Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches.

Neurodegenerative disorders, particularly Alzheimer's and Parkinson's diseases, continue to challenge modern medicine despite therapeutic advances. Orphan G-protein-coupled receptors (GPCRs) have emerged as promising targets in the central nervous system, offering new avenues for drug development. This review focuses on the structural biology of orphan GPCRs implicated in these disorders, providing a comprehensive analysis of their molecular architecture and functional mechanisms. We examine recent breakthroughs in structural determination techniques, such as cryo-electron microscopy and X-ray crystallography, which have elucidated the intricate conformations of these receptors. The review highlights how structural insights inform our understanding of orphan GPCR activation, ligand binding and signaling pathways. By integrating structural data with molecular pharmacology, we explore the potential of structure-guided approaches in developing targeted therapeutics toward orphan GPCRs. This structural-biology-centered perspective aims to deepen our comprehension of orphan GPCRs and guide future drug discovery efforts in neurodegenerative disorders.

A Versatile Redox-Active Electrolyte for Solid Fixation of Polyiodide and Dendrite-Free Operation in Sustainable Aqueous Zinc-Iodine Batteries.

Practical utilization of zinc-iodine (Zn-I2) batteries is hindered by significant challenges, primarily stemming from the polyiodide shuttle effect on the cathode and dendrite growth on the anode. Herein, a feasible redox-active electrolyte has been introduced with tetraethylammonium iodide as an additive that simultaneously addresses the above mentioned challenges via polyiodide solidification on the cathode and the electrostatic shielding effect on the anode. The tetraethylammonium (TEA+) captures water-soluble polyiodide intermediates (I3 -, I5 -), forming a solid complex at the cathode, thereby suppressing capacity loss during charge/discharge. Furthermore, the TEA+ mitigates dendrite growth on the Zn anode via the electrostatic shielding effect, promoting uniform and compact Zn deposition at the anode. Consequently, the Zn||Zn symmetric cell demonstrates superior cycling stability during Zn plating/stripping over 4,200 h at 1 mA cm-2 and 1 mAh cm-2. The Zn||NiNC full-cell exhibits a stable capacity retention of 98.4% after 20 000 cycles (>5 months) with near-unity Coulombic efficiency at 1 A g-1. The study provides novel insights for establishing a new direction for low-cost, sustainable, and long-lifespan Zn-I2 batteries.

Use of cortical hemodynamic responses in digital therapeutics for upper limb rehabilitation in patients with stroke.

BACKGROUND: Stroke causes long-term disabilities, highlighting the need for innovative rehabilitation strategies for reducing residual impairments. This study explored the potential of functional near-infrared spectroscopy (fNIRS) for monitoring cortical activation during rehabilitation using digital therapeutics. METHODS: This cross-sectional study included 18 patients with chronic stroke, of whom 13 were men. The mean age of the patients was 67.0 ± 7.1 years. Motor function was evaluated through various tests, including the Fugl-Meyer assessment for upper extremity (FMA-UE), grip and pinch strength test, and box and block test. All the patients completed the digital rehabilitation program (MotoCog®, Cybermedic Co., Ltd., Republic of Korea) while being monitored using fNIRS (NIRScout®, NIRx Inc., Germany). Statistical parametric mapping (SPM) was employed to analyze the cortical activation patterns from the fNIRS data. Furthermore, the K-nearest neighbor (K-NN) algorithm was used to analyze task performance and fNIRS data to classify the severity of motor impairment. RESULTS: The participants showed diverse task performances in the digital rehabilitation program, demonstrating distinct patterns of cortical activation that correlated with different motor function levels. Significant activation was observed in the ipsilesional primary motor area (M1), primary somatosensory area (S1), and contralateral prefrontal cortex. The activation patterns varied according to the FMA-UE scores. Positive correlations were observed between the FMA-UE scores and SPM t-values in the ipsilesional M1, whereas negative correlations were observed in the ipsilesional S1, frontal lobe, and parietal lobe. The incorporation of cortical hemodynamic responses with task scores in a digital rehabilitation program substantially improves the accuracy of the K-NN algorithm in classifying upper limb functional levels in patients with stroke. The accuracy for tasks, such as the gas stove-operation task, increased from 44.4% using only task scores to 83.3% when these scores were combined with oxy-Hb t-values from the ipsilesional M1. CONCLUSIONS: The results advocated the development of tailored digital rehabilitation strategies by combining the behavioral and cerebral hemodynamic data of patients with stroke. This approach aligns with the evolving paradigm of personalized rehabilitation in stroke recovery, highlighting the need for further extensive research to optimize rehabilitation outcomes.

Biophysical and functional characterization of Norrin signaling through Frizzled4.

Wnt signaling is initiated by Wnt ligand binding to the extracellular ligand binding domain, called the cysteine-rich domain (CRD), of a Frizzled (Fzd) receptor. Norrin, an atypical Fzd ligand, specifically interacts with Fzd4 to activate ß-catenin-dependent canonical Wnt signaling. Much of the molecular basis that confers Norrin selectivity in binding to Fzd4 was revealed through the structural study of the Fzd4CRD-Norrin complex. However, how the ligand interaction, seemingly localized at the CRD, is transmitted across full-length Fzd4 to the cytoplasm remains largely unknown. Here, we show that a flexible linker domain, which connects the CRD to the transmembrane domain, plays an important role in Norrin signaling. The linker domain directly contributes to the high-affinity interaction between Fzd4 and Norrin as shown by ∼10-fold higher binding affinity of Fzd4CRD to Norrin in the presence of the linker. Swapping the Fzd4 linker with the Fzd5 linker resulted in the loss of Norrin signaling, suggesting the importance of the linker in ligand-specific cellular response. In addition, structural dynamics of Fzd4 associated with Norrin binding investigated by hydrogen/deuterium exchange MS revealed Norrin-induced conformational changes on the linker domain and the intracellular loop 3 (ICL3) region of Fzd4. Cell-based functional assays showed that linker deletion, L430A and L433A mutations at ICL3, and C-terminal tail truncation displayed reduced ß-catenin-dependent signaling activity, indicating the functional significance of these sites. Together, our results provide functional and biochemical dissection of Fzd4 in Norrin signaling.

Schlieren-style stroboscopic nonscan imaging of the field-amplitudes of acoustic whispering gallery modes.

We report a schlieren-style stroboscopic phase-contrast field-amplitude imaging of two-dimensional acoustic whispering gallery modes in a circular shell cavity immersed in liquid. A schlieren signal is combined with a presplit reference beam to enable nonscan field-amplitude imaging. Excitation mechanisms of standing and traveling eigenmodes, respectively, are analyzed with acoustic ray simulations presented in a Poincaré surface of sections. The time evolutions for both standing and traveling eigenmodes are reconstructed using the stroboscopic capability.

SAW Chemical Array Device Coated with Polymeric Sensing Materials for the Detection of Nerve Agents.

G nerve agents are colorless, odorless, and lethal chemical warfare agents (CWAs). The threat of CWAs, which cause critical damage to humans, continues to exist, e.g., in warfare or terrorist attacks. Therefore, it is important to be able to detect these agents rapidly and with a high degree of sensitivity. In this study, a surface acoustic wave (SAW) array device with three SAW sensors coated with different sensing materials and one uncoated sensor was tested to determine the most suitable material for the detection of nerve agents and related simulants. The three materials used were polyhedral oligomeric silsesquioxane (POSS), 1-benzyl-3-phenylthiourea (TU-1), and 1-ethyl-3-(4-fluorobenzyl) thiourea (TU-2). The SAW sensor coated with the POSS-based polymer showed the highest sensitivity and the fastest response time at concentrations below the median lethal concentration (LCt50) for tabun (GA) and sarin (GB). Also, it maintained good performance over the 180 days of exposure tests for dimethyl methylphosphonate (DMMP). A comparison of the sensitivities of analyte vapors also confirmed that the sensitivity for DMMP was similar to that for GB. Considering that DMMP is a simulant which physically and chemically resembles GB, the sensitivity to a real agent of the sensor coated with POSS could be predicted. Therefore, POSS, which has strong hydrogen bond acid properties and which showed similar reaction characteristics between the simulant and the nerve agent, can be considered a suitable material for nerve agent detection.

Design of Reconfigurable Time-to-Digital Converter Based on Cascaded Time Interpolators for Electrical Impedance Spectroscopy.

This paper presents a reconfigurable time-to-digital converter (TDC) used to quantize the phase of the impedance in electrical impedance spectroscopy (EIS). The TDC in the EIS system must handle a wide input-time range for analysis in the low-frequency range and have a high resolution for analysis in the high-frequency range. The proposed TDC adopts a coarse counter to support a wide input-time range and cascaded time interpolators to improve the time resolution in the high-frequency analysis without increasing the counting clock speed. When the same large interpolation factor is adopted, the cascaded time interpolators have shorter measurement time and smaller chip area than a single-stage time interpolator. A reconfigurable time interpolation factor is adopted to maintain the phase resolution with reasonable measurement time. The fabricated TDC has a peak-to-peak phase error of less than 0.72° over the input frequency range from 1 kHz to 512 kHz and the phase error of less than 2.70° when the range is extended to 2.048 MHz, which demonstrates a competitive performance when compared with previously reported designs.

Comparison of orbicularis oris muscle strength and endurance in young and elderly adults.

[Purpose] The purpose of this study was to compare the strength and endurance of the orbicularis oris muscle in healthy Korean (young vs. elderly adults). [Participants and Methods] A total of 60 participants (30 young adults and 30 elderly adults) were recruited. The Iowa Oral Performance Instrument was used to measure orbicularis oris muscle maximal strength and endurance. [Results] Elderly adults showed significantly lower orbicularis oris muscle strength and endurance than younger adults. [Conclusion] This study confirmed a significant age-related decrease in orbicularis oris muscle strength and endurance. The data collected will be useful as a basis for future on speech and swallowing therapy.

Oropharyngeal swallowing function in patients with presbyphagia.

[Purpose] This study investigated the characteristics of oropharyngeal swallowing function in patients with presbyphagia. [Participants and Methods] Data for 25 patients with presbyphagia were retrospectively analyzed. The oropharyngeal swallowing function was evaluated using VDS based on videofluoroscopic swallowing study. [Results] Lip closure, mastication, laryngeal elevation, and aspiration showed a relative decrease in function. [Conclusion] This study showed a reduction in oropharyngeal swallowing in patients with presbyphagia. Our results may help in the diagnosis and treatment of presbyphagia.

Analysis of the incidence and risk factors for the progression of proximal junctional kyphosis following surgical treatment for lumbar degenerative kyphosis: minimum 2-year follow-up.

BACKGROUND CONTEXT. Proximal junctional kyphosis (PJK) following surgical treatment of lumbar degenerative kyphosis (LDK) is one of the critical complications leading to the failure of instrumentation and additional extensive surgery. However, most previous studies have focused on idiopathic scoliosis resulting from variable surgical techniques. LDK usually differ from other scoliotic deformities in terms of patient characteristics and disease mechanisms. PURPOSE. Identification of the prevalence of PJK after the surgical treatment of LDK and searching for the predictable value for the progression of PJK. Study design. Retrospective comparative study. Patient sample (must be included in clinical studies). Forty-seven consecutive patients who underwent surgical correction of a sagittal imbalance due to LDK, from January 2005 to December 2008 in a single spine clinic, were evaluated with a minimum 2 years follow-up (mean 3.8 years). METHODS. Patients were divided into 2 groups: with or without the occurrence of PJK, and three categorized factors according to patient characteristics, surgical variables, and the radiographic spinopelvic parameters were evaluated. RESULTS. PJK had occurred in 29 of 47 patients (61.7%). Among variable factors, old age, upper-instrumented vertebra below L2, lumbar lordosis to PI ratio, and the sum of lumbar lordosis, and the sacral slope related to PI were found to be statistically significant. CONCLUSIONS. The overall incidence of PJK following surgical treatment of LDK patients was higher than expected. Spinal biomechanics may be changed after long instrumented fusion surgery. Thorough consideration of these factors is needed in the treatment strategy of LDK patients. A long-term follow-up study should be conducted.

Frequency pushing enhanced by an exceptional point in an atom-cavity coupled system.

We observed the frequency pushing of the cavity resonance as a result of the coupling of the cavity field with the ground state 138Ba in a high-Q cavity. A weak probe laser propagated along the axis of a Fabry-Pérot cavity while ground-state barium atoms traversed the cavity mode perpendicularly. By operating the atom-cavity composite in the vicinity of an exceptional point, we could observe a greatly enhanced frequency shift of the cavity transmission peak, which was pushed away from the atomic resonance, resulting in up to 41 ± 7 kHz frequency shift per atom from the empty cavity resonance. We analyzed our results by using the Maxwell-Schrödinger equation and obtained good agreement with the measurements.

Thresholdless coherence in a superradiant laser.

Lasing threshold in the conventional lasers is the minimum input power required to initiate laser oscillation. It has been widely accepted that the conventional laser threshold occurring around a unity intracavity photon number can be eliminated in the input-output curve by making the so-called ß parameter approach unity. The recent experiments, however, have revealed that even in this case the photon statistics still undergo a transition from coherent to thermal statistics when the intracavity mean photon number is decreased below unity. Since the coherent output is only available above the diminished threshold, the long-sought promise of thresholdless lasers to produce always coherent light has become questionable. Here, we present an always-coherent thresholdless laser based on superradiance by two-level atoms in a quantum superposition state with the same phase traversing a high-Q cavity. Superradiant lasing was observed without the conventional lasing threshold around the unity photon number and the photon statistics remained near coherent even below it. The coherence was improved by reducing the coupling constant as well as the excited-state amplitude in the superposition state. Our results pave a way toward always-coherent thresholdless lasers with more practical media such as quantum dots, nitrogen-vacancy centers and doped ions in crystals.

Toward maximum energy density enabled by anode-free lithium metal batteries: Recent progress and perspective.

Owing to the emergenceof energy storage and electric vehicles, the desire for safe high-energy-density energy storage devices has increased research interest in anode-free lithium metal batteries (AFLMBs). Unlike general lithium metal batteries (LMBs), in which excess Li exists to compensate for the irreversible loss of Li, only the current collector is employed as an anode and paired with a lithiated cathode in the fabrication of AFLMBs. Owing to their unique cell configuration, AFLMBs have attractive characteristics, including the highest energy density, safety, and cost-effectiveness. However, developing AFLMBs with extended cyclability remains an issue for practical applications because the high reactivity of Li with limited inventory causes severely low Coulombic efficiency (CE), poor cyclability, and dendrite growth. To address these issues, tremendous effort has been devoted to stabilizing Li metal anodes for AFLMBs. In this review, the importance and challenges of AFLMBs are highlighted. Then, diverse strategies, such as current collectors modification, advanced electrolytes, cathode engineering, and operation protocols are thoroughly reviewed. Finally, a future perspective on the strategy is provided for insight into the basis of future research. It is hoped that this review provides a comprehensive understanding by reviewing previous research and arousing more interest in this field.

Effect of Bone Marrow Stimulation on Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis.

Background: Arthroscopic rotator cuff repair (RCR) is a common orthopaedic procedure, but it has a high rate of retears that can negatively affect the functional outcomes. Bone marrow stimulation (BMS) has been suggested as an additional treatment to improve the outcomes of RCR. Purpose: To compare the effectiveness of the BMS procedure during RCR with conventional RCR. Study Design: Systematic review; Level of evidence, 2. Methods: A systematic literature search was conducted in MEDLINE/PubMed, Embase, Cochrane Library, and Scopus, on March 1, 2023, for studies comparing postoperative retear rates and functional outcomes between patients who underwent primary arthroscopic RCR with and without the BMS procedure. Only level 1 and 2 randomized controlled trials with a minimum 12-month follow-up were included. The primary outcomes were retear rates and functional outcomes as measured by the Constant; American Shoulder and Elbow Surgeons (ASES); and University of California, Los Angeles (UCLA) scores and by postoperative range of motion. Subgroup analyses were performed based on repair technique (single-row repair vs double-row or suture-bridge repair). The standardized mean difference (SMD) and odds ratio (OR) were utilized to synthesize continuous and dichotomous outcomes, respectively. Homogeneity was evaluated using the chi-square test and I2 statistic. Results: The literature search yielded 661 articles, of which 6 studies (522 patients; 261 with BMS, 261 without BMS) met the eligibility criteria. The combined analysis showed no significant decrease in retear rates with the utilization of the BMS procedure during RCR (OR, 0.60; 95% CI, 0.35 to 1.03; P = .07; I2 = 24%). There was no significant intergroup difference in functional outcomes (Constant score: SMD, 0.13; 95% CI, -0.04 to 0.31; P = .13; I2 = 0%; ASES score: SMD, 0.04; 95% CI, -0.20 to 0.28; P = .73; I2 = 0%; UCLA score: SMD, -0.13; 95% CI, -0.50 to 0.23; P = .47; I2 = 0%). Subgroup analyses revealed no significant differences in postoperative retear risk or total Constant score according to the repair technique. Conclusion: Based on the available evidence, this systematic review did not find a significant benefit of the BMS procedure at the footprint during arthroscopic RCR compared with conventional RCR in terms of retear rates and functional outcomes at short-term follow-up.

Effect of Programed Walking Exercise Using Bot Fit in Younger Adults.

INTRODUCTION: Physical inactivity and sedentary behavior both increase the risk of chronic disease and mortality. Regular participation in physical activity and reducing sedentary behavior play important roles in maintaining physical health and disease prevention. OBJECTIVE: The purpose of this study was to investigate the effect of programed walking exercise using a wearable hip exoskeleton, Bot Fit on muscle strength, muscle effort, and the kinematics of the pelvis in younger adults. METHODS: We designed three parallel experimental conditions and randomly assigned participants to one of three groups: those assigned to exercise using an interval program of Bot Fit (interval group), those who used a power program of Bot Fit (power group), and a control group who exercised without Bot Fit. A total of 45 young adults participated in 18 exercise-intervention sessions over six weeks, and all participants were assessed at two time points: before and after the 18 exercise sessions. Each assessment evaluated muscle strength, muscle effort, and the kinematics of the pelvis during walking. In addition, the number of steps, distance, energy expenditure, and heart rate for 30 min during the exercise sessions were recorded. RESULTS: A significant increase in the maximum voluntary contraction (MVC) of the left biceps femoris (BF) was evident in the interval group, while significant changes in the MVC of the bilateral BF were seen in the power group after Bot Fit exercise. A significant decrease of muscle effort in the right BF in the interval group and right lumbar erector spinae and bilateral BF in the power group were also observed. In addition, the symmetry index of pelvic tilt significantly improved in the interval group, and greater exercise volume and intensity in both the interval and power groups compared with the control group were confirmed as measured by the number of steps, distance, energy expenditure, and heart rate. CONCLUSIONS: The results of this study confirmed the beneficial effect of programed walking exercise using the Bot Fit on muscle strength of trunk and lower extremities, muscle effort, and pelvic movement symmetry in younger adults. Personalized exercise programs can be provided for younger adults using various resistance or assistance modes of robotic device with the Bot Fit. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05862077. Registered 22 March 2022, https://register. CLINICALTRIALS: gov/ .

Anisotropic lens-shaped mesoporous carbon from interfacially perpendicular self-assembly for potassium-ion batteries.

Anisotropic lens-shaped nitrogen-doped carbon (Lens-NMC) with unidirectionally aligned mesopores was achieved via perpendicular block copolymer self-assembly at the polymer interface. Lens-NMC is applied as a potassium-ion battery anode material as a next-generation battery system.

A Complete Facet Resection and Cervical Pedicle Screw Placement Enhances Both Gross Total Resection and Motion Preservation for the Cervical Spinal Dumbbell Tumor.

OBJECTIVE: To describe single-index-level fusion surgery using a cervical pedicle screw (CPS) after the complete facet resection of spinal dumbbell tumors and to compare it with partial facet resection without fusion. METHODS: We retrospectively reviewed patients who underwent surgery for dumbbell-shaped cervical spine tumors. They were categorized into the fused group (complete facet resection with fusion using CPS) and the unfused group (partial facet resection without fusion). We compared demographics, tumor characteristics, resection rates (gross total, subtotal, or partial), and regrowth rates between the groups. Complete facet resection was performed for maximal tumor removal. In the fused group, single-index-level fusion was achieved using CPS. Despite tumor-associated erosion of the index vertebra's pedicle and/or lateral mass, the CPS was directly inserted into the vertebral body through an imaginary virtual pedicle without a lateral mass or pedicle purchase. RESULTS: A total of 34 patients underwent surgery for dumbbell-shaped cervical tumors; half were classified into each group. There were no significant differences in demographic or tumor characteristics, including Asazuma classification, or histological diagnosis (P > 0.05). However, the gross total resection rate was significantly higher in the fused group (16/17, 94.1% vs. 9/17, 52.9%; P value = 0.011). Tumor recurrence was observed in 3 (17.6%) patients in the unfused group; no recurrence (0%) occurred in the fused group. CONCLUSIONS: Complete facet resection with fusion using CPS significantly increased the gross total tumor removal rate, compared with partial resection without fusion. Therefore, CPS improved fusion surgery for maximal motion preservation, resulting in single-level fusion surgery.

Human cytomegalovirus harnesses host L1 retrotransposon for efficient replication.

Genetic parasites, including viruses and transposons, exploit components from the host for their own replication. However, little is known about virus-transposon interactions within host cells. Here, we discover a strategy where human cytomegalovirus (HCMV) hijacks L1 retrotransposon encoded protein during its replication cycle. HCMV infection upregulates L1 expression by enhancing both the expression of L1-activating transcription factors, YY1 and RUNX3, and the chromatin accessibility of L1 promoter regions. Increased L1 expression, in turn, promotes HCMV replicative fitness. Affinity proteomics reveals UL44, HCMV DNA polymerase subunit, as the most abundant viral binding protein of the L1 ribonucleoprotein (RNP) complex. UL44 directly interacts with L1 ORF2p, inducing DNA damage responses in replicating HCMV compartments. While increased L1-induced mutagenesis is not observed in HCMV for genetic adaptation, the interplay between UL44 and ORF2p accelerates viral DNA replication by alleviating replication stress. Our findings shed light on how HCMV exploits host retrotransposons for enhanced viral fitness.

Alterations in cognitive function and blood biomarkers following transcranial direct current stimulation in patients with amyloid positron emission tomography-positive Alzheimer's disease: a preliminary study.

Introduction: Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive cognitive decline. To address this, we conducted a randomized, double-blinded, sham-controlled study to investigate the therapeutic potential of transcranial direct current stimulation (tDCS) on patients with amyloid positron emission tomography (PET)- positive AD. Methods: Participants already undergoing pharmacological treatment and testing positive for amyloid PET were divided into Active-tDCS (n = 8) and Sham-tDCS (n = 8) groups. For 12 weeks, participants or their caregivers administered daily bi-frontal tDCS (YMS-201B+, Ybrain Inc., Seongnam, Korea) at home (2 mA, 30 min). Pre- and post-intervention assessments included neuropsychological tests and blood sample measurements for oligomerized beta-amyloid. Results: The Active-tDCS group demonstrated significant improvements in cognitive domains such as language abilities, verbal memory, and attention span and in frontal lobe functions compared to the Sham-tDCS group. Furthermore, the Active-tDCS group showed a marked reduction in post-intervention plasma Aß oligomerization tendency level, suggesting changes in pivotal AD-associated biomarkers. Discussion: Our results emphasize the potential therapeutic benefits of tDCS for mild AD patients with amyloid PET positivity and stress the urgency for broader research, considering the global challenges of dementia and the need to pursue innovative therapeutic strategies.

Impact of Chronic Obstructive Pulmonary Disease on Outcomes After Total Joint Arthroplasty: A Meta-analysis and Systematic Review.

Background: Comorbid chronic obstructive pulmonary disease (COPD) is increasingly common and may have an adverse impact on outcomes in patients undergoing total joint arthroplasty (TJA) of lower extremity. The purpose of this meta-analysis is to compare the postoperative complications between COPD and non-COPD patients undergoing primary TJA including total hip and knee arthroplasty. Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for relevant studies published before December 2021. Postoperative outcomes were compared between patients with COPD versus those without COPD as controls. The outcomes were mortality, re-admission, pulmonary, cardiac, renal, thromboembolic complications, surgical site infection (SSI), periprosthetic joint infection (PJI), and sepsis. Results: A total of 1,002,779 patients from nine studies were finally included in this meta-analysis. Patients with COPD had an increased risk of mortality (OR [odds ratio] = 1.69, 95% confidence interval [CI] 1.42-2.02), re-admission (OR = 1.54, 95% CI 1.38-1.71), pulmonary complications (OR = 2.73, 95% CI 2.26-3.30), cardiac complications (OR = 1.40, 95% CI 1.15-1.69), thromboembolic complications (OR = 1.21, 95% CI 1.15-1.28), renal complications (OR = 1.50, 95% CI 1.14-1.26), SSI (OR = 1.23, 95% CI 1.18-1.30), PJI (OR = 1.26, 95% CI 1.15-1.38), and sepsis (OR = 1.36, 95% CI 1.22-1.52). Conclusion: Patients with comorbid COPD showed an increased risk of mortality and postoperative complications following TJA compared with patients without COPD. Therefore, orthopedic surgeons can use the study to adequately educate these potential complications when obtaining informed consent. Furthermore, preoperative evaluation and medical optimization are crucial to minimizing postoperative complications from arising in this difficult-to-treat population. Level of evidence: Level III. Registration: None. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00794-2.