Integrative Proteomic Characterization of Human Lung Adenocarcinoma.

Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics analysis of 103 cases of LUAD in Chinese patients. Integrative analysis of proteome, phosphoproteome, transcriptome, and whole-exome sequencing data revealed cancer-associated characteristics, such as tumor-associated protein variants, distinct proteomics features, and clinical outcomes in patients at an early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Further, we nominated potential drug targets and validated the plasma protein level of HSP 90ß as a potential prognostic biomarker for LUAD in an independent cohort. Our integrative proteomics analysis enables a more comprehensive understanding of the molecular landscape of LUAD and offers an opportunity for more precise diagnosis and treatment.

Emerging role of N6-methyladenosine in the homeostasis of glucose metabolism.

N6-methyladenosine (m6A) is the most prevalent post-transcriptional internal RNA modification, which is involved in the regulation of diverse physiological processes. Dynamic and reversible m6A modification has been shown to regulate glucose metabolism, and dysregulation of m6A modification contributes to glucose metabolic disorders in multiple organs and tissues including the pancreas, liver, adipose tissue, skeletal muscle, kidney, blood vessels, and so forth. In this review, the role and molecular mechanism of m6A modification in the regulation of glucose metabolism were summarized, the potential therapeutic strategies that improve glucose metabolism by targeting m6A modifiers were outlined, and feasible directions of future research in this field were discussed as well, providing clues for translational research on combating metabolic diseases based on m6A modification in the future.

Stable Lithium Metal Batteries Enabled by Lithiophilic Core-Shell Nanowires on Copper Foam.

Lithium (Li) metal batteries have attracted considerable research attention due to their exceptionally high theoretical capacity. However, the commercialization of Li metal batteries faces challenges, primarily attributed to uncontrolled growth of Li dendrites, which raises safety concerns and lowers coulombic efficiency. To mitigate Li dendrites growth and attain dense Li deposition, the hybrid SiO2-Cu2O lithiophilic film applied to a 3D copper foam current collector is developed to regulate the interfacial properties for achieving even and dense Li deposition. The SiO2-Cu2O possesses strong Li+ trapping capability through strong lithiophilicity from Cu2O. Additionally, the SiO2-Cu2O enables uniform ion diffusion through the domain-limiting effect of the holes in the SiO2 layer, inducing an even and dense Li plating/stripping behavior at a large capacity. Furthermore, the SiO2 layer promotes the formation of an initial high inorganic content Solid Electrolyte Interphase (SEI) through selective preferential binding with anion and solvent molecules. When the SiO2-Cu2O@Li anode is coupled with a LiFePO4 (LFP) cathode, the resulting full cell exhibits superior cycling stability and rate performance. These results provide a facile approach to construct a lithiophilic current collector for practical Li metal anodes.

Risk Factors of Distant Metastatic Parathyroid Carcinoma and Insights into Therapeutic Perspectives.

BACKGROUND: Distant metastatic parathyroid carcinoma (DM-PC) is a rare but often lethal entity with limited data about prognostic indicators. We sought to investigate the risk factors, patterns, and outcomes of DM-PC. METHODS: In this observational cohort study, 126 patients who underwent surgery for PC at a tertiary referral center from 2010 to 2023 were enrolled, among whom 38 had DMs. Univariate and multivariate Cox regression analyses were used to assess the effects of prognostic factors on DM. RESULTS: The cumulative incidence of DM was 14.1%, 33.8%, and 66.9% at 5, 10, and 20 years in the duration of disease course, respectively. DM-PC patients suffered a worse 5-year overall survival of 37.1% compared with 89.8% in the non-DM patients (p < 0.001). DM-PC patients also suffered more previous operations (p < 0.001), higher preoperative serum calcium (p<0.001) and parathyroid hormone (PTH) levels (p < 0.001), lower frequencies of R0 resection (p < 0.001), higher rates of pathological vascular invasion (p = 0.020), thyroid infiltration (p = 0.027), extraglandular extension (p = 0.001), upper aerodigestive tract (UAT) invasion (p < 0.001), and lymph node metastasis (p < 0.001). Multivariate Cox regression revealed that non-R0 resection (HR 6.144, 95% CI 2.881-13.106, p < 0.001), UAT invasion (HR 3.718, 95% CI 1.782-7.756, p < 0.001), and higher preoperative PTH levels (HR 1.001, 95% CI 1.000-1.001, p = 0.012) were independent risk factors of DM. CONCLUSIONS: Upper aerodigestive tract invasion and higher preoperative PTH levels might be risk factors for possible metastatic involvement of PC. R0 resection and closer surveillance should be considered in such cases to minimize the risk of DM and to optimize patient care.

Safety and efficacy of the second-generation cryoballoon for left atrial appendage electrical isolation in canines.

AIMS: Left atrial appendage electrical isolation (LAAEI) has demonstrated a significant enhancement in the success rate of atrial fibrillation (AF) ablation. Nevertheless, concerns persist about the safety of LAAEI, particularly regarding alterations in left atrial appendage (LAA) flow velocity and the potential risks of thrombus. This study aimed to assess the efficacy and safety of LAAEI, investigating changes in LAA flow velocity in canines. METHODS AND RESULTS: The study comprised a total of 10 canines. The LAAEI procedure used by a 23 mm cryoballoon of the second generation was conducted at least 180 s. Intracardiac ultrasonography (ICE) was employed to quantify the velocity flow of the LAA both prior to and following LAAEI. Following a 3-month period, subsequent evaluations were performed to assess the LAA velocity flow and the potential reconnection. Histopathological examination was conducted. Left atrial appendage electrical isolation was effectively accomplished in all canines, resulting in a 100% acute success rate (10/10). The flow velocity in the LAA showed a notable reduction during LAAEI as compared with the values before the ablation procedure (53.12 ± 5.89 vs. 42.01 ± 9.22 cm/s, P = 0.007). After the follow-up, reconnection was observed in four canines, leading to a success rate of LAAEI of 60% (6/10). The flow velocity in the LAA was consistently lower (53.12 ± 5.89 vs. 44.33 ± 10.49 cm/s, P = 0.006), and no blood clot development was observed. The histopathological study indicated that there was consistent and complete injury to the LAA, affecting all layers of its wall. The injured tissue was subsequently replaced by fibrous tissue. CONCLUSION: The feasibility of using cryoballoon ablation for LAAEI was confirmed in canines, leading to a significant reduction of LAA flow velocity after ablation. Some restoration of LAA flow velocity after ablation may be linked to the passive movement of the LAA and potential reconnecting. However, this conclusion is limited to animal study; more clinical data are needed to further illustrate the safety and accessibility of LAAEI in humans.

Spatially Confined LiF Nanoparticles in an Aligned Polymer Matrix as the Artificial SEI Layer for Lithium Metal Anodes.

The uncontrollable growth of lithium (Li) dendrites and the instability of the Li/electrolyte interface hinder the development of next-generation rechargeable lithium metal batteries. The combination of inorganic nanoparticles and polymers as the artificial SEI layer shows great potential in regulating lithium-ion flux. Here, we design spatially confined LiF nanoparticles in an aligned polymer matrix as the artificial SEI layer. A high dielectric polymer matrix homogenizes the electric field near the surface of lithium metal. Aligned pores with LiF nanoparticles promote the lithium-ion transport across the artificial SEI layer. The synergistic effect of the highly polar ß-phase PVDF and LiF nanoparticles provides high stability over 900 h for the Li//Li symmetrical cell. Besides, a Li//LFP full battery equipped with this artificial layer shows good performance in the commercial carbonate electrolyte, demonstrating the great potential of this protective film in lithium metal batteries.

Phase sensitivity of an SU(1,1) interferometer in photon-loss via photon operations.

We study the phase sensitivity of an SU(1,1) interferometer with photon loss by using three different photon operations schemes, i.e., performing photon-addition operation on the input port of the SU(1,1) interferometer (Scheme A), the interior of SU(1,1) interferometer (Scheme B), and both of them (Scheme C). We compare the performance of the three schemes in phase estimation by performing the same times of photon-addition operation to the mode b. The results show that Scheme B improves the phase sensitivity best in ideal case, and Scheme C performs well against internal loss, especially in the case of strong loss. All the three schemes can beat the standard quantum limit in the presence of photon loss, but Scheme B and Scheme C can break through the standard quantum limit in a larger loss range.

Continuous-variable quantum key distribution based on non-Gaussian operations with on-off detection.

Quantum key distribution (QKD) with continuous variable (CV) is an effective method for achieving the high key rate, but is also limited to a short transmission distance. To overcome this limitation, some solutions have been proposed, including non-Gaussian operations, such as photon addition and photon subtraction using ideal photon source and number-resolving detection. Here we consider the effect of non-Gaussian operation for realistic photon source and ideal on-off photon detection. In the realistic case, it is shown that the performance of CVQKD can not be improved by both photon-subtraction/addition on the right side before the entangled source reaches the channel and photon-subtraction on the left side preceding the entangled source to the sender Alice before performing heterodyne detection, but be enhanced by the photon addition on the left side in a long distance case. These results may provide a useful reference for quantum information with continuous variable.

Microbe community composition differences of hand skin on similar lifestyle volunteers: a small-scale study.

AIMS: Human skin is the first barrier against pathogens and environmental hazards and the highest contact frequency occurs with the hands. Environmental and personal metabolic factors may affect skin microbes. This study was conducted to clarify the diversity in the skin microbial community that was mainly due to individual skin metabolites rather than lifestyle and environmental factors. METHODS AND RESULTS: Skin microbiota samples were collected from 11 volunteers who met similar lifestyle inclusion criteria. The V3-V4 region of the 16S rRNA gene was amplified. After library construction and sequencing, we compared the composition and diversity of the hand skin microbiota in different sexes and BMI groups with bioinformation analysis. The whole sequence data were annotated as 42 phyla, 538 families, and 1215 genera. Four dominant phyla accounted for 97% of the total including Actinobacteriota (50.18%), Firmicutes (23.85%), Proteobacteria (21.64%) and Bacteroidota (2.05%). The genera that were detected in all subjects with high relative abundance were Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Enhydrobacter, Escherichia-Shigella, Asaia and Micrococcus. CONCLUSIONS: The diversity and richness of the microbiota of male hand skin in our study was higher than that of females. Interestingly, Cutibacterium, Staphylococcus, and Corynebacterium might serve as important skin microbiota to distinguish sexes.

A novel nomogram to predict lymph node metastasis in cT1 non-small-cell lung cancer based on PET/CT and peripheral blood cell parameters.

BACKGROUND: Accurately evaluating the lymph node status preoperatively is critical in determining the appropriate treatment plan for non-small-cell lung cancer (NSCLC) patients. This study aimed to construct a novel nomogram to predict the probability of lymph node metastasis in clinical T1 stage patients based on non-invasive and easily accessible indicators. METHODS: From October 2019 to June 2022, the data of 84 consecutive cT1 NSCLC patients who had undergone PET/CT examination within 30 days before surgery were retrospectively collected. Univariate and multivariate logistic regression analyses were performed to identify the risk factors of lymph node metastasis. A nomogram based on these predictors was constructed. The area under the receiver operating characteristic (ROC) curve and the calibration curve was used for assessment. Besides, the model was confirmed by bootstrap resampling. RESULTS: Four predictors (tumor SUVmax value, lymph node SUVmax value, consolidation tumor ratio and platelet to lymphocyte ratio) were identified and entered into the nomogram. The model indicated certain discrimination, with an area under ROC curve of 0.921(95%CI 0.866-0.977). The calibration curve showed good concordance between the predicted and actual possibility of lymph node metastasis. CONCLUSIONS: This nomogram was practical and effective in predicting lymph node metastasis for patients with cT1 NSCLC. It could provide treatment recommendations to clinicians.

Preparing future general practitioners: the effects of individual, familial, and institutional characteristics.

BACKGROUND: There is a substantially increasing need for general practitioners (GPs) for future unpredictable pandemic crises, especially at the community-based health services (CBHS) level to protect the vast and varied grassroot-level population in China. Thus, it is crucial to understand the factors that affect Chinese medical students' GP career choices and commitments to CBHS. METHODS: Leveraging the self-administered data collected across the country, this study conducted logistic regressions with 3,438 medical students. First, descriptive statistics of outcome variables and independent variables were provided. Then, stepwise logistic regression models were built, starting from adding individual characteristics, and then familial and institutional characteristics. Last, post-estimation was conducted to further assess whether there were significant marginal effects. RESULTS: Results showed that women students were 24% less likely to choose GP careers but were 1.25 times more likely to commit to CBHS than their men peers, holding other individual, familial, and institutional characteristics constant. In addition, students who major in GP-orientated were more likely to choose GP careers and commit to CBHS, respectively, than those who major in clinical medicine. Furthermore, familial characteristics like annual income and mother's educational level only significantly predicted commitments to CBHS. Notably, sex-related differences in GP career choices and commitments to CBHS - by different regions - were observed. CONCLUSIONS: Understanding the factors that affect medical students' GP career choices sheds light on how medical education stakeholders can make informed decisions on attracting more medical students to GP-orientated majors, which in turn cultivates more GP professionals to meet the nation's demand for GPs. In addition, by understanding the factors that influence medical students' commitment to CBHS, policymakers could make beneficial policies to increase medical students' motivations to the grassroot-level health institutions, and devote to CBHS as gatekeepers for a large population of residents' health.

Photoluminescence Anisotropy in Eutectic Crystals of Polynuclear Lanthanide Complexes and Silver Clusters.

Anisotropy is an intrinsic property of crystalline materials. However, the photoluminescence anisotropy in eutectic crystals of organometallic complexes has remained unexplored. Herein, the eutectic of polynuclear lanthanide complexes and Ag clusters was prepared, and the crystal shows significant photoluminescence anisotropy. The polarization anisotropy of emission δ and degree of excitation polarization P are 2.62 and 0.53, respectively. The rare excitation polarization properties have been proved to be related to the regular arrangement of electric transition dipole moments of luminescent molecules in the crystal. Our design provides a reference for developing new photoluminescence anisotropy materials and expanding their applications.

A Designed Lithiophilic Carbon Channel on Separator to Regulate Lithium Deposition Behavior.

Issues with unstable SEI formation and uncontrollable lithium dendrite growth impede the practical use of lithium anode in high-energy batteries. Herein, a lithiophilic carbon channel on separator is designed to regulate lithium deposition behavior. The designed channel is formed by carbon nanosheet with cubic cavity (CNCC) prepared by hard template method. The CNCC with a large specific surface area and good electrolyte wettability can effectively reduce the local current density. Besides, the CNCC coated separator with high Young's modulus can mechanically inhibit the growth of lithium dendrites. Notably, CNCC coating can become lithiophilic during lithium plating/striping process, which is beneficial for homogeneous lithium deposition and low lithium nucleation overpotential. As a result, based on the CNCC coated separator, the symmetric Li|Li cell cycle over 2600h at 6 mA cm-2 for 2 mAh cm-2 , while the Li|Cu cell reaches average Coulombic efficiency of 98.5% at 2 mA cm-2 for 2 mAh cm-2 .

Extended En Bloc Reoperation for Recurrent or Persistent Parathyroid Carcinoma: Analysis of 31 Cases in a Single Institute Experience.

BACKGROUND: Parathyroid carcinoma (PC) is a rare malignancy that is difficult to eradicate completely after recurrence. We assessed the efficiency of extended en bloc resection (EEBR) in the management of recurrent or persistent PC. METHODS: In this observational cohort study, 31 patients who underwent reoperations for recurrent or persistent PC were enrolled after 2-9 surgeries by other medical teams. EEBRs, which provided the oncologic resection by removing all possible tumor-bearing scar tissues, were adopted in 25 patients. The other 6 with gross infiltration into the upper aerodigestive tract (UAT) underwent less radical procedures for unwillingness to sacrifice laryngeal function. RESULTS: The 5-year overall survival (OS) rate after EEBR was 59.6% compared with 16.7% after less radical procedures, with an improved median expected survival time of 90.0 months compared with 13.0 months after local excision. EEBR exhibited a favorable local control of relapses in 84.0% of patients after a median follow-up period of 27.0 months, 40.0% even achieved disease-free survival, although 56.0% had subsequent distant metastases (DMs) and suffered a worse 5-year OS of 36.7% in contrast with 100.0% in the absence of DM (p = 0.011). UAT invasion, rather than age, number of previous operations, or preoperative PTH levels, was the unique independent factor associated with both DM (HR = 5.466, p = 0.006) and mortality (HR = 7.606, p = 0.011). CONCLUSION: EEBRs provide better outcomes than other conventional surgical approaches and might offer a second chance of cure for patients with recurrent or persistent PC in the absence of DM.

Circ_0008365 Suppresses Apoptosis, Inflammation and Extracellular Matrix Degradation of IL-1ß-treated Chondrocytes in Osteoarthritis by Regulating miR-324-5p/BMPR2/NF-κB Signaling Axis.

BACKGROUND: Recent studies have revealed that circular RNAs (circRNAs) play crucial roles in the progression of osteoarthritis (OA). This study aimed to investigate the biological function and regulatory mechanism of circ_0008365 in OA. METHODS: OA cell model in vitro was established in chondrocytes by treatment with Interleukin-1ß (IL-1ß). The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of circ_0008365, microRNA-324-5p (miR-324-5p) and bone morphogenetic protein type 2 receptor (BMPR2) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was assessed using flow cytometry and caspase3 activity assays. The protein expression was determined via a western blot assay. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down assays were used to analyze the correlation between targets. RESULTS: IL-1ß level and miR-324-5p expression were increased, while circ_0008365 was downregulated in OA patients. IL-1ß treatment-induced cell apoptosis, inflammation and extracellular matrix (ECM) degradation in chondrocytes. Besides, circ_0008365 overexpression partly relieved IL-1ß-induced cell damage in chondrocytes. Circ_0008365 could interact with miR-324-5p, and BMPR2 was a downstream target of miR-324-5p. Overexpression of miR-324-5p or BMPR2 knockdown partly overturned the inhibiting effect of circ_0008365 on cell damage in IL-1ß-induced chondrocytes. In addition, circ_0008365 inactivated NF-κB pathway via regulating miR-324-5p/BMPR2 axis. CONCLUSION: Circ_0008365 reduced IL-1ß-induced cell damage in chondrocytes via inactivating NF-κB signaling pathway and regulating miR-324-5p/BMPR2 axis.Abbreviations OA: osteoarthritis; BMPR2: bone morphogenetic protein type 2 receptor.

Exosomal mir-625-3p derived from hypoxic lung cancer cells facilitates metastasis by targeting SCAI.

BACKGROUND: Tumor hypoxia is a feature of tumor micro-environment (TME), which provides a suitable environment for tumor cells migration and invasion. However, up to now, the function of exosomes derived from hypoxic tumor cells is still not fully understood. The present study is aimed to explore the underlying mechanisms of lung cancer-secreted exosomes-mediated tumor metastasis under hypoxia. METHODS & RESULTS: Exosomes were isolated from normoxic or hypoxic NCI-H446 cells. Some characteristic proteins were detected by western blots. Levels of CD63, CD 9 and CD 81 proteins were up-regulated on the membrane of exosomes secreted by hypoxic NCI-H446 cells. Basing on the results from miRNA sequencing, qRT-PCR and wound healing assay, hsa-miR-625-3p was discovered to be accumulated inside hypoxic exosomes and responsible for the metastasis of lung cancer cell. Further experiments from luciferase reporter gene assay demonstrated hsa-miR-625-3p could directly inhibit SCAI expression through binding with its 3'UTR, which suggested the mechanisms by which exosomal hsa-miR-625-3p suppressed tumor cells migration. CONCLUSIONS: Exosomal miR-625-3p derived from hypoxic small lung cancer cells accelerated tumor cells migration through inhibiting SCAI directly.

Ultranarrow spectral line of the radiation in double qubit-cavity ultrastrong coupling system.

The ultrastrongly coupling (USC) system has very important research significance in quantum simulation and quantum computing. In this paper, the ultranarrow spectrum of a circuit QED system with two qubits ultrastrongly coupled to a single-mode cavity is studied. In the regime of USC, the JC model breaks down and the counter-rotating terms in the quantum Rabi Hamiltonian leads to the level anti-crossing in the energy spectrum. Choosing a single-photon driving field at the point of avoided-level crossing, we can get an equivalent four-level dressed state model, in which the dissipation of the two intermediate states is only related to the qubits decay. Due to the electron shelving of these two metastable states, a narrow peak appears in the cavity emission spectrum. Furthermore, we find that the physical origin for the spectral narrowing is the vacuum-induced quantum interference between two transition pathways. And this interference effect couples the slowly decaying incoherent components of the density matrix into the equations of the sidebands. This result provides a possibility for the study of quantum interference effect in the USC system.

ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations.

ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake. In keeping with this, both proteins bind to AP-2 complex components as well as to clathrin, suggesting roles in endocytosis and vesicle recycling. The two proteins play complementary roles in the DDR; ATM is engaged in the repair of double-strand breaks, while ATR deals mainly with single-strand damage. Unexpectedly, this complementarity extends to these proteins' synaptic function as well. Superresolution microscopy and coimmunoprecipitation reveal that ATM associates exclusively with excitatory (VGLUT1+) vesicles, while ATR associates only with inhibitory (VGAT+) vesicles. The levels of ATM and ATR respond to each other; when ATM is deficient, ATR levels rise, and vice versa. Finally, blocking NMDA, but not GABA, receptors causes ATM levels to rise while ATR levels respond to GABA, but not NMDA, receptor blockade. Taken together, our data suggest that ATM and ATR are part of the cellular "infrastructure" that maintains the excitatory/inhibitory balance of the nervous system. This idea has important implications for the human diseases resulting from their genetic deficiency.

Portable Device Improves the Detection of Atrial Fibrillation After Ablation.

Asymptomatic recurrences of atrial fibrillation (AF) have been found to be common after ablation.A randomized controlled trial of AF screening using a handheld single-lead ECG monitor (BigThumb®) or a traditional follow-up strategy was conducted in patients with non-valvular AF after catheter ablation. Consecutive patients were randomized to either BigThumb Group (BT Group) or Traditional Follow-up Group (TF Group). The ECGs collected via BigThumb were compared using the automated AF detection algorithm, artificial intelligence (AI) algorithm, and cardiologists' manual review. Subsequent changes in adherence to oral anticoagulation of patients were also recorded. In this study, we examined 218 patients (109 in each group). After a follow-up of 345.4 ± 60.2 days, AF-free survival rate was 64.2% in BT Group and 78.9% in TF Group (P = 0.0163), with more adherence to oral anticoagulation in BT Group (P = 0.0052). The participants in the BT Group recorded 26133 ECGs, among which 3299 (12.6%) were diagnosed as AF by cardiologists' manual review. The sensitivity and specificity of the AI algorithm were 94.4% and 98.5% respectively, which are significantly higher than the automated AF detection algorithm (90.7% and 96.2%).As per our findings, it was determined that follow-up after AF ablation using BigThumb leads to a more frequent detection of AF recurrence and more adherence to oral anticoagulation. AI algorithm improves the accuracy of ECG diagnosis and has the potential to reduce the manual review.

High Risk of Influenza Virus Infection Among Swine Workers: Examining a Dynamic Cohort in China.

BACKGROUND: China is thought to be a hotspot for zoonotic influenza virus emergence, yet there have been few prospective studies examining the occupational risks of such infections. METHODS: We present the first 2 years of data collected from a 5-year, prospective, cohort study of swine-exposed and -unexposed participants at 6 swine farms in China. We conducted serological and virological surveillance to examine evidence for swine influenza A virus infection in humans. RESULTS: Of the 658 participants (521 swine-exposed and 137 swine-unexposed), 207 (31.5%) seroconverted against at least 1 swine influenza virus subtype (swine H1N1 or H3N2). Swine-exposed participants' microneutralization titers, especially those enrolled at confined animal feeding operations (CAFOs), were higher against the swine H1N1 virus than were other participants at 12 and 24 months. Despite elevated titers, among the 187 study subjects for whom we had complete follow-up, participants working at swine CAFOs had significantly greater odds of seroconverting against both the swine H1N1 (odds ratio [OR] 19.16, 95% confidence interval [CI] 3.55-358.65) and swine H3N2 (OR 2.97, 95% CI 1.16-8.01) viruses, compared to unexposed and non-CAFO swine workers with less intense swine exposure. CONCLUSIONS: While some of the observed increased risk against swine viruses may have been explained by exposure to human influenza strains, study data suggest that even with elevated preexisting antibodies, swine-exposed workers were at high risk of infection with enzootic swine influenza A viruses.