Intelligent Image-Activated Cell Sorting.

A fundamental challenge of biology is to understand the vast heterogeneity of cells, particularly how cellular composition, structure, and morphology are linked to cellular physiology. Unfortunately, conventional technologies are limited in uncovering these relations. We present a machine-intelligence technology based on a radically different architecture that realizes real-time image-based intelligent cell sorting at an unprecedented rate. This technology, which we refer to as intelligent image-activated cell sorting, integrates high-throughput cell microscopy, focusing, and sorting on a hybrid software-hardware data-management infrastructure, enabling real-time automated operation for data acquisition, data processing, decision-making, and actuation. We use it to demonstrate real-time sorting of microalgal and blood cells based on intracellular protein localization and cell-cell interaction from large heterogeneous populations for studying photosynthesis and atherothrombosis, respectively. The technology is highly versatile and expected to enable machine-based scientific discovery in biological, pharmaceutical, and medical sciences.

Modulating the Structure and Optoelectronic Properties of Solution-Processed Bismuth-Based Nanocrystals.

Bismuth-based chalcogenides have emerged as promising candidates for next-generation, solution-processable semiconductors, mainly benefiting from their facile fabrication, low cost, excellent stability, and tunable optoelectronic properties. Particularly, the recently developed AgBiS2 solar cells have shown striking power conversion efficiencies. High performance bismuth-based photodetectors have also been extensively studied in the past few years. However, the fundamental properties of these Bi-based semiconductors have not been sufficiently investigated, which is crucial for further improving the device performance. Here, we introduce multiple time-resolved and steady-state techniques to fully characterize the charge carrier dynamics and charge transport of solution-processed Bi-based nanocrystals. It was found that the Ag-Bi ratio plays a critical role in charge transport. For Ag-deficient samples, silver bismuth sulfide thin films behave as localized state induced hopping charge transport, and the Ag-excess samples present band-like charge transport. This finding is crucial for developing more efficient Bi-based semiconductors and optoelectronic devices.

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation.

Skeletal muscle is striated muscle that moves autonomously and is innervated by peripheral nerves. Peripheral nerve injury is very common in clinical treatment. However, the commonly used treatment methods often focus on the regeneration of the injured nerve but overlook the pathological changes in the injured skeletal muscle. Acupuncture, as the main treatment for denervated skeletal muscle atrophy, is used extensively in clinical practice. In the present study, a mouse model of lower limb sciatic nerve detachment was constructed and treated with electroacupuncture Stomach 36 to observe the atrophy of lower limb skeletal muscle and changes in skeletal muscle fibre types before and after electroacupuncture Stomach 36 treatment. Mice with skeletal muscle denervation showed a decrease in the proportion of IIa muscle fibres and an increase in the proportion of IIb muscle fibres, after electroacupuncture Stomach 36. The changes were reversed by specific activators of p38 MAPK, which increased IIa myofibre ratio. The results suggest that electroacupuncture Stomach 36 can reverse the change of muscle fibre type from IIb to IIa after denervation of skeletal muscle by inhibiting p38 MAPK. The results provide an important theoretical basis for the treatment of clinical peripheral nerve injury diseases with electroacupuncture, in addition to novel insights that could facilitate the study of pathological changes of denervated skeletal muscle.

Optofluidic time-stretch imaging flow cytometry with a real-time storage rate beyond 5.9 GB/s.

Optofluidic time-stretch imaging flow cytometry (OTS-IFC) provides a suitable solution for high-precision cell analysis and high-sensitivity detection of rare cells due to its high-throughput and continuous image acquisition. However, transferring and storing continuous big data streams remains a challenge. In this study, we designed a high-speed streaming storage strategy to store OTS-IFC data in real-time, overcoming the imbalance between the fast generation speed in the data acquisition and processing subsystem and the comparatively slower storage speed in the transmission and storage subsystem. This strategy, utilizing an asynchronous buffer structure built on the producer-consumer model, optimizes memory usage for enhanced data throughput and stability. We evaluated the storage performance of the high-speed streaming storage strategy in ultra-large-scale blood cell imaging on a common commercial device. The experimental results show that it can provide a continuous data throughput of up to 5891 MB/s.

Multidimensional ultrashort optical pulse manipulation using spatial light modulation.

Ultrashort optical pulse manipulation is one of the key techniques for applications such as high-speed imaging and high-precision laser processing. In this study, we demonstrate the multidimensional manipulation of ultrashort optical pulses by integrating spatial dispersion and spatial light modulation. Specifically, by modulating the phase of each wavelength, we achieve arbitrary adjustments in multiple dimensions, including number of sub pulses, time interval, intensity, and pulse width simultaneously and independently with a simple setup and few calculations. The performance of the optical pulse manipulation method is verified through both numerical simulations and experiments.

Sequentially timed all-optical mapping photography with quantitative phase imaging capability.

Sequentially timed all-optical mapping photography (STAMP) is considered a powerful tool to observe highly dynamic events; however, its application is significantly hindered by its incapability to acquire quantitative phase images. In this work, by integrating diffraction phase microscopy (DPM) and STAMP, we achieve ultrafast single-shot quantitative phase imaging with a frame rate of up to 3.3 trillion fps. The performance of the system is evaluated using a homemade phase module. Experimental results show that the system can accurately record the propagation of laser filamentation in air. We believe our method will greatly enhance the capability of STAMP to measure highly transparent targets.

Flexible fabrication of core/shell nanoparticles for tailored infrared emissivity on aluminum via femtosecond laser self-deposition.

A metal surface with controllable infrared emissivity has a wide range of applications. However, a flexible and simple fabrication method is needed. Here, a controllable femtosecond laser self-deposition technology was developed to fabricate Al@AlOx core/shell micropillars (MPs) with diverse size distribution on the aluminum surface in a single-step operation under ambient conditions. By establishing a deterministic relationship between pulse-repetition frequency (PRF) and particle size distribution (PSD), we achieved continuous control of the infrared emissivity of the surface by lower PRF, ranging from low (0.31) to high (0.93). Additionally, by using higher PRF, we attained dual-band emissivity control, featuring high emissivity in the range of 10-14 µm and near-continuous change in the range of 2.5-10 µm.

Comparison of Thulium Fiber Laser versus Holmium laser in ureteroscopic lithotripsy: a Meta-analysis and systematic review.

OBJECTIVES: To compare the efficacy and safety of thulium fiber laser (TFL) to holmium: YAG (Ho: YAG) laser in ureteroscopic lithotripsy for urolithiasis. METHODS: PubMed, Web of Science, Embase, CENTRAL, SinoMed, CNKI database, VIP and Wanfang Database were systematically searched for all relevant clinical trials until September 2023. References were explored to identify the relevant articles. Meta-analysis was carried out for the retrieved studies using RevMan5.4.1 software, and the risk ratio, mean difference and 95% confidence interval were expressed. Statistical significance was set at p < 0.05. The main outcomes of this meta-analysis were stone-free rate (SFR), perioperative outcomes and intraoperative or postoperative complications. RESULTS: Thirteen studies, including 1394 patients, were included. According to the results of pooled analysis, TFL was associated with significantly higher stone-free rate (SFR) [0.52, 95% CI (0.32, 0.85), P = 0.009], shorter operation time [-5.47, 95% CI (-8.86, -2.08), P = 0.002], and less stone migration [0.17, 95% CI (0.06, 0.50), P = 0.001]. However, there was no significant difference in terms of the laser time, duration of hospital stay, drop of hemoglobin level, total energy, postoperative ureteral stenting, the incidence of intraoperative complications or postoperative complications between TFL and Ho: YAGs. CONCLUSION: The findings of this study demonstrated several advantages of TFL in terms of higher SFR, shorter operative time and less stone migration. TRIAL REGISTRATION: The protocol of this systematic review was listed in PROSPERO ( www.crd.york.ac.uk/PROSPERO ) (Protocol number: CRD42022362550).

May Measurement Month 2021: an analysis of blood pressure screening results from China.

We reported findings from participants screened during the May Measurement Month 2021 in China, which aimed to raise awareness of raised blood pressure (BP), and to investigate the risk factors of BP. The study participants were adults (≥18 years), ideally in whom BP had not been measured in the previous year. Blood pressure was measured three times consecutively with 1 min intervals in the sitting position, using a validated upper-arm cuff automated BP monitor (Omron HEM-7081IT), and transmitted to a central cloud database via a smartphone app. The measurement was performed in 218 844 participants in 183 sites across 31 China provinces. The mean (standard deviation) age was 47.0 (15.7) years, and 51.8% (n = 113 466) were women. The mean systolic/diastolic BP was 120.2/77.5 mmHg. Among 57 178 (26.1%) participants with hypertension, the awareness, treatment, and control rates of hypertension were 30.4% (n = 17 354), 28.7% (n = 16 369), and 17.1% (n = 9743), respectively. After adjustment for age, sex, and use of antihypertensive medication, both systolic and diastolic BP were significantly (P ≤ 0.01) higher in current smokers (n = 22 344, +0.4/+0.7 mmHg) and with moderate (n = 4780, +1.4/+4.2 mmHg) or daily alcohol intake (n = 2427, +1.3/+2.5 mmHg). Blood pressure was lower in those reporting regular exercise (n = 32 328, -2.2/-1.4 mmHg). In addition, individuals with previous COVID-19 vaccination had lower systolic and diastolic BP (n = 88 945, -1.8/-1.5 mmHg, P ≤ 0.001). In conclusion, our study showed that long-term large-scale screening for hypertension is feasible, and there is a strong association between BP and major lifestyle factors.

High-Performance Sodium-Ion Batteries Enabled by 3D Nanoflowers Comprised of Ternary Sn-Based Dichalcogenides Embedded in Nitrogen and Sulfur Dual-Doped Carbon.

To make sodium-ion batteries a realistic option for everyday energy storage, a practicable method is to enhance the kinetics of Na+ reactions through the development of structurally stable electrode materials. This study utilizes ternary Sn-based dichalcogenide (SnS1.5 Se0.5 ) in the design of electrode material to tackle several issues that adversely hinder the performance and longevity of sodium-ion batteries. First, the incorporation of Se into the SnS structure enhances its electrical conductivity and stability. Second, the ternary composition restricts the formation of intermediates during the desodiation/sodiation process, resulting in better electrode reaction reversibility. Finally, SnS1.5 Se0.5 lowers the diffusion barrier of Na, thereby facilitating rapid and efficient ion transport within the electrode material. Moreover, nitrogen and sulfur dual-doped carbon (NS-C) is used to enhance surface chemistry and ionic/electrical conductivity of SnS1.5 Se0.5 , leading to a pseudocapacitive storage effect that presents a promising potential for high-performance energy storage devices. The study has successfully developed a SnS1.5 Se0.5 /NS-C anode, exhibiting remarkable rate capability and cycle stability, retaining a capacity of 647 mAh g-1 even after 10 000 cycles at 5 A g-1 in half-cell tests. In full-cell tests, Na3 V2 (PO4 )3 //SnS1.5 Se0.5 /NS-C delivers a high energy density of 176.6 Wh kg-1 . In addition, the Na+ storage mechanism of SnS1.5 Se0.5 /NS-C is explored through ex situ tests and DFT calculations. The findings suggest that the ternary Sn-based dichalcogenides can considerably enhance the performance of the anode, enabling efficient large-scale storage of sodium. These findings hold great promise for the advancement of high-performance energy storage devices for practical applications.

Cell damage evaluation by intelligent imaging flow cytometry.

Essential thrombocythemia (ET) is an uncommon situation in which the body produces too many platelets. This can cause blood clots anywhere in the body and results in various symptoms and even strokes or heart attacks. Removing excessive platelets using acoustofluidic methods receives extensive attention due to their high efficiency and high yield. While the damage to the remaining cells, such as erythrocytes and leukocytes is yet evaluated. Existing cell damage evaluation methods usually require cell staining, which are time-consuming and labor-intensive. In this paper, we investigate cell damage by optical time-stretch (OTS) imaging flow cytometry with high throughput and in a label-free manner. Specifically, we first image the erythrocytes and leukocytes sorted by acoustofluidic sorting chip with different acoustic wave powers and flowing speed using OTS imaging flow cytometry at a flowing speed up to 1 m/s. Then, we employ machine learning algorithms to extract biophysical phenotypic features from the cellular images, as well as to cluster and identify images. The results show that both the errors of the biophysical phenotypic features and the proportion of abnormal cells are within 10% in the undamaged cell groups, while the errors are much greater than 10% in the damaged cell groups, indicating that acoustofluidic sorting causes little damage to the cells within the appropriate acoustic power, agreeing well with clinical assays. Our method provides a novel approach for high-throughput and label-free cell damage evaluation in scientific research and clinical settings.

A highly stable human single-domain antibody-drug conjugate exhibits superior penetration and treatment of solid tumors.

The inefficient tumor penetration of therapeutic antibodies has hampered their effective use in treating solid tumors. Here, we report the identification of a fully human single-domain antibody (UdAb), designated as n501, targeting the oncofetal antigen 5T4. The high-resolution crystal structure indicates that n501 adopts a compact structure very similar to that of camelid nanobodies, and binds tightly to all eight leucine-rich repeats of 5T4. Furthermore, the UdAb n501 exhibits exceptionally high stability, with no apparent activity changes over 4 weeks of storage at various temperatures. Importantly, the UdAb-based antibody-drug conjugate (n501-SN38) showed much deeper tumor penetration, significantly higher tumor uptake, and faster accumulation at tumor sites than conventional IgG1-based antibody-drug conjugate (m603-SN38), resulting in improved tumor inhibition. These results highlight the potential of UdAb-based antibody-drug conjugates as a potential class of antitumor therapeutics with characteristics of high stability and strong tumor penetration for the effective treatment of solid tumors.

Coexistent Sjogren's syndrome and Birt-Hogg-Dube´ syndrome: a case report.

We report a rare case of Sjogren's syndrome complicated with Birt-Hogg-Dubé syndrome (BHDS) not previously mentioned in the literature. Further, there is insufficient evidence linking the two diseases. Here, we review existing diagnostic algorithms for diagnosing diffuse cystic lung disease and provide new insights. The patient initially complained of thirst and dry eyes for ten years, and gradually developed shortness of breath. After admission, physical examination showed five missing teeth, decreased respiratory sounds in both lower lungs, and Velcro rales. Computed tomography showed multiple thin-walled cystic lesions in both lungs. Initial xerophthalmia and labial gland biopsy seemed to reveal a pulmonary cystic change associated with Sjogren's syndrome. Before discharge, a rash suspected to indicate a fibrofollicular tumor in the neck was observed, and then FLCN variant has been found. The challenges how to clarify the diagnosis of DCLD causes are discussed.

Electromagnetic-Thermal Coupling Study for RF Compression Cavity Applied to Ultrafast Electron Diffraction.

Ultrafast electron diffraction (UED) is a powerful tool for observing the evolution of transient structures at the atomic level. However, temporal resolution is a huge challenge for UEDs, mainly depending on the pulse duration. Unfortunately, the Coulomb force between electrons causes the pulse duration to increase continually when propagating, reducing the temporal resolution. In this paper, we theoretically design a radio frequency (RF) compression cavity using the finite-element method of electromagnetic-thermal coupling to overcome this limitation and obtain a high-brightness, short-pulse-duration, and stable electron beam. In addition, the cavity's size parameters are optimized, and a water-cooling system is designed to ensure stable operation. To the best of our knowledge, this is the first time that the electromagnetic-thermal coupling method has been used to study the RF cavity applied to UED. The results show that the RF cavity operates in TM010 mode with a resonant frequency of 2970 MHz and generates a resonant electric field. This mode of operation generates an electric field that varies periodically and transiently, compressing the electronic pulse duration. The electromagnetic-thermal coupling method proposed in this study effectively improves the temporal resolution of UED.

A novel 7 RNA-based signature for prediction of prognosis and therapeutic responses of wild-type BRAF cutaneous melanoma.

BACKGROUND: The prognosis of wild-type BRAF cutaneous melanoma (WT Bf-CM) patients remains poor due to the lack of therapeutic options. However, few studies have investigated the factors contributing to the prognosis of WT Bf-CM patients. METHODS: In this paper, we proposed and validated a novel 7-RNA based signature to predict the prognosis of WT Bf-CM by analyzing the information from TCGA database. RESULTS: Dependence of this signature to other clinical factors were verified and a nomogram was also drawn to promote its application in clinical practice. Functional analysis suggested that the predictive function of this signature might attribute to the prediction of the up-regulation of RNA splicing, transcription, and cellular proliferation in the high-risk group, which have been demonstrated to be linked to malignancy of cancer. Moreover, functional analysis and therapy response analysis supported that the prognosis is highly related to PI3K/Akt/mTOR pathway among WT Bf-CM patients. CONCLUSION: Collectively, this study will provide a preliminary bioinformatics evidence for the molecular mechanism and potential drug targets that could improving WT Bf-CM prognosis.

DRC1 deficiency caused primary ciliary dyskinesia and MMAF in a Chinese patient.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a heterogeneous disease characterized by the failure of mucociliary clearance. Dynein regulatory complex subunit 1 (DRC1) variants can cause PCD by disrupting the nexin link connecting the outer doublets. In this study, we aimed to investigate the clinical and functional impacts of DRC1 variants on respiratory cilia and sperm. METHODS: We identified and validated the DRC1 variant by using whole-exome and Sanger sequencing. High-speed video microscopy analysis (HSVA) was used to measure the nasal ciliary beating frequency and pattern in a patient and a healthy control. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were applied to analyze the morphological and ultrastructural sperm defects resulting from the DRC1 variant. RESULTS: NM_145038.5:c.1296 G>A, p.(Trp432*), a novel homozygous DRC1 nonsense variant, was identified in a patient from a consanguineous Chinese family. The patient exhibited bronchiectasis, chronic sinusitis, situs solitus, and male infertility. The markedly reduced nasal nitric oxide production rate (3.0 nL/min) was consistent with PCD diagnosis. HSVA showed reduced bending capacity and higher beating frequency of nasal cilia in the patient compared with those in healthy control. The diagnosis of multiple morphological abnormalities of the sperm flagella (MMAF) was confirmed through sperm HE staining and TEM analysis. Following the intracytoplasmic sperm injection treatment, the patient fathered a healthy daughter. CONCLUSION: This report is the first to describe a novel DRC1 variant in a patient with PCD and MMAF, and in vitro fertilization was effective for treating infertility in this male patient. Our findings expand the genetic spectrum of PCD and MMAF, and provide a detailed clinical summary and functional analysis of patients with DRC1 variants.

Flexible and efficient fabrication of a terahertz absorber by single-step laser direct writing.

Laser direct writing (LDW) is a promising candidate for the fabrication of all-dielectric THz absorbers for its high flexibility and material compatibility. However, multi-step processing or multi-layer materials are required to compensate for the nonideal features of LDW to realize good absorption performance. To further explore the potential of LDW in flexible and cost-effective THz absorber fabrication, in this work, we demonstrate a design method of THz absorbers fully considering and utilizing the characteristics of laser processing. Specifically, we first numerically analyze that by properly combining basic structures processed by single-step LDW, good and adjustable absorption performance can be achieved on a single-layer substrate. Then we experimentally fabricate THz absorbers by processing periodic composite structures, which are combined by grooves and circular holes, on single-layer doped silicon using LDW. Experimental results show that our method can fabricate THz absorbers at a speed of 3.3 mm2/min with an absorptivity above 90% over a broadband of 1.8-3 THz. Our method provides a promising solution for the flexible and efficient fabrication of all-dielectric broadband THz absorbers.

Real-time and high-sensitivity refractive index sensing with an arched optofluidic waveguide.

Refractive index (RI) sensing plays an important role in analytical chemistry, medical diagnosis, and environmental monitoring. The optofluidic technique is considered to be an ideal tool for RI sensor configuration for its high integration, high sensitivity, and low cost. However, it remains challenging to achieve RI measurement in real time with high sensitivity and low detection limit (DL) simultaneously. In this work, we design and fabricate a RI sensor with an arched optofluidic waveguide by monitoring the power loss of the light passing through the waveguide, which is sandwiched by the air-cladding and the liquid-cladding under test, we achieve RI detection of the sample in real time and with high sensitivity. Furthermore, both numerical simulation and experimental investigation show that our RI sensor can be designed with different geometric parameters to cover multiple RI ranges with high sensitivities for different applications. Experimental results illustrate that our sensor is capable to achieve a superior sensitivity better than -19.2 mW/RIU and a detection limit of 5.21×10-8 RIU in a wide linear dynamic range from 1.333 to 1.392, providing a promising solution for real-time and high-sensitivity RI sensing.

Hybrid-plane spectrum slicing for sequentially timed all-optical mapping photography.

Sequentially timed all-optical mapping photography (STAMP) is an effective tool for observing ultrafast and non-repetitive events. In the classical design of STAMP, the spatial resolution of the acquired images is different in two directions, severely limiting the scalability of STAMP. Here, by introducing an asymmetric optical design, we make the slicing mirror locate in the hybrid plane of the system, i.e., the image plane in the direction of the short edge, while the Fourier plane is in the direction of the long edge. This avoids the loss of the high-frequency components of the images and hence offers the possibility to further extend the frame number of the system.

Viral etiology among children hospitalized for acute respiratory tract infections and its association with meteorological factors and air pollutants: a time-series study (2014-2017) in Macao.

BACKGROUND: The associations between viral etiology of acute respiratory infections (ARI) with meteorological factors and air pollutants among children is not fully understood. This study aimed to explore the viral etiology among children hospitalized for ARI and the association of meteorological factors and air pollutants with children hospitalization due to viral ARI. METHODS: Electronic health record data about children (aged between 1 month and 14 years) admitted for ARI at Kiang Wu Hospital in Macao between 2014 and 2017 was analyzed retrospectively. xMAP multiplex assays were used to detect viruses in the nasopharyngeal swab and distributed-lag nonlinear model (DLNM) was used to evaluate associations. RESULTS: Among the 4880 cases of children hospitalization due to ARI, 3767 (77.2%) were tested positive for at least one virus and 676 (18%) exhibited multiple infections. Enterovirus (EV)/rhinovirus (HRV), adenovirus (ADV), respiratory syncytial virus (RSV) and influenza virus (IFV) were the most common viral pathogens associated with ARI and human bocavirus (hBOV) exhibited the highest multiple infection rates. Meteorological factors and air pollutants (PM10, PM2.5 and NO2) were associated with the risk of viral ARI hospitalization. The relative risk of viral infection increased with daily mean temperature but plateaued when temperature exceeded 23 °C, and increased when the relative humidity was < 70% and peaked at 50%. The effect of solar radiation was insignificant. Air pollutants (including PM10, PM2.5, NO2 and O3) showed strong and immediate effect on the incidence of viral infection. CONCLUSIONS: The effects of mean temperature, relative humidity and air pollutants should be taken into account when considering management of ARI among children.