Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Tooth extraction is a common and widely employed therapeutic procedure in oral and maxillofacial surgery.Minimally invasive tooth extraction can reduce both physical and psychological trauma to the patients,and is widely recommended as a first-line clinical treatment.But currently no guidelines or consensus has been available to provide a systematic introduction of minimally invasive tooth extraction to guide the clinical practices.To address this issue,this consensus,based on a comprehensive literature review and clinical experiences of experts,systematically summarizes the indications,target patients,and contraindications of minimally invasive tooth extraction,the overall workflow of this procedure(preoperative preparation,surgical steps,postoperative management,postoperative instructions,medications,and follow-up),and its common postoperative complications to provide a comprehensive guidance for clinical application of this technique.

Tooth extraction is a common and widely employed therapeutic procedure in oral and maxillofacial surgery.Minimally invasive tooth extraction can reduce both physical and psychological trauma to the patients,and is widely recommended as a first-line clinical treatment.But currently no guidelines or consensus has been available to provide a systematic introduction of minimally invasive tooth extraction to guide the clinical practices.To address this issue,this consensus,based on a comprehensive literature review and clinical experiences of experts,systematically summarizes the indications,target patients,and contraindications of minimally invasive tooth extraction,the overall workflow of this procedure(preoperative preparation,surgical steps,postoperative management,postoperative instructions,medications,and follow-up),and its common postoperative complications to provide a comprehensive guidance for clinical application of this technique.

Redox-sensitive cysteine(RSC)thiol plays an important role in many biological processes such as photosynthesis,cellular metabolism,and transcription.Therefore,it is necessary to identify red-ox-sensitive cysteine accurately.However,traditional redox-sensitive cysteine identification is very ex-pensive and time-consuming.At present,there is an urgent need for a mathematical calculation method to identify sequence information and redox-sensitive cysteines quickly and accurately.Here,we devel-oped an effective predictor called iRSC-PseAAC,which used the dimension reduction algorithm LDA combined with the support vector machine to predict redox-sensitive cysteine sites.In the cross-validation results,the specificity(Sp),sensitivity(Sn),accuracy(Acc)and Matthews correlation coefficient(MCC)were 0.841,0.868,0.859 and 0.692 respectively.In the independent dataset results,the Sp,Sn,Acc and MCC were 0.906,0.882,0.890 and 0.767 respectively.compared with existing prediction methods,iRSC-PseAAC had obvious improvement effect.The method proposed for this study can also be used for many problems in computational proteomics.

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals ; Autism Spectrum Disorder ; Macaca mulatta ; Disease Models, Animal ; Behavior, Animal ; Macaca fascicularis ; Male ; Humans

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Chimeric RNA is a fusion transcript composed of exons from two or more different genes and generated by chromosome rearrangement or RNA splicing. Chimeric RNAs have the potential to encode novel proteins or function as non-coding RNAs. Chimeric RNAs were ubiquitously expressed across different cancers and normal tissues. To date, mechanistic and functional studies of chimeric RNAs still remain unclear. Precise definition and terminology in the research field of chimeric RNA will be discussed in this review. The formation, classification and clinical significance of chimeric RNAs in cancer progression will be summarized. Previous studies showed that products of chimeric RNAs may play important roles in regulating cell proliferation, motility, invasion and apoptosis through encoded fusion proteins or long non-coding chimeric RNAs. In cancer, chimeric RNA and its encoded specific protein or non-coding RNA can regulate tumorigenesis by changing cell phenotypes or directly affecting gene expression or regulatory pathways, which have the potential to be important diagnostic biomarkers and therapeutic targets. In recent years, more and more cancer-specific chimeric RNAs have been discovered from multiple types of cancers and used as therapeutic targets due to their vital roles in disease prognosis. Therefore, this review will focus on the functions and applications of chimeric RNAs in different tumors, which can shed a light on cancer diagnosis and therapeutics from the new perspective.

The current study explored the hepatotoxicity among closed-ring genipin, open-ring tautomer of genipin and gardenia blue that generated from genipin and amino acid reaction using HepaRG cells to identify the material basis of genipin-induced hepatotoxicity in vitro. The effects of temperature, pH value and different kinds of amino acids on the chemical structure tautomerism between closed-ring and open-ring tautomer of genipin and the production of gardenia blue were investigated firstly, which aimed to explicit the conditions that could distinguish the closed-ring genipin and its open-ring tautomer, and the conditions generating gardenia blue, which were applied to prepare different kinds of gardenia blue; the CCK-8 kit was employed to analyze the hepatotoxicity of closed-ring genipin, open-ring tautomer of genipin and gardenia blue. From the results, it was found that, the structure transformation from close-ring to open-ring of genipin could be inhibited under the condition with acid environment; being essential groups to generate gardenia blue, the primary amino group and the open-ring tautomer of genipin reacting to generate the dihydropyridine ring was probably the key structure of gardenia blue; the structure characteristics existed apparent distinction at the reactive temperature of 37 ℃ and 80 ℃; compared to the culture condition with pH = 7.4, the concentration of genipin with close-ring in culture medium was significantly increased at pH = 5, but the cell viability did not decreased; the cell toxicity of gardenia blue was apparently lower than open-ring tautomer of genipin, and even some kinds of gardenia blue showed growth promoting effect on HepaRG cells. Here, it was suggested potentially that open-ring tautomer of genipin be the important material basis to induce hepatotoxicity, which could provide a cue and lay a foundation for the elucidation of the underlying mechanism of genipin-induced hepatotoxicity.

OBJECTIVE: To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency. METHODS: This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded. RESULTS: TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment. CONCLUSIONS The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.
Female ; Humans ; Progesterone/therapeutic use* ; Qi ; Oligomenorrhea/drug therapy* ; Quality of Life ; Prospective Studies ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/adverse effects* ; Capsules ; Kidney