Two kinds of different functional groups modified RuBpy-doped silica fluorescent nanoprobes Probe A and B that conjugated with avidin were prepared for the recognition of liver cancer cells. Firstly RuBpy-doped silica nanoparticles were synthesized by reverse microemulsion and modified with different functional groups, then Probe A was prepared by the conjugation of avidin with carboxyl modified nanoparticles through covalent binding using 1-ethyl-3-( 3-dimethylamino propyl ) carbodiimide hydrochloride ( EDC )/sulfo-NHS, whereas Probe B was prepared by the conjugation of avidin with the polyethylene glycol ( PEG) linkers on the surface nanoparticles using cyanogen bromide method. Therefore, compared with Probe A, Probe B was obtained by coupling avidin to the nanoparticles through long-chain PEG molecules. The two probes were incubated with liver cancer cells respectively, and microscopic fluorescence imaging shows that Probe B which contained PEG molecules could be more effectively applied for the recognition of tumor marker carcinoembryonic antigen ( CEA) in liver cancer cells.

Objective To study the clinical features,diagnosis and treatment of neonatal very early onset inflammatory bowel disease(VEO-IBD) to improve the diagnosis and treatment of the disease.Method From Jan 2013 to Dec 2015,five infants with VEO-IBD admitted to Peking University First Hospital were reviewed and analyzed.Their clinical data included general condition,clinical symptoms,laboratory tests,autoimmune antibodies (ANCA,dsDNA,ANA and ENA),colonoscopy,pathological results and therapeutic response.Interleukin-10 receptor A (IL-10RA) gene was examined in all patients.All the patients were followed up for more than 1 year.Result Three of the five patients had a family history.Persistent diarrhea was the most common presenting symptom.One of them received surgery because of intestinal necrosis and developed typical symptoms of IBD half a year later.Bloody stool or positive fecal occult blood test were found in all infants.Fever,anemia,oral ulcer,perianal lesions and malnutrition were common concomitant symptoms.Most of the patients had elevated WBC,CRP and ESR,and 4 of them had positive autoimmune antibodies.Colonoscopy showed multiple ulcers affecting the colon.Intestinal biopsies revealed acute and chronic inflammation.4 of patients were found to have cryptitis and crypt abscesses.Gene sequencing revealed IL-10RAgene mutation in all five patients,including 1 case with homozygous mutation and 4 heterozygous mutations.4 patients received steroid and mesalazine therapy and only 1 patient's symptoms were controlled.However,the colonoscopy result was still abnormal in this patient.4 patients had poor response to further infliximab and (or) thalidomide therapy.1 of them received surgery because of intestinal obstruction at 2-year-old.Conclusion Neonatal VEO-IBD was associated with IL-10RA gene mutation.The patients had severe symptoms and poor response to conventional medications.The effects of biological agents and thalidomide were still not sure.

Objective To analyze and summarize clinical manifestations of inflammatory bowel disease (IBD) in neonates.Methods From 2007 to 2013,three neonates were diagnosed with IBD in Peking University First Hospital.Data on these three cases with neonatal IBD were analyzed.The coding region of the interleukin 10 receptor A (IL10RA) gene was detected using direct Sanger sequencing in one of the patients.The literature was reviewed.Results The three newborns were 4-12 days old,all had symptoms of diarrhca,mucosanguineous feces and oral ulcers,accompanied by hypoalbuminemia and a family history.Two of these infants had perianal lesions,and one had liver damage and scizures.All three patients had elevated white blood cells and were anti-proteinase 3 positive.Two had elevated C-reactive protein and erythrocyte sedimentation rate,and one had positive antinuclcar antibodies and double stranded DNA antibodies.Colonoscopy showed multiple ulcers affecting the ileocecum and colon.The infants received treatment including antibiotics,switching formula feeding and 5-aminosalicylic acid.After treatment,one infant was cured,one died although glucocorticoids and azathioprine were used,and the other with a IL10RA gene mutation recovered,this infant had a compound heterozygous mutation with c.301C ＞ T (p.Arg101Trp),c.421G ＞ A (p.Gly141Arg) and whose parents were carriers.The literature review showed that fever and abnorrnal defecation were the main clinical features,and examination of serum antibodies showed a lower positive rate.The patients had a poor response to medications and most required surgery.IL10RA gene mutations were detected in some patients.Conclusions Neonates with diarrhea and a family history may have IBD and should undergo colonoscopy as early as possible.

Objective To explore the clinical features, treatment and follow-up of Cockayne syndrome with renal involvement. Method The clinical data of one child with Cockayne syndrome confirmed by gene detection with renal injury were reviewed, and the clinical features of renal involvement in Cockayne syndrome were summarized. Results A male child aged 3 years and 8 months had clinical manifestations of mental retardation, growth retardation, special face and photosensitive dermatitis, and renal involvement was manifested by nephrotic syndrome. Cranial CT showed symmetrically calcification in bilateral basal ganglia. The targeted next generation sequencing results showed homozygous mutations of c.394_398del and p.Leu132Asnfs in ERCC8 gene (NM_000082) of the child, and the same heterozygous mutation was found in both his parents (non-consanguineous marriage). After the diagnosis of nephrotic syndrome, full dose prednisone was given for experimental treatment. The urine protein decreased but did not disappear, which was considered hormone resistance. After 4 months of combined treatment with cyclosporin, the urine protein turned negative. During 20 months of follow-up, urine protein remained negative and renal function remained stable. The renal involvement in Cockayne syndrome was seldomly reported, and its clinical manifestations are heterogeneous. Condusion Renal involvement in Cockayne syndrome may be manifested with nephrotic syndrome which should be noticed.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*