CRISPLD1 promotes gastric cancer progression by regulating the Ca2+/PI3K-AKT signaling pathway.

Gastric cancer (GC) is a malignant tumor with poor prognosis. Studies have shown that cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is associated with tumor progression. However, its role in GC is unclear. The present study aimed to determine the pathogenic mechanism of CRISPLD1 in GC. Analysis of public databases revealed high mRNA expression of CRISPLD1 in GC, which was associated with poor prognosis. Additionally, CRISPLD1 expression levels showed significant correlations with T stage, overall survival events, and stage. Knockdown of CRISPLD1 reduced cell proliferation, invasion, and migration. Furthermore, CRISPLD1 knockdown decreased intracellular calcium levels in GC cells and inhibited the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. Treatment with an AKT activator reversed the inhibitory effect of CRISPLD1 knockdown on GC cell migration and invasion. Our findings suggest that CRISPLD1 promotes tumor cell progression in GC by mediating intracellular calcium levels and activating the PI3K-AKT pathway, highlighting CRISPLD1 as a potential therapeutic target for GC.

Functionalized PLGA Microsphere Loaded with Fusion Peptide for Therapy of Bone Defects.

The challenges in the treatment of extensive bone defects are infection control and bone regeneration. Bone tissue engineering is currently one of the most promising strategies. In this study, a short biopeptide with specific osteogenic ability is designed by fusion peptide technology and encapsulated with chitosan-modified poly(lactic acid-glycolic acid) (PLGA) microspheres. The fusion peptide (FP) mainly consists of an osteogenic functional sequence (P-15) and a bone-specific binding sequence (Asp-6), which can regulate bone formation accurately and efficiently. Chitosan-modified PLGA with antimicrobial and pro-healing effects is used to achieve the sustained release of fusion peptides. In the early stage, the antimicrobial and soft tissue healing effects can stop the wound infection as soon as possible, which is relevant for the subsequent bone regeneration process. Our data show that CS-PLGA@FP microspheres have antibacterial and pro-cell migration effects in vitro and excellent pro-wound-healing effects in vivo. In addition, CS-PLGA@FP microspheres promote the expression of osteogenic-related factors and show excellent bone regeneration in a rat defect model. Therefore, CS-PLGA@FP microspheres are an efficient biomaterial that can accelerate the recovery of bone defects.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

TBOPP, a DOCK1 Inhibitor, Potentiates Cisplatin Efficacy in Breast Cancer by Regulating Twist-mediated EMT.

BACKGROUND: DOCK1 has been reported to be involved in tumor progression and resistance. 1-(2-(30-(trifluoromethyl)-[1,10-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl2(1H)- pyridone (TBOPP) is a selective DOCK1 inhibitor; however, the role and molecular mechanisms of DOCK1 and its inhibition in breast cancer (BC) resistance remain poorly understood. OBJECTIVE: This study aims toinvestigate the underlying mechanisms of DOCK1 in BC resistance. METHODS: DOCK1 or Twist siRNA and Twist plasmid were used to explore the function of DOCK1 in vitro experiments. A mouse xenograft model was used for in vivo experiments. RESULTS: In the present study, we demonstrated that DOCK1 siRNA promoted cisplatin sensitivity in BC cells. Moreover, TBOPP also enhances the therapeutic effect of cisplatin both in vitro and in vivo. Mechanistically, DOCK1 siRNA inhibited EMT. Twist 1 is one of the EMT-inducing transcription factors and is known to induce EMT. To further reveal the effect of DOCK in BC cells, we co-transfected with DOCK1 and Twist1 siRNA to BC cells and found that co-transfection with DOCK1 and Twist siRNA could not further enhance the cisplatin sensitivity of BC cells. Moreover, DOCK1 siRNA failed to reverse the effect of Twist 1 up-regulation. CONCLUSION: Taken together, these results demonstrate that DOCK1 may function as a potential therapeutic target in BC and that combining cisplatin with TBOPP may provide a promising therapeutic strategy for cisplatin-resistant BC patients.

Fe-codoped carbon dots serving as a peroxidase mimic to generate in situ hydrogen peroxide for the visual detection of glucose.

Nanozyme technology has gained significant regard and been successfully implemented in various applications including chemical sensing, bio-medicine, and environmental monitoring. Fe-CDs were synthesized and characterized well in this study. As compared to HRP (3.7 mM), the Fe-CDs exhibited a higher affinity towards H2O2 (0.2 mM) using the steady-state kinetic assay and stronger catalytic capability by changing the color of TMB to the blue color of the oxidized state, oxTMB. Additionally, an efficient peroxidase mimic, Fe-CDs/GOx, based on the hybrid cascade system to produce in situ H2O2 for the visual detection of glucose (color change: colorless to blue, and then to green), has been developed in detail, with limits of detection (LODs) for H2O2 and glucose of 0.33 µM and 1.17 µM, respectively. The changes further demonstrate a linear relationship between absorbance and H2O2 concentration, ranging from 10 to 60 µM, and for glucose (1 to 60 µM). To assess the accuracy and detection capability of the Fe-CDs/GOx system, we evaluated a real human serum sample obtained from adult males in a local hospital. In conclusion, Fe-CDs serving as a peroxidase mimic have the potential for various applications in the fields of biomedicine and nanozymes.

BRG1 mediates epigenetic regulation of TNFα-induced CCL2 expression in oral tongue squamous cell carcinoma cells.

Strong evidence has indicated that upregulation of chemokine (CC motif) ligand-2 (CCL2) expression and the presence of an inflammatory tumor microenvironment significantly contribute to the migratory and invasive properties of oral squamous cell carcinoma, specifically oral tongue squamous cell carcinoma (OTSCC). However, the precise epigenetic mechanism responsible for enhanced CCL2 expression in response to the inflammatory mediator tumor necrosis factor alpha (TNF-α) in OTSCC remains inadequately elucidated. We have demonstrated that the production of CCL2 can be induced by TNF-α, and this induction is mediated by the chromatin remodel protein BRG1. Through the use of a chromatin immunoprecipitation (ChIP) assay, we have found that BRG1 was involved in the recruitment of acetylated histones H3 and H4 at the CCL2 promoter, thereby activating TNF-α-induced CCL2 transcription. Furthermore, we have observed that recruitment of NF-κB p65 to the CCL2 promoter was increased following BRG1 overexpression and decreased after BRG1 knockdown in OTSCC cells. Our Re-ChIP assay has shown that BRG1 knockdown completely inhibits the recruitment of both acetylated histone H3 or H4 and NF-κB to the CCL2 promoter. In summary, the findings of our study demonstrate that BRG1 plays a significant role in mediating the production of CCL2 in OTSCC cells in response to TNF-α stimulation. This process involves the cooperative action of acetylated histone and NF-κB recruitment to the CCL2 promoter site. Our data suggest that BRG1 serves as a critical epigenetic mediator in the regulation of TNF-α-induced CCL2 transcription in OTSCC cells.

Effect of safety and security equipment on patient and visitor violence towards nurses in multiple public hospitals of China during the COVID-19 pandemic: a retrospective, difference-in-difference analysis.

OBJECTIVES: This study aimed to analyse whether safety and security equipment decreased patient and visitor violence (PVV) towards nurses in the COVID-19 period and quantify to what extent safety and security equipment affects PVV. DESIGN: Controlled before and after study and difference-in-difference (DID) analysis. SETTING: A large hospital medical group, consisting of three public tertiary teaching hospitals, namely, Xinjiekou Branch, Huilongguan Branch and Xinlongze Branch of Beijing Jishuitan Hospital, located in the west and north parts of Beijing, China. PARTICIPANTS: A panel of nine departments recruited using two-step sampling method, administered online surveys in 2021 and 2022. A total of 632 eligible nurses participated in the survey in 2021 and 725 eligible nurses in 2022. MEASURES: We assessed impacts of the safety and security equipment on the PVV. The policy had been enacted in June 2020, and the corresponding measures were established after mid-December 2020, and therefore, we use a DID design to evaluate changes in nurses' PVV incidence. Departments are classified as either department installed or non installed, and nurses are classified based on their department. RESULTS: Within the treatment group, the incidence of physical PVV significantly decreased from 13.8% in 2020 to 2.0% in 2021. In the control group, the incidence of physical PVV increased from 0.6% in 2020 to 2.7% in 2021. The application of the safety and security equipment decreased the incidence of physical PVV by 13.93% (95% CI: -23.52% to -4.34%). In contrast, no difference was observed between the treatment and control groups for the incidence of psychological PVV (6.23%, 95% CI: -11.56% to 24.02%) and overall PVV (0.88, 95% CI: -20.90% to 22.66%). CONCLUSION: The safety and security equipment reduced the incidence of physical PVV towards nurses. For hospital managers in public hospitals, longer-term strategies roadmap for PVV prevention measures are needed to create a more supportive work environment in employees.

AcMYB10 Involved in Anthocyanin Regulation of 'Hongyang' Kiwifruit Induced via Fruit Bagging and High-Postharvest-Temperature Treatments.

Light and temperature are key factors influencing the accumulation of anthocyanin in fruit crops. To assess the effects of fruit bagging during development and high post-ripening temperature on 'Hongyang' kiwifruit, we compared the pigmentation phenotypes and expression levels of anthocyanin-related genes between bagged and unbagged treatments, and between 25 °C and 37 °C postharvest storage temperatures. Both the bagging and 25 °C treatments showed better pigmentation phenotypes with higher anthocyanin concentrations. The results of the qRT-PCR analysis revealed that the gene expression levels of LDOX (leucoanthocyanidin dioxygenase), F3GT (UDP-flavonoid 3-O-glycosyltransferase ), AcMYB10, and AcbHLH42 were strongly correlated and upregulated by both the bagging treatment and 25 °C storage. The results of bimolecular fluorescence complementation and luciferase complementation imaging assays indicated an interaction between AcMYB10 and AcbHLH42 in plant cells, whereas the results of a yeast one-hybrid assay further demonstrated that AcMYB10 activated the promoters of AcLODX and AcF3GT. These results strongly suggest that enhanced anthocyanin synthesis is caused by the promoted expression of AcLODX and AcF3GT, regulated by the complex formed by AcMYB10-AcbHLH42.

Repurposing endogenous type II CRISPR-Cas9 system for genome editing in Streptococcus thermophilus.

Streptococcus thermophilus has been extensively used in industrial milk fermentation. However, lack of efficient genetic manipulation approaches greatly hampered the industrial application of this species. Here, we repurposed the endogenous CRISPR1 and CRISPR3 systems, both belong to type II-A CRISPR-Cas9, by delivering a self-targeting CRISPR array with DNA repair template into S. thermophilus LMD-9. We achieved 785-bp deletion in lacZ gene by repurposing CRISPR1 and CRISPR3 systems with efficiencies of 35% and 59%, respectively, when 1-kb DNA repair template was provided. While providing with 1.5-kb repair template, the editing efficiency for deletion in lacZ gene reached 90% using CRISPR3 systems. Diverse editing outcomes encompassing a stop code insertion and single nucleotide variation within lacZ, as well as a 234-bp DNA fragment insertion upstream of ster_0903, were generated with high efficiencies of 75%-100% using the CRISPR3 system. Harnessing the customized endogenous CRISPR3 system to target six genes of eps gene cluster, we obtained six single-gene knockout mutants with efficiencies of 29%-80%, and proved that the epsA, epsE, and epsG were the key genes affecting exopolysaccharides biosynthesis in S. thermophilus LMD-9. Altogether, repurposing the native type II-A CRISPR-Cas9 can be served as a toolkit for precise genome engineering in S. thermophilus for biotechnological applications.

Histatin 1-modified SIS hydrogels enhance the sealing of peri-implant mucosa to prevent peri-implantitis.

Dental implants make it possible to replace teeth in more sophisticated ways. Nevertheless, peri-implantitis is one of the leading causes of implant failure, which can be avoided with proper soft tissue sealing. The aim of this study was to achieve the promotion of the synthesis of peri-implant epithelial hemidesmosome through Histatin 1 and porcine small intestinal submucosa (SIS) hydrogel to form a good peri-implant seal. The results show that hydrogel can improve the biological barrier function around implants by combining antibacterial, promoting soft tissue healing and promoting epithelial bonding. This means that the morphology and anti-infection ability of soft tissue are enhanced, which ensures the long-term stability of the implant.SIS-Hst1 hydrogel has certain clinical application in the prevention and early treatment of peri-implantitis. In conclusion, Hst1-SIS hydrogel, as a local administration system, provides experimental evidence for the prevention of peri-implant disease.

Prevalence of frailty among elderly patients with hip fracture in China: protocol for a systematic review and meta-analysis.

INTRODUCTION: Frailty is a clinical syndrome characterised by a reduced ability to adapt to external stressors owing to a reduced physiological reserve, which is caused by degeneration of multiple organ systems. Frailty is particularly prevalent among patients with hip fractures. Research on frailty in China started late; thus, evidence regarding the prevalence of frailty among older patients with hip fracture in China is scarce. The aim of this systematic review and meta-analysis is to systematically search for available data on the prevalence of frailty among older patients with hip fracture in China, assess the pooled prevalence of frailty and describe the association between frailty and clinical outcomes. METHOD AND ANALYSIS: We will systematically search electronic databases, including Web of Science, Embase, PubMed, the Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang data Database, to identify studies on the prevalence of frailty in older patients with hip fracture. Two reviewers will independently identify eligible studies according to defined inclusion criteria and critically appraise them using the Joanna Briggs Institute's standardised critical appraisal tool. Data will be analysed using Stata V.12.0. ETHICS AND DISSEMINATION: Ethics approval is not required as this review will only include data from published sources. The results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022265321.

Exploring elderly patients' experiences and concerns about early mobilization implemented in postoperative care following lumbar spinal surgery: a qualitative study.

BACKGROUND: Given its apparent benefits, early mobilization is becoming increasingly important in spinal surgery. However, the time point at which patients first get out of bed for mobilization after spinal surgery varies widely. Beginning in January 2022, we conducted a study of early mobilization (mobilization within 4 h postoperatively) following multi-segment lumbar decompression and fusion surgery in elderly patients. The study goal was to better understand elderly patients' perceptions of early mobilization and ultimately contribute to the improvement of elderly patients' perioperative experiences and quality of life. METHODS: We employed a qualitative descriptive study design involving face-to-face semi-structured interviews. Forty-five consecutive patients were invited, among whom 24 were enrolled and completed the qualitative investigation from February to June 2022. Of these 24 patients, 10 underwent early mobilization (mobilization within 4 h postoperatively) and 14 underwent mobilization at ≥ 24 h postoperatively. Three researchers conducted a 15-question interview the day before each patient's discharge. The interviews were audio-recorded, and content analysis was used to assess the data. RESULTS: Six themes regarding the patients' experiences and concerns about early mobilization were identified: worries, benefits, daily routines, pain, education, and support. The study results revealed the obstacles in early mobilization practice and highlighted the importance of perioperative education on early mobilization. CONCLUSIONS: Clear and explicit guidance on early mobilization and a multidisciplinary mobilization protocol that incorporates a comprehensive pain management plan are essential for effective patient education. These measures may have positive effects on reducing patients' stress and anxiety regarding postoperative early mobilization.

The RNA binding protein MEX3A promotes tumor progression of breast cancer by post-transcriptional regulation of IGFBP4.

PURPOSE: Breast cancer (BC) is the most frequent malignant tumor in women worldwide with exceptionally high morbidity. The RNA-binding protein MEX3A plays a crucial role in genesis and progression of multiple cancers. We attempted to explore its clinicopathological and functional significance in BC in which MEX3A is expressed. METHODS: The expression of MEX3A detected by RT-qPCR and correlated the results with clinicopathological variables in 53 BC patients. MEX3A and IGFBP4 profile data of BC patients were downloaded from TCGA and GEO database. Kaplan-Meier (KM) analysis was used to estimate the survival rate of BC patients. Western Blot, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MEX3A and IGFBP4 in BC cell proliferation, invasion and cell cycle in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of BC cells after MEX3A knockdown. The interactions among MEX3A and IGFBP4 were measured by RNA pull-down and RNA immunoprecipitation. RESULTS: The expression of MEX3A was upregulated in BC tissues compared to adjacent tissues and high expression of MEX3A was associated with poor prognosis. Subsequent in vitro studies demonstrated that MEX3A knockdown inhibited BC cells proliferation and migration, as well as xenograft tumor growth in vivo. The expression of IGFBP4 was significantly negatively correlated with MEX3A in BC tissues. Mechanistic investigation showed that MEX3A binds to IGFBP4 mRNA in BC cells, decreasing IGFBP4 mRNA levels, which further activated the PI3K/AKT and other downstream signaling pathways implicated cell cycle progression and cell migration. CONCLUSION: Our results indicate that MEX3A plays a prominent oncogenic role in BC tumorigenesis and progression by targeting IGFBP4 mRNA and activating PI3K/AKT signaling, which can be used as a novel therapeutic target for BC.

MCM5 is an oncogene of colon adenocarcinoma and promotes progression through cell cycle control.

Many patients with colon adenocarcinoma (COAD) are diagnosed at an advanced stage, and the molecular mechanism of COAD progression is intricate and controversial. Therefore, there is an urgent need to identify more novel prognosis biomarkers for COAD and elucidate the molecular mechanism of this disease. The present study aimed to screen out key genes correlated with COAD prognosis. In this study, a key module was identified and four hub genes (MCM5 (encoding minichromosome maintenance complex component 5), NOLC1 (encoding nucleolar and coiled-body phosphoprotein 1), MYC (encoding MYC proto-oncogene, BHLH transcription factor), and CDK4 (encoding cyclin dependent kinase 4)) were selected that correlated with COAD prognosis, based on the GSE9348 dataset in Gene Expression Omnibus database. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that MCM5 correlated with the cell cycle. Furthermore, MCM5 expression was upregulated in tumor tissues of patients with COAD compared with that in adjacent tissues, based on various databases, including The Cancer Genome Atlas, the Clinical Proteomic Tumor Analysis Consortium database, and the Human Protein Atlas database. Small interfering RNA-mediated knockdown of MCM5 inhibited the cell cycle and migration of colorectal cancer cells in vitro. And western blotting results indicated that factors correlated with cell cycle (CDK2/6, Cyclin D3, P21) were downregulated after knockdown of MCM5 in vitro. Besides, downregulation of MCM5 was demonstrated to inhibit lung metastasis of COAD in nude mice model. In conclusion, MCM5 is an oncogene of COAD that promotes COAD progression via cell cycle control.

Bacterial genome reduction for optimal chassis of synthetic biology: a review.

Bacteria with streamlined genomes, that harbor full functional genes for essential metabolic networks, are able to synthesize the desired products more effectively and thus have advantages as production platforms in industrial applications. To obtain streamlined chassis genomes, a large amount of effort has been made to reduce existing bacterial genomes. This work falls into two categories: rational and random reduction. The identification of essential gene sets and the emergence of various genome-deletion techniques have greatly promoted genome reduction in many bacteria over the past few decades. Some of the constructed genomes possessed desirable properties for industrial applications, such as: increased genome stability, transformation capacity, cell growth, and biomaterial productivity. The decreased growth and perturbations in physiological phenotype of some genome-reduced strains may limit their applications as optimized cell factories. This review presents an assessment of the advancements made to date in bacterial genome reduction to construct optimal chassis for synthetic biology, including: the identification of essential gene sets, the genome-deletion techniques, the properties and industrial applications of artificially streamlined genomes, the obstacles encountered in constructing reduced genomes, and the future perspectives.

Annexin A9 promotes cell proliferation by regulating the Wnt signaling pathway in colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Expression of Annexin A9 (ANXA9), a member of the annexin A family, is upregulated in CRC. However, the molecular role of ANXA9 in CRC remains unknown. In the present study, we aimed to investigate the function of ANXA9 and to elucidate the mechanisms underlying its regulation in CRC. In this study, mRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and GEPIA database, respectively. Kaplan-Meier analysis was used to analyze the survival rates. LinkedOmics and Metascape databases were used to explore the potential mechanisms of regulation of ANXA9 and to identify genes co-expressed with ANXA9. Finally, in vitro experiments were used to evaluate the function of ANXA9 and explore potential mechanisms. We found that ANXA9 expression was significantly elevated in CRC tissue and cells. High ANXA9 expression was associated with shorter overall survival, poorer disease specific survival, as well as with patient age, clinical stage, M stage, and OS events in CRC. Knockdown of ANXA9 inhibited cell proliferation, invasion, migratory potential, and cell cycle arrest. Mechanistically, functional analysis revealed that genes co-expressed with ANXA9 were mainly enriched in the Wnt signaling pathway. ANXA9 deletion suppressed cell proliferation via the Wnt signaling pathway, while Wnt activation reversed the effects of ANXA9. In conclusion, ANXA9 may promote CRC progression by regulating the Wnt signaling pathway and may be a potential diagnostic biomarker in the clinical management of CRC.

A cell transmembrane peptide chimeric M(27-39)-HTPP targeted therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, with a growing incidence and death rate worldwide. The aims and challenges of treating HCC include targeting the tumor, entering the tumor tissue, inhibiting the spread and growth of tumor cells. M27-39 is a small peptide isolated from the antimicrobial peptide Musca domestica cecropin (MDC), whereas HTPP is a liver-targeting, cell-penetrating peptide obtained from the circumsporozoite protein (CSP) of Plasmodium parasites. In this study, M27-39 was modified by HTPP to form M(27-39)-HTPP, which targeted tumor penetration to treat HCC. Here, we revealed that M(27-39)-HTPP had a good ability to target and penetrate the tumor, effectively limit the proliferation, migration, and invasion, and induce the apoptosis in HCC. Notably, M(27-39)-HTPP demonstrated good biosecurity when administered at therapeutic doses. Accordingly, M(27-39)-HTPP could be used as a new, safe, and efficient therapeutic peptide for HCC.

Adaptive Evolution of the Spike Protein in Coronaviruses.

Coronaviruses are single-stranded, positive-sense RNA viruses that can infect many mammal and avian species. The Spike (S) protein of coronaviruses binds to a receptor on the host cell surface to promote viral entry. The interactions between the S proteins of coronaviruses and receptors of host cells are extraordinarily complex, with coronaviruses from different genera being able to recognize the same receptor and coronaviruses from the same genus able to bind distinct receptors. As the coronavirus disease 2019 pandemic has developed, many changes in the S protein have been under positive selection by altering the receptor-binding affinity, reducing antibody neutralization activities, or affecting T-cell responses. It is intriguing to determine whether the selection pressure on the S gene differs between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses due to the host shift from nonhuman animals to humans. Here, we show that the S gene, particularly the S1 region, has experienced positive selection in both SARS-CoV-2 and other coronaviruses. Although the S1 N-terminal domain exhibits signals of positive selection in the pairwise comparisons in all four coronavirus genera, positive selection is primarily detected in the S1 C-terminal domain (the receptor-binding domain) in the ongoing evolution of SARS-CoV-2, possibly owing to the change in host settings and the widespread natural infection and SARS-CoV-2 vaccination in humans.