Highlights d 54 antibodies have neutralizing IC 50 values in the range of 3.3-81 ng/mL d Neutralization by 47D1 is achieved without direct blocking of RBD-ACE2 binding d 47D1 binds only to one side of the receptor binding surface on the RBD d Convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2

ObjectiveTo evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China.MethodsA total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis.ResultsThe Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10^9/L vs. 1.31 (0.94, 1.85)×10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28 (3.31, 8.13) vs. 9.10 (4.37, 15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13 (0.00, 0.09) vs. 0.12 (0.03, 0.41), p<0.05; 0.02 (0.00, 0.14) vs. 1.94 (0.54, 6.40), p<0.05; 5.46 (2.41, 9.26) vs. 73.63 (54.63, 86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13).ConclusionUnvaccinated children may be an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2), which indicated an urgent need of vaccination for this particular population.

Purpose Acute kidney injury (AKI) is a devastating disorder associated with considerably high morbidity and mortality. Reports have shown that AST-120, an oral charcoal adsorbent, can reduce oxidative stress by lowering serum indoxyl sulfate levels. The effects of AST-120 and indoxyl sulfate on kidney injury and cardiac dysfunction were investigated in vivo and in vitro. Patients and Methods Patients were tracked for enrollment upon receiving a diagnosis of AKI. Plasma was collected to determine the renal and inflammatory parameters. Renal ischemia/reperfusion (I/R) induced AKI or sham operation was performed in C57BL/6J mice. Animals were divided into sham, AKI+vehicle, and AKI+AST-120 groups. Plasma and tissues were assembled after 48 h to assess apoptotic and inflammatory responses. We also conducted human umbilical vein endothelial cell (HUVECs) and HL-1 cardiomyocyte culture studies to determine the underlying mechanisms of indoxyl sulfate’s effects. Echocardiography, histopathology, biochemical indexes, ELISA, terminal dUTP nick-end labeling (TUNEL) and Western blot analysis were performed. Results The cohort included 25 consecutive patients with AKI and 25 non-AKI. Plasma levels of creatinine, indoxyl sulfate, IL-1β and ICAM-1 were significantly higher in patients with AKI than in non-AKI controls. Plasma levels of blood urea nitrogen, creatinine, indoxyl sulfate, IL-1β and renal tubular injury were increased in mice after renal I/R and were decreased by AST-120 treatment. In addition, AST-120 therapy not only improved the parameters assessed by echocardiography but also substantially attenuated the elevation of plasma BNP. Oral administration of AST-120 significantly downregulated NF-κB/ICAM-1 expression and reduced cell apoptosis in both kidney and heart after renal I/R injury. Conclusion Our investigations demonstrated that AST-120 administration improves cardiac dysfunction in AKI mice via the suppression of apoptosis and proinflammatory NF-κB/ICAM-1 signaling.

Objective: To compare the trauma of 3 different surgical approaches and provide a reference for clinicians in choosing the operative procedure. Patients and Methods: A total of 150 patients were divided into the total endoscopic thyroidectomy (TET), endoscopic-assisted thyroidectomy (EAT), and conventional open thyroidectomy (COT) groups, with 50 patients in each group. The peripheral blood C-reactive protein (CRP) levels at different postoperative time points, operative time, intraoperative blood loss, postoperative drainage volume, postoperative pain, degree of satisfaction with the incision appearance, postoperative extubation time, and swallowing discomfort 3 months after surgery were compared among the groups that received different surgical approaches. Results: The operative time of TET was longer than that of COT and EAT. The intraoperative blood loss was significantly lower in the TET and EAT groups than in the COT group. The postoperative drainage volume was lowest after EAT and highest after TET. The extubation time was significantly shorter after EAT than after TET and COT. The 6-hour CRP level was significantly higher after TET than after EAT and COT, and the 24-hour CRP level was better in the EAT group than in the other 2 groups. The CRP levels at 72 hours postoperatively were lowest in the EAT group and highest in the TET group. Postoperative pain was significantly lower after EAT than after TET and COT. Cosmetic satisfaction was highest in the TET group and lowest in the COT group. Swallowing discomfort was lowest in the EAT group and highest in the TET group. There was a positive correlation between the drainage volume on the first postoperative day, the drainage tube removal time, dysphagia, and the CRP level in each period. There was a positive correlation between pain, cosmetic satisfaction and CRP in 2 of the time periods. Conclusions: All 3 types of thyroidectomy are safe and reliable in benign tumor resection. Therefore, in clinical practice, the age, sex, and cosmetic needs of the patients, and the oncological safety should all be considered to provide patients with the most appropriate recommendations. In view of oncological safety, TET should be carefully selected for malignant tumor resection.

ObjectiveTo evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics in unvaccinated children aged < 12 y with vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China.MethodsA total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Realtime PCR positive and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; the effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis.ResultsThe Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84(1.32,2.71)×10^9/L vs. 1.31(0.94,1.85)×10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28(3.31,8.13) vs. 9.10(4.37,15.14); p< 0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13(0.00,0.09) vs. 0.12(0.03,0.41), p<0.05; 0.02(0.00,0.14) vs. 1.94(0.54,6.40), p <0.05; 5.46(2.41,9.26) vs. 73.63 (54.63,86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13).ConclusionChildren aged < 12y may be critical hidden spreaders, which indicates an urgent need of vaccination for this particular population.

Science and Technology Plan Projects of Putian City (2018s3001) Background:Acute pancreatitis (AP) is a symptom of sudden pancreas inflammation, which causes patients severe suffering.In general, fibroblast growth factor (FGF) levels are increased and amylase and lipase activities are elevated during AP pathogenesis, but protein concentration are low. However, the mechanism through which FGF signaling regulates AP pathogenesis remains elusive. Material/Methods:The concentrations of PGE2, TNF-a, sCRP, FGF1, and FGF2 in the serum samples of the AP group and healthy control group were detected by enzyme-linked immunosorbent assay. In addition, IkBa and p-IkBa levels were analyzed in the serum samples. Subsequently, the AP rat model was established, and FGF1, FGF2, anti-FGF1, and anti-FGF2 antibodies and Bay11-7082 were injected into AP rats. TNF-a, PAI-1 JNK, p-JNK, IkBa, and p-IkBa levels were also examined. Results:Results showed that levels of PGE2, TNF-a, sCRP, p-IkBa, FGF1, and FGF2, as well as amylase and lipase activity were increased in patients with AP compared with those in healthy people. In addition, protein concentrations were lower in patients with AP than in the healthy group. Activation of FGF signaling by injecting FGF1 or FGF2 also inhibited AP-induced inflammation response in the pancreas and increased amylase and lipase activities, as well as protein concentration. However, the injection of FGF1 and FGF2 antibodies accelerated APmediated inflammation responses in the serum. In addition, Bay11-7082 injection inhibited AP activation of inflammation response and amylase and lipase activities. Protein concentration were also increased in AP rats. Conclusions:FGF signaling protects against AP-mediated damage by inhibition of AP-activating inflammatory responses.

Nitrogen-doped carbon quantum dots (N-CQDs) with citric acid and ethylenediamine as raw materials were synthesized by an efficient one-step strategy. The N-CQDs showed a special property that the fluorescence was quenched by Fe. The quenched fluorescence of N-CQDs could be recovered by glutathione (GSH). Therefore, a "signal-on" fluorescent sensor was developed to detect GSH. The fluorescent sensor could favorably avoid the interference of ascorbic acid, dopamine, glucose, oxidized glutathione, and other amino acids in the detecting process of GSH. The proposed sensor showed a great feature that GSH can be accurately detected in the range from 0.001 to 0.1 mol/L and can be applied to detect GSH in the human serum. Therefore, the proposed method has a promising application for monitoring the blood drug concentration of GSH in clinical studies.

A digital detection strategy based on a portable personal glucometer (PGM) was developed for the simple, rapid, and sensitive detection of hepatitis C virus (HCV) RNA, involving the release of glucose-loaded nanoliposomes due to coupling-site-specific cleavage by the endonuclease BamHI. The glucose-loaded nanoliposomes were synthesized using a reversed-phase evaporation method and provided an amplified signal at the PGM in the presence of HCV RNA. Initially, a 21-mer oligonucleotide complementary to HCV RNA was covalently conjugated to a magnetic bead through the amino group at the 5' end of the oligonucleotide, and then bound to a glucose-loaded liposome by typical carbodiimide coupling at its 3' end. In the presence of the target HCV RNA, the target hybridized with the oligonucleotide to form double-stranded DNA. The symmetrical duplex sequence 5'-GGATCC-3' between guanines was then catalytically cleaved by BamHI, which detached the glucose-loaded liposome from the magnetic bead. Following magnetic separation of the bead, the detached glucose-loaded liposome was lysed using Triton X-100 to release the glucose molecules within it, which were then detected as an amplified signal at the digital PGM. Under optimal conditions, the PGM signal increased with increasing HCV RNA, and displayed a strongly linear dependence on the level of HCV RNA for concentrations ranging from 10 pM to 1.0 μM. The detection limit (LOD) of the system was 1.9 pM. Good reproducibility and favorable specificity were achieved in the analysis of the target HCV RNA. Human serum samples containing HCV RNA were analyzed using this strategy, and the developed sensing platform was observed to yield satisfactory results based on a comparison with the corresponding results from a Cobas Amplicor HCV Test Analyzer. Graphical abstract A digital detection strategy utilizing a personal glucometer was developed for the detection of hepatitis C virus RNA. The strategy involved the use of the endonuclease BamHI along with a 21-mer oligonucleotide conjugated to both a magnetic bead and a glucose-loaded nanoliposome. Hybridization of the nucleotide with the target RNA triggered the coupling-site-specific cleavage of the duplex by BamHI, leading to the release of the glucose-loaded nanoliposome. Following separation of the magnetic bead, the free nanoliposome was dissolved, liberating the glucose molecules within it, which in turn were detected as an amplified signal by the glucometer.