during calcination and from being corroded by the electrolyte. Moreover, the experimental results demonstrated that the calcination temperature and chemical components of the catalyst precursors greatly affect the morphology, structure, composition, and ultimately electrocatalytic activity of the calcined products. The obtained optimum catalyst material exhibited significant electrocatalytic effects on both the oxygen reduction reaction and oxygen evolution reaction with a small ΔE of 0.715 V. The Zn-air battery utilizing this material as the air electrode catalyst showed a power density of 235.5 mW cm-2, an energy density of 1073.5 Wh kg-1, and a round-trip efficiency of 62.3% after 1000 cycles, superior to the benchmark battery based on the mixed commercial catalyst of Pt/C and RuO2. An all-solid-state battery was also assembled to confirm the practical application prospect of the prepared composite material as the air electrode catalyst. More importantly, both experimental data and density functional theory calculations verified that the superior bifunctional catalytic activity was mainly attributed to the synergy between the Co-Nx activated carbon net and Co2Fe alloy.

Impact of environmental comfort on urban vitality in small and medium-sized cities: A case study of Wuxi County in Chongqing, China.

China's urbanization has exceeded 64% and a large number of small and medium-sized cities are the key development areas in the new stage. In urban planning, it is very important to reveal the influence of environmental comfort on urban vitality to improve the life quality of residents in these towns. Thus, the study investigated the impact of environmental comfort on urban vitality using ordinary least squares regression in Wuxi County. Environmental comfort was assessed through a comprehensive analysis of a built-up area and urban vitality was represented by vitality intensity. In addition, the influence pathways were identified and model validation was verified. The conclusions are as follows: (1) Environmental comfort and urban vitality are distributed spatially similarly, and both gradually decline from the center to the periphery. It is high in the east and low in the west, high in the south and low in the north. (2) Population density, POI mixing degree, building density, and road network density have significant positive effects on urban vitality. Population density has the greatest impact on urban vitality. Building height, building age, and river buffer have significant negative effects on urban vitality. (3) The impact of comprehensive environmental comfort on urban vitality is positive, and in terms of time, the order of impact is afternoon > morning > evening. Finally, a method for assessing the impact of environmental comfort on urban vitality was constructed, and the promoting effect of environmental comfort improvements on the vitality was verified. These findings will fill the gap between urban physical space and social needs in planning practices and provide reference to improve vitality for urban planning in small and medium-sized cities.

Utilization of the By-Product of Corn: Guided Identification of Bioactive Terpenoids from Stigma Maydis (Corn Silk).

Stigma maydis (corn silk) (S. maydis) is a food-based by-product of maize and possesses great nutritional and pharmaceutical value. This study aimed to explore bioactive components from S. maydis. By the guidance of bioactivity-guided approach and Global Natural Products Social (GNPS) molecular networking, 12 terpenoids were discovered from S. maydis. The structures of 11 undescribed compounds (1-11) were determined by detailed spectroscopic analyses, single-crystal X-ray diffraction analysis, specific rotation calculations, electronic circular dichroism (ECD) calculations, and NMR calculations. The neuroprotective and acetylcholinesterase (AChE) inhibitory effects of 1-12 were examined, and most of them showed significant or moderate activities. The underlying neuroprotective mechanism of 4 and 5 was revealed by Hoechst 33258, AO-EB, and JC-1 staining assays. This work illustrated the potential of S. maydis as a prospective natural source of bioactive compounds in food and pharmaceutical industries.

Dual-loop diode-tuned Fourier domain harmonically mode-locked opto-electronic oscillator with over 50†dB side-mode spur reduction.

We propose and demonstrate a dual-loop harmonic Fourier domain mode-locked optoelectronic oscillator (FDML-OEO) for drastically reducing the side-mode spurs. The frequency domain mode-locking is achieved by synchronizing the scanning period of the filter to an integer fraction of the round trip times of the two loops with a self-made low cost diode-tuned RF filter. We found, for the first time to the best of authors' knowledge, that the frequency scanning bandwidth (FSBW) of the mode-locked output is strongly affected by the length mismatch between the two fiber loops. By using the phase noise of FDML OEO's delayed self-heterodyne signal as a performance indicator, we found experimentally that both the locking bandwidth and the FSBW of the device are inversely proportional to the length mis-match of the two loops. Finally, with dual-loop fiber lengths of 2041m and 2449.2m, including 2039m common fiber loop, we successfully obtained linearly chirped microwave signals around 9GHz with a phase noise of -127dBc/Hz at 10kHz offset from the 9GHz carrier, a FSBW of 0.4GHz, and a chirp rate of 200THz/s at 500.38 kHz repetition rate. More impressively, the side-mode spur ratio of the linear frequency modulated (LFM) signal is reduced to less than -83dB, the lowest ever achieved for a FDML OEO to the best of authors' knowledge, which is more than 50dB improvement over that achieved with a single loop FDML OEO reported previously.

Intelligent COVID-19 screening platform based on breath analysis.

The spread of coronavirus disease 2019 (COVID-19) results in an increasing incidence and mortality. The typical diagnosis technique for severe acute respiratory syndrome coronavirus 2 infection is reverse transcription polymerase chain reaction, which is relatively expensive, time-consuming, professional, and suffered from false-negative results. A reliable, non-invasive diagnosis method is in urgent need for the rapid screening of COVID-19 patients and controlling the epidemic. Here we constructed an intelligent system based on the volatile organic compound (VOC) biomarkers in human breath combined with machine learning models. The VOC profiles of 122 breath samples (65 of COVID-19 infections and 57 of controls) were identified with a portable gas chromatograph-mass spectrometer. Among them, eight VOCs exhibited significant differences (p< 0.001) between the COVID-19 and the control groups. The cross-validation algorithm optimized support vector machine (SVM) model was employed for the prediction of COVID-19 infection. The proposed SVM model performed a powerful capability in discriminating COVID-19 patients from healthy controls, with an accuracy of 97.3%, a sensitivity of 100%, a specificity of 94.1%, and a precision of 95.2%, and anF1 score of 97.6%. The SVM model was also compared with other common machine models, including artificial neural network,k-nearest neighbor, and logistic regression, and demonstrated obvious superiority in the prediction of COVID-19 infection. Furthermore, user-friendly software was developed based on the optimized SVM model. The developed intelligent platform based on breath analysis provides a new strategy for the point-of-care screening of COVID and shows great potential in clinical application.

Electrochemical Biosensor Based on l-Arginine and rGO-AuNSs Deposited on the Electrode Combined with DNA Probes for Ultrasensitive Detection of the Gastric Cancer-Related PIK3CA Gene of ctDNA.

Gene biomarkers of circulating tumor DNA (ctDNA) in liquid biopsies have been explored for use in the precise diagnosis of tumors. There is a great clinical need to realize the ultrasensitive detection of gene biomarkers in ctDNA. Here we reported that an ultrasensitive label-free biosensor was developed for the detection of the gastric cancer-related PIK3CA gene of ctDNA in peripheral blood. The polymeric l-arginine and graphene oxide-wrapped gold nanostars (rGO-AuNSs) were prepared and deposited on the glass electrode. The capturing DNA probes for the PIK3CA gene were prepared and successfully immobilized on the rGO-AuNS-modified electrode surface via π-π interaction among the rGO-AuNS composites and DNA probes. The resultant electrochemical sensor was effectively applied to detect the PIK3CA gene of ctDNA via the hybridization between the capturing DNA probe and ctDNA, the result of which showed that the biosensor exhibited desirable sensitivity, stability, and a wider dynamic response in a ctDNA concentration range from 1.0 × 10-20 to 1.0 × 10-10 M (R2 = 0.997). Moreover, the low limit of detection of 1.0 × 10-20 M (S/N = 3) indicates the biosensor owns satisfactory detection sensitivity. Fourteen PIK3CA genes and two PIK3CA gene mutations were detected in 60 clinical ctDNA samples of gastric cancer patients by using the developed biosensor. In conclusion, this ultrasensitive label-free electrochemical biosensor possesses a significant application prospect in the detection of the PIK3CA gene in ctDNA and in early screening for gastric cancer in the near future.

Topology optimization based deterministic lateral displacement array design for cell separation.

Circulating tumor cell (CTC) can be used to guide cancer theranostics. How to isolate efficiently CTCs from blood owns great clinical requirement. Deterministic lateral displacement (DLD) is a pillar-array-based effective passive microfluidic method to separate cells based on their sizes. DLD is a potential CTC isolation tool. Pillar shape is one of the key priorities in DLD array design. Altered zigzag mode is a normally undesired phenomenon that leads zigzag particles away from flow direction. This work makes use of the altered zigzag mode to manipulate zigzag particles for the first time, and developed a novel DLD chip with topology optimized pillar shape and a wide DLD channel. The novel designing method based on topology optimization (TO) greatly increases lateral displacement of different sized cells, meanwhile demonstrates its universality and expansibility. The proposed structure has the ability to shorten the device and to manipulate cells flexibly. Bead experiment has been applied to determine the critical diameter of the DLD array. Numerical, bead and cell experiment have been carried out to verify the separation efficiency of the structure. The TO-based wide DLD channel promotes the separation efficiency.

Geometric structure design of passive label-free microfluidic systems for biological micro-object separation.

Passive and label-free microfluidic devices have no complex external accessories or detection-interfering label particles. These devices are now widely used in medical and bioresearch applications, including cell focusing and cell separation. Geometric structure plays the most essential role when designing a passive and label-free microfluidic chip. An exquisitely designed geometric structure can change particle trajectories and improve chip performance. However, the geometric design principles of passive and label-free microfluidics have not been comprehensively acknowledged. Here, we review the geometric innovations of several microfluidic schemes, including deterministic lateral displacement (DLD), inertial microfluidics (IMF), and viscoelastic microfluidics (VEM), and summarize the most creative innovations and design principles of passive and label-free microfluidics. We aim to provide a guideline for researchers who have an interest in geometric innovations of passive label-free microfluidics.