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PDF file - 77K, LCN2 does not affect MMP9 expression.

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PDF file - 142K, The AKT signaling pathway is partly inactivated after NGALR knockdown.

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PDF file - 344K, Endogenous HIC1 knockdown promotes cell migration and invasion in MCF-10A cells.

PDF file - 131K, LCN2 does not affect ERK and NF-kB pathways.

PDF file - 623K, Effects of restoring HIC1 expression in MDA-468 cells.

PDF file - 141K, HIC1 and LCN2 do not affect epithelial-mesenchymal transition (EMT).

PDF file - 116K, Correlation between expression of HIC1 and clinical pathological features in tissue microarrays.

PDF file - 118K, Serum levels of LCN2 in breast cancer patients.

Fang-xue Gong,1 Xin Zhou,2 Zhao-he Niu,1 Yan Mao,1 Yong-mei Wang,1 Meng Lv,1 Xue-qiang Gao,1 Wen-jing Liu,1 Hai-bo Wang1 1Department of Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 2Qingdao Medical College of Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Hai-bo Wang, Department of Breast Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao City, Shandong Province, People’s Republic of China, Tel +86 18661805787, Email hbwang66@126.comPurpose: Autologous fat grafting (AFG) is a technique that can improve the appearance of breasts in surgical patients. There are currently few studies on breast-conserving surgery (BCS) combined with immediate AFG, although we believe that it could achieve satisfactory effects. Therefore, the purpose of this study is to observe the effects of BCS combined with immediate AFG on oncologic safety, satisfaction and psychology of breast cancer patients.Patients and Methods: We retrospectively collected the data of 85 breast cancer patients from February 2018 to October 2018. After screening, 40 patients in AFG group (AG, BCS combined with immediate AFG) and 40 patients in control group (CG, BCS alone) were finally included in the study. The primary outcomes were the survival, tumor recurrence and metastasis, and BREAST-Q score of patients. The secondary outcomes were short and long-term complications, degree of depression and anxiety of patients.Results: A total of 80 patients were included in the analysis. There was no significant difference in the clinicopathological data between the two groups (P> 0.05). The average follow-up time of the two groups was 40.58± 2.630 and 40.28± 2.679 months. In the analysis of oncologic safety, no patients died in AG and 1 patient died in CG. In addition, there was no significant difference between the two groups in terms of the overall recurrence rate and the distribution of recurrence types (P> 0.05). As for satisfaction, the BREAST-Q score of AG was significantly higher than that of CG (57.85± 4.833 vs 51.93± 5.045, P< 0.001). In the secondary outcomes, there was no short-term complication specified in the study; in the long-term complications, the incidence of calcification in AG was not significantly higher than that in CG (P=0.065). In the analysis of depression and anxiety, there was no significant difference between the two groups (P> 0.05).Conclusion: BCS combined with immediate AFG can significantly improve patients’ satisfaction without increasing the risk of death and tumor recurrence. However, it does not seem to play a role in improving the conditions of depression and anxiety.Keywords: breast cancer, breast-conserving surgery, autologous fat grafting, oncologic safety, BREAST-Q, psychology

The problems existing in the online education courses of engineering majors in colleges and universities are studied, and the online education platform under the background of engineering certification is designed and researched. Artificial intelligence (AI) technology and wireless network technology are used in the in-depth study of online education courses. In terms of AI, the storage of data is specifically divided into three levels, namely, the source layer (operational data layer), the historical storage layer, and the data model layer. Data analysis includes the total number of data, spatial scope, and period, etc. The results show that the overall response time of the designed platform to the operation of university teachers and students is controlled within 3 s. The test results of two online education platforms show that the performance of the designed online education platform is relatively stable. It provides hardware support for online curriculum reform. In addition, in terms of the platform test pass rate, after many tests, the online education platform security test pass rate is above 98%. In the end, these conclusions are drawn: AI technology and wireless network technology can effectively improve the performance of online education platforms. Meanwhile, this can also further improve the learning efficiency of online education courses for college engineering students.

Exposure to extended periods of darkness is a common source of abiotic stress that significantly affects plant growth and development. To understand how Nicotiana benthamiana responds to dark stress, the proteomes and metabolomes of leaves treated with darkness were studied. In total, 5763 proteins and 165 primary metabolites were identified following dark treatment. Additionally, the expression of autophagy‐related gene (ATG) proteins was transiently upregulated. Weighted gene coexpression network analysis (WGCNA) was utilized to find the protein modules associated with the response to dark stress. A total of four coexpression modules were obtained. The results indicated that heat‐shock protein (HSP70), SnRK1‐interacting protein 1, 2A phosphatase‐associated protein of 46 kDa (Tap46), and glutamate dehydrogenase (GDH) might play crucial roles in N. benthamiana’s response to dark stress. Furthermore, a protein–protein interaction (PPI) network was constructed and top‐degreed proteins were predicted to identify potential key factors in the response to dark stress. These proteins include isopropylmalate isomerase (IPMI), eukaryotic elongation factor 5A (ELF5A), and ribosomal protein 5A (RPS5A). Finally, metabolic analysis suggested that some amino acids and sugars were involved in the dark‐responsive pathways. Thus, these results provide a new avenue for understanding the defensive mechanism against dark stress at the protein and metabolic levels in N. benthamiana., Exposure to prolonged periods of darkness can affect plant growth and development. In this study, the response of Nicotiana benthamiana to dark stress was investigated by analyzing changes to the proteome and metabolome across 13 time points. A number of hub proteins were filtered through weighted gene coexpression network analysis to identify potential key proteins involved in the dark stress response.

Intraocular lens (IOL) implantation surgery is quite effective in the treatment of blindness caused by cataracts. However, in clinical applications, IOLs readily form glistening. This phenomenon usually occurs for a period after IOL implantation ranging from a few months to several years. The molecular mechanism of the formation of glistening in IOLs is still inconclusive. Failure to understand and explain the molecular mechanism of glistening formation greatly hinders the design and application of new glistening-free IOL materials. Here, in this study, we use molecular dynamics simulation methods to conduct in-depth research on the molecular mechanism of the glistening formation of IOLs, aiming to provide a possible molecular mechanism of glistening. Furthermore, based on this molecular mechanism, we propose a novel strategy of a glistening-free material based on a composite design method to reasonably copolymerize several types of molecules or functional groups, so that the glistening phenomenon can be effectively eliminated. The possible molecular mechanism of glistening formation proposed in this research can offer a solid theoretical basis and guidance for the subsequent construction of glistening-free IOL materials.

BackgroundOwing to the emergence of drugs targeting human epidermal growth factor receptor 2 (HER2), remarkable prognostic enhancement has been seen for patients with HER2-positive breast carcinoma. However, anti-HER2 medicines are applicable merely to individuals with HER2-positive tumors, and the benefit for those with low HER2 expression is unclear. The DESTINY-Breast04 phase III and RC48 clinical trial results showed the benefit of antibody-drug couples for low HER2-expressing individuals with breast carcinoma, challenging the traditional dichotomy between HER2-negative and -positive tumors. Hence, the purposes of the present work are to explore the clinicopathological traits and prognostic differences in the HER2-low expression Chinese population with early-stage breast carcinoma.MethodsData from the database of the Breast Center of the Affiliated Hospital of Qingdao University were collected from January 2008 to December 2017. We screened a total of 4,598 patients, of which 2,837 had HER2-0 tumors and 1,761 had HER2-low tumors. Additionally, clinicopathological characteristics, survival, and prognostic information were obtained. Difference comparisons were made between HER2-0 and HER2-low groups regarding the clinical traits and outcomes.ResultsWe enrolled 4598 patients, with the HR-positive subjects suffering from HER2-low breast carcinoma higher in proportion than the HR-negative patients. In contrast to HER2-0 tumors, the HER2-low tumors were linked to an older median age at diagnosis, T1 tumors, N1 stage, a higher Ki-67 index, as well as inferior histological grade. Insignificant inter-group difference was noted regarding overall survival (OS), although the HER2–0 group exhibited better disease-free survival (DFS) than the HER2-low group for the entire (P = 0.003), lymph node-negative (P = 0.009) and HR-positive (P = 0.007) populations. According to the multivariate regression finding, low HER2 expression was an inferior DFS prognostic factor in the HER2-negative population with early-stage breast cancer (HR,1.33;95% CI, 1.06-1.66; P = 0.013).ConclusionThe clinical traits of the HER2-low carcinomas differed from those of HER2–0 tumors. Despite the insignificant inter-group difference in OS, the differences in DFS were found for the overall, lymph node-negative and HR-positive subjects, suggesting the possibility of HER2-low as an inferior prognostic factor for disease progression in early-stage breast cancer.

This study includes China and 197 countries from 1995 to 2019 as the research subjects. It considers trade in cultural products and inbound tourism as proxy variables of cultural communication and the visitor economy to analyze cultural communication’s impact on the visitor economy’s development and finds that cultural communication significantly promotes the visitor economy’s development. A robustness test of the benchmark regression results was conducted using the shrinktail treatment, substitute variable, and subsample selection methods. Cultural products were divided into three types, and the influence of trade in different cultural products on inbound tourism varies. Forty-nine categories had the largest promoting effect on inbound tourism, followed by thirty-seven categories and ninety-seven categories. There are significant differences in the influence of cultural product exports on inbound tourism in different cultural circles and continents. The influence effect within each circle was in the following order: Indian cultural circles (0.49), Islamic cultural circles (0.42), East Asian cultural circles (0.40), Western cultural circles (0.39), and Eastern European cultural circles (0.33). From the aspect continents, the export of cultural products to Europe significantly impacted China’s inbound tourism, followed by Africa, Asia, and the Americas. Finally, countermeasures and suggestions are proven to promote the visitor economy’s development. This study provides a reference for the cultural inheritance and development of the global tourism economy.

Under the background of my country’s “9073” pension model, for the elderly who are recovering at home to more actively and effectively carry out hand function rehabilitation training; based on the self-efficacy theory, this paper discusses its application in the design of hand rehabilitation training instruments for the elderly. Apply, analyze and study the self-efficacy of elderly hand rehabilitation patients, and build a user model based on this, and finally produce corresponding solutions and complete product design and implementation, stimulate and enhance their self-driven potential and self-efficacy value, and provide the elderly with a sense of self-efficacy. The product design of human hand rehabilitation aids provides an innovative idea.

Background: Congenital cataract is a leading cause of treatable childhood blindness and both clinically and genetically heterogeneous. Among the already characterized phenotypes, coralliform cataract is a rare special form of congenital cataracts. Although previous studies had shown that mutations in the γD-crystallin (CRYGD) gene can result in congenital coralliform cataracts, no conclusive genotype-phenotype correlation might be drawn. Here we aimed to identify the spectrum and frequency of CRYGD gene mutations in congenital coralliform cataracts of Chinese origin. Methods: The medical records of 392 Chinese families with congenital cataracts were reviewed between January 2011 and December 2021. The families, clinically documented to have congenital coralliform cataracts, were screened for mutations in candidate CRYGD gene. The genomic DNA of all subjects was extracted from peripheral blood leukocytes. PCR amplified and direct sequencing were performed to identify the disease-causing mutation. Results: A total of 12 families with coralliform cataracts were recruited in this study in the past 10 years, accounting for 3.1% of the families with congenital cataracts. Of the 12 families, all affected individuals presented with bilateral non-progressive coralliform cataracts since birth. A recurrent c.70 C>A (p. P24T) mutation in CRYGD was identified in 10 families (83.3%) with congenital cataract, which co-segregated with all affected individuals and was not observed in unaffected family members or ethnically matched normal controls. Conclusions: The coralliform cataract is characterized by being bilateral, non-progressive and present at birth. A recurrent P24T CRYGD mutation occurs independently in 83.3% of the Chinese families with congenital coralliform cataracts and most likely represents a mutational hot spot, which underscore the relations between coralliform cataract and P24T CRYGD.

The heavy hadron spectrum is constrained by symmetries, of which two of the most important ones are heavy-quark spin and SU(3)-flavor symmetries. Here we argue that in the molecular picture the Y(4230) [or Y(4260)], the Y(4360), and the recently discovered Y(4500) and Y(4620) vectorlike resonances are linked by these two symmetries. By formulating a contact-range effective field theory for the DD¯1 and DsD¯s1 family of S- and P-wave charmed meson-antimeson systems, we find that if the Y(4230) were to be a pure DD¯1 molecular state, there would be a D*D¯1 partner with a mass similar to the Y(4360), a DsD¯s1 partner with a mass close to the Y(4500), and three J=1, 2 Ds*D¯s1 and J=3 Ds*D¯s2* bound states with a mass in the vicinity of 4630 MeV, of which the first one (J=1) might correspond with the Y(4620). The previous predictions can in turn be improved by modifying the assumptions we have used to build the effective field theory. In particular, if we consider the closeness of the D*D¯1−D*D¯2* and Ds*D¯s1−Ds*D¯s2* thresholds and include the related coupled channel dynamics, we predict a J=2 positive C-parity state with a mass around 4650 MeV. This hidden-strange and hidden-charm state might in turn be identified with the X(4630) that has been discovered during the past year by the LHCb in the J/ψϕ invariant mass distribution.

We investigate the B0→π−K+X(3872) decay via the Ds1(2536)D¯D* rescattering diagram. The line shape of the K+X(3872) distribution curve around Ds1(2536)D¯ threshold is very sensitive to the X(3872) mass because the triangle singularity (TS) can be generated from the loop. By means of this characteristic, we can determine whether the X(3872) mass is below or above the D*0D¯0 threshold with high precision. The narrowness of Ds1(2536) in the loop is one of the key reasons why the TS mechanism of measuring the X(3872) mass may work. The X(3872) width impact on the K+X(3872) line shape is also crucial in the TS mechanism. If the width is as large as 1 MeV, the proposed method of measuring the X(3872) mass would be ruined.

Recently, research on using plant-derived drugs as anticancer agents has been greatly developed. Terminalia chebula (T. chebula) Retz., the mature fruit of T. chebula, contains active ingredients that have antioxidant, antimicrobial, and antitumor effects. Because traditional Chinese medicine components have unstable physical and chemical properties, such as poor solubility, fast decomposition, and high irritation, drug nanocarriers that effectively increase their solubility and reduce irritation are desirable. Additionally, T. chebula fruit can inhibit tyrosinase activity. This study aimed to determine whether T. chebula nanostructured lipid carriers can regulate the proliferation and apoptosis of melanoma cells by inhibiting tyrosinase activity. Tyrosinase activity in drug-treated melanoma cells was detected by MTT and DOPA oxidation assays, and cell proliferation rate was observed. Western blot (MTT) was used to detect the activity of apoptotic factors, and flow cytometry was used to determine the apoptotic rate. The results showed that tyrosinase activity and cell proliferation rate decreased with increasing drug concentration in cultured cells. Furthermore, the inhibitory effect was concentration-dependent. Additionally, cells cultured with a high concentration of T. chebula nanostructured lipid carriers could activate apoptotic factors and increase cell apoptosis. Thus, this study showed that T. chebula fruit nanostructured lipid carriers could inhibit the proliferation of melanoma cells and increase apoptosis by inhibiting tyrosinase activity, demonstrating a new plant-derived drug for melanoma treatment.

We previously reported that cytoprotective Heme oxygenase-1, HO-1 (HMOX1) gene-modified human placenta-derived mesenchymal stem cell (HO-1-PMSC) improved placental vascularization in vitro. In the current study, we explored the protective benefit of HO-1-PMSC transplantation in a preeclampsia (PE)-like rat model. A model of PE was successfully constructed by intraperitoneal injection of N-nitro-L-arginine methyl ester (L-NAME). Blood pressure and urinary protein levels were measured. Doppler ultrasound was examined to understand uteroplacental perfusion. ELISA was used to examine the serum levels of VEGF, PlGF, sFlt-1, and sEng. The placentas and fetuses were weighed to verify the improvement in pregnancy outcome. Immunohistochemical and H&E staining was used to detect microvessel density (MVD) in placental tissues and kidney pathology, respectively. The distribution of GFP-labeled PMSC in the placenta were observed under fluorescence microscopy. Blood pressure and proteinuria were reduced and kidney damage was improved. PE rat models treated with PMSC and HO-1-PMSC exhibited an increase in the quality of fetuses and placentas, MVD, VEGF, and PlGF expression, but substantially decreased expression of sFlt-1 and sEng. Doppler ultrasound showed that the placental perfusion was improved. Green fluorescent tracing experiments verified that the cells were successfully transplanted into the placenta and distributed in the blood vessels, indicating that the cells might participate in the process of angiogenesis. These results indicate that therapy with HO-1-PMSC could improve placental vascular dysplasia, increase placental perfusion, control PE symptoms, and promote pregnancy outcome by regulating the balance of angiogenic and antiangiogenic factors or directly participating in the repair of placental vessels in a PE-like rat model.

To investigate the refractive outcomes of second-eye adjustment (SEA) methods in different intraocular lens (IOL) power calculation formulas for second eye following bilateral sequential cataract surgery.This retrospective consecutive case-series study included 234 eyes from 234 patients who underwent bilateral sequential phacoemulsification and implantation of enVista MX60 in a hospital setting. Postoperative refraction outcomes calculated by standard formulas (SRK/T and Barrett Universal II, BUII) with SEA method were compared with those calculated by an artificial intelligence-based IOL power calculation formula (PEARL DGS) under second eye enhancement (SEE) method. The median absolute error (MedAE), mean absolute error (MAE) and percentage prediction errors (PE) of eyes within ±0.25 diopters (D), ±0.50 D, ±0.75 D and ± 1.00 D were determined.Overall, the improvement in MedAE after SEA was significant for PEARL DGS (p 0.01), SRK/T (p 0.001) and BUII (p = 0.031), which increased from 74.36, 71.37, and 77.78% to 83.33, 80.34, and 79.49% of eyes within a PE of ±0.50 D, respectively. For first eyes with a medium axial length (22-26 mm), PEARL DGS with SEE had the lowest MedAE (0.21 D). For a first-eye MAE over 0.50 D, SEA method led to significant improvement in the second eye (p 0.01). Interocular axis length differences exceeding 0.3 mm were associated with weaker effects using SEA in the studied formulas (p 0.05).Either SEA method with SRK/T and BUII formulas or second-eye enhancement method based on the PEARL DGS formula can improve postoperative refractive outcomes in second eye.

BackgroundLactate has long been considered an intermediate by-product of glucose metabolism. However, in recent years, accumulating evidence reveals that lactate has unique biological activities. In previous studies, lactate signaling was shown to inhibit inflammation. Furthermore, in vitro experiments have shown that lactate can promote the transformation of pro-inflammatory macrophages into anti-inflammatory macrophages. However, no in vivo studies have shown whether lactate can alleviate inflammation.MethodsRAW 264.7 macrophages were stimulated by LPS to induce an M1 phenotype, and cultured with low and high concentrations of lactate. The cells were then observed for phenotypic transformations and expression of inflammatory mediators and surface markers. The expression of inflammatory factors was also analyzed in the cell-free supernatant fraction. Further, a mouse model of DSS-induced colitis was established and treated with lactate. Colonic tissue injury was monitored by histopathological examinations.ResultsThe in vitro experiments showed that lactate promoted the transformation of activated macrophages to M2 phenotype and decreased the expression of TLR4-mediated NF-κB signaling proteins and inflammatory factors. In the DSS-induced colitis mouse model, lactate promoted the phenotypic transformation of macrophages in colonic tissue, reduced inflammation and organ damage, inhibited the activation of TLR4/NF-κB signaling pathway, decreased the serum levels of pro-inflammatory factors, increased the expression of anti-inflammatory factors, promoted the repair of the intestinal mucosal barrier and reduced the severity of colitis.ConclusionsLactate inhibits the TLR/NF-κB signaling pathway and the production of pro-inflammatory factors by promoting polarization of macrophages. In addition, lactate promotesthe repair of the intestinal mucosal barrier and protects intestinal tissue in inflammation. Furthermore, lactate is relatively safe. Therefore, lactate is a promising and effective drug for treating inflammation through immunometabolism regulation.

This study aims to decipher the mechanism underlying the effect of Shaofu Zhuyu Decoction on endometriosis(EMT)-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis based on mitogen-and stress-activated protein kinase 1/2(MSK1/2).We employed a random number table to randomly assign SPF female non-pregnant rats into the sham group, and treated the rest rats with autologous transplantation+refrigerator freezing for the modeling of the syndrome of cold coagulation and blood stasis.The modeled rats were then randomly assigned into the control group and high-, medium-and low-dose Shaofu Zhuyu Decoction groups.The rats in the low-, medium-, and high-dose decoction groups were respectively administrated with 9, 4.5, and 2.3 g·kg~(-1) decoction through gavage once a day for 2 consecutive weeks, and those in the control group were administrated with 0.24 mg·kg~(-1) gestrinone through gavage once every 3 days for 2 weeks.After that, the size of ectopic focus in each rat was measured via laparotomy.Enzyme-linked immunosorbent assay(ELISA) was adopted to determine the expression of interleukin(IL)-6, IL-10, prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α).Western blot was employed to determine the protein levels of MSK1/2 and dual-specificity phosphatase 1(DUSP1) and real-time quantitative polymerase chain reaction(RT-PCR) to determine the mRNA levels of the two genes in rat eutopic endometrial tissue.Compared with the sham group, the model group showed increased levels of IL-6, PGE2, and TNF-α while decrease level of IL-10 in the serum(Plt;0.01).Compared with the model group, the high-and medium-dose decoction groups and the gestrinone group had declined levels of IL-6, PGE2, and TNF-α while risen level of IL-10 in the serum(Plt;0.01).The model group had lower protein levels and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the sham group(Plt;0.01). The high-and medium-dose decoction groups and the gestrinone group had higher protein and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the model group(Plt;0.01).The results indicated that Shaofu Zhuyu Decoction can regulate the abnormal expression of pro-inflammatory cytokines TNF-α, IL-6, and PGE2 and anti-inflammatory cytokines IL-10 and DUSP1 via MSK1/2 to alleviate EMT-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis.

The novel coronavirus (COVID-19 or 2019-nCoV) is a respiratory virus that can exist in the mouth and saliva of patients and spreads through aerosol dispersion. Therefore, stomatological hospitals and departments have become high-infection-risk environments. Accordingly, oral disinfectants that can effectively inactivate the virus have become a highly active area of research. Hexadecyl pyridinium chloride, povidone-iodine, and other common oral disinfectants are the natural primary choices for stomatological hospitals. Therefore, this study investigated the inhibitory effect of hexadecyl pyridinium chloride on SARS-CoV-2 in vitro. Vero cells infected with SARS-CoV-2 were used to determine the disinfection effect; the CCK-8 method was used to determine cytotoxicity, and viral load was determined by real-time PCR. The results showed that hexadecyl pyridinium chloride has no obvious cytotoxic effect on Vero cells in the concentration range 0.0125–0.05 mg/mL. The in vitro experiments showed that hexadecyl pyridinium chloride significantly inhibits the virus at concentrations of 0.1 mg/mL or above at 2 min of action. Thus, the results provide experimental support for the use of hexadecyl pyridinium chloride in stomatological hospitals.

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants.METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains.RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV.CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).