The identification and optimization of mutations in nanobodies are crucial for enhancing their therapeutic potential in disease prevention and control. However, this process is often complex and time-consuming, which limit its widespread application in practice. In this study, we developed a workflow, named Evolutionary-Nanobody (EvoNB), to predict key mutation sites of nanobodies by combining protein language models (PLMs) and molecular dynamic (MD) simulations. By fine-tuning the ESM2 model on a large-scale nanobody dataset, the ability of EvoNB to capture specific sequence features of nanobodies was significantly enhanced. The fine-tuned EvoNB model demonstrated higher predictive accuracy in the conserved framework and highly variable complementarity-determining regions of nanobodies. Additionally, we selected four widely representative nanobody-antigen complexes to verify the predicted effects of mutations. MD simulations analyzed the energy changes caused by these mutations to predict their impact on binding affinity to the targets. The results showed that multiple mutations screened by EvoNB significantly enhanced the binding affinity between nanobody and its target, further validating the potential of this workflow for designing and optimizing nanobody mutations. Additionally, sequence-based predictions are generally less dependent on structural absence, allowing them to be more easily integrated with tools for structural predictions, such as AlphaFold 3. Through mutation prediction and systematic analysis of key sites, we can quickly predict the most promising variants for experimental validation without relying on traditional evolutionary or selection processes. The EvoNB workflow provides an effective tool for the rapid optimization of nanobodies and facilitates the application of PLMs in the biomedical field.

OBJECTIVE: To investigate the structural abnormalities of brain in patients with antisocial personality disorder (ASPD) but without alcoholism and drug abuse. METHODS: Volunteers from Hunan Reformatory (n=36) and the matched healthy subjects (n=26) were examined by high-spatial resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Voxel-based morphometry and fractional anisotropy (FA) maps were generated for each subject to reveal structural abnormalities in patients with ASPD. RESULTS: Compared with the healthy controls, ASPD patients showed significantly higher gray matter volumes in the inferior parietal lobule (P≤0.001, uncorrected), white matter volumes in the precuneus (P≤0.001, uncorrected), FA in the left lingual gyrus, bilateral precuneus, right superior frontal gyrus and right middle temporal gyrus (P≤0.01, uncorrected). CONCLUSION Our results revealed the abnormal neuroanatomical features in ASPD patients, which might be related to the external behavioral traits in ASPD patients.
Anisotropy ; Antisocial Personality Disorder ; diagnosis ; Brain ; anatomy & histology ; Case-Control Studies ; Diffusion Tensor Imaging ; Humans ; Magnetic Resonance Imaging

BACKGROUNDTo investigate the diagnosis and treatment of pulmonary sclerosing hemangioma (PSH).

METHODSThe clinical features, radiographic manifestations and treatment of 21 patients with PSH were reviewed.

RESULTSNone of the 21 patients was diagnosed as PSH preoperatively. There were 18 females and 3 males, and the average age was 48.0 years in this group. Twelve patients were symptom free. The plain chest roentgenograms showed a well defined, homogeneous, round or oval nodulous shadow in most cases. All patients received operation. There was no postoperative morbidity and mortality. Postoperative follow-up showed a good prognosis.

CONCLUSIONSPreoperative diagnosis of PSH is quite difficult. PSH should be suspected in middle to old aged female patients who show a well defined, homogeneous, round or oval shadow in plain chest roentgenograms. PSH has a good prognosis if it is treated surgically.

BACKGROUNDTo investigate the role of curative and palliative surgical treatment of lung cancer with video-assisted thoracoscopic surgery (VATS).

METHODSForty-three patients with lung cancer were prescribed operations with VATS, which included 5 cases of stage IA, 14 cases of IB, 1 case of IIA, 4 cases of IIB, 7 cases of IIIA, 6 cases of T4-IIIB and 6 cases of IV. The 7 patients of stage IIIA were previously staged as N0 before operation, but reevaluated as N2-IIIA after operation. There were 3 cases of malignant pleural effusion and 3 cases of pleural implantation in stage IIIB cases. There were 2 cases of cardiac tamponade, 1 case of solitary brain metastasis, and 3 cases of ipsilateral or contralateral solitary lung metastasis in cases of stage IV. The main methods of operation performed included lobectomy in 36 cases, wedge resection in 5 cases, and pericardial opening in 2 cases. Systemly mediastinal lymph node dissections were performed in 36 cases. Concurrent contralateral pulmonary wedge resections were performed in 2 cases of contralateral solitary lung metastasis. Malignant pleural effusions were prescribed resection of implantation nodules, electrocautery and pleurodesis.

RESULTSThere was no perioperative death or bronchial leak. Five cases suffered lung infection, and 2 cases occurred with incision infection. Malignant pleural effusion in the 3 cases was controlled satisfactorily. Two cases of pericardial opening died in 4 months and 8 months after operation respectively. The other patients were alive till present. Postoperative hospital stay was 5-15 days with average of 7.4 days, except of two cases of pericardial opening.

CONCLUSIONSVATS is an alternative way for complete resection of early stage lung cancer. It is technically feasible to dissect mediastinal lymph node for accidental N2 lung cancer. VATS has significant advantage in concurrent bilateral pulmonary resection. The palliative operation of malignant pleural effusion and cardiac tamponade by VATS can markedly improve the quality of life of patients.