SYNBIP 2.0: epitopes mapping, sequence expansion and scaffolds discovery for synthetic binding protein innovation.

Synthetic binding proteins (SBPs) represent a pivotal class of artificially engineered proteins, meticulously crafted to exhibit targeted binding properties and specific functions. Here, the SYNBIP database, a comprehensive resource for SBPs, has been significantly updated. These enhancements include (i) featuring 3D structures of 899 SBP-target complexes to illustrate the binding epitopes of SBPs, (ii) using the structures of SBPs in the monomer or complex forms with target proteins, their sequence space has been expanded five times to 12 025 by integrating a structure-based protein generation framework and a protein property prediction tool, (iii) offering detailed information on 78 473 newly identified SBP-like scaffolds from the RCSB Protein Data Bank, and an additional 16 401 555 ones from the AlphaFold Protein Structure Database, and (iv) the database is regularly updated, incorporating 153 new SBPs. Furthermore, the structural models of all SBPs have been enhanced through the application of the AlphaFold2, with their clinical statuses concurrently refreshed. Additionally, the design methods employed for each SBP are now prominently featured in the database. In sum, SYNBIP 2.0 is designed to provide researchers with essential SBP data, facilitating their innovation in research, diagnosis and therapy. SYNBIP 2.0 is now freely accessible at https://idrblab.org/synbip/.

The effect of robotic surgery on low anterior resection syndrome in patients with lower rectal cancer: a propensity score-matched analysis.

BACKGROUND: Many patients experience anorectal dysfunction after rectal surgery, which is known as low anterior resection syndrome (LARS). Robotic systems have many technical advantages that may be suitable for functional preservation after low rectal resection. Thus, the study aimed to explore whether robotic surgery can reduce the incidence and severity of LARS. METHODS: Patients undergoing minimally invasive sphincter-sparing surgery for low rectal cancer were enrolled between January 2015 and December 2020. The patients were divided into robotic or laparoscopic groups. The LARS survey was conducted at 6, 12 and 18 months postoperatively. Major LARS scores were analysed as the primary endpoint. In order to reduce confounding factors, one-to-two propensity score matches were used. RESULTS: In total, 342 patients were enrolled in the study. At 18 months postoperatively, the incidence of LARS was 68.7% (235/342); minor LARS was identified in 112/342 patients (32.7%), and major LARS in 123/342 (36.0%). After matching, the robotic group included 74 patients, and the laparoscopic group included 148 patients. The incidence of major LARS in the robotic group was significantly lower than that in the laparoscopic group at 6, 12, and 18 months after surgery. In multivariate logistic regression analysis, tumour location, laparoscopic surgery, intersphincteric resection, neoadjuvant therapy, and anastomotic leakage were independent risk factors for major LARS after minimally invasive sphincter-sparing surgery for low rectal cancer. Furthermore, a major LARS prediction model was constructed. Results of model evaluation showed that the nomogram had good prediction accuracy and efficiency. CONCLUSIONS: Patients with low rectal cancer may benefit from robotic surgery to reduce the incidence and severity of LARS. Our nomogram could aid surgeons in setting an individualized treatment program for low rectal cancer patients.

Comparison of robotic versus laparoscopic lateral lymph node dissection for advanced lower rectal cancer: a retrospective study at two institutions.

BACKGROUND: Lateral lymph node dissection (LLND) represents a technically challenging procedure. This study aimed to evaluate the perioperative, genitourinary functional and mid-term oncological outcomes of laparoscopic lateral lymph node dissection (LLLND) and robotic lateral lymph node dissection (RLLND) for advanced lower rectal cancer (ALRC). METHODS: Between January 2015 and April 2021, consecutive patients who underwent RLLND and LLLND at two high-volume centres were enrolled. The perioperative outcomes, genitourinary function recovery and mid-term oncological outcomes of the patients were compared. A subgroup analysis of patients who underwent neoadjuvant chemoradiotherapy (nCRT) was performed. RESULTS: A total of 205 patients were included in the analysis, with 95 in the RLLND group and 110 in the LLLND group. The patients in the RLLND group had a longer operative time, less blood loss, and more harvested internal iliac lymph nodes than did those in the LLLND group. In postoperative complication, urinary retention was less frequent in the RLLND group than in the LLLND group. Additionally, the RLLND group had better genitourinary function recovery. Similar results were also observed from the nCRT subgroup analysis. Moreover, there was no significant difference in mid-term oncological outcomes between the two groups. Further subgroup analysis indicated that the patients who underwent nCRT + LLLND/RLLND had better local control than those who underwent only LLLND/RLLND. CONCLUSIONS: RLLND is safe and feasible for ALRC and is associated with more harvested internal iliac lymph nodes and better genitourinary function recovery. NCRT combined with minimally invasive LLND could constitute an improved strategy for ALRC.

Anti-biofilm effect of salivary histatin 5 on Porphyromonas gingivalis.

This study aimed to investigate the effects of salivary histatin 5 (Hst5) on Porphyromonas gingivalis (P. gingivalis) biofilms in vitro and in vivo and the possible mechanisms. In in vitro experiments, P. gingivalis biomass was determined by crystal violet staining. Polymerase chain reaction, scanning electron microscopy, and confocal laser scanning microscopy were used to determine the Hst5 concentration. A search for potential targets was performed using transcriptomic and proteomic analyses. In vivo experimental periodontitis was established in rats to evaluate the effects of Hst5 on periodontal tissues. Experimental results showed that 25 µg/mL Hst5 effectively inhibited biofilm formation, and increased concentrations of Hst5 increased the inhibitive effect. Hst5 might bind to the outer membrane protein RagAB. A combination of transcriptomic and proteomic analyses revealed that Hst5 could regulate membrane function and metabolic processes in P. gingivalis, in which RpoD and FeoB proteins were involved. In the rat periodontitis model, alveolar bone resorption and inflammation levels in periodontal tissues were reduced by 100 µg/mL Hst5. This study showed that 25 µg/mL Hst5 inhibited P. gingivalis biofilm formation in vitro by changing membrane function and metabolic process, and RpoD and FeoB proteins might play important roles in this process. Moreover, 100 µg/mL Hst5 inhibited periodontal inflammation and alveolar bone loss in rat periodontitis via its antibacterial and anti-inflammatory effects. KEY POINTS: • Anti-biofilm activity of histatin 5 on Porphyromonas gingivalis was investigated. • Histatin 5 inhibited Porphyromonas gingivalis biofilm formation. • Histatin 5 showed inhibitory effects on the occurrence of rat periodontitis.

Clinical features and risk factors of plastic bronchitis caused by Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: We analyzed the clinical characteristics of children with plastic bronchitis (PB) caused by Mycoplasma pneumoniae (MP) and explored its risk factors. METHODS: We prospectively analyzed clinical data of children with MP pneumonia (MPP) treated with fiberoptic bronchoscopy (FB). Patients were classified into a PB and non-PB group. General information, clinical manifestations, laboratory tests, results of computed tomography scan, and FB findings were compared between groups. We conducted statistical analysis of risk factors for developing PB. RESULTS: Of 1169 children who had MPP and were treated with FB, 133 and 1036 were in the PB and non-PB groups, respectively. There were no significant differences in sex, age, and incident season between groups (P > 0.05). The number of children in the PB group decreased during the COVID-19 pandemic. Compared with children in the non-PB group, those in the PB group had longer duration of hospitalization, increased levels of neutrophil (N), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST); lower levels of lymphocyte (L) and platelet (PLT); and higher incidence of lack of appetite, decreased breath sounds, single lobar infiltrate, pleural effusion, pericardial effusion, mucosal erosion and/or necrosis, and bronchial embolization. L levels and pleural effusion were identified as risk factors in multivariate logistic regression. CONCLUSIONS: Children with PB caused by MPP had a strong and local inflammatory response. L levels and pleural effusion were independent risk factors of PB with MPP in children. Our findings will help clinicians identify potential PB in pediatric patients for early and effective intervention.

Lactobacillus rhamnosus GG defense against Salmonella enterica serovar Typhimurium infection through modulation of M1 macrophage polarization.

Lactobacillus rhamnosus GG (LGG), a model probiotic strain, plays an important role in immune regulatory activity to prevent and treat intestinal inflammation or diarrhea. However, the effect of the immune modulation of LGG on macrophages to prevent Salmonella infection has not been thoroughly studied. In this study, C57BL/6 mice were pre-administered LGG for 7 days continuously, and then infected with Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium). The results of the in vivo study indicated that LGG could reduce body weight loss, death rate and intestinal inflammatory response caused by S. Typhimurium. LGG also limited S. Typhimurium dissemination to liver and spleen, and thereby protected against infection. In vitro study, we observed that LGG enhanced the phagocytic and bactericidal ability of macrophages and upregulated M1 macrophage characters (e.g. iNOS, NO and IL-12) against S. Typhimurium. In addition, LGG also elevated IL-10 secretion, which was helpful to ameliorate intestinal inflammatory injury caused by S. Typhimurium. In conclusion, LGG could modulate M1 macrophage polarization and offer protective effects against S. Typhimurium infection.

Interaction of Microplastics with Antibiotics in Aquatic Environment: Distribution, Adsorption, and Toxicity.

As two major types of pollutants of emerging concerns, microplastics (MPs) and antibiotics (ATs) coexist in aquatic environments, and their interactions are a source of increasing concern. Therefore, this work examines the interaction mechanisms of MPs and ATs, and the effect of MPs on ATs bioavailability and antibiotic resistance genes (ARGs) abundance in aquatic environments. First, the mechanisms for ATs adsorption on MPs are summarized, mainly including hydrophobic, hydrogen-bonding, and electrostatic interactions. But other possible mechanisms, such as halogen bonding, CH/π interaction, cation-π interaction, and negative charge-assisted hydrogen bonds, are newly proposed to explain the observed ATs adsorption. Additionally, environmental factors (such as pH, ionic strength, dissolved organic matters, minerals, and aging conditions) affecting ATs adsorption by MPs are specifically discussed. Moreover, MPs could change the bioaccumulation and toxicity of ATs to aquatic organisms, and the related mechanisms on the joint effect are reviewed and analyzed. Furthermore, MPs can enrich ARGs from the surrounding environment, and the effect of MPs on ARGs abundance is evaluated. Finally, research challenges and perspectives for MPs-ATs interactions and related environmental implications are presented. This review will facilitate a better understanding of the environmental fate and risk of both MPs and ATs.

Mediator 1 Is Atherosclerosis Protective by Regulating Macrophage Polarization.

OBJECTIVE: MED1 (mediator 1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated. APPROACH AND RESULTS: To study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1ΔMac/ApoE-/-) mice and found that atherosclerosis was greater in MED1ΔMac/ApoE-/- mice than in MED1fl/fl/ApoE-/- littermates. The gene expression of M1 markers was increased and that of M2 markers decreased in both aortic wall and peritoneal macrophages from MED1ΔMac/ApoE-/- mice, whereas MED1 overexpression rectified the changes in M1/M2 expression. Moreover, LDLR (low-density lipoprotein receptor)-deficient mice received bone marrow from MED1ΔMac mice showed greater atherosclerosis. Mechanistically, MED1 ablation decreased the binding of PPARγ (peroxisome proliferator-activated receptor γ) and enrichment of H3K4me1 and H3K27ac to upstream region of M2 marker genes. Furthermore, interleukin 4 induction of PPARγ and MED1 increased the binding of PPARγ or MED1 to the PPAR response elements of M2 marker genes. CONCLUSIONS: Our data suggest that MED1 is required for the PPARγ-mediated M2 phenotype switch, with M2 marker genes induced but M1 marker genes suppressed. MED1 in macrophages has an antiatherosclerotic role via PPARγ-regulated transactivation.

Celecoxib induces epithelial-mesenchymal transition in epithelial ovarian cancer cells via regulating ZEB1 expression.

PURPOSE: The purpose of our study was to investigate the therapeutic potential of Celecoxib for epithelial ovarian cancer, especially on cellular morphological changes, proliferation invasion and epithelial-mesenchymal transition (EMT). METHOD: The MTT and transwell assays were performed to evaluate the effect of Celecoxib on proliferation and invasion ability of ovarian cancer cell lines, respectively. Western blot was carried out to detect the expression of epithelial phenotypes, E-cadherin and Keratin, and mesenchymal phenotypes, N-cadherin and Vimentin, as well as p-AKT, p-ERK and ZEB1. ZEB1 small-interfering RNA (siRNA) was used to downregulate the expression of ZEB1 to further inquiring into the downstream of Celecoxib-induced EMT. RESULTS: Cellular morphological assessment revealed that both A2780 and SKOV3 cells gradually appeared in the morphology of mesenchymal cells after Celecoxib treatment. The MTT assay demonstrated that celecoxib had no effect on cell proliferation. Transwell assay showed that Celecoxib significantly increased the cell invasion ability. Western blot data proved that the expression of E-cadherin and keratin was elevated, whereas the expression of N-cadherin and Vimentin was decreased in a dose-dependent manner compared with the untreated cells, the expression of p-AKT, p-ERK and ZEB1 was also obviously elevated. However, ZEB1 siRNA reversed Celecoxib-induced E-cadherin expression and N-cadherin expression, as well as cellular invasiveness. CONCLUSION: Our results indicated that Celecoxib might induce EMT and increase cellular invasiveness in ovarian cancer cells in vitro, which also implied that it needed a comprehensive evaluation in preclinical researches before introducing Celecoxib into the clinical regimen.

The role of circRNAs and miRNAs in drug resistance and targeted therapy responses in breast cancer.

MicroRNAs (miRNAs) are small non-coding RNAs comprising 19-24 nucleotides that indirectly control gene expression. In contrast to other non-coding RNAs (ncRNAs), circular RNAs (circRNAs) are defined by their covalently closed loops, forming covalent bonds between the 3' and 5' ends. circRNAs regulate gene expression by interacting with miRNAs at transcriptional or post-transcriptional levels. Accordingly, circRNAs and miRNAs control many biological events related to cancer, including cell proliferation, metabolism, cell cycle, and apoptosis. Both circRNAs and miRNAs are involved in the pathogenesis of diseases, such as breast cancer. This review focuses on the latest discoveries on dysregulated circRNAs and miRNAs related to breast cancer, highlighting their potential as biomarkers for clinical diagnosis, prognosis, and chemotherapy response.

Lissencephaly caused by a de novo mutation in tubulin TUBA1A: a case report and literature review.

Tubulin plays an essential role in cortical development, and TUBA1A encodes a major neuronal α-tubulin. Neonatal mutations in TUBA1A are associated with severe brain malformations, and approximately 70% of patients with reported cases of TUBA1A mutations exhibit lissencephaly. We report the case of a 1-year-old boy with the TUBA1A nascent mutation c.1204C >T, p.Arg402Cys, resulting in lissencephaly, developmental delay, and seizures, with a brain MRI showing normal cortical formation in the bilateral frontal lobes, smooth temporo-parieto-occipital gyri and shallow sulcus. This case has not been described in any previous report; thus, the present case provides new insights into the broad disease phenotype and diagnosis associated with TUBA1A mutations. In addition, we have summarized the gene mutation sites, neuroradiological findings, and clinical details of cases previously described in the literature and discussed the differences that exist between individual cases of TUBA1A mutations through a longitudinal comparative analysis of similar cases. The complexity of the disease is revealed, and the importance of confirming the genetic diagnosis from the beginning of the disease is emphasized, which can effectively shorten the diagnostic delay and help clinicians provide genetic and therapeutic counseling.

Eukaryotic translation initiation factor EIF4G1 p.Ser637Cys mutation in a family with Parkinson's disease with antecedent essential tremor.

Essential tremor (ET) and Parkinson's disease (PD) are common chronic movement disorders that can cause a substantial degree of disability. However, the etiology underlying these two conditions remains poorly understood. In the present study, Whole-exome sequencing of peripheral blood samples from the proband and Sanger sequencing of the other 18 family members, and pedigree analysis of four generations of 29 individuals with both ET and PD in a nonconsanguineous Chinese family were performed. Specifically, family members who had available medical information, including historical documentation and physical examination records, were included. A novel c.1909A>T (p.Ser637Cys) missense mutation was identified in the eukaryotic translation initiation factor 4γ1 (EIF4G1) gene as the candidate likely responsible for both conditions. In total, 9 family members exhibited tremor of the bilateral upper limbs and/or head starting from ages of ≥40 years, 3 of whom began showing evidence of PD in their 70s. Eukaryotic initiation factor 4 (eIF4)G1, a component of the translation initiation complex eIF4F, serves as a scaffold protein that interacts with many initiation factors and then binds to the 40S ribosomal subunit. The EIF4G1 (p.Ser637Cys) might inhibit the recruitment of the mRNA to the ribosome. In conclusion, the results from the present study suggested that EIF4G1 may be responsible for the hereditary PD with 'antecedent ET' reported in the family assessed.

Tensile Overload Injures Human Alveolar Epithelial Cells through YAP/F-Actin/MAPK Signaling.

BACKGROUND: Explosion shockwaves can generate overloaded mechanical forces and induce lung injuries. However, the mechanism of lung injuries caused by tensile overload is still unclear. METHODS: Flow cytometry was used to detect the apoptosis of human alveolar epithelial cells (BEAS-2B) induced by tensile overload, and cell proliferation was detected using 5-ethynyl-2'-deoxyuridine (EdU). Immunofluorescence and Western blot analysis were used to identify the tensile overload on the actin cytoskeleton, proteins related to the mitogen-activated protein kinase (MAPK) signal pathway, and the Yes-associated protein (YAP). RESULTS: Tensile overload reduced BEAS-2B cell proliferation and increased apoptosis. In terms of the mechanism, we found that tensile overload led to the depolymerization of the actin cytoskeleton, the activation of c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase 1/2 (ERK1/2), and the upregulation of YAP expression. Jasplakinolide (Jasp) treatment promoted the polymerization of the actin cytoskeleton and reduced the phosphorylation of tension-overload-activated JNK and ERK1/2 and the apoptosis of BEAS-2B cells. Moreover, the inhibition of the JNK and ERK1/2 signaling pathways, as well as the expression of YAP, also reduced apoptosis caused by tensile overload. CONCLUSION: Our study establishes the role of the YAP/F-actin/MAPK axis in tensile-induced BEAS-2B cell injury and proposes new strategies for the treatment and repair of future lung injuries.

Aging characteristics of degradable and non-biodegradable microplastics and their adsorption mechanism for sulfonamides.

As emerging pollutants, microplastics (MPs) and antibiotics (ATs) became a research hotspot in recent years. To evaluate the carrier effect of degradable and non-biodegradable MPs in the aquatic environment, the adsorption behaviors of polyamide (PA) and polylactic acid (PLA) towards two sulfonamide antibiotics (SAs) were investigated. Both chemical and photo-aging were used to handle the virgin MPs. Compared with PA, PLA was aged more drastically, showing the obvious grooves, notches and folds. However, due to the higher temperature during chemical aging, the tiny KPLA (PLA aged by K2S2O8) particles were agglomerated and the specific surface area was reduced to nearly 95 %. For PA, the oxidation of chemical aging was stronger than photo-aging. After aging, the hydrophilicity and polarity of MPs increased. In the adsorption experiments, the adsorption capacity of PA towards SAs was 1.7 times higher than that of PLA. Aging process enabled the adsorption capacity of PLA increased 1.22-3.18 times. Overall, the adsorption capacity of sulfamethoxazole (SMX) by both MPs was superior to sulfamerazine (SMR). These results would help to understand the carrier effects and potential ecological risks of MPs towards co-existing contaminants.

Association between periodontal disease and oral squamous cell carcinoma: a systematic review and meta-analysis.

To investigate the relation between periodontal disease (PD) and oral squamous cell carcinoma (OSCC) we systematically searched records published up to August 2022. Odds ratios (OR) and relative risk (RR) with 95% confidence intervals (95% CI) were estimated to evaluate this relation, then sensitivity analysis was performed accordingly. Begg's test and Egger's test were used to detect publication bias. Out of 970 papers from several databases, 13 studies were included. Summary estimates showed that PD was positively associated with the prevalence of OSCC (OR = 3.28, 95% CI: 1.87 to 5.74), especially for severe PD (OR = 4.23, 95% CI: 2.92 to 6.13). No evident publication bias was revealed. No increased OSCC risk among patients with PD was shown according to the combined results (RR = 1.50, 95% CI: 0.93 to 2.42). Patients with OSCC exhibited significant differences in alveolar bone loss, clinical attachment loss, and bleeding on probing, when compared with controls. The systematic review and meta-analysis suggested that there was a positive association between PD and prevalence of OSCC. However, according to the current evidence, a causal relation is unclear.

Coupling relationships between urban block spatial morphology and microclimate in severe cold regions.

This study investigates the relationship between urban block spatial morphology and microclimate in severe cold regions, using Shenyang, China as a case study. We employed computational fluid dynamics theory-based numerical simulation software and a controlled variable approach to analyze the microclimate effects of four key aspects: street conforming line ratio, street interface density, street aspect ratio, and building roof forms. The primary findings are as follows: Decreasing conforming line ratios initially increase average wind speed and temperature. Lower interface densities reduce average wind speed but raise temperature. Higher aspect ratios correspond to increased wind speed and decreased temperature. Additionally, upward sloping roofs correlate with higher average wind speed and temperature. This research provides a perspective for evaluating urban microclimates, considering human perception of urban block space. It also suggests spatial layout design strategies for different types of streets in severe cold regions, considering the climate environment.

New insights into adsorption mechanism of pristine and weathered polyamide microplastics towards hydrophilic organic compounds.

The widespread coexistence of hydrophilic organic compounds and microplastics (MPs) in the environment has greatly increased their associated environmental problems. To evaluate the potential carrier effect of oxygen-containing MPs on coexisting pollutants, adsorption behaviors of four hydrophilic organic compounds (benzoic acid, sulfamethoxazole, sulfamerazine and ciprofloxacin) on MPs (pristine and weathered polyamide (PA)) were studied in the aquatic environment. The results showed that the surface morphology, size, oxygen content, molecular structure, surface charge and crystallinity of PA were changed after weathering, and the weathering degree of PA treated with heat-activated potassium persulfate was the highest. The main adsorption mechanisms included hydrogen bonding, hydrophobic interaction, charge-assisted hydrogen bonding, and electrostatic interaction. Hydrogen bonding and hydrophobic interaction contributed to the adsorption, while electrostatic interaction weakened the adsorption under the specific pH conditions. The formation of charge-assisted hydrogen bonding (CAHB) was also verified through pH influence experiments, and this force can overcome the electrostatic repulsion. The high adsorption of KPA (PA weathered by K2S2O8) under alkaline conditions was well explained by the formation of homonuclear CAHB due to the increase of oxygen-containing functional groups compared to the other three PA. Additionally, weathering did not always enhance the adsorption of hydrophilic organic compounds on PA, which was related to the changes in surface charge, crystallinity and hydrophilicity of PA. Overall, the physical and chemical properties (e.g., specific surface area, oxygen content, molecular structure) of PA after weathering and its trend of adsorption were different from other oxygen-free MPs in this study. This work can provide basic data for environmental risk of MPs and contribute to clarify and understand the processes of oxygenated MPs in the aquatic environment.

Genetically determined serum bilirubin level and the risk of heart failure: A mendelian randomization study.

Background: The association between serum bilirubin level and heart failure (HF) was controversial in previous observational studies and the causal effects of bilirubin on HF have not been investigated. Here, we conducted a Mendelian randomization (MR) study to investigate the associations between genetically determined bilirubin level and HF. Methods: Summary data on the association of single nucleotide polymorphisms (SNPs) with serum bilirubin levels were obtained from genome-wide association study (GWAS) for individuals of European descent and East Asian descent separately. Statistical data for gene-HF associations were extracted from three databases: the HERMES Consortium (47,309 cases and 930,014 controls), FinnGen study (30,098 cases and 229,612 controls) for European population and Biobank Japan (2,820 HF cases and 192,383 controls) for East Asian population. We applied a two-sample Mendelian randomization framework to investigate the causal association between serum bilirubin and HF. Results: Findings from our MR analyses showed that genetically determined serum bilirubin levels were not causally associated with HF risk in either European or East Asian population (odds ratio [OR] = 1.01 and 95% confidence interval [CI] = .97-1.05 for HERMES Consortium; OR = 1.01 and 95% CI = .98-1.04 for FinnGen Study; OR = .82, 95% CI: .61-1.10 for Biobank Japan). These results remained unchanged using different Mendelian randomization methods and in sensitivity analyses. Conclusion: Our study did not find any evidence to support a causal association between serum bilirubin and HF.

[Research progress in vaccines of SARS-CoV-2].

Since the outbreak of corona virus disease 2019 (COVID-19), viral strains have mutated and evolved. Vaccine research is the most direct and effective way to control COVID-19. According to different production mechanisms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines included inactivated virus vaccine, live attenuated vaccine, mRNA vaccine, DNA vaccine, viral vector vaccine, virus-like particle vaccine and protein subunit vaccine. Among them, viral protein subunit vaccine has a wide application prospect due to its high safety and effectiveness. Viral nucleocapsid protein has high immunogenicity and low variability which could be a new direction for vaccine production. We summarized the current development of vaccine research by reviewing the current progress, vaccine safety and vaccine immune efficiency. It is hoped that the proposed possible development strategies could provide a reference for epidemic prevention work in future.