Alzheimer′s disease(AD)is a chronic neurodegenerative diseasecommonly seen in the elderlys. Several therapeutic drugs have failed in phase III clinical trials in recent years and there have been no efficient treatment for AD currently. Thus, there has been an urgent need for the effective methods of AD diagnosis at early stage. Developingnear-infrared fluorescentprobes for AD hallmarks detection has been a promising research field. In this review, we summarized a variety of near-infrared fluorescence(NIRF)probes reported in the past decade, which capable of detecting β-amyloid, Tau protein and reactive oxygen species, including their chemical strucutres、optical properties, in vitro and in vivo studies. Furthermore, we alsoraised some new directions for AD diagnosing. We believe that these new directions raised herein will benefit the future development of NIRF probes in the field of AD research.

Phosphoinositide 3-kindase,an important signal transduction molecule in cells,plays a key role in the process of cell survival,proliferation and differentiation.Significant progress has been made in the treatment of cancer with PI3K inhibitors,yet the drug resistance of PI3K inhibitors affects their long-term efficacy in clinical treatment.In order to overcome the drug resistance,a variety of rational combined therapies have been developed.In this paper,the research progress of phosphoinositide-3 kinase inhibitors in combination with other drugs to overcome the drug resistance were reviewed.

Objective:To explore the mediating role of aging attitude and anxiety in the relationship between self-worth and depression among the elderly.Methods:From July to August 2022, a total of 536 elderly people in Shijiazhuang University for the Elderly were surveyed by the elderly self-worth scale, generalized anxiety disorder-7(GAD-7), attitudes to aging questionnaire(AAQ) and patient health questionnaire(PHQ-9). SPSS 26.0 software was used for descriptive statistics and correlation analysis.AMOS 24.0 was used to construct an intermediation model, and Bootstrap method was used for mediating effect testing.Results:(1)The score of self-worth was 101.00 (92.00, 112.00), the score of aging attitude was 92.00 (83.00, 101.75), the score of anxiety was 2.00(0, 6.00), and the score of depression was 2.00 (0, 5.00). (2)Self-worth was positively correlated with aging attitude ( r=0.67, P<0.01), while negatively correlated with anxiety ( r=-0.45, P<0.01) and depression ( r=-0.48, P<0.01). The aging attitude was negatively correlated with anxiety ( r=-0.41, P<0.01) and depression ( r=-0.41, P<0.01). Anxiety was positively correlated with depression ( r=0.71, P<0.01). (3)The indirect effect of aging attitude between self-worth and depression in the elderly was -0.016, accounting for 19.75% (-0.016/-0.081)of the total indirect effect.The indirect effect of anxiety between self-worth and depression in the elderly was -0.045, accounting for 55.56%(-0.045/-0.081) of the total indirect effect.The chain mediating effect of aging attitude and anxiety between self-worth and depression in the elderly was -0.020, accounting for 24.69%(-0.020/-0.081) of the total indirect effect. Conclusion:Aging attitude and anxiety play a chain mediating role between self-worth and depression in the elderly.

Objective:To effectively express the receptor binding domain (RBD) of SARS-CoV-2 spike protein in Pichia pastoris and to evaluate its immunogenicity. Methods:The gene encoding the RBD protein was synthesized and cloned into the pPICZαA plasmid. After linearization, the plasmid was transferred and integrated into the genome of Pichia pastoris. The expressed RBD protein in culture supernatant was analyzed by Western blot and Biolayer interferometry. After screening, a single clone expressing the RBD protein was selected. The high-level expression of RBD protein was achieved by optimizing the fermentation process, including the salt concentration adjusting of the medium and induction condition optimization (pH, temperature and duration). The immunogenicity of the expressed RBD protein was evaluated in a mouse model. Results:A single clone with a high expression level of RBD protein was obtained and named RBD-X33. The expression level of RBD protein in the fermentation supernatant reached up to 240 mg/L after optimization of the induction condition (HBSM medium, pH=6.5±0.3, 22℃ and 120 h). In the mouse experiment, the recombinant RBD protein was formulated with Alum+ CpG dual adjuvant and injected into mice. The binding IgG antibody levels were up to 2.7×10 6 tested by ELISA and the neutralizing antibody levels were up to 726.8 tested by live virus neutralizing antibody assay (prototype). Conclusions:The RBD protein could be efficiently expressed in Pichia pastoris and induce stronger immune response in animals. This study suggested that the recombinant SARS-CoV-2 RBD protein expressed in Pichia pastoris could serve as a candidate antigen in the development of SARS-CoV-2 vaccine.

Objective: Study the clinical significance of HBX gene detection, sequence analysis in peripheral blood mononuclear cell(PBMC) of chronic hepatitis B(CHB) patients with serum HBV DNA negative conversion after treatment by nucleoside analogues(NAs). Methods: Detected and analyzed the HBX gene sequence by real time PCR in PBMC of 60 patients with CHB including some with cirrhosis or hepatocellular carcinoma(HCC), all the serum HBV DNA had turned negative after treatment by NAs, and explore the clinical significance of the HBX gene. Results: HBX genes were detected in 37 cases(61.67%, 37/60). HBX positive rates of PBMC in HCC and cirrhosis patients were higher than that of CHB patients(P=0.000, P=0.010). HBX △120, HBX△129, HBX△131 truncations were detected in two HCC and one CHB cases. Two hotspot mutation including A389T/G391A, T380C had been found, and A389T/G391A double mutation in HCC patients was significantly higher than that in CHB patients(P=0.021). In cirrhosis and HCC patients, T380C mutation rate in HBeAg(-) cases was higher than that in HBeAg(+ ) cases(P=0.035). Conclusions In patients with serum HBV DNA negative conversion after treatment by NAs, PBMC HBX gene positive rates in cirrhosis or HCC cases are higher than that in CHB cases. A389T/G391A double mutation rate in HCC cases is significantly higher than that in CHB cases. In cirrhosis and HCC patients, T380C mutation rate in HBeAg(-) cases is higher than that in HBeAg(+ ) cases.