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The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1.617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.

Background Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism. Methods The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway. Results We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC. Conclusions Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum.

Background Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC. Methods The expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invasion assay and xenograft experiment. The expression of selected genes was detected by western blot or real time PCR. Results SRSF3 is overexpressed in CRC tissues and its high expression was associated with CRC differentiation, lymph node invasion and AJCC stage. Upregulation of SRSF3 was also associated with shorter overall survival. Knockdown of SRSF3 in CRC cells activated ArhGAP30/Ace-p53 and decreased cell proliferation, migration and survival; while ectopic expression of SRSF3 attenuated ArhGAP30/Ace-p53 and increases cell proliferation, migration and survival. Targeting SRSF3 in xenograft tumors suppressed tumor progression in vivo. Conclusions Taken together, our data identify SRSF3 as a regulator for ArhGAP30/Ace-p53 in CRC, and highlight potential prognostic and therapeutic significance of SRSF3 in CRC.

SARS-CoV-2 is quickly evolving from wild-type to many variants and spreading around the globe. Since many people have been vaccinated with various types of vaccines, it is crucial to develop a high throughput platform for measuring the antibody responses and surrogate neutralizing activities against multiple SARS-CoV-2 variants. To meet this need, the present study developed a SARS-CoV-2 variant (CoVariant) array which consists of the extracellular domain of spike variants, e.g., wild-type, D614G, B.1.1.7, B.1.351, P.1, B.1.617, B.1.617.1, B.1.617.2, and B.1.617.3. A surrogate virus neutralization on the CoVariant array was established to quantify the bindings of antibody and host receptor ACE2 simultaneously to spike variants. By using a chimeric anti-spike antibody, we demonstrated a broad binding spectrum of antibodies while inhibiting the bindings of ACE2 to spike variants. To monitor the humoral immunities after vaccination, we collected serums from unvaccinated, partial, or fully vaccinated individuals with either mRNA-1273 or AZD1222 (ChAdOx1). The results showed partial vaccination increased the surrogate neutralization against all the mutants while full vaccination boosted the most. Although IgG, IgA, and IgM isotypes correlated with surrogate neutralizing activities, they behave differently throughout the vaccination processes. Overall, this study developed CoVariant arrays and assays for profiling the humoral responses which are useful for immune assessment, vaccine research, and drug development.

// Ji-Lin Wang 1, * , Wen-Yu Su 1, * , Yan-Wei Lin 2 , Hua Xiong 1 , Ying-Xuan Chen 1 , Jie Xu 1 , Jing-Yuan Fang 1 1 Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China 2 Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China * These authors have contributed equally to this work Correspondence to: Ji-Lin Wang, email: wangjilin811123@163.com Jie Xu, email: xujieletter@163.com Jing-Yuan Fang, email: jingyuanfang@sjtu.edu.cn Keywords: CD44v6, prognosis, colorectal cancer, meta-analysis Received: October 04, 2016 Accepted: November 24, 2016 Published: December 24, 2016 ABSTRACT CD44v6 has recently been reported as a biomarker for colorectal cancer. However, the clinical and prognostic significance of CD44v6 in colorectal cancer remains controversial. Therefore, we performed a meta-analysis to clarify this issue. A comprehensive literature search was performed using Medline, Embase and Web of Science, and the statistical analysis was conducted using Stata software. A total of twenty-one studies including 3918 colorectal cancer cases were included. The pooled analysis showed that CD44v6 overexpression in colorectal cancer was an independent prognostic marker correlating with lower 5-year overall survival rate (OR=0.78, 95%CI =0.67-0.91, p=0.001). CD44v6 overexpression was also associated with more lymph node invasion (OR=1.48, 95%CI= 1.02-2.15, p=0.04), and advanced Dukes stage (OR=2.47, 95%CI= 1.29-4.73, p=0.01). In addition, while excluding Zolbec’s study, CD44v6 overexpression was associated with distance metastasis (OR=1.65, 95%CI =1.13-2.40, p=0.01). Taken together, this meta-analysis suggested that CD44v6 is an efficient prognostic factor in colorectal cancer.