Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

ObjectiveTo analyze the epidemiological characteristics of foodborne disease outbreaks in Wuhan from 2006 to 2023, and to provide a scientific basis for the development of foodborne disease prevention and control measures. MethodsDescriptive statistical analyses were performed on foodborne disease outbreaks confirmed by the district and municipal center for disease control and prevention (CDC) in Wuhan from 2006 to 2023, and the attack rate and case fatality rate were calculated as well. ResultsA total of 182 foodborne disease outbreaks were reported in Wuhan from 2006 to 2023, with a cumulative of 2 820 cases. Among which, 3 cases were dead, with an annual average attack rate of 1.22% and a case fatality rate of 0.11%. The highest number of outbreaks occurred in collective canteens (43.96%, 80/182), the highest attack rate was observed in catering facilities (11.03%), and the highest case fatality rate was found in households (1.45%). Among the foodborne disease outbreaks with identified etiologies, microbial factors were the leading causes (36.26%, 66/182), with the main pathogens being norovirus, Bacillus cereus, and other unspecified bacteria. Fungal factors were mainly attributed to poisonous mushrooms, with a relatively high fatality rate of 2.22% (2/90). Outbreaks caused by bacterial factors were more common in the central urban area (30.28%, 33/109), while fungal-related outbreaks were more frequent in the outlying urban areas (24.66%, 18/73). ConclusionCollective canteens are the main venues for foodborne disease outbreaks in Wuhan. Microbial factors are the main pathogenic factors, and poisonous mushrooms are the leading causes to death. It is necessary to strengthen the supervision on collective canteens, carry out various forms of public awareness campaigns on poisonous mushroom poisoning, and, if required, cooperate with the gardening department to eradicate wild poisonous mushrooms in the green belts. A collaborative cooperation involving multiple departments is essential to reduce the occurrence of foodborne disease outbreaks.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules （SSNX） in alleviating myocardial ischemia-reperfusion injury （MIRI） in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley （SD） rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group， model group， SSNX group （90 mg·kg^-1） and trimetazidine group （5.4 mg·kg^-1）. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were detected by micro method. Changes in mitochondrial membrane potential （△Ψm） and the degree of mitochondrial permeability transition pore （mPTP） opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate （ATP） level was detected by the luciferase assay. The messenger ribonucleic acid （mRNA） and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 （DRP1）， mitochondrial fission 1 protein （FIS1）， optic atrophy protein 1 （OPA1）， mitochondrial outer membrane fusion protein 1 （MFN1）， and MFN2 were detected by real-time polymerase chain reaction （real-time PCR） and Western blot. ResultCompared with the sham operation group， the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP， the level of △Ψm and ATP content decreased， the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased， and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group，SSNX significantly increased serum SOD activity， reduced MDA content， increased intracellular ATP level and △Ψm， reduced the opening level of mPTP， downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1， and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1， and increases the expressions of fusion related factors OPA1 and MFN1， inhibiting mitochondrial fission and increasing mitochondrial fusion， thereby alleviating MIRI.

BackgroundThere exist differences in the subjective and objective cognitive functions of patients with depressive disorder， ane there are limited research on influencing factors of such phenomenon currently. ObjectiveTo explore the differences in subjective and objective cognitive function in patients with depressive disorder as well as influencing factors， and to provide references for further understanding of cognitive impairment in patients with depressive disorder. MethodsA total of 77 patients with depressive disorder who received outpatient or inpatient treatment in the Fourth People's Hospital of Chengdu from January 13， 2022 to December 11， 2023 were selected for the study. These patients also met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition（DSM-5）. Various tools were employed to assess patients in this study： Montgomery-Asberg Depression Rating Scale （MADRS） for the depressive symptoms， Perceived Deficits Questionnaire for Depression （PDQ-D） and Chinese Version of Brief Neurocognitive Test Battery （C-BCT） for the subjective and objective cognitive function， Sheehan Disability Scale （SDS） for the social function， and Clinical Global Impression-Severity of Illness（CGI-SI） for the severity of patient's condition. Pearson correlation analysis was used to examine the correlation of subjective and objective cognitive function and their differences with age， years of education， MADRS total score， SDS total score， and CGI-SI score. Multiple linear regression was used to explore the influencing factors of the differences between subjective and objective cognitive function. ResultsThere was a statistically significant difference in the total PDQ-D scores and the difference of subjective and objective cognitive function （D value） between depressive patients with and without medication （t=-4.228， -2.392， P<0.05 or 0.01）. There was no statistically significant correlation in subjective and objective cognitive function in patients with depressive disorder （r=-0.148， P>0.05）. Negative correlations can be observed between the PDQ-D total score and age or years of education （r=-0.333， -0.369， P<0.01）. The PDQ-D total score was positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.487， 0.637， 0.434， P<0.01）. D value was negatively correlated with age and years of education （r=-0.411， -0.362， P<0.01）， while positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.259， 0.468， 0.299， P<0.05 or 0.01）. Age （β=-0.328， P<0.01） and SDS total score （β=0.409， P<0.01） were two predictive factors for D value. ConclusionThe difference between subjective and objective cognitive function among patients with depressive disorder is related to several factors including age， years of education， severity of symptoms and impairment of social function. ［Funded by Surface Project of National Natural Science Foundation of China （number， 62173069）； Technological Innovation 2030-Major Project of "Brain Science and Brain-Like Research" （number， 2022ZD0211700）； Key R&D Support Program and Major Application Demonstration Project of Chengdu Science and Technology Bureau （number， 2022-YF09-00023-SN）］

ObjectiveTo investigate the effect of galvanic vestibular stimulation on stroke patients with lateropulsion. MethodsFrom February to October, 2023, 30 stroke patients with lateropulsion in the First Affiliated Hospital of Nanjing Medical University were divided into control group (n = 15) and experimental group (n = 15) randomly. The control group received routine rehabilitation and sham galvanic vestibular stimulation, and the experimental group received routine rehabilitation and true galvanic vestibular stimulation, for two weeks. They were assessed with Scale for Contraversive Pushing (SCP), subjective visual vertical (SVV), Line Cancellation Test (LCT), Star Cancellation Test (SCT), Berg Balance Scale (BBS), Holden Functional Ambulation Category (FAC) and Barthel Index (BI) before and after treatment. ResultsAll the indexes improved in both groups after intervention (|t| > 2.461, Z > 3.000, P < 0.05), except the SVV orientation, SVV certainty and SCT in the control group; while the SCP, SVV certainty, LCT and FAC were better in the experimental group than in the control group (|t| > 2.189, Z = -2.862, P < 0.05), and the differences before and after intervention were better in the experimental group than in the control group (|t| > 2.382, P < 0.05), except LCT. SCP was correlated with SVV orientation, SVV certainty, SCT, BBS, BI and FAC (|r| > 0.381, P < 0.05). ConclusionGalvanic vestibular stimulation can improve the lateropulsion, balance, walking function and activities of daily living in stroke patients, which may be related to improvement for spatial cognitive function, especially vertical perception.