Protein lysine β-hydroxybutyrylation (Kbhb) is a newly discovered post-translational modification associated with a wide range of biological processes. Identifying Kbhb sites is critical for a better understanding of its mechanism of action. However, biochemical experimental methods for probing Kbhb sites are costly and have a long cycle. Therefore, a feature embedding learning method based on the Transformer encoder was proposed to predict Kbhb sites. In this method, amino acid residues were mapped into numerical vectors according to their amino acid class and position in a learnable feature embedding method. Then the Transformer encoder was used to extract discriminating features, and the bidirectional long short-term memory network (BiLSTM) was used to capture the correlation between different features. In this paper, a benchmark dataset was constructed, and a Kbhb site predictor, AutoTF-Kbhb, was implemented based on the proposed method. Experimental results showed that the proposed feature embedding learning method could extract effective features. AutoTF-Kbhb achieved an area under curve (AUC) of 0.87 and a Matthews correlation coefficient (MCC) of 0.37 on the independent test set, significantly outperforming other methods in comparison. Therefore, AutoTF-Kbhb can be used as an auxiliary means to identify Kbhb sites.
Protein Processing, Post-Translational ; Lysine/chemistry* ; Proteins/chemistry* ; Machine Learning ; Algorithms

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

The purpose of this article is to systematically review the effectiveness of pivotal response training （PRT） for children with autism spectrum disorder （ASD）， so as to provide evidence-based guidance for the implementation of effective PRT for children with ASD. Randomized controlled trials （RCTs） investigating the effectiveness of PRT for children with ASD were collected， and the methodological quality of the trails was evaluated using the Cochrane Collaboration's tool for risk of bias assessment. A total of 6 RCTs were included in this review. Then the empirical findings including the implementation of PRT and the role of PRT in improving general social skills and verbal communication skills of children with ASD were elaborated. And its limitations and possible future research directions were also summarized. ［Funded by Special Project for Construction of Innovation Environment in Autonomous Region： Construction of Science and Technology Innovation Base （number， PT2306）］

【Objective】 To observe the effects of early postnatal immune activation (EPIA) on social behaviors of male and female mice, and to explore the possible role of the functional state of astrocytes and microglia in this process. 【Methods】 Using lipopolysaccharide (LPS) induced EPIA mice as study subjects, mice were divided into the male-control, male-model, female-control, and female-model groups, each containing 10 mice (n=10). Behavioral tests were performed at 25 - 32 days of age, and the social behavior ability of mice was evaluated by open field test, three-chamber sociability test, and marble burying test. The expression levels of GFAP, IBA-1, TLR4, and NFκB p65 in the cortex and hippocampus were detected by Western blot (n=3). 【Results】 In behavioral tests, social index significantly decreased in LPS treatment group (F=14.907, P<0.05). The interaction effect between treatment and sex was significant in the residence time (F=5.260, P<0.05) and the number of buried marbles (F=7.788, P<0.05). LPS treatment decreased the retention time of the central region in male mice (F=4.261, P<0.05), and increased the number of buried marbles in males (F=20.645, P<0.05). Western blot results showed that LPS treatment increased the expression of GFAP protein in the hippocampus (F=50.443, P<0.05) and cortex (F=30.116, P<0.05), as well as the expression of IBA-1 protein (F=21.844. P<0.05) and TLR4 protein (F=6.215, P<0.05) in the cortex. The results of NFκB p65 showed a significant interaction between treatment and sex in the cortex (F=6.558, P<0.05), and LPS increased the expression of NFκB p65 protein in the cortex in female mice (F=16.317, P<0.05). 【Conclusions】 EPIA is sufficient to induce sex-specific autism spectrum disorder (ASD)-like behavior and enhance astroglial and microglial reactivity in mice. ASD-like behavior induced by EPIA may be related to the TLR4/NFκB signaling pathway in the cortex.

Fetuin-B (FETUB) is a glycoprotein mainly synthesized and secreted by the liver. It is involved in many physiological and pathological processes including glucose metabolism, inflammatory response, nonalcoholic fatty liver disease, myocardial infarction, tumor and so on. In recent years, FETUB has also been confirmed to play roles in the female reproductive system. FETUB may affect follicular development and play an important role in in vivo and in vitro fertilization. In addition, serum FETUB level is elevated significantly during pregnancy and labor. FETUB expression is changed in a variety of reproductive diseases (polycystic ovary syndrome, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy). In this review, we summarize FETUB related studies in female reproduction, and focus on the roles of FETUB in female reproductive physiology and pathology, in order to provide information for the pathogenesis of reproductive disorders.
Humans ; Female ; Pregnancy ; Polycystic Ovary Syndrome/physiopathology* ; Fetuin-B/physiology* ; Pregnancy Complications/metabolism* ; Animals ; Diabetes, Gestational/physiopathology* ; Cholestasis, Intrahepatic/metabolism* ; Reproduction/physiology* ; Ovarian Follicle/physiology*

BackgroundThe incidence of autism spectrum disorders （ASD） is showing an upward trend， and the treatment and training process for children with ASD is lengthy， placing a heavy burden on their families. Such fact results in parents being prone to feelings of stigma. However， there exists a lack of research studying on the stigma among parents of children with ASD. ObjectiveTo explore the relationship between stigma and coping styles and social support of parents with ASD， and to provide references for practices of reducing stigma level and taking targeted interventions in this group. MethodsThis study involved parents of children diagnosed with ASD and admitted to the children's health clinic of a tertiary hospital in Urumqi between January 2021 and May 2022. General information questionnaire， Affiliate Stigma Scale （ASS）， Simplified Coping Style Questionnaire （SCSQ） and Social Support Rating Scale （SSRS） were employed to conduct investigation. Pearson correlation analysis was used analyze the correlation between stigma， coping styles and social support. ResultsThe ASS total score of parents of children with ASD was （52.40±11.22）. Correlation analysis results showed that the ASS total score of parents was positively correlated with the score of negative coping dimension in SCSQ （r=0.787， P<0.01）， and negatively correlated with the score of positive coping dimension in SCSQ and SSRS total score （r=-0.565， -0.795， P<0.01）. The result of regression analysis suggested that stigma among parents of children with ASD was affected by coping style and social support （∆R²=0.768， F=114.931， P<0.01）. These two factors could explain 76.80% of the total variance. ConclusionParents of children with ASD have stigma of moderate to high level， and coping styles and social support are two important factors influencing the stigma. ［Funded by Xinjiang Uygur Autonomous Region Science and Technology Program Resource Sharing Platform Construction Project （number， PT2215）］

Objective:To measure the space of motion of index finger with and without injury, to apply it in rehabilitation. Methods:Thirty healthy undergraduate volunteers (controls) and three undergraduate volunteers with recent index finger injury (patients) were asked to flex, extend, adduct, abduct and ring the index finger independently and combined with middle finger, twice for a motion with an interval of 30 seconds. The index finger movement trajectory was recorded with a high-definition camera, and analyzed the range of flexion, extension, adduction, abduction and ring rotation motion with MATLAB. The movement space and defect of the injured fingers were drawn. Results:The ranges of independent flexion-extension and adduction-abduction reduced 26.5% and 24.6% in the patients compared with those of the controls, respectively. The defects of ring rotation space were very different with the degrees of recovery, and the maximum loss happened on 160°, 70° and 170°. Conclusion:Loss in index fingers motion space in range and direction may help for rehabilitation assessment.

Objective The evaluation management of scientific research projects is the core work content of scientific research management institutions at all levels.The primary causes of bias in project evaluation are the acquaintance social network relationship and the unit-based unitism,especially in the case of small academic circles.The purpose of this essay is to study how to circumvent this problem,to select projects objectively and fairly,and to benefit the evaluation and management of scientific research projects at all levels.Methods Including information construction,expert database construction,expert rotation system,expert avoidance system,supervision and examination system,peer-expert review and strengthen the expert project evaluation.For the first time,we proposed a double-blind,random,centralized,and group-based independent evaluation system.Results This method has a positiveeffect on view.Conclusions In the case where the relative or absolute numberof experts in a single field is small,implementing a series of normative systems and measures through organizational management can avoid interference factors that affect the project evaluation effectively and achieve more scientific and fair results.

Drug toxicology,as a discipline which studies drug toxicity mechanisms and evaluates comprehensive drug safety is of crucial importance for guiding sensible clinical drug use,reducing adverse drug reactions and reducing failures of new drug development caused by toxicity. This article summarizes the basic situation of Natural Science Foundation of China(NSFC)funded projects in drug toxicology between 2001 and 2015,involving the amount of approved grants,funding rate,funding category and supported faculty,and the change of NSFC guidelines. Research topics,ideas and contents of NSFC funded projects are generalized and characteristics,problems and future trends are also analyzed to provide reference for research on drug toxicology.