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.

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Objective: To determine the expression of melanoma-associated antigens D4(MAGED4) and SIRT7 in human glioma, and to analyze the potential effects of MAGED4 and SIRT7 on glioma cell proliferation. Methods: The MAGED4 and SIRT7 expression levels and their correlation were compared by the China glioma genome atlas(CGGA), human protein atlas(HPA), and UALCAN databases. Survival analysis, ROC curve analysis, and Cox regression analysis were used to predict the outcome of MAGED4 and SIRT 7 in glioma patients. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) signaling pathway enrichment analysis were used to explore the biological functions of MAGED4 and SIRT7 in glioma. Western blot experiment was used to investigate whether MAGED4 protein exerted its regulatory effects on the activity of the PI3K/AKT signaling pathway via SIRT7. The effect of MAGED4 on cell proliferation in glioma through SIRT7 was explored by CCK-8. Results: The analysis results of CGGA, UALCAN, and HPA databases showed that the expression levels of MAGED4 and SIRT7 in glioma tissues were higher than those in normal brain tissue, and the expression were positively correlated. Results of survival, ROC, and Cox analysis showed that high expression of MAGED4 and SIRT7 mRNA were risk factors for poor prognosis in glioma. Results of KEGG enrichment analysis showed that MAGED4 and SIRT7 were associated with the PI3K/AKT signaling in glioma, and Western blot results showed that MAGED4 activated the PI3K/AKT signaling pathway by regulating SIRT7. The CCK-8 results showed that MAGED4 promotes the proliferation of glioma cells through SIRT7. Conclusion MAGED4 and SIRT7 are highly expressed in glioma and associated with poor prognosis, and MAGED4 promotes glioma cell proliferation through activation of the PI3K/AKT signaling pathway by SIRT7.

Objective To analyze the nutrition status of primary and middle school students in Baodi district,Tianjin in 2021 and 2023,as to provide scientific basis for improving the nutritional status of students.Methods A stratified random cluster sampling method was adopted to select 12 schools in Baodi district,Tianjin.Students' nutrition status were assessed from September to November of every year in 2021 and 2023,including questionnaire survey,physical examination and biochemical indicators.Results Compared with the same gender and age students in 2021,the height of boys aged 7-13 and girls aged 7-12 will significantly increase in 2023,while the body mass of boys and girls aged 8 and 11 will significantly increase.Compared with 2021,the overweight and obesity rates among males have significantly decreased in 2023,while the emaciation rates among males and females have significantly increased.The anemia rate,serum ferritin and vitamin A,and vitamin D deficiency rate among students in 2023 were 12.25％,3.77％,15.70％,and 50.31％,respectively,with no statistically significant difference compared to 2021(P＞0.05).The awareness rate of nutrition knowledge and the proportion of related behaviors among students in 2023 have significantly increased compared to 2021.Conclusion Compared with 2021,the overweight and obesity rates among primary and secondary school students will decrease in 2023,while anemia,serum ferritin,vitamin A,and vitamin D deficiencies will not improve.Targeted intervention activities are urgently needed.

Objective:To elucidate the causal association between gut microbiota and osteoporosis, we conducted a two-sample Mendelian randomization(MR)analysis to evaluate the causality between gut microbiota and osteoporosis.Methods:We assessed genome-wide association study (GWAS)summary statistics for gut microbiota and osteoporosis in older patients to perform the MR analysis.Independent single nucleotide polymorphisms closely associated with 211 gut bacterial taxa were identified as instrumental variables.The summary statistic data for osteoporosis were obtained from the latest release from the FinnGen consortium as the outcome of interest.Two-sample MR was performed to evaluate the causal effect of gut microbiota on osteoporosis, including the inverse-variance-weighted(IVW)method, weighted median method, MR-Egger, mode-based estimation, and MR-PRESSO.A series of sensitivity analyses were conducted to validate the robustness of the results.The robustness of the estimation was assessed through a series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plot to evaluate the causal association. Results:The population primarily consisted of individuals from Europe, with a total sample size of 7 300, including 1 762 males and 5 538 females, and average ages of 65.6 years for males and 67.8 years for females, respectively.The mean ages of the 5 538 patients were 65.6 years for males and 67.8 years for females, respectively.Through MR analysis in this study, 10 intestinal flora(comprising 1 class, 7 genera, and 2 orders)were identified as being associated with senile osteoporosis.Notably, the phylum Firmicutes( OR=1.324, P=0.019), Clostridium difficile( OR=1.274, P=0.038), fecal coliforms( OR=1.565, P=0.009), Verrucomicrobium( OR=1.231, P=0.033), and Selenomonas( OR=1.324, P=0.019)may serve as risk factors for senile osteoporosis.Conversely, Coprococcus( OR=0.620, P=0.024), Haemophilus( OR=0.815, P=0.016), Prevotella( OR=0.813, P=0.027), Sellimonas( OR=0.858, P=0.034), and RF9( OR=0.821, P=0.021)may function as protective factors against senile osteoporosis. Conclusions:This study suggests a causal relationship between the Firmicutes phylum and its nine subgroups and senile osteoporosis, thereby providing new insights into the mechanisms by which gut microbiota mediate senile osteoporosis and confirming the significant role of gut microbiota in this condition.

Helicobacter pylori(H.pylori)can colonize the gastric mucosa of humans and animals,leading to persistent infection,chronic inflammation,and tissue damage.To understand the preva-lence of H.pylori in dogs,this study designed specific primers targeting a unique region of the H.pylori virulence gene vacA and established a SYBR Green Ⅰ-based real-time PCR(qPCR)method.The specificity,sensitivity,and repeatability of this method were evaluated.Using the es-tablished method,alongside conventional PCR and H.pylori stool antigen(HpSA)detection,we conducted an epidemiological survey of H.pylori infection in pet dogs in urban Hangzhou.The re-sults showed that the standard curve demonstrated a good linear relationship within the concentra-tion range of 3.26×106 to 3.26×101 copies/μL.The method specifically detected H.pylori,with a minimum detection limit of 3.26×101 copies/μL.The intra-and inter-assay coefficients of variation ranged from 0.84％to 1.87％and 0.96％to 1.93％,respectively.Applying this method to canine fe-cal samples collected in Hangzhou from 2023 to 2024 revealed an overall H.pylori positive rate of 25.21％.In comparison,the detection rates by conventional PCR and HpSA were 10.68％and 8.97％,respectively.These results indicate that the established qPCR method is suitable for detec-ting H.pylori infection in dogs,providing a rapid,sensitive,specific,and reproducible quantitative detection method.Additionally,this study confirms the significant prevalence of H.pylori infection in household dogs.Given the widespread dissemination of H.pylori and its potential zoonotic risk,So recommend implementing risk communication and ongoing regional monitoring programs to protect the health of both humans and pets.

Objective To investigate the association between body roundness index(BRI)and hyperuricemia(HUA)in patients with type 2 diabetes mellitus(T2DM).Methods 555 T2DM inpatients were selected from July 2022 to October 2023 in Gansu Province People's Hospital Endocrinology.According to BRI,the T2DM patients were divided into four group:low BRI(L-BRI,BRI≤3.579,n=140)group,moderate BRI(M-BRI,3.579

Objective To develop a rehabilitation exercise program for the patients with osteoporotic vertebral compression fractures.Methods An online search was performed across both Chinese and English databases and websites to retrieve literature on rehabilitation exercises and related therapeutic measures for patients with osteoporotic vertebral compression fractures.Two researchers independently screened the retrieved literature,evaluated the quality,and extracted relevant evidence.Semi-structured interviews were conducted among 15 patients at various rehabilitation phases about the requirements of rehabilitation.A preliminary exercise program was developed and verified for the validity and feasibility using Delphi method.Results A rehabilitation exercise program was formulated.The program included five periods of preoperative period,bedridden period after surgery,ambulation period(1 week after surgery),weeks 2-8 after surgery and weeks 9-12 after surgery covering six domains of exercise type,exercise items,exercise duration,exercise frequency,exercise intensity and exercise safety.The response rate and effective rate over the two rounds of expert consultation were both 100.00%,with an authority coefficient of 0.94.The Kendall's W coefficients for secondary indicators in the two rounds of expert consultation were 0.184 and 0.334,respectively(both P<0.001).Conclusion The exercise program developed in this study for the patients with osteoporotic vertebral compression fractures is scientifically reliable and reasonable.The two features of continuity and staged characteristics in rehabilitation process are fully considered,thereby it offers a guidance for clinical healthcare professionals as well as the patients in development of practical and effective rehabilitation exercise plans.

Objective To explore the work experiences and needs of nutrition specialist nurses,so as to provide a basis in career development and management practices among the nutrition specialist nurses.Methods A method of descriptive phenomenological research was adopted in this study.Purposive sampling was used to select 12 nutrition specialist nurses who came from different regions across the country with over one year of clinical working experiences as well as had completed the specialist training and been qualified by the Nutrition Committee of Guangdong Nursing Association between January and February 2024.Semi-structured on-line interviews were conducted among the participants and the data acquired from the interviews were analysed and summarised.Themes were extracted using NVivo12 and Colaizzi's seven-step analysis from the data from interview.Results Three main themes and eight sub-themes were identified regarding the work experience of nutrition specialist nurses:growth and gains(continuously learning in nutrition therapy-related knowledge to enhance professional skills;actively practice in nutrition therapy to achieve the self-worth);sense of responsibility and mission(increased awareness of responsibility and proactive services;sense of mission to cultivate talents and promotion of the development of nutrition nursing discipline);challenges(lack of an established role in nutrition nursing,conflict in responsibilities;insufficient communication in a medical team regarding nutrition therapy;limited resource to support the development of nutrition nursing;and the professional knowledge and skills unable to fully meet the job demands).Conclusion Hospitals managers should strengthen the support and training for nutrition specialist nurses,clarify their roles,leverage their professional value and promote the career development.

Objective Compare the clinicopathological factors of microsatellite unstable(dMMR)and microsatellite stable(pMMR)in right colon cancer and analyze the factors affecting overall survival(OS)and disease-free survival(DFS)between the two groups.Methods Clinical data with right colon cancer of patients who underwent radical resection from January 1,2016 to December 31,2023 were retrospectively analyzed(a total of 247 patients were included,including 43 dMMR and 204 pMMR).Through propensity score matching,the baseline difference between the two groups was matched 1∶1,and a total of 86 cases were obtained,43 cases in dMMR and 43 cases in pMMR.The difference of relevant indicators between the two groups was analyzed,and univariate and multivariate Cox analysis was performed for OS and DFS.The survival curve was plotted,and the comparison of survival rates was conducted using the Log rank test.Results According to age,location,tumor length,shape,histological type,T,N,TNM stage,nerve invasion,and differentiation degree with 1∶1 matching(P＜0.05),there was no statistical difference in baseline data between dMMR and pMMR patients with right colon cancer(P＞0.05).It was found that 5-year OS of dMMR patients with right colon cancer was significantly better than pMMR(P＜0.05),and 5-year DFS dMMR was better than pMMR(P＜0.05).Protective factors affecting OS of dMMR right colon cancer included tumor length＜5 cm,T1-3,M0,Stage Ⅰ-Ⅲ,absence of intravascular cancer thrombi and absence of nerve invasion(P＜0.05).In survival analysis,M0 was compared with M,(95％vs.60％,P＜0.05).Stage Ⅰ-Ⅲ compared with stage Ⅳ(95％vs.54％,P＜0.05);No vascular cancer thrombus vs.cancer thrombus(94％vs.88％,P＜0.05).Protective factors affecting DFS of dMMR right colon cancer included age＜50 years,no mucous or sig-ring cells,M0,StageⅠ-Ⅲ,and no intravascular cancer thrombus(P＜0.05).In survival analysis,M0 was compared with M,(90％vs.63％,P＜0.05).Stage Ⅰ-Ⅲ compared with stage Ⅳ(92％vs.57％,P＜0.05);There was a significant difference between non-vascular cancer thrombus and vascular cancer thrombus(91％vs.77％,P＜0.05).Conclusion The patients with dMMR had higher OS and DFS than pMMR,which were not affected by clinical factors.