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.

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*

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 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 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 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:To systematically evaluate the risk of hypotension induced by sodium-glucose transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus.Methods:Randomized controlled trials of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus, in which hypotension were evaluated as an outcome indicator of adverse events, were collected by searching relevant databases at home and abroad (up to February 15, 2023). Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies. Stata 15.1 software was used to conduct Bayesian network meta-analysis, including drawing the network evidence plot, the league map of pairwise comparison, and the surface under the cumulative ranking curve (SUCRA) for hypotension risk under different interventions of SGLT2 inhibitors, and ranking the risks of hypotension induced by different interventions of SGLT2 inhibitors. The effect sizes were expressed by relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 20 studies were included in the analysis, involving 22 525 patients with 15 260 in the trial group and 7 265 in the control group. Drugs that used in the trial group included dapagliflozin (in 1 517 patients), canagliflozin (in 6 053 patients), and ertugliflozin (in 7 690 patients); drugs that used in the control group included glimepiride (in 482 patients) and placebo (in 6 783 patients). The results of the network meta-analysis showed that the risk of hypotension was higher after treatment with 300 mg of canagliflozin, compared with those with 5 mg and 15 mg of ertugliflozin, and placebo ( RR=2.13, 95% CI: 1.31-3.47; RR=2.21, 95% CI: 1.35-3.61; RR=2.49, 95% CI: 1.62-3.82; all P<0.05); the risk of hypotension was higher after treatment with 100 mg of canagliflozin, compared with placebo ( RR=1.61, 95% CI: 1.04-2.50, P<0.05); the differences in comparison between any other 2 interventions with SGLT2 inhibitors were not statistically significant. According to the relative risks for hypotension of different interventions with SGLT2 inhibitors in the results of SUCRA, interventions were ranked as ertugliflozin 5 mg, placebo, dapagliflozin 2.5 mg, ertugliflozin 10 mg, ertugliflozin 15 mg, canagliflozin 50 mg, canagliflozin 100 mg, dapagliflozin 5 mg, dapagliflozin 10 mg, canagliflozin 150 mg, and canagliflozin 300 mg. Conclusions:Different treatment regimens with SGLT2 inhibitors had different risks of hypotension in patients with type 2 diabetes. The risk of hypotension caused by ertugliflozin is lower, especially at the dose of 5 mg. The risk of hypotension caused by canagliflozin is higher, especially at relatively high doses.

Objective:To systematically evaluate the risk of hypotension induced by sodium-glucose transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus.Methods:Randomized controlled trials of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus, in which hypotension were evaluated as an outcome indicator of adverse events, were collected by searching relevant databases at home and abroad (up to February 15, 2023). Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies. Stata 15.1 software was used to conduct Bayesian network meta-analysis, including drawing the network evidence plot, the league map of pairwise comparison, and the surface under the cumulative ranking curve (SUCRA) for hypotension risk under different interventions of SGLT2 inhibitors, and ranking the risks of hypotension induced by different interventions of SGLT2 inhibitors. The effect sizes were expressed by relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 20 studies were included in the analysis, involving 22 525 patients with 15 260 in the trial group and 7 265 in the control group. Drugs that used in the trial group included dapagliflozin (in 1 517 patients), canagliflozin (in 6 053 patients), and ertugliflozin (in 7 690 patients); drugs that used in the control group included glimepiride (in 482 patients) and placebo (in 6 783 patients). The results of the network meta-analysis showed that the risk of hypotension was higher after treatment with 300 mg of canagliflozin, compared with those with 5 mg and 15 mg of ertugliflozin, and placebo ( RR=2.13, 95% CI: 1.31-3.47; RR=2.21, 95% CI: 1.35-3.61; RR=2.49, 95% CI: 1.62-3.82; all P<0.05); the risk of hypotension was higher after treatment with 100 mg of canagliflozin, compared with placebo ( RR=1.61, 95% CI: 1.04-2.50, P<0.05); the differences in comparison between any other 2 interventions with SGLT2 inhibitors were not statistically significant. According to the relative risks for hypotension of different interventions with SGLT2 inhibitors in the results of SUCRA, interventions were ranked as ertugliflozin 5 mg, placebo, dapagliflozin 2.5 mg, ertugliflozin 10 mg, ertugliflozin 15 mg, canagliflozin 50 mg, canagliflozin 100 mg, dapagliflozin 5 mg, dapagliflozin 10 mg, canagliflozin 150 mg, and canagliflozin 300 mg. Conclusions:Different treatment regimens with SGLT2 inhibitors had different risks of hypotension in patients with type 2 diabetes. The risk of hypotension caused by ertugliflozin is lower, especially at the dose of 5 mg. The risk of hypotension caused by canagliflozin is higher, especially at relatively high doses.