Unraveling the Ligand-Binding Sites of CYP3A4 by Molecular Dynamics Simulations with Solvent Probes.

Cytochrome P450 3A4 (CYP3A4) is one of the most important drug-metabolizing enzymes in the human body and is well known for its complicated, atypical kinetic characteristics. The existence of multiple ligand-binding sites in CYP3A4 has been widely recognized as being capable of interfering with the active pocket through allosteric effects. The identification of ligand-binding sites other than the canonical active site above the heme is especially important for understanding the atypical kinetic characteristics of CYP3A4 and the intriguing association between the ligand and the receptor. In this study, we first employed mixed-solvent molecular dynamics (MixMD) simulations coupled with the online computational predictive tools to explore potential ligand-binding sites in CYP3A4. The MixMD approach demonstrates better performance in dealing with the receptor flexibility compared with other computational tools. From the sites identified by MixMD, we then picked out multiple sites for further exploration using ensemble docking and conventional molecular dynamics (cMD) simulations. Our results indicate that three extra sites are suitable for ligand binding in CYP3A4, including one experimentally confirmed site and two novel sites.

Artemisinin: a novel chiral electrochemiluminescence luminophore-assisted enantiospecific recognition and mechanism identification.

Exploring novel electrochemiluminescence (ECL) molecules with high efficiency and good stability in aqueous solutions is crucial for achieving highly sensitive detection of analytes. However, developing chiral luminophores with efficient ECL performance is still a challenge. Herein, we first uncover that artemisinin (ART), a well-known chiral antimalarial drug, features a strong ECL emission at 726 nm with the assistance of a co-reactant potassium persulfate (K2S2O8), and an ECL efficiency of 195.3%, compared to that of standard Ru(bpy)3Cl2/K2S2O8. Mechanistic studies indicate that the strong ECL signal of ART is generated when the excited state formed by the reduction of ART peroxide bonds and combination with persulfate returns to the ground state. Significantly, we found that the ECL sensor based on chiral ART could efficiently identify and detect chiral cysteine (Cys) through ECL signals, with a lower limit of detection of 3.7 nM for l-Cys. Density functional theory calculations and scanning electrochemical microscopy technology further confirm that the disparity in the ECL signals is attributed to the different affinity between chiral ART and d/l-Cys, resulting in distinct electron transfer rates. The study demonstrates a new role of ART in ECL investigation and for the first time, achieves the development of ART for the enantioselective recognition and sensitive detection of chiral substances. This will be of vital significance for ECL and chirality research.

Evaluation of machine learning models for cytochrome P450 3A4, 2D6, and 2C9 inhibition.

Cytochrome P450 (CYP) enzymes are involved in the metabolism of approximately 75% of marketed drugs. Inhibition of the major drug-metabolizing P450s could alter drug metabolism and lead to undesirable drug-drug interactions. Therefore, it is of great significance to explore the inhibition of P450s in drug discovery. Currently, machine learning including deep learning algorithms has been widely used for constructing in silico models for the prediction of P450 inhibition. These models exhibited varying predictive performance depending on the use of machine learning algorithms and molecular representations. This leads to the difficulty in the selection of appropriate models for practical use. In this study, we systematically evaluated the conventional machine learning and deep learning models for three major P450 enzymes, CYP3A4, CYP2D6, and CYP2C9 from several perspectives, such as algorithms, molecular representation, and data partitioning strategies. Our results showed that the XGBoost and CatBoost algorithms coupled with the combined fingerprint/physicochemical descriptor features exhibited the best performance with Area Under Curve (AUC)  of 0.92, while the deep learning models were generally inferior to the conventional machine learning models (average AUC reached 0.89) on the same test sets. We also found that data volume and sampling strategy had a minor effect on model performance. We anticipate that these results are helpful for the selection of molecular representations and machine learning/deep learning algorithms in the P450 model construction and the future model development of P450 inhibition.

A review of nuclear Dbf2-related kinase 1 (NDR1) protein interaction as promising new target for cancer therapy.

Nuclear Dbf2-related kinase 1 (NDR1) is a nuclear Dbf2-related (NDR) protein kinase family member, which regulates cell functions and participates in cell proliferation and differentiation through kinase activity. NDR1 regulates physiological functions by interacting with different proteins. Protein-protein interactions (PPIs) are crucial for regulating biological processes and controlling cell fate, and as a result, it is beneficial to study the actions of PPIs to elucidate the pathological mechanism of diseases. The previous studies also show that the expression of NDR1 is deregulated in numerous human cancer samples and it needs the context-specific targeting strategies for NDR1. Thus, a comprehensive understanding of the direct interaction between NDR1 and varieties of proteins may provide new insights into cancer therapies. In this review, we summarize recent studies of NDR1 in solid tumors, such as prostate cancer and breast cancer, and explore the mechanism of action of PPIs of NDR1 in tumors.

Clinical Observation of Various Types of Idiopathic Hypertrophic Cranial Pachymeningitis.

BACKGROUND: To assist doctors in making better treatment decisions and improve patient prognosis, it is important to determine which therapy modalities are suitable for various forms of idiopathic hypertrophic cranial pachymeningitis (IHCP). METHODS: All cases were received from the hospital medical record system, and some follow-up information was gathered through telephone follow-up. RESULTS: A total of 26 patients, 14 men and 12 women, with ages ranging from 20 to 73 years and a mean of 47.42 years, were included in the research. Regular types were less likely to recur than irregular and nodular types, focal types were less likely to recur than diffuse types, and corticosteroid-refractory types were more likely to recur than corticosteroid-sensitive types. CONCLUSIONS: The extent and shape of the lesion and susceptibility to corticosteroids are potential factors that could influence recurrence. Futhermore, this paper also proposes the fibroblasts as a new therapeutic target which may improve the quality of prognostic survival of patients.

Confinement Effects in Carbonized ZIF-Confined Hollow PtCo Nanospheres Enable the Methanol Oxidation Reaction.

Confinement effects in highly porous nanostructures can effectively adjust the selectivity and kinetics of electrochemical reactions, which can boost the methanol oxidation reaction (MOR). In this work, carbonized ZIF-8-confined hollow PtCo nanospheres (PtCo@carbonized ZIF-8) were fabricated using a facile strategy. A monodisperse confined region was successfully prepared, and the dispersion of the PtCo nanoparticles (NPs) could be precisely regulated, allowing for the effective tuning of the confined region. Thus, the precise regulation of the catalytic reaction was achieved. Importantly, hollow PtCo NPs were prepared using a method based on the Kirkendall effect, and their forming mechanism was systematically investigated. Because of the confinement effects of carbonized zeolitic imidazolate framework-8 (ZIF-8), the crystal and electronic structures of the PtCo NPs were able to be effectively tuned. Our electrochemical results show that PtCo@carbonized ZIF-8 composites manifest a higher mass activity (1.4 A mgPt-1) and better stability compared to commercial Pt/C.

Precise Modulation of Intramolecular Aggregation-induced Electrochemiluminescence by Tetraphenylethylene-based Supramolecular Architectures.

The precisely modulated synthesis of programmable light-emitting materials remains a challenge. To address this challenge, we construct four tetraphenylethylene-based supramolecular architectures (SA, SB, SC, and SD), revealing that they exhibit higher electrochemiluminescence (ECL) intensities and efficiencies than the tetraphenylethylene monomer and can be classified as highly efficient and precisely modulated intramolecular aggregation-induced electrochemiluminescence (PI-AIECL) systems. The best-performing system (SD) shows a high ECL cathodic efficiency exceeding that of the benchmark tris(2,2'-bipyridyl)ruthenium(II) chloride in aqueous solution by nearly six-fold. The electrochemical characterization of these architectures in an organic solvent provides deeper mechanistic insights, revealing that SD features the lowest electrochemical band gap. Density functional theory calculations indicate that the band gap of the guest ligand in the SD structure is the smallest and most closely matched to that of the host scaffold. Finally, the SD system is used to realize ECL-based cysteine detection (detection limit=14.4 nM) in real samples. Thus, this study not only provides a precisely modulated supramolecular strategy allowing chromophores to be controllably regulated on a molecular scale, but also inspires the programmable synthesis of high-performance aggregation-induced electrochemiluminescence emitters.

Enhancing the Electrochemiluminescence of Porphyrin via Crystalline Networks of Metal-Organic Frameworks for Sensitive Detection of Cardiac Troponin I.

Porphyrins easily aggregate due to unfavorable π-π accumulation, causing luminescent quenching in the aqueous phase and subsequently reducing luminescent efficiency. It is a feasible way to immobilize porphyrin molecules through metal-organic framework materials (MOFs). In this study, 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) was introduced into the metal-organic skeleton (PCN-224) as a ligand. The result showed that the electrochemiluminescence (ECL) and photoluminescence (PL) efficiency of the MOF skeleton was 8.2 and 6.5 times higher than TCPP, respectively. Impressively, the periodic distribution of porphyrin molecules in the MOF framework can overcome the bottleneck of porphyrin aggregation, resulting in the organic ligand TCPP participating in the electron transfer reaction. Herein, based on the PCN-224, a sandwich-type ECL immunosensor was constructed for the determination of cardiac troponin I (cTnI). It provided sensitive detection of cTnI in the range of 1 fg/mL to 10 ng/mL with a detection limit of 0.34 fg/mL. This work not only innovatively exploited a disaggregation ECL (DIECL) strategy via the crystalline framework of MOF to enhance the PL and ECL efficiency of porphyrin but also provided a promising ECL platform for the ultrasensitive monitoring of cTnI.

Photogenerated charge separation at BiVO4 photoanodes enhanced by a Ag-modified porphyrin polymer skeleton.

Bismuth vanadate (BiVO4) has been considered a promising photoactive material in photoelectrochemical (PEC) water-splitting systems. However, the performance of BiVO4-based photoanodes is currently unsatisfactory, indicating the need for new architectural designs to improve their efficiency. In this paper, a porphyrin-phosphazene polymer (THPP-HCCP) was synthesized with a sizeable conjugated structure, and Ag particles were deposited on its surface as an organic-inorganic composite interface improvement layer. The deposition of the composite polymer film on BiVO4 resulted in a significant increase in photocurrent density, reaching up to 2.2 mA cm-2 (1.23 V vs. RHE), almost three times higher than pristine BiVO4, which benefits from the synergistic effect of Ag nanoparticles and porphyrin-phosphazene. Furthermore, photophysical and intensity-modulated photocurrent analysis demonstrated that the Ag-THPP-HCCP heterostructures could broaden the light-absorbing range and facilitate hole transfer to the semiconductor surface, resulting in an improved water oxidation process. The dynamic charge transport behavior of Ag-THPP-HCCP/BiVO4 was investigated using scanning photoelectrochemical microscopy, which showed that the rate constant (Keff) exhibits an almost 4-fold increase compared to pristine BiVO4, indicating a significant improvement in the transport of photogenerated holes. This experiment presents a novel strategy for designing high-efficiency polymer-based photoanodes.

Prediction of Sites of Metabolism of CYP3A4 Substrates Utilizing Docking-Derived Geometric Features.

Cytochrome P450 3A4 (CYP3A4) is one of the major drug-metabolizing enzymes in the human body and is responsible for the metabolism of ∼50% of clinically used drugs. Therefore, the identification of the compound's sites of metabolism (SOMs) mediated by CYP3A4 is of utmost importance in the early stage of drug discovery and development. Herein, docking-based approaches incorporating geometric features were used for SOMs prediction of CYP3A4 substrates. The cross-docking poses of a relatively large data set containing 474 substrates were analyzed in depth, and a widely observed geometric pattern called the close proximity of SOMs was derived from the poses. On the basis of the close proximity, several structure-based models have been constructed, which demonstrated better performance than those structure-based models using the criterion of Fe-SOM distance. For further improving the prediction performance, the structure-based models were also combined with the well-known ligand-based model SMARTCyp. One combined model exhibited good performance on the SOMs prediction of an external substrate set containing kinase inhibitors, PROTACs, approved drugs, and some lead compounds.

Predictive factors and risk analysis of recurrent laryngeal nerve invasion in papillary thyroid carcinoma ≤ 1 cm

ABSTRACT Objective: The recurrent laryngeal nerve (RLN) may be involved by papillary thyroid carcinoma ≤ 1 centimeter (PTC ≤ 1 cm). Current study investigated the predictive factors of RLN invasion in PTC ≤ 1 cm, the risk factors of disease recurrence in RLN invaded cases and the results of surgical management for RLN invasion. Materials and methods: Data of 374 PTC ≤ 1 cm patients were retrospectively collected. We performed univariate and multivariate analysis to identify predictive factors of RLN invasion and risk factors of disease recurrence. The abilities of factors in predicting RLN invasion were evaluated. Surgical outcomes and recurrence free survival (RFS) of patients were analyzed. Results: A total of 28 patients suffered RLN invasion, among which seven had disease recurrence. Preoperative vocal cord palsy (VCP), gross extrathyroidal extension, larger tumor size and tumor on the dorsal side of thyroid were verified as predictive factors of RLN invasion. RLN involved patients had poorer RFS, but better than those who also had upper-aerodigestive tract invasion. Upper-aerodigestive tract invasion, lateral neck lymph nodes metastasis (LNM) and BRAF V600E mutation were independent risk factors of disease recurrence in RLN invaded cases. Tumor shaving showed better RLN function preservation without increasing recurrent risk. Conclusions: Current study confirmed the rarity of RLN invasion in PTC ≤ 1 cm. Various aggressive features were verified as predictive factors of RLN invasion. Tumor shaving showed superiority in preserving nerve function without increasing recurrent risk. Special attentions should be paid for disease recurrence when RLN invasion accompanied by upper-aerodigestive tract invasion, lateral neck LNM or BRAF V600E mutation.

The prognostic value of hedgehog signaling in bladder cancer by integrated bioinformatics.

Bladder cancer is the second most prevalent urological malignancy. It's a big contributor to cancer-related deaths throughout the globe. Researchers discovered that the hedgehog signaling (HhS) pathway contributed to the onset and spread of many different kinds of cancer. Nevertheless, the present understanding of the function of HhS in the bladder cancer molecular landscape is incomplete. Raw data were gotten from the IMvigor210, the Gene Expression Omnibus, and The Cancer Genome Atlas databases. Bioinformatics was used to examine the HhS score of each sample, and the enrichment of differentially expressed genes (DEGs), differentiation characteristics, immunological infiltration, and metabolic activity. The HhS prognostic signature was developed with significant assistance from the least absolute shrinkage and selection operator regression and Cox regression. An HhS-related nomogram was developed to assist in the prediction of patients' survival probability. We found that HhS was linked to poor prognosis in bladder cancer, and its activation was linked to the Basal subtype of bladder cancer. Bladder cancer with high HhS activity has higher glycolysis, nucleotide metabolism, amino acid metabolism, and other cancer-promoting metabolic activities. Furthermore, HhS mediates an immunosuppressive microenvironment in bladder cancer on the basis that HhS negatively correlates with the CD8 + T cells and correlates positively with immune checkpoints and T cell exhaustion scores. Finally, an HhS-related signature was developed for predicting the prognosis of patients with bladder cancer. Targeting HhS may be a potential therapy choice for bladder cancer.

Assessment of factors influencing the olfactory bulb volume in patients with post-viral olfactory dysfunction.

PURPOSE: To investigate the factors influencing the volume of the olfactory bulb (OB) in patients with post-viral olfactory dysfunction (PVOD). METHODS: We collected 92 olfactory bulb volumes from patients with PVOD who underwent a sinus computed tomographic and magnetic resonance imaging (MRI) scan of the head and collected clinical information including gender, age, disease course, minimal cross-sectional area, nasal airway resistance, and olfactory function. OB volume was measured in MRI and the scans were evaluated according to the Lund-Mackay (LM) scoring system. RESULTS: Male patients with PVOD had a larger OB volume (ß = 0.284, P < 0.05). OB volume was smaller in patients with a longer course of olfactory dysfunction (ß = - 0.254, P < 0.05). According to the LM scoring system, patients with a higher anterior ethmoidal sinus score had smaller OB volume (ß = - 0.476, P < 0.05). CONCLUSIONS: The study revealed that gender, disease course, and the score of anterior ethmoidal sinusitis can affect the OB volume in patients with PVOD.

Predictive factors and risk analysis of recurrent laryngeal nerve invasion in papillary thyroid carcinoma ≤ 1 cm.

Objective: The recurrent laryngeal nerve (RLN) may be involved by papillary thyroid carcinoma ≤ 1 centimeter (PTC ≤ 1 cm). Current study investigated the predictive factors of RLN invasion in PTC ≤ 1 cm, the risk factors of disease recurrence in RLN invaded cases and the results of surgical management for RLN invasion. Materials and methods: Data of 374 PTC ≤ 1 cm patients were retrospectively collected. We performed univariate and multivariate analysis to identify predictive factors of RLN invasion and risk factors of disease recurrence. The abilities of factors in predicting RLN invasion were evaluated. Surgical outcomes and recurrence free survival (RFS) of patients were analyzed. Results: A total of 28 patients suffered RLN invasion, among which seven had disease recurrence. Preoperative vocal cord palsy (VCP), gross extrathyroidal extension, larger tumor size and tumor on the dorsal side of thyroid were verified as predictive factors of RLN invasion. RLN involved patients had poorer RFS, but better than those who also had upper-aerodigestive tract invasion. Upper-aerodigestive tract invasion, lateral neck lymph nodes metastasis (LNM) and BRAF V600E mutation were independent risk factors of disease recurrence in RLN invaded cases. Tumor shaving showed better RLN function preservation without increasing recurrent risk. Conclusion: Current study confirmed the rarity of RLN invasion in PTC ≤ 1 cm. Various aggressive features were verified as predictive factors of RLN invasion. Tumor shaving showed superiority in preserving nerve function without increasing recurrent risk. Special attentions should be paid for disease recurrence when RLN invasion accompanied by upper-aerodigestive tract invasion, lateral neck LNM or BRAF V600E mutation.

Accuracy of Xpert® MTB/RIF Ultra test for posterior oropharyngeal saliva for the diagnosis of paucibacillary pulmonary tuberculosis: a prospective multicenter study.

BACKGROUND: Posterior oropharyngeal saliva (POS) is increasingly recognized as an alternative specimen for detecting respiratory pathogens. The accuracy of Xpert® MTB/RIF Ultra (X-Ultra), when performed on POS obtained from patients with paucibacillary pulmonary tuberculosis (TB) is unclear. METHODS: We consecutively recruited adults with symptoms suggestive of pulmonary TB who were negative by both smear microscopy and Xpert MTB/RIF (X-Classic). Each participant was required to provide one bronchoalveolar lavage fluid (BALF) and one POS specimen, respectively. Diagnostic performances of X-Ultra and X-Classic on POS were compared against clinical and mycobacterial reference standards. FINDINGS: 686 participants meeting inclusion criteria were consecutively enrolled into the study. The overall diagnostic sensitivities of X-Ultra and X-Classic on POS samples were 78.9% [95% confidence interval (CI): 72.8-83.8] and 56.4% (95% CI: 49.7-62.9), respectively; the specificities were 96.6% (95% CI: 94.3-98.1) for X-Ultra and 97.6 (95CI: 95.5-98.8) for X-Classic in POS specimens. Notably, the sensitivity of X-Ultra on POS was as sensitive as X-Classic on BALF against microbiological reference standard (78.9% VS 73.1%). Against clinical diagnosis as a reference standard, the sensitivities of X-Ultra and X-Classic on POS were 55.9% (95% CI: 50.5-61.2; 193/345) and 40.0% (95% CI: 34.8-45.4; 138/345), respectively. The risk of negative results with POS was dramatically increased with decreasing bacterial loads. CONCLUSIONS: The testing of POS using X-Ultra shows promise as a tool to identify patients with paucibacillary TB. Considering that bronchoscopy is a semi-invasive procedure, POS testing ahead of bronchoscopy, may decrease the need for bronchoscopic procedures, and the cost of care.

The intraoral growth patterns of parapharyngeal tumors: A proposed classification system.

OBJECTIVE: Nearly half of parapharyngeal space (PPS) tumors present as an intraoral mass, which is diagnostically challenging. In this study, we studied whether preoperative growth patterns were associated with histopathological diagnosis for planning surgery. METHODS: We performed a cross-sectional study in patients with PPS tumors. A simplified classification scheme based on intraoral tumor growth patterns (patterns 1 and 2) was then proposed. In pattern 1, tumors bulge submucosally to the oropharynx from the soft palate, with the center convexity above the uvula. In pattern 2, tumors bulge submucosally to the oropharynx from the lateral oropharynx wall, with the center convexity below the uvula. The association of this classification with postoperative histopathological diagnosis and surgical-related events was studied. RESULTS: Twenty-two patients were enrolled in this study (12 with pattern 1, 10 with pattern 2). Of these, 91.7% (11/12) of pattern 1 tumors were salivary gland tumors (P < .001), and 90% (9/10) of pattern 2 tumors were neurogenic (P < .001). Pattern 2 tumors had fewer bleeding complications or needed external approaches when a transoral approach was chosen. CONCLUSIONS: This new classification of PPS tumors facilitates the prediction of salivary gland and neurogenic tumors and can improve the accuracy of preoperative radiologic diagnosis. This system will be helpful for planning surgical interventions, such as implementing transoral approaches.

Survival analysis of patients with subglottic squamous cell carcinoma based on the SEER database

Abstract Objective: This study aimed to investigate the demographic and clinicopathological characteristics, and survival outcomes of subglottic Squamous Cell Carcinoma (SCC) based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Demographic and clinicopathological information, including age, sex, race, tumor size, histologic grade, clinical/TNM stage, tumor invasion extent, Lymph Node Metastasis (LNM) extent, size of metastatic lymph nodes, LNM ratio and treatment data, of 842 subglottic SCC patients diagnosed between 1996 and 2016 were acquired. Kaplan-Meier survival analyses were performed to assess the effects of clinicopathological characteristics, treatment modalities, surgical procedures, and adjuvant therapies on overall survival and cancer-specific survival. Results: Subglottic SCC was more frequent among males aged 60-70 years, with low-grade but locally advanced lesions without local or distant metastases. Age and several primary tumor/LNM related variables were independent risk factors for overall survival and cancer specific survival. Advanced-stage and high-grade disease led to unfavorable prognosis. The most common treatment modality and surgical procedure were surgery plus radiotherapy and total laryngectomy, respectively. Surgery plus radiotherapy provided favorable 5-year survival outcomes, while total laryngectomy had the worst. Surgery plus adjuvant therapy showed better survival outcomes than surgery alone. Conclusion: This study confirmed the rarity of subglottic SCC. Patients with subglottic SCCs suffered poor prognosis especially for those with advanced-stage or high-grade lesions. The prognosis of subglottic SCC remained poor over the years, despite recent progress in cancer therapies. Surgery plus adjuvant therapy improved the survival outcome. Although larynx preservation surgery was beneficial for early-stage disease, total laryngectomy was favored for patients with advanced tumors. Level of evidence: Level 4.

Rigid Enhanced Electrochemiluminescence of 1,2,3-Triaryl Indenes as an Ultrasensitive Sensor for D2O in H2O.

The intriguing aggregation-induced emission has recently been applied in the electrochemiluminescence, called aggregation-induced electrochemiluminescence (AIE-ECL), which is conducive to solving the water insolubility and aggregation-caused quenching for most organic luminescence probes. However, AIE-ECL still has the problems of low luminous efficiency and limited practical application. In this work, we disclosed the AIE-ECL properties of 1,2,3-triaryl-substituted indenes containing rigid structures. Experimental and theoretical investigations demonstrated that such a rigid structure could significantly enhance the aromaticity and stability and thereby the luminescence performance of these indenes. Moreover, according to the finding of hydrogen/deuterium exchange for active hydrogen in indene under electrical excitation, ultrasensitive detection for D2O in H2O was realized by such an indene-based AIE-ECL system. Our research not only provided an attractive strategy to enhance the luminescence property for an AIE-active luminophore but also established a superior sensor toward D2O.

Comparison of initial clinic characteristics of hospitalized patients in Suzhou City during the COVID-19 Omicron wave with ancestral variant wave.

BACKGROUND: Recently, the SARS-CoV-2 variant of concern, Omicron (B.1.1.529), was identified as responsible for a novel wave of COVID-19 worldwide. Here, we compared initial clinical features of hospitalized COVID-19 patients during recent wave (Omicron Variant) with those in ancestral variant wave (2020). METHODS: This is a cohort study of electronic health record (EHR) data from a signal center in the China. The clinical data of 116 cases of Omicron hospitalized in 2022 and 87 cases hospitalized in 2020 were collected. The comparisons were performed with the Mann-Whitney U test, Fisher exact test or the chi-square test, and multivariable logistic regression analysis. RESULTS: Clinically, compared with 2020-cohort, Omicron-cohort was more inclined to cluster in younger population and had more nonsymptomatic (25.0%) and nonsevere cases, as well as suffered from comparable extrapulmonary complication. Radiologically, although the major computed tomography (CT) findings of both cohorts were ground-glass opacities (GGOs), crazy-paving pattern was relatively less seen in the Omicron-cohort. Based on multiple logistic regression analysis, Omicron-cohort was associated with a lower risk of complaining with fever, the presence of lung opacity, and increased Sequential Organ Failure Assessment (SOFA) score. CONCLUSION: This study provided the data of different patterns of clinic characteristics and reduced severity from infections that occurred in Omicron variant as compared with the outbreak of the epidemic in 2020 wave (ancestral variant).