Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Objective:To observe the occurrence and closure of iatrogenic atrial septal defect (IASD) after left atrial appendage occlusion (LAAo) and atrial fibrillation cryoballoon ablation (CBA), and to identify potential factors that may affect the occurrence of IASD.Methods:A total of 383 patients who underwent successful LAAo surgery in the Department of Cardiology at the Nanjing Hospital Affiliated to Nanjing Medical University from June 7, 2016 to December 2, 2020, and atrial fibrillation CBA surgery from December 29, 2016 to September 10, 2020 were retrospectively selected. Patients were followed up with echocardiography at 1 month, 3 months, 6 months, 1 year, and>1 year after surgery to determine the occurrence of IASD. The incidence of IASD between the two groups was compared, and clinical data between the two groups with and without IASD were analyzed to identify the relevant factors for the occurrence of IASD.Results:One month after CBA surgery for atrial fibrillation [73.8%(138/187) vs 47.9%(67/140), P<0.001], 3 months [39.0%(57/146) vs 13.6%(16/118), P<0.001], 6 months [17.7%(22/124) vs 3.6%(4/110), P=0.001], 1 year [11.8%(15/127) vs 1.8%(2/112), P=0.003], and one year later [9.8%(13/133) vs 0.9%(1/116), P=0.002], the incidence of IASD was significantly higher than those in LAAo. Compared with the non IASD group, the IASD group had a lower proportion of males [59.0%(121/205) vs 83.6%(102/122), P<0.001], and a higher proportion of paroxysmal atrial fibrillation [61.5%(126/205) vs 45.9%(56/122), P=0.006]. Logistic regression analysis found a significant correlation between women and CBA with postoperative IASD. Conclusions:Compared with LAAo, the incidence of IASD after CBA for atrial fibrillation is higher, and some IASD persist for more than 1 year after surgery. Women are significantly associated with IASD.

The pathogenic microorganism laboratory is the main workplace for the detection of pathogenic microorganisms, including bacterium and virus, or related samples, which plays an important supporting role in the prevention and control of infectious disease and the fight against biological terrorist attacks. Unified biosecurity standard and sound biosecurity standard system should be established for the laboratory experiment of pathogenic microorganisms.

Objective:To better promote the standardization of public health management in China, and provide evidence for the development and improvement of the standardization strategy and management system in public health field in China.Methods:This paper summarizes and analyzes the information about the standardized management mechanism collected from international organizations related with standardization in public health.Results:The standards in public health varied in different management systems of the international organizations, and there were great differences in organization nature, standard types, application, release, organization structure, standard development principles, advantages, transformation, promotion and implementation, and evaluation.Conclusion:China can benefit from the studying of the working mechanism of the international organization related with standardization in public health to facilitate its own standardization in public health.

Objective To investigate the physical and magnetic properties and cytotoxity of 5-FAM-dextran-coated superparamagnetic iron oxide nanoparticles ( 5-FAM-dextran-Fe3 O4 ) , and to observe the cell-labeling character of these nanoparticles. Methods 5-FAM-dextran-Fe3 O4 were prepared by ultra-sonic and chemical coprecipitation method and the characteristics were evaluated. The size and distribution of 5-FAM-dextran-Fe3 O4 were measured by transmission electron microscope ( TEM) and Malvern Zetasizer. The organic structure of the coating was characterized by fourier translation infrared spectroscopy. The optical imaging ability was measured by ultraviolet visible spectrometer and the susceptibility was measured by vi-brating sample magnetometer. In vitro cytotoxities of 5-FAM-dextran-Fe3 O4 , dextran-Fe3 O4 and Fe3 O4 were detected by MTT assay. The area of labeled neuronal cells was observed by confocal microscopy after incuba-ted with nanoparticles under different magnetic intensities. One-way analysis of variance was used. Results The size of 5-FAM-dextran-Fe3 O4 was homogeneous under TEM, and the diameter ranged from 15 to 25 nm ( average=22 nm) by Malvern Zetasizer. The organic structure of the coating of Fe3 O4 was confirmed by fou-rier translation infrared spectroscopy. Ultraviolet visible spectrometer observation showed that the nanoparti-cles expressed unanimous green fluorescence under ultraviolet activation. The saturation magnetization, residu-al magnetization and coercivity of the nanoparticles by magnetometer detection were 86. 02 A · m2 · kg-1 , 15. 05 A·m2 ·kg-1 and 5414.01 A/m respectively, showing superparamagnetic character. MTT assay re-sults showed that 5-FAM-dextran-Fe3 O4 had no obvious cytotoxicity. The confocal microscopy observation in-dicated that the cell-labeled area reached the maximum under the magnetic field intensity of 500 mT ((0. 880±0.146) mm2, F=320.298, P<0.05). Conclusions 5-FAM-dextran-Fe3O4 prepared by ultra-sonic coprecipitation method have the advantages of small size, good homogeneity and magnetic property. Therefore, they might be used as the fluorescent magnetic bio-probe in laboratory and clinical studies.

Objective To study the antipyretic,anti-inflammatory and analgesic effects of Chaigeshubiao granules. Methods Animals were randomly divided into 6 groups:blank control group,indomethacin group,Fengreganmao granules group and the high, the medium and the low dosage groups of Chaigeshubiao granules ( 26, 13, 6. 5 g . kg-1 ) . Each group was administered via intragastric administration once a day for 5 days.Rat model suffering from fever by dried yeast,relieving fever of Chaigeshubiao granules was investigated;Rats with toe swelling by 1% carrageenin and mice with ear swelling by dimethylbenzene were applied to observe anti-inflammatory effects of Chaigeshubiao granules were observed;The pain models induced by 0. 6%acetic acid and the hot-plate tests in mice were used to observe the analgesic effects of Chaigeshubiao granules. Results Compared with negative control group,Chaigeshubiao granules in high dosage could obviously decrease the temperature of rat with fever induced by dried yeast 0.5 h later,and the medium dosage group decreased 4-6 h later. Moreover,Chaigeshubiao granules in high dosage could inhibit inflammatory reaction of rat with toe swelling caused by albumen at 1 h,2 h,3 h,when the medium dosage group inhibited at 2 h,3 h,4 h. The inhibition ratio of the mice with ear swelling induced by dimethylbenzene was 58.2%, 52.0% and 53.9%,respectively at the high,medium and low dose groups. And the inhibition ratio of retortion of mice by 0.6%acetic acid was 50.5%,68.8%,58.1%,respectively, at the high,medium and low dose groups. In addition,the high,medium and low dose groups reduced the pain reaction latency of mice in the hot-plate tests. Conclusion Chaigeshubiao granules have antipyretic,anti-inflammatory and analgesic actions.

Objective To compare the effect of diversification rehabilitation team mode on function in patients with cerebral infarction. Methods Sixty-six patients with cerebral infarction were divided into diversification rehabilitation team mode group (diversification group) and routine rehabilitation mode (routine group) according to the rehabililation method with 33 cases each. All patients of 2 groups were treated for 2 weeks. Evaluations were made before and after treatment. The simplified Fugl-Meyer motor function rating scale was used to evaluate motor function, modified Barthel index was used to evaluate activities of daily living, and MOS 36-item short form health survey was used to evaluate quality of life;and 0-100 digital simulation assessment was used to evaluate patient satisfaction after treatment. Results The simplified Fugl-Meyer motor function rating scale score, modified Barthel index score, MOS 36-item short form health survey score and patient satisfaction rate after treatment in diversification group were significantly better than those in routine group: (76 ± 4) scores vs. (63 ± 3) scores, (65 ± 3) scores vs. (52 ± 4 ) scores, (57 ± 7) scores vs. (44 ± 6) scores, (92 ± 5) scores vs. (77 ± 3) scores, and there were statistical differences (P<0.05). Conclusions Both kinds of rehabilitation model can promote functional recovery in patients with cerebral infarction, but diversification rehabilitation team model is better than conventional model.

Objective To practice the distance nursing and healthcare through mobile care clinic, and to provide a higher quality of specialist care to colostomy patients. Methods 76 colostomy patients who were operated during August 2015 to January 2016 were investigated and randomly divided into the intervention group ( n=40) and the control group ( n=36 ) . Based on the conventional nursing care, the intervention group received additional continuing care including the subsequent visit and telephone follow-up with the help of mobile care clinic. After one month of intervention, patients′satisfaction level and their awareness of health knowledge were surveyed using an autonomous questionnaire. Results The intervention group had much higher level of satisfaction compared to the control group [ ( 98. 4 ± 1. 6 ) vs ( 91. 3 ± 1. 7 ); t=18. 75, P<0. 05 ] . They also performed better wound care and knowledge awareness compared to the control group ( 92. 5% vs 69. 4%;82. 50% vs 58.33%; χ2=6.70, 5.38; P<0.05). Furthermore, the intervention group had significantly fewer cases of fecal dermatitis than the control group (2 vs 11; χ2=8.73,P<0.05).Conclusions With the help of home health care platform and mobile care clinic, more professional nursing guidelines can be provided in time. It can also improve the nursing satisfaction and reduce related compliances.

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Antiviral Agents ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Nucleosides ; therapeutic use ; Nucleotides ; therapeutic use ; Prognosis