Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone.

Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.

Cholecystokinin facilitates motor skill learning by modulating neuroplasticity in the motor cortex.

Cholecystokinin (CCK) is an essential modulator for neuroplasticity in sensory and emotional domains. Here, we investigated the role of CCK in motor learning using a single pellet reaching task in mice. Mice with a knockout of Cck gene (Cck-/-) or blockade of CCK-B receptor (CCKBR) showed defective motor learning ability; the success rate of retrieving reward remained at the baseline level compared to the wildtype mice with significantly increased success rate. We observed no long-term potentiation upon high-frequency stimulation in the motor cortex of Cck-/- mice, indicating a possible association between motor learning deficiency and neuroplasticity in the motor cortex. In vivo calcium imaging demonstrated that the deficiency of CCK signaling disrupted the refinement of population neuronal activity in the motor cortex during motor skill training. Anatomical tracing revealed direct projections from CCK-expressing neurons in the rhinal cortex to the motor cortex. Inactivation of the CCK neurons in the rhinal cortex that project to the motor cortex bilaterally using chemogenetic methods significantly suppressed motor learning, and intraperitoneal application of CCK4, a tetrapeptide CCK agonist, rescued the motor learning deficits of Cck-/- mice. In summary, our results suggest that CCK, which could be provided from the rhinal cortex, may surpport motor skill learning by modulating neuroplasticity in the motor cortex.

Solvent-Free Synthesis Enables Encapsulation of Subnanometric FeOx Clusters in Pure Siliceous Zeolites for Efficient Catalytic Oxidation Reactions.

Metal/metal oxide clusters possess a higher count of unsaturated coordination sites than nanoparticles, providing multiatomic sites that single atoms do not. Encapsulating metal/metal oxide clusters within zeolites is a promising approach for synthesizing and stabilizing these clusters. The unique feature endows the metal clusters with an exceptional catalytic performance in a broad range of catalytic reactions. However, the encapsulation of stable FeOx clusters in zeolite is still challenging, which limits the application of zeolite-encapsulated FeOx clusters in catalysis. Herein, we design a modified solvent-free method to encapsulate FeOx clusters in pure siliceous MFI zeolites (Fe@MFI). It is revealed that the 0.3-0.4 nm subnanometric FeOx clusters are stably encapsulated in the 5/6-membered rings intersectional voids of the pure siliceous MFI zeolites. The encapsulated Fe@MFI catalyst with a Fe loading of 1.4 wt % demonstrates remarkable catalytic activity and recycle stability in the direct oxidation of methane, while also promoting the direct oxidation of cyclohexane, surpassing the performance of conventional zeolite-supported Fe catalysts.

Flexible and Compressible Nanostructure-Assembled Aramid Nanofiber/Silica Composites Aerogel.

The Applications of silica aerogel are limited due to its brittleness and low strength. As a result, it is essential to strengthen and toughen it. Organic nanofibers are one of the preferred reinforcement materials. In this work, we designed and fabricated flexible and compressible nanostructure-assembled aramid nanofiber/silica composites aerogel (ANF/SiO2 aerogel) to improve the mechanical strength and flexibility of silica aerogel without compromising thermal insulation properties. The aramid nanofiber/silica composite aerogels were prepared by immersing the aramid nanofiber wet gel into the silica sol for a certain period of time followed by freeze drying without solvent replacement. The surface modifier 3-aminopropyltriethoxysilane (APTES) was used as a coupling agent to form chemical linkage between the ANF fiber and silica gel. It was observed that APTES can effectively drive the silica sol to infuse into ANF hydrogel, promoting the assembly of silica gel onto the fiber surface and a uniform distribution in the network of ANF. The compressive resilience, thermal stability, and thermal insulation properties of the composite aerogels were evaluated by inducing the silica aerogel into the ANF network to form a protective layer on the fiber and change the pore structure in the ANF network.

Exploring hospital resilience protective or risk factors: lessons for future disaster response efforts.

Background: Hospital resilience is essential in responding to disasters, but current research focuses mainly on frameworks and models rather than the protection of resilience and analysis of risk factors during public health emergencies. This study aims to examine the development of resilience in Chinese frontline hospitals during the initial COVID-19 outbreak in 2020, providing insights for future disaster response efforts. Objectives: We conducted interviews with 26 hospital staff members who were involved in the initial response to the COVID-19 outbreak in China. We used a semi-structured interview approach and employed purposive sampling and snowball sampling techniques. The interview outline was guided by the 'Action Framework' proposed by the World Health Organization (WHO) for responding to infectious disease emergencies. This framework includes dimensions such as command, surveillance, risk communication, medical response, and public health response. We analyzed the collected data using Colaizzi's seven-step data analysis method and the template analysis method. Results: WHO's 'action framework' effectively highlights the factors that contribute to hospital resilience. While medical response, including the availability of materials and facilities, the use of information technology, and the capacity for infectious disease diagnosis and treatment, remains crucial, other important aspects include awareness and beliefs about infections, treatment experience, interdisciplinary collaboration, and more. Additionally, it is essential to establish an intelligent command system, foster trusting partnerships between teams, improve monitoring capabilities for infectious disease agents, enhance risk communication through information synchronization and transparency, strengthen infection control planning, and improve environmental disinfection capabilities for effective public health emergency response. These contradictions significantly impact the enhancement of hospital resilience in dealing with major infectious disease outbreaks. Conclusion: In responding to sudden major infectious diseases, hospitals play a vital role within the healthcare system. Enhancing hospital resilience involves more than just improving treatment capabilities. It also requires effective command coordination at the hospital level, infection control planning, and the deployment of intelligent equipment. Additionally, planning for effective communication and coordination between hospitals, communities, and the national healthcare system can further enhance hospital resilience.

Associations between organic erectile dysfunction and the risk of herpes zoster and postherpetic neuralgia in men.

BACKGROUND: Whether erectile dysfunction (ED) leads to considerable stress for affected men remains unclear? In this study, we investigated whether organic ED (OED) is associated with increased risks of herpes zoster (HZ) and postherpetic neuralgia (PHN). METHODS: A representative subset of Taiwan's National Health Insurance Research Database was employed for this study. Enrollees with OED from the years 2000 to 2018 were selected. To ensure comparability between the case and control groups, we implemented 1:1 propensity score matching based on age, index year, comorbidities, and medications. RESULTS: The case group included 20,808 patients with OED, while the control group consisted of 20,808 individuals without OED. The OED group exhibited a significantly elevated risk of HZ (adjusted hazard ratio [aHR] = 1.74) and PHN (aHR = 1.56) compared to the non-OED group. CONCLUSIONS: Men experiencing OED seem to face elevated risks of HZ and PHN compared to those without OED. ED may serve as a warning sign for individuals at HZ risk.

An ethologically motivated neurobiology of primate visually-guided reach-to-grasp behavior.

The precision of primate visually guided reaching likely evolved to meet the many challenges faced by living in arboreal environments, yet much of what we know about the underlying primate brain organization derives from a set of highly constrained experimental paradigms. Here we review the role of vision to guide natural reach-to-grasp movements in marmoset monkey prey capture to illustrate the breadth and diversity of these behaviors in ethological contexts, the fast predictive nature of these movements [1,2], and the advantages of this particular primate model to investigate the underlying neural mechanisms in more naturalistic contexts [3]. In addition to their amenability to freely-moving neural recording methods for investigating the neural basis of dynamic ethological behaviors [4,5], marmosets have a smooth neocortical surface that facilitates imaging and array recordings [6,7] in all areas in the primate fronto-parietal network [8,9]. Together, this model organism offers novel opportunities to study the real-world interplay between primate vision and reach-to-grasp dynamics using ethologically motivated neuroscientific experimental designs.

Dopaminergic signaling regulates microglial surveillance and adolescent plasticity in the frontal cortex.

Adolescence is a sensitive period for frontal cortical development and cognitive maturation. The dopaminergic (DA) mesofrontal circuit is particularly malleable in response to changes in adolescent experience and DA activity. However, the cellular mechanisms engaged in this plasticity remain unexplored. Here, we report that microglia, the innate immune cells of the brain, are uniquely sensitive to adolescent mesofrontal DA signaling. Longitudinal in vivo two-photon imaging in mice shows that frontal cortical microglia respond dynamically to plasticity-inducing behavioral or optogenetic DA axon stimulation with increased parenchymal and DA bouton surveillance. Microglial-axon contact precedes new bouton formation, and both D1 and D2-type DA receptors regulate microglial-bouton interactions and axonal plasticity. Moreover, D2 antagonism in adults reinstates adolescent plasticity, including increased microglial surveillance and new DA bouton formation. Our results reveal that DA signaling regulates microglial surveillance and axonal plasticity uniquely in the adolescent frontal cortex, presenting potential interventions for restoring plasticity in the adult brain.

A High-Density Hydrogen Bond Locking Strategy for Constructing Anisotropic High-Strength Hydrogel-Based Meniscus Substitute.

Mimicking anisotropic features is crucial for developing artificial load-bearing soft tissues such as menisci). Here, a high-density hydrogen bond locking (HDHBL) strategy, involving preloading a poly(N-acryloylsemicarbazide) (PNASC) hydrogel with an aqueous solution containing a hydrogen bond breaking agent, followed by water exchange, to fabricate anisotropic high-strength hydrogels are proposed. During this process, multiple high-density hydrogen bonds of the PNASC network are re-established, firmly freezing oriented molecular chains, and creating a network with an anisotropic microstructure. The resulting anisotropic hydrogels exhibit superior mechanical properties: tensile strength over 9 MPa, Young's modulus exceeding 120 MPa along the orientation direction, and fatigue thresholds exceeding 1900 J m-2. These properties meet the mechanical demands for load-bearing tissue substitutes compared to other reported anti-fatigue hydrogels. This strategy enables the construction of an anisotropic meniscal scaffold composed of circumferentially oriented microfibers by preloading a digital light processing-3D printed PNASC hydrogel-based wedge-shaped construct with a resilient poly(N-acryloyl glycinamide) hydrogel. The 12-week implantation of a meniscus scaffold in rabbit knee joints after meniscectomy demonstrates a chondroprotective effect on the femoral condyle and tibial plateau, substantially ameliorating the progression of osteoarthritis. The HDHBL strategy enables the fabrication of various anisotropic polymer hydrogels, broadening their scope of application.

A new potential therapeutic approach for ALS: A case report with NGS analysis.

RATIONALE: Amyotrophic lateral sclerosis (ALS) poses a significant clinical challenge due to its rapid progression and limited treatment options, often leading to deadly outcomes. Looking for effective therapeutic interventions is critical to improve patient outcomes in ALS. PATIENT CONCERNS: The patient, a 75-year-old East Asian male, manifested an insidious onset of right-hand weakness advancing with dysarthria. Comprehensive Next-generation sequencing analysis identified variants in specific genes consistent with ALS diagnosis. DIAGNOSES: ALS diagnosis is based on El Escorial diagnostic criteria. INTERVENTIONS: This study introduces a novel therapeutic approach using artificial intelligence phenotypic response surface (AI-PRS) technology to customize personalized drug-dose combinations for ALS. The patient underwent a series of phases of AI-PRS-assisted trials, initially incorporating a 4-drug combination of Ibudilast, Riluzole, Tamoxifen, and Ropinirole. Biomarkers and regular clinical assessments, including nerve conduction velocity, F-wave, H-reflex, electromyography, and motor unit action potential, were monitored to comprehensively evaluate treatment efficacy. OUTCOMES: Neurophysiological assessments supported the ALS diagnosis and revealed the co-presence of diabetic polyneuropathy. Hypotension during the trial necessitated an adaptation to a 2-drug combinational trial (ibudilast and riluzole). Disease progression assessment shifted exclusively to clinical tests of muscle strength, aligning with the patient's well-being. LESSONS: The study raises the significance of personalized therapeutic strategies in ALS by AI-PRS. It also emphasizes the adaptability of interventions based on patient-specific responses. The encountered hypotension incident highlights the importance of attentive monitoring and personalized adjustments in treatment plans. The described therapy using AI-PRS, offering personalized drug-dose combinations technology is a potential approach in treating ALS. The promising outcomes warrant further evaluation in clinical trials for searching a personalized, more effective combinational treatment for ALS patients.

Preventing Subsidence Reoccurrence in Tianjin: New Preconsolidation Head and Safe Pumping Buffer.

Tianjin, a coastal metropolis in north China, has grappled with land subsidence for nearly a century. Yet, emerging evidence suggests a notable decrease in subsidence rates across Tianjin since 2019. This trend is primarily attributed to the importation of surface water from the Yangtze River system via the South-to-North Water Diversion Project, initiated in December 2014. Utilizing Sentinel-1A Interferometric Synthetic Aperture Radar (InSAR) data (2014-2023), this study reveals that one-third of the Tianjin plain has either halted subsidence or experienced land rebound. As a result, the deep aquifer system (~-200 to -450 m) beneath one third of the Tianjin plain has completed a consolidation cycle, leading to the establishment of new, locally specific preconsolidation heads. The identification of the newly established preconsolidation head seeks to answer a crucial question: How can we prevent the reoccurrence of subsidence in areas where it has already ceased? In essence, subsidence will stop when the local hydraulic head elevates to the new preconsolidation head (NPCH), and permanent subsidence will not be reinitiated as long as hydraulic head remains above the NPCH. The difference of the depth between current hydraulic head and the NPCH defines the safe pumping buffer (SPB). This study outlines detailed methods for identifying the NPCHs in the deep aquifer system from long-term InSAR and groundwater-level datasets. Determining NPCHs and ascertaining SPBs are crucial for estimating how much groundwater can be safely extracted without inducing permanent subsidence, and for developing sustainable strategies for long-term groundwater management and conservation.

Enhanced chromium and nitrogen removal by constructing a biofilm reaction system based on denitrifying bacteria preferential colonization theory.

Understanding the developmental characteristics of microbial communities in biofilms is crucial for designing targeted functional microbial enhancements for the remediation of complex contamination scenarios. The strong prioritization effect of microorganisms confers the ability to colonize strains that arrive first dominantly. In this study, the auto-aggregating denitrifying bacterial Pseudomonas stutzeri strain YC-34, which has both nitrogen and chromium removal characteristics, was used as a biological material to form a stable biofilm system based on the principle of dominant colonization and biofortification. The effect of the biofilm system on nitrogen and chromium removal was characterized by measuring the changes in the quality of influent and effluent water. The pattern of biofilm changes was analyzed by measuring biofilm content and thickness and characterizing extracellular polymer substances (EPS). Further analysis of the biofilm microbiota characteristics and potential functions revealed the mechanism of strain YC-34 biofortified biofilm. The results revealed that the biofilm system formed could achieve 90.56% nitrate-nitrogen removal with an average initial nitrate-nitrogen concentration of 51.9 mg/L and 40% chromium removal with an average initial hexavalent chromium Cr(VI) concentration of 7.12 mg/L. The biofilm properties of the system were comparatively analyzed during the biofilm formation period, the fluctuation period of Cr(VI)-stressed water quality, and the stabilization period of Cr(VI)-stressed water quality. The biofilm system may be able to increase the structure of hydrogen bonds, the type of protein secondary structure, and the abundance of amino acid-like components in the EPS, which may confer biofilm tolerance to Cr(VI) stress and allow the system to maintain a stable biofilm structure. Furthermore, microbial characterization indicated an increase in microbial diversity in the face of chromium stress, with an increase in the abundance of nitrogen removal-associated functional microbiota and an increasing trend in the abundance of nitrogen transfer pathways. These results demonstrate that the biofilm system is stable in nitrogen and chromium removal. This bioaugmentation method may provide a new way for the remediation of heavy metal-polluted water bodies and also provides theoretical and application parameters for the popularization and application of biofilm systems.

Identifying Functional Status Impairment in People Living With Dementia Through Natural Language Processing of Clinical Documents: Cross-Sectional Study.

BACKGROUND: Assessment of activities of daily living (ADLs) and instrumental ADLs (iADLs) is key to determining the severity of dementia and care needs among older adults. However, such information is often only documented in free-text clinical notes within the electronic health record and can be challenging to find. OBJECTIVE: This study aims to develop and validate machine learning models to determine the status of ADL and iADL impairments based on clinical notes. METHODS: This cross-sectional study leveraged electronic health record clinical notes from Mass General Brigham's Research Patient Data Repository linked with Medicare fee-for-service claims data from 2007 to 2017 to identify individuals aged 65 years or older with at least 1 diagnosis of dementia. Notes for encounters both 180 days before and after the first date of dementia diagnosis were randomly sampled. Models were trained and validated using note sentences filtered by expert-curated keywords (filtered cohort) and further evaluated using unfiltered sentences (unfiltered cohort). The model's performance was compared using area under the receiver operating characteristic curve and area under the precision-recall curve (AUPRC). RESULTS: The study included 10,000 key-term-filtered sentences representing 441 people (n=283, 64.2% women; mean age 82.7, SD 7.9 years) and 1000 unfiltered sentences representing 80 people (n=56, 70% women; mean age 82.8, SD 7.5 years). Area under the receiver operating characteristic curve was high for the best-performing ADL and iADL models on both cohorts (>0.97). For ADL impairment identification, the random forest model achieved the best AUPRC (0.89, 95% CI 0.86-0.91) on the filtered cohort; the support vector machine model achieved the highest AUPRC (0.82, 95% CI 0.75-0.89) for the unfiltered cohort. For iADL impairment, the Bio+Clinical bidirectional encoder representations from transformers (BERT) model had the highest AUPRC (filtered: 0.76, 95% CI 0.68-0.82; unfiltered: 0.58, 95% CI 0.001-1.0). Compared with a keyword-search approach on the unfiltered cohort, machine learning reduced false-positive rates from 4.5% to 0.2% for ADL and 1.8% to 0.1% for iADL. CONCLUSIONS: In this study, we demonstrated the ability of machine learning models to accurately identify ADL and iADL impairment based on free-text clinical notes, which could be useful in determining the severity of dementia.

Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy.

Physical stimulation with mild heat possesses the notable ability to induce immunomodulation within the tumor microenvironment (TME). It transforms the immunosuppressive TME into an immune-active state, making tumors more receptive to immune checkpoint inhibitor (ICI) therapy. Transient receptor potential vanilloid 1 (TRPV1), which can be activated by mild heat, holds the potential to induce these alterations in the TME. However, achieving precise temperature control within tumors while protecting neighboring tissues remains a significant challenge when using external heat sources. Taking inspiration from the heat sensation elicited by capsaicin-containing products activating TRPV1, this study employs capsaicin to chemically stimulate TRPV1, imitating immunomodulatory benefits akin to those induced by mild heat. This involves developing a glutathione (GSH)-responsive immunomodulatory prodrug micelle system to deliver capsaicin and an ICI (BMS202) concurrently. Following intravenous administration, the prodrug micelles accumulate at the tumor site through the enhanced permeability and retention effect. Within the GSH-rich TME, the micelles disintegrate and release capsaicin and BMS202. The released capsaicin activates TRPV1 expressed in the TME, enhancing programmed death ligand 1 expression on tumor cell surfaces and promoting T cell recruitment into the TME, rendering it more immunologically active. Meanwhile, the liberated BMS202 blocks immune checkpoints on tumor cells and T cells, activating the recruited T cells and ultimately eradicating the tumors. This innovative strategy represents a comprehensive approach to fine-tune the TME, significantly amplifying the effectiveness of cancer immunotherapy by exploiting the TRPV1 pathway and enabling in situ control of immunomodulation within the TME.

A contactless monitoring system for accurately predicting energy expenditure during treadmill walking based on an ensemble neural network.

The monitoring of treadmill walking energy expenditure (EE) plays an important role in health evaluations and management, particularly in older individuals and those with chronic diseases. However, universal and highly accurate prediction methods for walking EE are still lacking. In this paper, we propose an ensemble neural network (ENN) model that predicts the treadmill walking EE of younger and older adults and stroke survivors with high precision based on easy-to-obtain features. Compared with previous studies, the proposed model reduced the estimation error by 13.95% and 66.20% for stroke survivors and younger adults, respectively. Furthermore, a contactless monitoring system was developed based on Kinect, mm-wave radar, and ENN algorithms, and the treadmill walking EE was monitored in real time. This ENN model and monitoring system can be combined with smart devices and treadmill, making them suitable for evaluating, monitoring, and tracking changes in health during exercise and in rehabilitation environments.

Ultra-thin and Mechanically Stable LiCoO2 -Electrolyte Interphase Enabled by Mg2+ Involved Electrolyte.

LiCoO2 (LCO) cathode materials have attracted significant attention for its potential to provide higher energy density in current Lithium-ion batteries (LIBs). However, the structure and performance degradation are exacerbated by increasing voltage due to the catastrophic reaction between the applied electrolyte and delithiated LCO. The present study focuses on the construction of physically and chemically robust Mg-integrated cathode-electrolyte interface (MCEI) to address this issue, by incorporating Magnesium bis(trifluoromethanesulfonyl)imide (Mg[TFSI]2 ) as an electrolyte additive. During formation cycles, the strong MCEI is formed and maintained its 2 nm thickness throughout long-term cycling. Notably, Mg is detected not only in the robust MCEI, but also imbedded in the surface of the LCO lattice. As a result, the parasitic interfacial side reactions, surface phase reconstruction, particle cracking, Co dissolution and shuttling are considerably suppressed, resulting in long-term cycling stability of LCO up to 4.5 V. Therefore, benefit from the double protection of the strong MCEI, the Li||LCO coin cell and the Ah-level Graphite||LCO pouch cell exhibit high capacity retention by using Mg-electrolyte, which are 88.13% after 200 cycles and 90.4% after 300 cycles, respectively. This work provides a novel approach for the rational design of traditional electrolyte additives.

Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): an auditory evoked potential study of the duration-evoked mismatch negativity (MMN).

BACKGROUND: We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of "duration" processing. Given decrements in auditory processing abilities associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials. METHODS: We employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system. RESULTS: Data from individuals with CLN3 disease (N = 21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N = 41; ages 6-26 years). CONCLUSIONS: Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.

Simultaneous detection of SARS-CoV-2 S1 protein by using flexible electrochemical and Raman enhancing biochip.

Flexible laser-scribed graphene (LSG) substrates with gold nanoislands have been developed as biochips for in situ electrochemical (EC) and surface-enhanced Raman scattering (SERS) biodetection (biomolecules and viral proteins). A flexible biochip was fabricated using CO2 laser engraving polyimide (PI) films to form a 3D porous graphene-like nanostructure. Gold nanoislands were deposited on the LSG substrates to enhance the intensity of the Raman signals. Moreover, the addition of auxiliary and reference electrodes induced a dual-function EC-SERS biochip with significantly enhanced detection sensitivity. The biochip could selectively and easily capture SARS-CoV-2 S1 protein through the SARS-CoV-2 S1 antibody immobilized on EC-SERS substrates using 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The grafted antibody specifically bound to SARS-CoV-2, resulting in a significant increase in the SERS signal of the target analyte. The limit of detection (LOD) of the SARS-CoV-2 S1 protein was 5 and 100 ng/mL by using EC and SERS detection, respectively. Although the LOD of the SARS-CoV-2 S1 protein detected using SERS is only 100 ng/mL, it can provide fingerprint information for identification. To improve the LOD, EC detection was integrated with SERS detection. The three-electrode detection chip enables the simultaneous detection of SERS and EC signals, which provides complementary information for target identification. The dual-functional detection technology demonstrated in this study has great potential for biomedical applications, such as the rapid and sensitive detection of SARS-CoV-2.

circRNADisease v2.0: an updated resource for high-quality experimentally supported circRNA-disease associations.

circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.

[Sjögren's syndrome combined with cold agglutinin disease: A case report].

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.