Peptide ligands for the affinity purification of adenovirus from HEK293 and vero cell lysates.

Adenovirus (AdVs) is the viral vector of choice in vaccines and oncolytic applications owing to its high transduction activity and inherent immunogenicity. For decades, AdV isolation has relied on ultracentrifugation and ion-exchange chromatography, which are not suitable to large-scale production and struggle to deliver sufficient purity. Immunoaffinity chromatography resins of recent introduction feature high binding capacity and selectivity, but mandate harsh elution conditions (pH 3.0), afford low yield (< 20%), and provide limited reusability. Seeking a more efficient and affordable alternative, this study introduces the first peptide affinity ligands for AdV purification. The peptides were identified via combinatorial selection and in silico design to target hexons, the most abundant proteins in the adenoviral capsid. Selected peptide ligands AEFFIWNA and TNDGPDYSSPLTGSG were conjugated on chromatographic resins and utilized to purify AdV serotype 5 from HEK293 and Vero cell lysates. The peptide-functionalized resins feature high binding capacity (> 1010 active virions per mL at the residence time of 2 min), provide high yield (> 50%) and up to 100-fold reduction of host cell proteins and DNA. Notably, the peptide ligands enable gentle elution conditions (pH 8) that prevent the "shedding" of penton and fiber proteins, thus affording intact adenovirus particles with high cell-transduction activity. The study of the peptide ligands by surface plasmon resonance and molecular docking and dynamics simulations confirmed the selective targeting of hexon proteins and elucidated the molecular-level mechanisms underlying binding and release. Collectively, these results demonstrate the strong promise of peptide ligands presented herein for the affinity purification of AdVs from cell lysates.

Intra-osteal fixation of comminuted coronoid process fracture with mini plate for the treatment of complex elbow fracture.

Complex elbow fractures featuring a comminuted coronoid process are infrequent and pose considerable treatment challenges. The optimal strategy for maximizing recovery of elbow function through osteosynthesis remains a subject of ongoing debate among surgeons. We applied the principle of internal fixation by implementing intra-osteal fixation with a mini plate, which facilitated the successful restoration of exceptional elbow function in the patient. This approach adeptly managed the complexity of the coronoid process fracture, encompassing its fragmentation and associated injuries, thereby demonstrating its feasibility and efficacy in achieving favorable clinical outcomes. This article investigates the viability of this surgical technique for managing such complex fractures.

Intestinal epithelial vitamin D receptor defense against inflammatory bowel disease via regulating microfold cells.

Vitamin D receptor (VDR) is involved in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism of VDR in IBD is still unclear. Microfold cells (M cells) mediated antigen-sampling pathway is central in developing immune responses to pathogenic and commensal bacteria and related to IBD. We found that Intestinal epithelial cell-specific knockdown of VDR(VDRIEC-KO) increases the susceptibility of mice to experimental colitis induced by sodium dextran sulfate(DSS) by producing more M cells. Knockdown VDR in intestinal epithelial cells increased RANKL-induced microfold cells and promoted the ability of microfold cells to uptake S. Typhimurium (S. T.). Mechanistically, we demonstrated that knockdown VDR promoted the differentiation and maturation of M cells via the Spi-B-dependent pathway. We conclude that M cells may be a potential target of VDR for treating intestinal mucosal barrier dysfunction in IBD.

Facile fabrication of a thermal/pH responsive IPN hydrogel drug carrier based on cellulose and chitosan through simultaneous dual-click strategy.

Herein, an interpenetrating network hydrogel (IPN-Gel) based on cellulose and chitosan was synthesized via simultaneous amino-anhydride and azide-alkyne click reaction in water in one pot. The samples were characterized by various analytical methods including FTIR, SEM, XRD, XPS, 1H NMR and so forth. The fabrication conditions were optimized by single factor experiments with water uptake (WU) and gel mass fraction (GMF) as two indexes. The WU and GMF of the IPN-Gel prepared under optimized conditions were 1192.37 % and 74.00 %, respectively. Its WU descended with the ascension in temperature, and first descended and then gradually ascended with the ascension in pH, confirming that the IPN-Gel had thermal/pH dual responsiveness. Using 5-Fu as a model drug, the release behavior of 5-Fu in IPN-Gel was explored. Its release behavior could be regulated by changing temperature and pH values, and it followed the Korsmeyer Peppas model. The viability of 4 T1 cells and HUVEC cells exceeded 80 % after 48 h of incubation at a high concentration of 200 µg/mL IPN-Gel, and hemolytic percentage was below the allowed limit of 5 %. The study provides a new strategy for the preparation of the IPN-Gel with biocompatibility, swelling reversibility and controllable drug release.

Perspectives on phase engineering of nanomaterials.

This perspective highlights the representative progress of phase engineering of nanomaterials (PEN) with an emphasis on noble metals and transition metal dichalcogenides, and proposes future directions in this emerging field.

Extracellular vesicle-derived miR-146a as a novel crosstalk mechanism for high-fat induced atherosclerosis by targeting SMAD4.

INTRODUCTION: Exosome-miR-146a is significantly increased in patients with Atherosclerosis (AS), but its mechanism and effect on AS have not been fully elucidated. OBJECTIVES: To explore the change rule and mechanism of exosomes release, and the role and molecular mechanism of exosome-miR-146a in AS. METHODS: We isolated and identified exosomes from THP-1 macrophages after treating them with ox-LDL. Then used co-immunoprecipitation and silver staining to identify the proteins involved in regulating exosome release. PKH67 was used to label exosomes to confirm that cells can absorb them, and then co-culture with HVSMCs for cell proliferation and migration detection. The target genes of miR-146a were screened and identified through bioinformatics and luciferase activity assay, and the expression of miR-146a and related proteins was detected through qRT-PCR and Western blot in HUVECs. An AS model in LDLR-/- mice induced by a high-fat diet was developed to investigate the impact of exosome-miR-146a on AS. RESULTS: The results showed that experimental foam cells from AS showed higher expression of miR-146a. It was observed that NMMHC IIA and HSP70 interacted to regulate the release of exosomes. And HUVECs can absorb exosomes derived from macrophages. In addition, we also found that miR-146a directly targeted the SMAD4 gene to modulate the p38 MAPK signaling pathway, thereby mediating HUVECs damage. Furthermore, exosome-miR-146a induced abnormal proliferation and migration of HVSMCs. The expression of miR-146a was significantly reduced in miR-146a-mimics mice and increased in miR-146a inhibitor mice whereas the inhibition of miR-146a effectively reduced while increasing miR-146a worsened AS in mice. CONCLUSION: Our findings expressed the potential of miR-146a as a favorable therapeutic target for AS, however, further exploration is suggestive for deep understanding of the mechanisms regulating exosome-miR-146a release in vivo and to develop effective therapeutic strategies involving miR-146a.

Facile preparation of interpenetrating network hydrogel adsorbent from starch- chitosan for effective removal of methylene blue in water.

Hydrogels based on biopolymers have attracted considerable interest in the last decades. Herein, an interpenetrating network hydrogel (IPN-Gel) adsorbent from starch-chitosan was fabricated facilely in one-pot through tandem Schiff base reaction and photopolymerization. First, aldehyde starch (DAS) was synthesized by the reaction of soluble starch with sodium periodate. Afterward, acrylamide (AM), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), polyethylene glycol dimethacrylate (PEGDMA), photoinitiator, chitosan and DAS were dissolved in water to obtain a clear solution. Schiff base reaction between chitosan and DAS took place quickly to form the first network, and then photopolymerization of AM, AMPS, and PEGDMA occurred under ultraviolet radiation to form the second network. The preparation conditions of the as-prepared IPN-Gel were optimized with two indexes of gel mass fraction and swelling ratio. Its swelling behavior with pH and temperature change was explored. Finally, its adsorption performance was characterized with methylene blue (MB) as a model contaminant. The maximum adsorption capacity of IPN-Gel can reach 2039 mg·g-1 at pH =10. Its adsorption performance accords with Langmuir isothermal model and pseudo-second-order kinetic model and it was mainly controlled by chemisorption. This strategy is expected to found broad application prospects in the preparation of hydrogel adsorbents.

A mucosal vaccine formulation against tuberculosis by exploiting the adjuvant activity of S100A4-A damage-associated molecular pattern molecule.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains one of the top three causes of death. Currently, the only licensed vaccine against TB is the bacillus Calmette-Guerin (BCG), which lacks efficacy in preventing and controlling pulmonary TB in adults. We aimed to evaluate a nasal TB vaccine formulation composed of the Mtb-specific vaccine antigen ESAT-6, an Mtb-associated protein that can trigger protective immune responses, and S100A4, a recently characterized novel mucosal adjuvant. Mice were intranasally given recombinant ESAT-6 in the presence or absence of S100A4 as an adjuvant. We have provided experimental evidence demonstrating that S100A4 admixed to ESAT-6 could induce Mtb-specific adaptive immune responses after intranasal immunization. S100A4 remarkably augmented the levels of anti-ESAT-6 IgG in serum and IgA in mucosal sites, including lung exudates, bronchoalveolar lavage fluid (BALF) and nasal lavage. Furthermore, in both lung and spleen tissues, S100A4 strongly promoted ESAT-6-specific expansion of CD4 T cells. Both CD4 and CD8 T cells from these tissues expressed increased levels of IFN-γ, TNF-α, and IL-17, cytokines critical for antimicrobial activity. Antigen-reencounter-induced T cell proliferative responses, a key vaccine performance indicator, were augmented in the spleen of S100A4-adjuvanted mice. Furthermore, CD8 T cells from the spleen and lung tissues of these mice expressed higher levels of granzyme B upon antigen re-stimulation. S100A4-adjuvanted immunization may predict good mucosal protection against TB.

Extracellular vesicles in anti-tumor drug resistance: Mechanisms and therapeutic prospects.

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy. Prior research has illuminated reasons behind drug resistance, including increased drug efflux, alterations in drug targets, and abnormal activation of oncogenic pathways. However, there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment (TME). Recent studies on extracellular vesicles (EVs) have provided valuable insights. EVs are membrane-bound particles secreted by all cells, mediating cell-to-cell communication. They contain functional cargoes like DNA, RNA, lipids, proteins, and metabolites from mother cells, delivered to other cells. Notably, EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs. This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance, covering therapeutic approaches like chemotherapy, targeted therapy, immunotherapy and even radiotherapy. Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance. Additionally, targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance. We highlight the importance of conducting in-depth mechanistic research on EVs, their cargoes, and functional approaches specifically focusing on EV subpopulations. These efforts will significantly advance the development of strategies to overcome drug resistance in anti-tumor therapy.

Healthcare Outcomes of Patients and Antecedents via Teleophthalmology in Eastern Taiwan during COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has caused significant transformations in healthcare. Many countries began the rapid development and adoption of telemedicine to avoid the spread of the pandemic and created an innovative model for healthcare delivery. This study identified the critical antecedents that affected the considered healthcare outcomes via teleophthalmology in Eastern Taiwan during the COVID-19 pandemic. METHODS: This study's participants included residents of five towns in Taitung County who had experience with teleophthalmology. This study analyzed the structured questionnaires completed by the participants to validate the proposed research framework. Statistical methods were used to verify the research models, including descriptive statistical analysis, confirmatory factor analysis, and structural equation modeling. The date of this study was from 1 October 2020 to 31 July 2023. RESULTS: The results of this study reveal that the average monthly use of teleophthalmology by individuals in rural areas increased annually. Females tended to utilize teleophthalmology services more than males. There were no significant differences across any of the constructs with respect to age or educational level. Additionally, the patients' awareness of healthcare accessibility via and the communication quality of teleophthalmology simultaneously affected teleophthalmology's adoption and service quality, which in turn jointly affected health outcomes. Both healthcare accessibility and communication quality were the antecedents of the healthcare outcomes. The health outcomes refer to the impact of teleophthalmology on the quality of the patients' health and well-being. Additionally, teleophthalmology's adoption and service quality acted as mediators. CONCLUSIONS: This study's findings are expected to increase attention to the healthcare outcomes and antecedents of teleophthalmology to promote better telemedicine practices and services for rural residents.

Black holes regulate cool gas accretion in massive galaxies.

The nucleus of almost all massive galaxies contains a supermassive black hole (BH)1. The feedback from the accretion of these BHs is often considered to have crucial roles in establishing the quiescence of massive galaxies2-14, although some recent studies show that even galaxies hosting the most active BHs do not exhibit a reduction in their molecular gas reservoirs or star formation rates15-17. Therefore, the influence of BHs on galaxy star formation remains highly debated and lacks direct evidence. Here, based on a large sample of nearby galaxies with measurements of masses of both BHs and atomic hydrogen (HI), the main component of the interstellar medium18, we show that the HI gas mass to stellar masses ratio (µHI = MHI/M⋆) is more strongly correlated with BH masses (MBH) than with any other galaxy parameters, including stellar mass, stellar mass surface density and bulge masses. Moreover, once the µHI-MBH correlation is considered, µHI loses dependence on other galactic parameters, demonstrating that MBH serves as the primary driver of µHI. These findings provide important evidence for how the accumulated energy from BH accretion regulates the cool gas content in galaxies, by ejecting interstellar medium gas and/or suppressing gas cooling from the circumgalactic medium.

Atomically dispersed cobalt catalysts for tandem synthesis of primary benzylamines from oxidized ß-O-4 segments.

This work presents an innovative approach focusing on fine-tuning the coordination environment of atomically dispersed cobalt catalysts for tandem synthesis of primary benzylamines from oxidized lignin model compounds. By meticulously regulating the Co-N coordination environment, the activity of these catalysts in the hydrogenolysis and reductive amination reactions was effectively controlled. Notably, our study demonstrates that, in contrast to cobalt nanoparticle catalysts, atomically dispersed cobalt catalysts exhibit precise control of the sequence of hydrogenolysis and reductive amination reactions. Particularly, the CoN3 catalyst with a triple Co-N coordination number achieved a remarkable 94% yield in the synthesis of primary benzylamine. To our knowledge, there is no previous documentation of the synthesis of primary benzylamines from lignin dimer model compounds. Our study highlights a promising one-pot route for sustainable production of nitrogen-containing aromatic chemicals from lignin.

Biomechanical effects of different instrumented segments and trunk shifts on distal adjacent segments after congenital scoliosis posterior hemivertebrectomy: Preliminary results of a single case.

Objective: The present study aims to discuss the biomechanical effects of the sagittal vertical axis and different instrumented segments on distal adjacent segments after congenital scoliosis posterior hemivertebrectomy. Method: A case of congenital scoliosis caused by hemivertebra was selected for the reconstruction of the preoperative and postoperative 3D computed tomography data of the full spine. A finite element model of different fusion lengths and postoperative trunk shift (TS) values was established using the finite element method to compare the biomechanical effects of different models on the distal adjacent segment. Result: In the L1-L3 and T12-L1-L3-L4 fusion modes, the horizontal shift of the 1st vertebra below the lowest instrumented vertebra (LIV) increased with the trunk shift (TS) expansion after operation, and the imbalance between the left and right vertical stress of the 1st intervertebral disc below the LIV increased. With the decrease in fused segments in cases of TS = 10 mm and TS = 5 mm, the 1st vertebra below the LIV was subjected to a greater unbalanced force in the horizontal direction, and the 1st intervertebral disc below the LIV was subjected to a smaller imbalance between the left and right vertical stress after operation. Conclusion: When treating congenital scoliosis with hemivertebrectomy and pedicle screw fixation, fused segments can be properly extended and the postoperative TS shortened with a view of reducing the imbalance between the left and right stress of the 1st intervertebral disc below the LIV as well as the horizontal shift of the 1st vertebra below the LIV.

A phosphodiesterase CpdB in Yersinia pseudotuberculosis degrades CDNs to inhibit innate immune response.

Yersinia pseudotuberculosis (Yptb) is a pathogenic gram-negative bacterium that can colonize the intestines of different animals. Its infection leads to the activation of the host's innate immunity. Both host and bacterial-derived cyclic dinucleotides (CDNs) could activate the innate immune response of host cells. In bacteria, CDNs like c-di-AMP, c-di-GMP, or 3'3'-cGAMP can be hydrolyzed by different hydrolases. Recent studies showed that the degradation of those second messengers helps the pathogen evade immune detection. In this study, we identified a hydrolase, YPK_3776, namely CpdB in Yptb. CpdB is predicted to bind bacterial-derived c-di-AMP, c-di-GMP, 3'3'-cGAMP and host-derived 2'3'-cGAMP. Surprisingly, by using high-performance liquid chromatography (HPLC), we found that CpdB could only degrade bacterial-derived CDNs but not host-derived 2'3'-cGAMP. In addition, CpdB has 2'3'-cNMP activity. Consistently, the Yptb mutant lacking the cpdB gene exhibited a higher level of intracellular c-di-GMP. Furthermore, the ∆cpdB mutant elicited stronger innate immune responses during Yptb infection in macrophages, suggesting CpdB enables Yptb to evade host immune surveillance. Furthermore, CpdB inhibited the Yptb-induced innate immune response in a STING-dependent manner. Finally, we showed the ∆cpdB infection in mice model exhibited in lower bacterial burden, as compared to wild-type strain infection, indicating CpdB is important for bacterial survival in the host. Together, we identified a cyclic dinucleotide hydrolase CpdB in Yptb that could degrade bacterial-derived CDNs which help the pathogen to evade immune detection via the STING pathway.

Adsorption of Flavonoids in a Transcriptional Regulator TtgR: Relative Binding Free Energies and Intermolecular Interactions.

Antimicrobial resistance in bacteria often arises from their ability to actively identify and expel toxic compounds. The bacterium strain Pseudomonas putida DOT-T1E utilizes its TtgABC efflux pump to confer robust resistance against antibiotics, flavonoids, and organic solvents. This resistance mechanism is intricately regulated at the transcriptional level by the TtgR protein. Through molecular dynamics and alchemical free energy simulations, we systematically examine the binding of seven flavonoids and their derivatives with the TtgR transcriptional regulator. Our simulations reveal distinct binding geometries and free energies for the flavonoids in the active site of the protein, which are driven by a range of noncovalent forces encompassing van der Waals, electrostatic, and hydrogen bonding interactions. The interplay of molecular structures, substituent patterns, and intermolecular interactions effectively stabilizes the bound flavonoids, confining their movements within the TtgR binding pocket. These findings yield valuable insights into the molecular determinants that govern ligand recognition in TtgR and shed light on the mechanism of antimicrobial resistance in P. putida DOT-T1E.

Parametric analysis of SARS-CoV-2 dose-response models in transportation scenarios.

Transportation systems involve high-density crowds of geographically diverse people with variations in susceptibility; therefore, they play a large role in the spread of infectious diseases like SARS-CoV-2. Dose-response models are widely used to model the relationship between the trigger of a disease and the level of exposure in transmission scenarios. In this study, we quantified and bounded viral exposure-related parameters using empirical data from five transportation-related events of SARS-CoV-2 transmission. Dose-response models were then applied to parametrically analyze the infection spread in generic transportation systems, including a single-aisle airplane, bus, and railway coach, and then examined the mitigating efficiency of masks by performing a sensitivity analysis of the related factors. We found that dose level significantly affected the number of secondary infections. In general, we observed that mask usage reduced infection rates at all dose levels and that high-quality masks equivalent to FFP2/N95 masks are effective for all dose levels. In comparison, we found that lower-quality masks exhibit limited mitigation efficiency, especially in the presence of high dosage. The sensitivity analysis indicated that a reduction in the infection distance threshold is a critical factor in mask usage.

Non-linear relationship between TSH and psychotic symptoms on first episode and drug naïve major depressive disorder patients: a large sample sized cross-sectional study in China.

INTRODUCTION: Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD. METHODS: A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt. RESULTS: Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p < 0.05). Smoothing plots showed a nonlinear relationship between TSH and PD, with the inflection point of TSH being 4.94 mIU/L. On the right of the inflection point, for each unit increase in serum TSH level on the right side of the inflection point, the probability of PD increased substantially by 47% (OR = 1.47, 95% CI: 1.25 to 1.73, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 0.87, 95% CI: 0.67 to 1.14, p = 0.32). CONCLUSION: Our investigation showed a nonlinear TSH-PD relationship in FEDN MDD patients, thus contributing to effective intervention strategies for psychotic symptoms in depression patients.

CaAl-Layered Double Hydroxides-Modified Biochar Composites Mitigate the Toxic Effects of Cu and Pb in Soil on Pea Seedlings.

Compound contamination of soil with heavy metals copper (Cu) and lead (Pb) triggered by mining development has become a serious problem. To solve this problem, in this paper, corncob kernel, which is widely available and inexpensive, was used as the raw material of biochar and modified by loading CaAl-layered double hydroxides to synthesize biochar-loaded CaAl-layered double hydroxide composites (CaAl-LDH/BC). After soil remediation experiments, either BC or CaAl-LDH/BC can increase soil pH, and the available phosphorus content and available potassium content in soil. Compared with BC, CaAl-LDH/BC significantly reduced the available content of Cu and Pb in the active state (diethylenetriaminepentaacetic acid extractable state) in the soil, and the passivation rate of Cu and Pb by a 2% dosage of CaAl-LDH/BC reached 47.85% and 37.9%, respectively. CaAl-LDH/BC can significantly enhance the relative abundance of beneficial microorganisms such as Actinobacteriota, Gemmatimonadota, and Luteimonas in the soil, which can help to enhance the tolerance and reduce the enrichment ability of plants to heavy metals. In addition, it was demonstrated by pea seedling (Pisum sativum L.) growing experiments that CaAl-LDH/BC increased plant fresh weight, root length, plant height, catalase (CAT) activity, and protein content, which promoted the growth of the plant. Compared with BC, CaAl-LDH/BC significantly reduced the Cu and Pb contents in pea seedlings, in which the Cu and Pb contents in pea seedlings were reduced from 31.97 mg/kg and 74.40 mg/kg to 2.92 mg/kg and 6.67 mg/kg, respectively, after a 2% dosage of CaAl-LDH/BC, which was a reduction of 90.84% and 91.03%, respectively. In conclusion, compared with BC, CaAl-LDH/BC improved soil fertility and thus the plant growth environment, and also more effectively reduced the mobility of heavy metals Cu and Pb in the soil to reduce the enrichment of Cu and Pb by plants.

Evaluating the Prevalence of Burnout Among Health Care Professionals Related to Electronic Health Record Use: Systematic Review and Meta-Analysis.

BACKGROUND: Burnout among health care professionals is a significant concern, with detrimental effects on health care service quality and patient outcomes. The use of the electronic health record (EHR) system has been identified as a significant contributor to burnout among health care professionals. OBJECTIVE: This systematic review and meta-analysis aims to assess the prevalence of burnout among health care professionals associated with the use of the EHR system, thereby providing evidence to improve health information systems and develop strategies to measure and mitigate burnout. METHODS: We conducted a comprehensive search of the PubMed, Embase, and Web of Science databases for English-language peer-reviewed articles published between January 1, 2009, and December 31, 2022. Two independent reviewers applied inclusion and exclusion criteria, and study quality was assessed using the Joanna Briggs Institute checklist and the Newcastle-Ottawa Scale. Meta-analyses were performed using R (version 4.1.3; R Foundation for Statistical Computing), with EndNote X7 (Clarivate) for reference management. RESULTS: The review included 32 cross-sectional studies and 5 case-control studies with a total of 66,556 participants, mainly physicians and registered nurses. The pooled prevalence of burnout among health care professionals in cross-sectional studies was 40.4% (95% CI 37.5%-43.2%). Case-control studies indicated a higher likelihood of burnout among health care professionals who spent more time on EHR-related tasks outside work (odds ratio 2.43, 95% CI 2.31-2.57). CONCLUSIONS: The findings highlight the association between the increased use of the EHR system and burnout among health care professionals. Potential solutions include optimizing EHR systems, implementing automated dictation or note-taking, employing scribes to reduce documentation burden, and leveraging artificial intelligence to enhance EHR system efficiency and reduce the risk of burnout. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021281173; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021281173.