SHORT-ROOT paralogs mediate feedforward regulation of D-type cyclin to promote nodule formation in soybean.

Nitrogen fixation in soybean takes place in root nodules that arise from de novo cell divisions in the root cortex. Although several early nodulin genes have been identified, the mechanism behind the stimulation of cortical cell division during nodulation has not been fully resolved. Here we provide evidence that two paralogs of soybean SHORT-ROOT (GmSHR) play vital roles in soybean nodulation. Expression of GmSHR4 and GmSHR5 (GmSHR4/5) is induced in cortical cells at the beginning of nodulation, when the first cell divisions occur. The expression level of GmSHR4/5 is positively associated with cortical cell division and nodulation. Knockdown of GmSHR5 inhibits cell division in outer cortical layers during nodulation. Knockdown of both paralogs disrupts the cell division throughout the cortex, resulting in poorly organized nodule primordia with delayed vascular tissue formation. GmSHR4/5 function by enhancing cytokinin signaling and activating early nodulin genes. Interestingly, D-type cyclins act downstream of GmSHR4/5, and GmSHR4/5 form a feedforward loop regulating D-type cyclins. Overexpression of D-type cyclins in soybean roots also enhanced nodulation. Collectively, we conclude that the GmSHR4/5-mediated pathway represents a vital module that triggers cytokinin signaling and activates D-type cyclins during nodulation in soybean.

Association between ursodeoxycholic acid use and COVID-19 in individuals with chronic liver disease: a nationwide case-control study in South Korea.

BACKGROUND: Conflicting evidence exists regarding the effects of ursodeoxycholic acid (UDCA) on coronavirus disease 2019 (COVID-19). This study investigates the association between UDCA administration and COVID-19 infection and its related outcomes in individuals with chronic liver disease (CLD). METHODS: A customized COVID-19 research database (n = 3,485,376) was created by integrating data from the National Health Insurance Service (NHIS) and the Korea Disease Control and Prevention Agency's COVID-19 databases. The study focused on patients diagnosed with COVID-19 in 2021, using the NHIS data from 365 days before diagnosis. To create comparable groups with and without UDCA administration before COVID-19, we used propensity score matching. The primary endpoint was the first confirmed positive result for severe acute respiratory syndrome coronavirus-2. In addition, we identified severe COVID-19-related outcomes. Subgroup analysis were conducted based on the dose of UDCA exposure. RESULTS: Data from 74,074 individuals with CLD was analyzed. The participants' average age was 57.5 years, and 52.1% (19,277) of those in each group were male. Those with prior UDCA exposure had a significantly lower risk of COVID-19 infection (adjusted OR: 0.80, 95% CI [0.76-0.85]) compared to the non-UDCA group. Additionally, the UDCA group had a lower risk of severe COVID-19 outcomes (adjusted OR: 0.67, 95% CI [0.46-0.98]). Subgroup analyses indicated that there was a decrease in COVID-19 infection and its related outcomes with increasing UDCA exposure dose. CONCLUSIONS: Our large observational study highlights the potential use of readily available UDCA as an adjunctive therapy for COVID-19 in individuals with CLD.

TRIM11, a new target of p53, facilitates the migration and invasion of nasopharyngeal carcinoma cells.

BACKGROUND: Although tripartite motif-containing protein 11 (TRIM11) is known to be associated with a variety of cancers, its role in nasopharyngeal carcinoma (NPC) is unclear. METHODS AND RESULTS: To investigate the role of TRIM11 in NPC, TRIM11 was stably overexpressed in 6-10B and CNE2 cells with lentiviral vectors and knocked down in S18 and 5-8F cells using the CRISPR/Cas9 system. Transwell assays and wound-healing assays revealed that TRIM11 facilitated the migration and invasion of NPC cells. Mechanistically, we found that p53 inhibits TRIM11 expression by binding to its promoter. CONCLUSIONS: TRIM11 may serve as a potential diagnostic marker for NPC and has a certain therapeutic value.

Hyperelatolides A-D, Antineuroinflammatory Constituents with Unusual Carbon Skeletons from Hypericum elatoides.

Four new δ- and γ-lactone derivatives, hyperelatolides A-D (1-4, respectively), were discovered from the aerial portions of Hypericum elatoides R. Keller. Their structures were elucidated by analysis of NMR spectra, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and X-ray crystallographic data. Hyperelatolides A (1) and B (2) represent the first examples of δ-lactone derivatives characterized by a (Z)-(5,5-dimethyl-2-(2-oxopropyl)cyclohexylidene)methyl moiety and a benzoyloxy group attached to the ß- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C (3) and D (4) are unprecedented γ-lactone derivatives featuring substituents similar to those of 1 and 2. All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones 1 and 2 exhibited considerable antineuroinflammatory activity, with IC50 values of 5.74 ± 0.27 and 7.35 ± 0.26 µM, respectively. Moreover, the mechanistic study revealed that lactone 1 significantly suppressed nuclear factor kappa B signaling and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-induced cells, which may contribute to its antineuroinflammatory activity.

Effects of an urban forest healing program on cancer-related fatigue in cancer survivors.

PURPOSE: This study aimed to examine the effects of an eight-session structured urban forest healing program for cancer survivors with fatigue. BACKGROUND: Cancer-related fatigue (CRF) is a complex and multifactorial common symptom among cancer survivors that limits quality of life (QoL). Although health benefits of forest healing on physiological, physical, and psychological aspect as well as on the immune system have been reported in many studies, there is limited evidence on the efficacy of specialized forest program for cancer survivors. METHOD: A single-blinded, pre-test and post-test control group clinical trial was conducted with -75 cancer survivors assigned to either the forest healing group or the control group. The intervention was an eight-session structured urban forest program provided at two urban forests with easy accessibility. Each session consists of three or four major activities based on six forest healing elements such as landscape, phytoncides, anions, sounds, sunlight, and oxygen. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to examine whether sociodemographic, clinical, physiological (respiratory function, muscle strength, balance, 6-min walking test) and psychological (distress, mood state, sleep quality, QoL) characteristics at baseline moderated the intervention effect on fatigue severity at 9 weeks. RESULTS: Significant time-group interactions were observed muscle strength, balance, 6-min walking test, distress, fatigue, moods, and QoL. The mean difference in fatigue between pre- and post-forest healing program was 9.1 (95% CI 6.2 to 11.9), 11.9 (95% CI 7.6 to 16.1) in moods, and -93.9 (95% CI -123.9 to -64.0) in QoL, showing significant improvements in forest healing group, but no significant improvements in the control group. CONCLUSION: This study suggests that a forest healing program positively impacts the lives of cancer survivors, by addressing both physical and psychological challenges associated with CRF. TRIAL REGISTRATION NUMBER: KCT0008447 (Date of registration: May 19, 2023).

Downregulation of SUN2 promotes metastasis of colon cancer by activating BDNF/TrkB signalling by interacting with SIRT1.

Distant metastasis is the major cause of colon cancer (CC) treatment failure. SAD1/UNC84 domain protein-2 (SUN2) is a key component of linker of the nucleoskeleton and cytoskeleton (LINC) complexes that may be relevant for metastasis in several cancers. Here, we first confirmed that SUN2 levels were significantly lower in primary CC tissues and distant metastasis than in normal colon tissues, and high SUN2 expression predicted good overall survival. Overexpression of SUN2 or knockdown of SUN2 inhibited or promoted cell migration and invasion in vitro, respectively. Moreover, silencing of SUN2 promoted metastasis in vivo. Mechanistically, we showed that SUN2 exerts its tumour suppressor functions by decreasing the expression of brain derived neurotrophic factor (BDNF) to inhibit BDNF/tropomyosin-related kinase B (TrkB) signalling. Additionally, SUN2 associated with SIRT1 and increased the acetylation of methyl-CpG binding protein 2 (MeCP2) to increase its occupancy at the BDNF promoter. Taken together, our findings indicate that SUN2 is a key component in CC progression that acts by inhibiting metastasis and that novel SUN2-SIRT1-MeCP2-BDNF signalling may prove to be useful for the development of new strategies for treating patients with CC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Corneal endothelial expansion using human umbilical cord mesenchymal stem cell-derived conditioned medium.

Rabbit corneal endothelial cells are frequently used in pharmacological experiments and are useful for corneal transplant experiments. We performed the present study to analyze the effect of conditioned medium (CM) derived from human umbilical cord mesenchymal stem cells (HUMSCs) on the growth of rabbit corneal endothelial cells (RCECs) and to establish a program for expansion of RCECs in vitro. RCECs were cultured using a CM derived from HUMSCs (HUMSCs-CM) in vitro. The proliferation ability of RCECs cultured in the presence of HUMSCs-CM was evaluated by conducting 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation, and scratch migration assays. The proliferation ability of RCECs maintained in HUMSCs-CM was significantly enhanced as compared to RCECs cultivated in the control group. Immunofluorescence indicated that zonula occludens-1 (ZO-1) and N-cadherin were located at intercellular junctions. Real-time PCR and western blot analyses demonstrated that the CEC-relative functional markers were expressed in RCECs maintained in HUMSCs-CM. Flow cytometry analyses demonstrated that HUMSCs-CM promoted the G0/G1 entrance to the S phase in RCECs. Our results demonstrated that HUMSCs-CM induced the proliferation of RCECs in vitro and maintained the necessary characteristic phenotypes. The expanded RCECs may provide a promising cell source for experimental research and clinical therapy.

Review of applications of CRISPR-Cas9 gene-editing technology in cancer research.

Characterized by multiple complex mutations, including activation by oncogenes and inhibition by tumor suppressors, cancer is one of the leading causes of death. Application of CRISPR-Cas9 gene-editing technology in cancer research has aroused great interest, promoting the exploration of the molecular mechanism of cancer progression and development of precise therapy. CRISPR-Cas9 gene-editing technology provides a solid basis for identifying driver and passenger mutations in cancer genomes, which is of great value in genetic screening and for developing cancer models and treatments. This article reviews the current applications of CRISPR-Cas9 gene-editing technology in various cancer studies, the challenges faced, and the existing solutions, highlighting the potential of this technology for cancer treatment.

EPZ015666, a selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an antitumour effect in retinoblastoma.

Retinoblastoma (RB) is the most common intraocular malignant tumour in infants, and chemotherapy has been the primary therapy method in recent years. PRMT5 is an important member of the protein arginine methyltransferase family, which plays an important role in various tumours. Our study showed that PRMT5 was overexpressed in retinoblastoma and played an important role in retinoblastoma cell growth. EPZ015666 is a novel PRMT5 inhibitor, and we found that it inhibited retinoblastoma cell proliferation and led to cell cycle arrest at the G1 phase. At the same time, EPZ015666 regulated cell cycle related protein (P53, P21, P27, CDK2) expression. In brief, our study showed that PRMT5 promoted retinoblastoma growth, the PRMT5 inhibitor EPZ015666 inhibited retinoblastoma in vitro by regulating P53-P21/P27-CDK2 signaling pathways and slowed retinoblastoma growth in a xenograft model.

TdIF1-LSD1 Axis Regulates Epithelial-Mesenchymal Transition and Metastasis via Histone Demethylation of E-Cadherin Promoter in Lung Cancer.

We have previously found that TdT-interacting factor 1 (TdIF1) is a potential oncogene expressed in non-small cell lung cancer (NSCLC) and is associated with poor prognosis. However, its exact mechanism is still unclear. The lysine-specific demethylase 1 (LSD1) is a crucial mediator of the epithelial-mesenchymal transition (EMT), an important process triggered during cancer metastasis. Here, we confirm that TdIF1 is highly expressed in NSCLC and related to lymph node metastasis through The Cancer Genome Atlas (TCGA) analysis of clinical samples. Silencing TdIF1 can regulate the expression of EMT-related factors and impair the migration and invasion ability of cancer cells in vitro. An analysis of tumor xenografts in nude mice confirmed that silencing TdIF1 inhibits tumor growth. Furthermore, we determined the interaction between TdIF1 and LSD1 using immunoprecipitation. Chromatin immunoprecipitation (ChIP) revealed that TdIF1 was enriched in the E-cadherin promoter region. The knockdown of TdIF1 repressed the enrichment of LSD1 at the E-cadherin promoter region, thereby regulating the level of promoter histone methylation and modulating E-cadherin transcription activity, ultimately leading to changes in EMT factors and cancer cell migration and invasion ability. The LSD1 inhibitor and TdIF1 knockdown combination showed a synergistic effect in inhibiting the growth, migration, and invasion of NSCLC cells. Taken together, this is the first demonstration that TdIF1 regulates E-cadherin transcription by recruiting LSD1 to the promoter region, thereby promoting EMT and tumor metastasis and highlighting the potential of TdIF1 as a therapeutic target for NSCLC.

Histone deacetylase inhibitor, AR-42, exerts antitumor effects by inducing apoptosis and cell cycle arrest in Y79 cells.

Retinoblastoma (RB) is the most common type of intraocular malignant tumor that occurs in childhood. AR-42, a member of a newly discovered class of phenylbutyrate-derived histone deacetylase inhibitors, exerts antitumor effects on many cancers. In the present study, we initially evaluated the effect of AR-42 towards RB cells and explored the underlying mechanism in this disease. Our results found that AR-42 showed powerful antitumor effects at low micromolar concentrations by inhibiting cell viability, blocking cell cycle, stimulating apoptosis in vitro, and suppressing RB growth in a mouse subcutaneous tumor xenograft model. Furthermore, the AKT/nuclear factor-kappa B signaling pathway was disrupted in Y79 cells treated with AR-42. In conclusion, we propose that AR-42 might be a promising drug treatment for RB.

Symplastic signaling instructs cell division, cell expansion, and cell polarity in the ground tissue of Arabidopsis thaliana roots.

Cell-to-cell communication is essential for the development and patterning of multicellular organisms. In plants, plasmodesmata (PD) provide direct routes for intercellular signaling. However, the role that PD-mediated signaling plays in plant development has not been fully investigated. To gain a comprehensive view of the role that symplastic signaling plays in Arabidopsis thaliana, we have taken advantage of a synthetic allele of CALLOSE SYNTHASE3 (icals3m) that inducibly disrupts cell-to-cell communication specifically at PD. Our results show that loss of symplastic signaling to and from the endodermis has very significant effects on the root, including an increase in the number of cell layers in the root and a misspecification of stele cells, as well as ground tissue. Surprisingly, loss of endodermal signaling also results in a loss of anisotropic elongation in all cells within the root, similar to what is seen in radially swollen mutants. Our results suggest that symplastic signals to and from the endodermis are critical in the coordinated growth and development of the root.

Down-regulation of prostate stem cell antigen (PSCA) by Slug promotes metastasis in nasopharyngeal carcinoma.

Distant metastasis and local recurrence are still the major causes for failure of treatment in patients with nasopharyngeal carcinoma (NPC), making it urgent to further elicit the molecular mechanisms of NPC metastasis. Using a gene microarray including transcription factors and known markers for cancer stem cells, prostate stem cell antigen (PSCA) was found to be significantly down-regulated in metastatic NPC in lymph node, compared to its primary tumour, and in NPC cell lines with high metastatic ability compared to those with low metastatic ability. NPC patients with low PSCA expression had a consistently poor metastasis-free survival (p = 0.003). Knockdown and overexpression of PSCA respectively enhanced and impaired the migration and invasion in vitro and the lung metastasis in vivo of NPC cells. Mechanistically, the enhancement of NPC metastasis by knocking down PSCA probably involved epithelial-mesenchymal transition (EMT), by up-regulating N-cadherin and ZEB1/2 and by activating RhoA. The down-regulation of PSCA in NPC cells resulted directly from the binding of Slug to the PSCA promoter. PSCA may be a potential diagnostic marker and therapeutic target for patients with NPC.

The SWI2/SNF2 chromatin remodeling ATPase BRAHMA represses abscisic acid responses in the absence of the stress stimulus in Arabidopsis.

The survival of plants as sessile organisms depends on their ability to cope with environmental challenges. Of key importance in this regard is the phytohormone abscisic acid (ABA). ABA not only promotes seed dormancy but also triggers growth arrest in postgermination embryos that encounter water stress. This is accompanied by increased desiccation tolerance. Postgermination ABA responses in Arabidopsis thaliana are mediated in large part by the ABA-induced basic domain/leucine zipper transcription factor ABA INSENSITIVE5 (ABI5). Here, we show that loss of function of the SWI2/SNF2 chromatin remodeling ATPase BRAHMA (BRM) causes ABA hypersensitivity during postgermination growth arrest. ABI5 expression was derepressed in brm mutants in the absence of exogenous ABA and accumulated to high levels upon ABA sensing. This effect was likely direct; chromatin immunoprecipitation revealed BRM binding to the ABI5 locus. Moreover, loss of BRM activity led to destabilization of a nucleosome likely to repress ABI5 transcription. Finally, the abi5 null mutant was epistatic to BRM in postgermination growth arrest. In addition, vegetative growth defects typical of brm mutants in the absence of ABA treatment could be partially overcome by reduction of ABA responses, and brm mutants displayed increased drought tolerance. We propose a role for BRM in the balance between growth or stress responses.

SWI2/SNF2 chromatin remodeling ATPases overcome polycomb repression and control floral organ identity with the LEAFY and SEPALLATA3 transcription factors.

Patterning of the floral organs is exquisitely controlled and executed by four classes of homeotic regulators. Among these, the class B and class C floral homeotic regulators are of central importance as they specify the male and female reproductive organs. Inappropriate induction of the class B gene APETALA3 (AP3) and the class C gene AGAMOUS (AG) causes reduced reproductive fitness and is prevented by polycomb repression. At the onset of flower patterning, polycomb repression needs to be overcome to allow induction of AP3 and AG and formation of the reproductive organs. We show that the SWI2/SNF2 chromatin-remodeling ATPases SPLAYED (SYD) and BRAHMA (BRM) are redundantly required for flower patterning and for the activation of AP3 and AG. The SWI2/SNF2 ATPases are recruited to the regulatory regions of AP3 and AG during flower development and physically interact with two direct transcriptional activators of class B and class C gene expression, LEAFY (LFY) and SEPALLATA3 (SEP3). SYD and LFY association with the AP3 and AG regulatory loci peaks at the same time during flower patterning, and SYD binding to these loci is compromised in lfy and lfy sep3 mutants. This suggests a mechanism for SWI2/SNF2 ATPase recruitment to these loci at the right stage and in the correct cells. SYD and BRM act as trithorax proteins, and the requirement for SYD and BRM in flower patterning can be overcome by partial loss of polycomb activity in curly leaf (clf) mutants, implicating the SWI2/SNF2 chromatin remodelers in reversal of polycomb repression.

LATE MERISTEM IDENTITY2 acts together with LEAFY to activate APETALA1.

The switch from producing vegetative structures (branches and leaves) to producing reproductive structures (flowers) is a crucial developmental transition that significantly affects the reproductive success of flowering plants. In Arabidopsis, this transition is in large part controlled by the meristem identity regulator LEAFY (LFY). The molecular mechanisms by which LFY orchestrates a precise and robust switch to flower formation is not well understood. Here, we show that the direct LFY target LATE MERISTEM IDENTITY2 (LMI2) has a role in the meristem identity transition. Like LFY, LMI2 activates AP1 directly; moreover, LMI2 and LFY interact physically. LFY, LMI2 and AP1 are connected in a feed-forward and positive feedback loop network. We propose that these intricate regulatory interactions not only direct the precision of this crucial developmental transition in rapidly changing environmental conditions, but also contribute to its robustness and irreversibility.

Systematic evaluation of methods for iron-impregnation of biochar and effects on arsenic in flooded soils.

There is a need for innovative strategies to decrease the mobility of metal(loids) including arsenic (As) and cadmium (Cd) in agricultural soils, including rice paddies, so as to minimize dietary exposure to these toxic elements. Iron (Fe)-modified biochars (FBCs) are used to immobilize As and Cd in soil-water systems, but there is a lack of clarity on optimal methods for preparing FBCs because there are only limited studies that directly compare BCs impregnated with Fe under different conditions. There is also a lack of information on the long-term performance of FBCs in flooded soil environments, where reductive dissolution of Fe (oxy)hydroxide phases loaded onto biochar surfaces may decrease the effectiveness of FBCs. This study uses material characterization methods including FTIR, SEM-EDX, BET, and adsorption isotherm experiments to investigate the effects of Fe-impregnation methods (pH, pyrolysis sequence, and sonication) on the morphology and mineralogy of Fe loaded onto the biochar surface, and to FBC adsorbent properties for arsenate (As(V)), arsenite (As(III)), and Cd. Acidic impregnation conditions favored the adsorption of As(III) onto amorphous Fe phases that were evenly distributed on the biochar surface, including within the biochar pore structure. The combination of sonication with acidic Fe-impregnation conditions led to the best adsorption capacities for As(V) and As(III) (4830 and 11,166 µg As g-1 biochar, respectively). Alkaline Fe-impregnation conditions led to the highest Cd adsorption capacity of 3054 µg Cd g-1 biochar, but had poor effectiveness as an As adsorbent. Amending soil with 5% (w/w) of an acid-impregnated and sonicated FBC was more effective than an alkaline-impregnated FBC or ferrihydrite in decreasing porewater As concentrations. The acid-impregnated FBC also had greater longevity, decreasing As by 54% and 56% in two flooded phases, probably due to the greater stability of Fe(III) within the biochar pore structure that may have a direct chemical bond to the biochar surface. This study demonstrates that FBCs can be designed with selectivity towards different As species or Cd and that they can maintain their effectiveness under anaerobic soil conditions. This is the first study to systematically test how impregnation conditions affect the stability of FBCs in soils under multiple drying-rewetting cycles.

Association of oxcarbazepine concentration with seizure frequency in pregnant women with epilepsy.

The management of epilepsy during pregnancy presents particular challenges for neurologists worldwide. Currently, there are no clear recommendations for oxcarbazepine (OXC) specific target concentration during pregnancy. We conducted this retrospective observational cohort study on pregnant women with epilepsy (WWE) who received OXC monotherapy or polytherapy, at the epilepsy outpatient clinic of a tertiary hospital in eastern China. Sixteen pregnancies of 16 WWE were split into the seizure-free group or the non-seizure-free group, according to whether they had been seizure free for more than one year prior to conception or not. There was a significantly decrease in OXC concentration throughout pregnancy, as indicated by the concentration/dose ratio and the ratio of target concentration (RTC). The second trimester of pregnancy was the period when seizure deterioration occurred the most, particularly in the non-seizure-free group. Lower RTC_OXC was identified to be a risk factor for increasing seizure frequency in both the total group and the non-seizure-free group in both univariate and multivariate analysis, with a threshold of 0.575 for differentiating patients at high-risk and low-risk for seizure deterioration. In conclusion, this study suggested an OXC concentration threshold of 0.575 during pregnancy for assisting neurologists in OXC drug monitoring and dose adaptation.

Global research on RNA vaccines for COVID-19 from 2019 to 2023: a bibliometric analysis.

Background: Since the global pandemic of COVID-19 has broken out, thousands of pieces of literature on COVID-19 RNA vaccines have been published in various journals. The overall measurement and analysis of RNA vaccines for COVID-19, with the help of sophisticated mathematical tools, could provide deep insights into global research performance and the collaborative architectural structure within the scientific community of COVID-19 mRNA vaccines. In this bibliometric analysis, we aim to determine the extent of the scientific output related to COVID-19 RNA vaccines between 2019 and 2023. Methods: We applied the Bibliometrix R package for comprehensive science mapping analysis of extensive bibliographic metadata retrieved from the Web of Science Core Collection database. On January 11th, 2024, the Web of Science database was searched for COVID-19 RNA vaccine-related publications using predetermined search keywords with specific restrictions. Bradford's law was applied to evaluate the core journals in this field. The data was analyzed with various bibliometric indicators using the Bibliometrix R package. Results: The final analysis included 2962 publications published between 2020 and 2023 while there is no related publication in 2019. The most productive year was 2022. The most relevant leading authors in terms of publications were Ugur Sahin and Pei-Yong, Shi, who had the highest total citations in this field. The core journals were Vaccines, Frontiers in Immunology, and Viruses-Basel. The most frequently used author's keywords were COVID-19, SARS-CoV-2, and vaccine. Recent COVID-19 RNA vaccine-related topics included mental health, COVID-19 vaccines in humans, people, and the pandemic. Harvard University was the top-ranked institution. The leading country in terms of publications, citations, corresponding author country, and international collaboration was the United States. The United States had the most robust collaboration with China. Conclusion: The research hotspots include COVID-19 vaccines and the pandemic in people. We identified international collaboration and research expenditure strongly associated with COVID-19 vaccine research productivity. Researchers' collaboration among developed countries should be extended to low-income countries to expand COVID-19 vaccine-related research and understanding.