Protein nanopore-based sensors for public health analyte detection.

High-throughput and label-free protein nanopore-based sensors are extensively used in DNA sequencing, single-protein analysis, molecular sensing and chemical catalysis with single channel recording. These technologies show great potential for identifying various harmful substances linked to public health by addressing the limitations of current portability and the speed of existing techniques. In this review, we provide an overview of the fundamental principles of nanopore sensing, with a focus on chemical modification and genetic engineering strategies aimed at enhancing the detection sensitivity and identification accuracy of protein nanopores. The engineered protein nanopores enable direct sensing, while the introduction of aptamers and substrates enables indirect sensing, translating the physical structure and chemical properties of analytes into readable signals. These scientific discoveries and engineering efforts have provided new prospects for detecting and monitoring trace hazardous substances.

The triangular relationship of physical activity, depression, and inflammatory markers: A large cross-sectional analysis with NHANES data.

Depression is a major public health problem worldwide and is closely related with systemic inflammatory responses. Additionly, physical activity (PA) is thought to be associated with lower levels of depression and inflammatory markers. This study aimed to elucidate the complex interactions between PA, depression, and inflammatory markers. Based on the National Health and Nutrition Examination Survey (NHANES), various logistic regression were applied to analyze the pairwise correlations among the three. Restrictive cubic splines were constructed to explore the nonlinear relationship between PA and depression. Mediation models were used to identify the mediating role of inflammatory markers. The findings revealed a positive link between depression and inflammatory marker, whereas PA was inversely correlated with both inflammatory marker and depression. Particularly, we noticed the greatest reduction in the risk of depression when the level of PA was between 1200 and 1722 MET-min/week. Besides, we demonstrated that inflammatory markers mediate the potential effects of physical inactivity on depression, ranging from 1.72 % to 6.25 %. In conclusion, PA appear to protect against depression, in which inflammatory markers may play a mediating role. Moreover, we determined the optimal dosage of PA to minimize the likelihood of depression, thereby offering valuable guidance for managing depression.

The Role of SF1 and SF2 Helicases in Biotechnological Applications.

Helicases, which utilize ATP hydrolysis to separate nucleic acid duplexes, play crucial roles in DNA and RNA replication, repair, recombination, and transcription. Categorized into the major groups superfamily 1 (SF1) and superfamily 2 (SF2), alongside four minor groups, these proteins exhibit a conserved catalytic core indicative of a shared evolutionary origin while displaying functional diversity through interactions with various substrates. This review summarizes the structures, functions and mechanisms of SF1 and SF2 helicases, with an emphasis on conserved ATPase sites and RecA-like domains essential for their enzymatic and nucleic acid binding capabilities. It highlights the unique 1B and 2B domains in SF1 helicases and their impact on enzymatic activity. The DNA unwinding process is detailed, covering substrate recognition, ATP hydrolysis, and conformational changes, while addressing debates over the active form of UvrD helicase and post-unwinding dissociation. More importantly, this review discusses the biotechnological potential of helicases in emerging technologies such as nanopore sequencing, protein sequencing, and isothermal amplification, focusing on their use in pathogen detection, biosensor enhancement, and cancer treatment. As understanding deepens, innovative applications in genome editing, DNA sequencing, and synthetic biology are anticipated.

Synthesis of P, N-dopped carbon nanosheets for highly sensitive fluorescence analysis of nitrofuran antibiotics in fish.

The misuse of antibiotics has caused serious impacts on food safety and human health, making it crucial to develop rapidly and highly sensitive methods for detecting trace nitrofuran antibiotics (NFs). In this study, phosphorus, nitride-doped carbon nanosheets (PN/CNs) were synthesized using a simple hydrothermal method based on graphitic carbon nitride. This prepared material showed excellent water solubility and stable optical properties. A new fluorescence sensing platform based on PN/CNs was constructed for the highly sensitive detection of four NFs. This sensitivity was mainly attributed to the fluorescence resonance energy transfer (FRET) mechanism. The limits of detection for nitrofurazone, nitrofurantoin, furazolidone and furaltadone were determined to be 13.41, 15.24, 16.37 and 19.94 nM, respectively. The high sensitivity and selectivity of PN/CNs for these four NFs were thoroughly evaluated by the Stern-Volmer equation and FRET quenching efficiency. This proposed method exhibited high sensitivity and can be successfully applied to detect NFs in fish.

Label-free fluorescence platform based on SiO2-coated CdTeS quantum dots for trace analysis of Ag+ in environmental water.

In this study, a core-shell structural nano-composite material, namely CdTeS@SiO2, is synthesized by a simple silanization of Te-doped CdS quantum dots (CdTeS QDs). Through SiO2 capping, CdTeS QDs not only improve the fluorescence performance effectively, but also greatly enhance the anti-interference ability in the environment. Based on its excellent optical properties, a novel fluorescence sensor is constructed for the ultramicro detection of Ag+. The fluorescence of CdTeS@SiO2 is strongly quenched in the presence of Ag+ and shows good linearity in the range of 0.005-5.0 µmol L-1 with a detection limit as low as 1.6 nmol L-1. This is mainly due to its unique quenching mechanism: Ag+ destroys the spherical structure of SiO2 and promotes the formation of non-radiative electron-hole pairs through electron transfer, leading to fluorescence quenching. At the same time, it competes with Cd for Te, S and MPA on the CdTeS surface, forming Ag-Te, Ag-S and Ag-MPA complexes attached to the CdTeS surface leading to wavelength red-shift. The feasibility of the proposed sensor is demonstrated through spiking experiments, which confirmed the potential value of the constructed fluorescence probe for real-world applications in detecting Ag+ in environmental water.

Electroacupuncture Inhibits Neural Ferroptosis in Rat Model of Traumatic Brain Injury via Activating System Xc-/GSH/GPX4 Axis.

BACKGROUND: Ferroptosis is an iron-dependent regulating programmed cell death discovered recently that has been receiving much attention in traumatic brain injury (TBI). xCT, a major functional subunit of Cystine/glutamic acid reverse transporter (System Xc-), promotes cystine intake and glutathione biosynthesis, thereby protecting against oxidative stress and ferroptosis. OBJECTIVE: The intention of this research was to verify the hypothesis that electroacupuncture (EA) exerted an anti-ferroptosis effect via an increase in the expression of xCT and activation of the System Xc-/GSH/GPX4 axis in cortical neurons of TBI rats. METHODS: After the TBI rat model was prepared, animals received EA treatment at GV20, GV26, ST36 and PC6, for 15 min. The xCT inhibitor Sulfasalazine (SSZ) was administered 2h prior to model being prepared. The degree of neurological impairment was evaluated by means of TUNEL staining and the modified neurological severity score (mNSS). Specific indicators of ferroptosis (Ultrastructure of mitochondria, Iron and ROS) were detected by transmission electron microscopy (TEM), Prussian blue staining (Perls stain) and flow cytometry (FCM), respectively. GSH synthesis and metabolism-related factors in the content of the cerebral cortex were detected by an assay kit. Real-time quantitative PCR (RT-QPCR), Western blot (WB), and immunofluorescence (IF) were used for detecting the expression of System Xc-/GSH/GPX4 axisrelated proteins in injured cerebral cortex tissues. RESULTS: EA successfully relieved nerve damage within 7 days after TBI, significantly inhibited neuronal ferroptosis, upregulated the expression of xCT and System Xc-/GSH/GPX4 axis forward protein and promoted glutathione (GSH) synthesis and metabolism in the injured area of the cerebral cortex. However, aggravation of nerve damage and increased ferroptosis effect were found in TBI rats injected with xCT inhibitors. CONCLUSIONS: EA inhibits neuronal ferroptosis by up-regulated xCT expression and by activating System Xc-/GSH/GPX4 axis after TBI, confirming the relevant theories regarding the EA effect in treating TBI and providing theoretical support for clinical practice.

Disrupted cognitive and affective empathy network interactions in autistic children viewing social animation.

Empathy can be divided into two core components, cognitive empathy (CE) and affective empathy (AE), mediated by distinct neural networks. Deficient empathy is a central feature of autism spectrum conditions (ASCs), but it is unclear if this deficit results from disruption solely within empathy networks or from disrupted functional integration between CE and AE networks. To address this issue, we measured functional connectivity (FC) patterns both within and between empathy networks in autistic children (4-8 years, n = 31) and matched typically developing (TD) children (n = 26) using near-infrared spectroscopy during the presentation of an animated story evoking CE and AE. Empathy and social communication ability were also assessed using the Empathy Quotient/Systemizing Quotient (EQ/SQ) and Social Responsiveness Scale, respectively. The results showed that the FC in the AE network of autistic children did not differ from the TD group across conditions; however, the ASC group showed weaker FC in the CE network under the CE condition and weaker FC between networks when processing AE information, the latter of which was negatively correlated with EQ scores in ASC. The empathy defect in ASC may involve abnormal integration of CE and AE network activities under AE conditions.

Migration through Resolution Cell Correction and Sparse Aperture ISAR Imaging for Maneuvering Target Based on Whale Optimization Algorithm-Fast Iterative Shrinkage Thresholding Algorithm.

Targets faced by inverse synthetic aperture radar (ISAR) are often non-cooperative, with target maneuvering being the main manifestation of this non-cooperation. Maneuvers cause ISAR imaging results to be severely defocused, which can create huge difficulties in target identification. In addition, as the ISAR bandwidth continues to increase, the impact of migration through resolution cells (MTRC) on imaging results becomes more significant. Target non-cooperation may also result in sparse aperture, leading to the failure of traditional ISAR imaging algorithms. Therefore, this paper proposes an algorithm to realize MTRC correction and sparse aperture ISAR imaging for maneuvering targets simultaneously named whale optimization algorithm-fast iterative shrinkage thresholding algorithm (WOA-FISTA). In this algorithm, FISTA is used to perform MTRC correction and sparse aperture ISAR imaging efficiently and WOA is adopted to estimate the rotational parameter to eliminate the effects of maneuvering on imaging results. Experimental results based on simulation and measured datasets prove that the proposed algorithm implements sparse aperture ISAR imaging and MTRC correction for maneuvering targets simultaneously. The proposed algorithm achieves better results than traditional algorithms under different signal-to-noise ratio conditions.

A graphitic C3N4 nanocomposite-based fluorescence platform for label-free analysis of trace mercury ions.

In this study, a nanocomposite consisting of graphitic carbon nitride nanosheets loaded with graphitic carbon nitride quantum dots (CNQDs/CNNNs) was synthesized via a one-step pyrolysis method. This nanocomposite exhibited excellent thermal stability, photobleaching and salt resistance. Then a new fluorescence sensing platform based on CNQDs/CNNNs was constructed, which showed high sensitivity and selectivity towards trace mercury ions (Hg2+). By using X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectra and density functional theory, the fluorescence response mechanism was elucidated where Hg2+ could interact with CNQDs/CNNNs, causing a structural change in the nanocomposite, further affecting its bandgap structure, and finally leading to fluorescence quenching. The linear range for detecting Hg2+ was found to be 0.025-4.0 µmol L-1, with a detection limit of 7.82 nmol L-1. This strategy provided the advantages of a rapid response and a broad detection range, making it suitable for quantitative detection of Hg2+ in environmental water.

Local structural and functional MRI markers of compulsive behaviors and obsessive-compulsive disorder diagnosis within striatum-based circuits.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a classic disorder on the compulsivity spectrum, with diverse comorbidities. In the current study, we sought to understand OCD from a dimensional perspective by identifying multimodal neuroimaging patterns correlated with multiple phenotypic characteristics within the striatum-based circuits known to be affected by OCD. METHODS: Neuroimaging measurements of local functional and structural features and clinical information were collected from 110 subjects, including 51 patients with OCD and 59 healthy control subjects. Linked independent component analysis (LICA) and correlation analysis were applied to identify associations between local neuroimaging patterns across modalities (including gray matter volume, white matter integrity, and spontaneous functional activity) and clinical factors. RESULTS: LICA identified eight multimodal neuroimaging patterns related to phenotypic variations, including three related to symptoms and diagnosis. One imaging pattern (IC9) that included both the amplitude of low-frequency fluctuation measure of spontaneous functional activity and white matter integrity measures correlated negatively with OCD diagnosis and diagnostic scales. Two imaging patterns (IC10 and IC27) correlated with compulsion symptoms: IC10 included primarily anatomical measures and IC27 included primarily functional measures. In addition, we identified imaging patterns associated with age, gender, and emotional expression across subjects. CONCLUSIONS: We established that data fusion techniques can identify local multimodal neuroimaging patterns associated with OCD phenotypes. The results inform our understanding of the neurobiological underpinnings of compulsive behaviors and OCD diagnosis.

Near-infrared dye IRDye800CW-NHS coupled to Trastuzumab for near-infrared II fluorescence imaging in tumor xenograft models of HER-2-positive breast cancer.

Near-infrared II fluorescent probes targeting tumors for diagnostic purposes have received much attention in recent years. In this study, a fluorescent probe for the NIR-II was constructed by using IRDye800CW-NHS fluorescent dye with Trastuzumab, which was investigated for its ability to target HER-2-positive breast cancer in xenograft mice models. This probe was compared with Trastuzumab-ICG which was synthesized using a similar structure, ICG-NHS. The results demonstrated that the IRDye800CW-NHS had significantly stronger fluorescence in the NIR-I and NIR-II than ICG-NHS in the aqueous phase. And the different metabolic modes of IRDye800CW-NHS and ICG-NHS were revealed in bioimaging experiments. IRDye800CW-NHS was mainly metabolised by the kidneys, while ICG-NHS was mainly metabolised by the liver. After coupling with Trastuzumab, Trastuzumab-800CW (TMR = 5.35 ± 0.39) not only had a stronger tumor targeting ability than Trastuzumab-ICG (TMR = 4.42 ± 0.10) based on the calculated maximum tumor muscle ratio (TMR), but also had a comparatively lower hepatic uptake and faster metabolism. Histopathology analysis proved that both fluorescent probes were non-toxic to various organ tissues. These results reveal the excellent optical properties of IRDye800CW-NHS, and the great potential of coupling with antibodies to develop fluorescent probes that will hopefully be applied to intraoperative breast cancer navigation in humans.

A new ratiometric fluorescence nanosensor based on NaYF4:3%Er@NaYF4 upconversion nanoparticles for sensitive determination of Rose Bengal in water.

Rose Bengal (RB) is used as a sensitizer in ambient water due to its property of catalyzing the production of singlet oxygen (1O2). However, this property also brings phototoxicity and carcinogenicity. The NaYF4:3%Er@NaYF4 core-shell upconversion nanoparticles (UCNPs) with higher upconversion efficiency was synthesized to detect RB in ambient water. Due to fluorescence resonance energy transfer (FRET) between RB and UCNPs, the upconversion fluorescence at 538 nm emitted by UCNPs was quenched by the RB, while the emission at 566 nm of RB raised. In the best conditions, the ratiometric emission intensity F566/F538 was positively proportional to RB concentration and the linear range was 0.04-15.0 µg·mL-1 (R2 = 0.996). The detection limit (S/N = 3) of RB was 2.46 ng·mL-1. The recoveries ranged from 99.0% to 105.6% (relative standard deviation 0.97-3.24%, n = 3) in tap water and 100.3%-104.9% (relative standard deviation 0.66-1.94%, n = 3) in lake water. This proposed method exhibits lower detection limit and larger linear, which possesses practical application value to the detection of RB in water.

Gold Nanoparticles: Construction for Drug Delivery and Application in Cancer Immunotherapy.

Cancer immunotherapy is an innovative treatment strategy to enhance the ability of the immune system to recognize and eliminate cancer cells. However, dose limitations, low response rates, and adverse immune events pose significant challenges. To address these limitations, gold nanoparticles (AuNPs) have been explored as immunotherapeutic drug carriers owing to their stability, surface versatility, and excellent optical properties. This review provides an overview of the advanced synthesis routes for AuNPs and their utilization as drug carriers to improve precision therapies. The review also emphasises various aspects of AuNP-based immunotherapy, including drug loading, targeting strategies, and drug release mechanisms. The application of AuNPs combined with cancer immunotherapy and their therapeutic efficacy are briefly discussed. Overall, we aimed to provide a recent understanding of the advances, challenges, and prospects of AuNPs for anticancer applications.

Long-term warming impacts grassland ecosystem function: Role of diversity loss in conditionally rare bacterial taxa.

The impact of microbial communities on ecosystem function varies due to the diverse biological attributes and sensitivities exhibited by different taxonomic groups. These groups can be classified as always rare (ART), conditionally rare (CRT), dominant, and total taxa, each affecting ecosystem function in distinct ways. Thus, understanding the functional traits of organisms within these taxa is crucial for comprehending their contributions to overall ecosystem function. In our study, we investigated the influence of climate warming on the biogeochemical cycles of the ecosystem in the Qinghai-Tibet Plateau, utilizing an open top chamber experiment. Simulated warming significantly lowered ecosystem function in the grassland but not in the shrubland. This discrepancy was due to the diverse responses of the various taxa present in each ecosystem to warming conditions and their differing roles in determining and regulating ecosystem function. The microbial maintenance of ecosystem function was primarily reliant on the diversity of bacterial dominant taxa and CRT and was less dependent on ART and fungal taxa. Furthermore, bacterial CRT and dominant taxa of the grassland ecosystem were more sensitive to changing climatic conditions than grassland ART, resulting in a more pronounced negative diversity response. In conclusion, the biological maintenance of ecosystem function during climate warming is dependent on microbiome composition and the functional and response characteristics of the taxa present. Thus, understanding the functional traits and response characteristics of various taxa is crucial for predicting the effects of climate change on ecosystem function and informing ecological reconstruction efforts in alpine regions of the plateau.

Advances of MnO2 nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics.

As an essential micronutrient, manganese plays an important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous and endogenous DNA for activation, has been widely reported to play critical roles in the innate immunity against some important diseases, such as infections and tumor. Manganese ion (Mn2+) has been recently proved to specifically bind with cGAS and activate cGAS-STING pathway as a potential cGAS agonist, however, is significantly restricted by the low stability of Mn2+ for further medical application. As one of the most stable forms of manganese, manganese dioxide (MnO2) nanomaterials have been reported to show multiple promising functions, such as drug delivery, anti-tumor and anti-infection activities. More importantly, MnO2 nanomaterials are also found to be a potential candidate as cGAS agonist by transforming into Mn2+, which indicates their potential for cGAS-STING regulations in different diseased conditions. In this review, we introduced the methods for the preparation of MnO2 nanomaterials as well as their biological activities. Moreover, we emphatically introduced the cGAS-STING pathway and discussed the detailed mechanisms of MnO2 nanomaterials for cGAS activation by converting into Mn2+. And we also discussed the application of MnO2 nanomaterials for disease treatment by regulating cGAS-STING pathway, which might benefit the future development of novel cGAS-STING targeted treatments based on MnO2 nanoplatforms.

Cross-Image Dependency Modeling for Breast Ultrasound Segmentation.

We present a novel deep network (namely BUSSeg) equipped with both within- and cross-image long-range dependency modeling for automated lesions segmentation from breast ultrasound images, which is a quite daunting task due to (1) the large variation of breast lesions, (2) the ambiguous lesion boundaries, and (3) the existence of speckle noise and artifacts in ultrasound images. Our work is motivated by the fact that most existing methods only focus on modeling the within-image dependencies while neglecting the cross-image dependencies, which are essential for this task under limited training data and noise. We first propose a novel cross-image dependency module (CDM) with a cross-image contextual modeling scheme and a cross-image dependency loss (CDL) to capture more consistent feature expression and alleviate noise interference. Compared with existing cross-image methods, the proposed CDM has two merits. First, we utilize more complete spatial features instead of commonly used discrete pixel vectors to capture the semantic dependencies between images, mitigating the negative effects of speckle noise and making the acquired features more representative. Second, the proposed CDM includes both intra- and inter-class contextual modeling rather than just extracting homogeneous contextual dependencies. Furthermore, we develop a parallel bi-encoder architecture (PBA) to tame a Transformer and a convolutional neural network to enhance BUSSeg's capability in capturing within-image long-range dependencies and hence offer richer features for CDM. We conducted extensive experiments on two representative public breast ultrasound datasets, and the results demonstrate that the proposed BUSSeg consistently outperforms state-of-the-art approaches in most metrics.

[Effect of electroacupuncture on behavior and cell apoptosis of brain tissue in traumatic brain injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on behavior, pathomorphology and brain cell apoptosis in traumatic brain injury (TBI) rats, so as to explore its mechanisms underlying treatment of TBI. METHODS: Male SD rats were randomly divided into control (n=10), sham (n=30), model (n=30) and EA (n=30) groups, the latter three groups were further divided into 3, 7, 14 d subgroups （n=10）. TBI model was established by using a free fall brain injury striking device after exposing the local cranial bone (to induce the left parietal cerebral contusion). Twenty-four hours after modeling, EA (2 Hz, 1 mA) was applied at "Quchi"(LI11), "Neiguan"(PC6), "Zusanli"(ST36) and "Yongquan" (KI1) combined with acupuncture at "Shuigou"(GV26) and "Baihui"(GV20) for 15 min, once a day for 14 consecutive days. After 3, 7, and 14 days treatment, the behavioral function (balance, walking, nerve, and limb retraction) of the rats was evaluated. The histopathological changes of the injured brain tissue were observed by HE staining. TUNEL method was used to detect the apoptosis of cells in the brain injury area. RESULTS: After modeling, the scores of balance and walking in the model group were higher than those in the sham group (P<0.01, P<0.05), the neurological function score and the right limb retraction force were lower than those in the sham group(P<0.01). After 3 days treatment, the neurological function score and the right limb retraction force in the EA group were higher than those in the model group (P<0.05). After 7 and 14 days treatment, the scores of balance and walking function in the EA group were lower than those in the model group (P<0.05, P<0.01), while the scores of nerve function and right limb retraction force were higher (P<0.05, P<0.01). HE staining showed that modeling induced pathological changes such as the inflammatory cell infiltration, interstitial edema, necrosis, nuclear pyknosis and nuclear lysis were relatively milder in the EA group on the 7th and 14th day. Compared with the sham group, the cell apoptosis of brain injury area was higher in the model group (P<0.01); while it was lower on day 7 and 14 in the EA group in comparison with the model group (P<0.01, P<0.05). CONCLUSION: EA can improve the behavioral function, reduce the apoptosis of brain cells in the injured area, and promote the rehabilitation of craniocerebral injury.

Relationship between urinary dichlorophenols and cognitive function among people over 60 years old from NHANES.

Studies have shown that exposure to dichlorophenols (DCPs) and their precursors might have potential neurotoxicity, which may be related to low cognitive function, but there are few large-scale, representative population data to explore the association between DCP exposure and cognitive function. We aimed to examine the relationship between urinary DCPs and cognitive function in the US older people. A total of 952 participants ≥ 60 years old from the National Health and Nutrition Examination Survey (NHANES) in two cycles (2011-2014) were enrolled. The Consortium to Establish a Registry for Alzheimer's disease Word Learning subtest (CERAD W-L), the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST) were used to assess cognition. Multivariate logistic regression and restricted cubic spline (RCS) were used to evaluate the relationship between DCP exposure and cognitive function. A positive association between 2,5-DCP and the risk of bad performance of DSST was observed (P for trend = 0.024) after adjusting for the covariates. Compared to the lowest quartile, OR of DSST for the highest quartile of 2,5-DCP was 1.72 (95%CI:1.03-2.87, P = 0.039). There were no significant associations between DCPs and the other tests. The RCS plot showed an inverted J-shaped relationship between 2,5-DCP, 2,4-DCP, and the DSST score. The inflection points for the curves were found at 1.531 µg/L and 0.230 µg/L, respectively. On the right side of the inflection points, the DSST score dropped sharply. In subgroup analysis, those under 70 years old, smokers, and alcohol drinkers had a higher risk of bad performance in DSST when exposed to 2,5-DCP. The higher concentration of urinary DCPs is associated with a lower score of DSST in the US older people.

Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein.

ABSTRACTThe COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development, and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus-neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. This study predicted several potential T cell epitopes with web-based analytic tools and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants and compatible with a presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

The Relationship between Metal Exposure and Chronic Obstructive Pulmonary Disease in the General US Population: NHANES 2015-2016.

The effects of metal on pulmonary function are inconsistent, and abnormal distribution of metals can decrease lung function. However, the effects of metals exposure on chronic obstructive pulmonary disease (COPD) are still unclear. This study aims to explore the relationship between metal exposure and COPD risk. Cross-sectional data from the National Health and Nutrition Survey (NHANES) 2015-2016 was analyzed. Inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS) was used to measure the metals concentration in the blood. The multiple linear regression and restricted cubic spline (RCS) were used to analyze the relationship between metals exposure and COPD risk. In this study, 1399 participants were included, of which 107 participants were diagnosed with COPD using self-reported chronic bronchitis, emphysema, and COPD. The second and third tertiles of copper increased the COPD risk by 1.98-fold (95% CI: 1.08-3.62) and 2.43-fold (95% CI: 1.32-4.48) compared with the first tertile, using p = 0.005 for the trend after adjusting for the covariates. RCS showed a positive linear correlation between copper and COPD risk (p = 0.006 for overall association) in all participants. When stratified by sex, the multi-factor analysis showed that the third tertile of copper increased male's COPD risk by 3.42-fold (95% CI: 1.52-7.76), with p = 0.003 for the trend, and RCS also showed a positive linear correlation (p = 0.013 for overall association). Although RCS showed that selenium can reduce the COPD risk (p = 0.008 for overall association) in males, an association between selenium and COPD was not observed (p > 0.05). Our findings suggest that a high concentration of copper may increase COPD risk in males in the general US population, and more research is needed to explore its possible mechanism of action.