Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

ObjectiveTo provide technical support for the molecular surveillance of pathogenic bacteria strains carrying mobile colistin resistance-1 （mcr⁃1） gene isolate from inlet of wastewater treatment plants （WWTP）. MethodsThe Enterobacteriaceae strains carrying mcr⁃1 resistance gene isolate from inlet of WWTP during April 1 to June 30， 2023 in Shanghai were cultured on blood-rich and SS culture medium and were identified using a mass spectrometry analyzer. The mcr⁃1 gene and copy number were detected by real-time fluorescence quantitative PCR. Drug susceptibility test was performed by microbroth dilution method. The copy numbers of Escherichia coli carrying mcr⁃1 gene isolated from wastewater and human fecel were statistically analyzed by SPSS 25.0. ResultsA total of 14 strains carrying the mcr⁃1 gene were isolated from 49 WWTP samples， and the positive isolation rate was 28.6%， including 12 non-diarrheal E. coli strains and 2 Klebsiella pneumoniae strains. The drug susceptibility results showed that all 14 strains were multi-drug resistant bacteria. They were all sensitive to imipenem and tigecycline， but were ampicillin- and cefazolin-resistant. There was no significant difference in the copy number between human-sourced diarrheal E. coli and wastewater-sourced non-diarrheal E. coli （t=0.647， P>0.05）. ConclusionThe isolation and identification of strains carrying the mcr⁃1 gene from inlet of WWTP samples were firstly established in Shanghai. The multi-drug resistance among the isolated strains is severe. To effectively prevent and control the spread of colistin-resistant bacteria， more attention should be paid to the surveillance of mcr⁃1 gene.

More than 80% of the world’s populations are at risk of vector-borne diseases, with mosquito-borne diseases as a significant global public health problem. Mosquito populations control is critical to interrupting the transmission of mosquito-borne diseases. This review summarizes the physical attributes, smell, vision, touch, and hearing of mosquitoes to unravel the preferences of female mosquitoes, and describes the mechanisms underlying the best male mating by female mosquitoes, so as to provide new insights into management of mosquito-borne diseases.

Transgenic 5 × FAD mice are APP/PS1 transgenic mice carrying five familial Alzheimer's disease(AD)gene mutations.Beta-amyloid precursor protein(amyloid precursor protein,APP)expression is related to the K670N/M671L(Swedish),1716V(Florida),and V7171(London)mutations,and presenilin 1(PSI)is affected by the M146L and L286V mutations.5 × FAD mice express high levels of β-amyloid in the brain at 1.5 months old,and neuritic plaques began to appear at 2 months old.The pathological phenotypes of 5 × FAD mice include amyloid plaque aggregation,neuronal loss,gliosis,and memory dysfunction,while their biological characteristics include changes in the formation of brain β-amyloid plaques,hyperphosphorylation of Tau protein,synaptic dysfunction,neuroinflammatory response,mitochondrial dysfunction,blood-brain barrier injury,neuronal injury,endoplasmic reticulum stress,and eye lesions.As a classic animal model of AD,5 × FAD transgenic mice can simulate the neuropathological process and behavioral manifestations of late-stage AD in humans,and these mice are thus widely used in research into the pathogenesis of AD and the development of new drugs.In this review,we summarize the model construction,biological background,and biological characteristics of 5 x FAD transgenic mice,and the development and application of drugs for the prevention and treatment of AD,to provide references for the application of 5 x FAD transgenic transgenic mice in AD research.

Drugs and physical stimulation,including light,electricity,and magnetic fields,can be used to influence how neurons operate,among which chemogenetic and optogenetic technologies are most widely used.In recent years,magnetogenetic technology has also been developed that can acti-vate neurons in magnetic fields through magnetic sensitive actuators,leading to non-invasive and instanta-neous activation of specific brain regions.This article reviews the evolution of and problems with chemoge-netic and optogenetic techniques commonly used in brain science research.It also outlines the latest progress in magnetogenetic technologies,which are not full-fledged yet,as well as the role of transcra-nial electrical stimulation,transcranial magnetic stimulation,deep brain stimulation and transcranial ultra-sound stimulation technology in the functional regulation of brain diseases.Constant adjustment and improvement can make it possible for these technologies to be used more widely for the study of brain sciences and the treatment of brain diseases.

The five movements and six qi theory(hereinafter referred to as"movement qi theory")runs through Liu Wansu's med-ical theoretical system,which is mainly reflected in its influence on the theory of pathogenesis,the creation of fiery heat theory,and the influence of Liu Wansu's clinical diagnosis and treatment thoughts.The influence of movement qi theory on Liu Wansu's pathogen-esis theory includes three aspects:six qi alternation on pathogenesis,five movement hyperactivities on pathogenesis,and the root and branch of movement qi on pathogenesis.Liu's understanding of the pathogenesis of six qi and the philosophical thought of"water is good and fire is evil"mainly influenced the creation of Liu Wansu's"fire theory".The influence of movement qi theory on Liu Wansu's clinical diagnosis and treatment thoughts is mainly reflected in the classification of viscera,meridian and collateral diseases based on the theory of root and branch of middle qi,the diagnosis of pulses based on movement qi theory,the deduction of disease transmission and change using movement qi thinking,and the preparation of medicines based on qi.Liu Wansu initiated the innovation and debate of medical theory in the Jin and Yuan Dynasties,and had a profound impact on the rise of warm febrile diseases in the Ming and Qing Dynasties.

[Objective] To investigate the value of total cholesterol to high-density lipoprotein cholesterol ratio (THR), monocyte to high-density lipoprotein cholesterol ratio (MHR), and neutrophil to high-density lipoprotein cholesterol ratio (NHR) in predicting patients’ coronary artery stenosis severity and percutaneous coronary intervention (PCI). [Methods] A total of 6 281 patients who underwent coronary angiography at our hospital between June 2021 and June 2023 were retrospectively included in this study. These patients were divided into two groups: PCI group and non-PCI group. The clinical data, laboratory findings, and interventional treatment data of all patients were collected and analyzed. Pearson correlation analysis was employed to evaluate the correlation of THR, MHR and NHR with the degree of coronary artery stenosis. Binary Logistic stepwise regression and receiver operating characteristic (ROC) curve were utilized to assess the influencing factors and predictive value of THR, MHR and NHR single and combined indexes for coronary artery disease patients undergoing PCI. [Results] The PCI group was observed to be older, with a higher proportion of males, individuals with diabetes mellitus, and those who had undergone THR, MHR, NHR, and a Gensini score than the non-PCI group. Conversely, the proportion of previous stent implantation was less than that of the non-PCI group (P<0.05). The results of Pearson correlation analysis showed a significant and positive correlation of the Gensini score with THR (r=0.351, P<0.001), MHR (r=0.192, P<0.001), and NHR (r=0.236, P<0.001) levels, indicating that these variables had a significantly positive correlation with the degree of coronary artery stenosis. The results of multifactorial Logistic regression demonstrated that age >50 years, male sex, diabetes mellitus, THR, MHR, and NHR were independent risk factors for PCI in patients with coronary artery disease. Conversely, a history of previous stent implantation was identified as a protective factor for PCI in patients with coronary artery disease. Furthermore, the results of ROC curves indicated that the combined area under the curve (AUC) was the largest for THR, MHR, and NHR (AUC=0.809, 95%CI: 0.798-0.820). [Conclusion] THR, MHR and NHR correlate with the degree of coronary stenosis and have strong clinical applications in the assessment of coronary artery disease for PCI.

Objective:To explore the differences in the performance and tissue repair promotion effects of small intestinal submucosa membrane (SIS membrane) and Bio-Gide resorbable collagen membrane (Bio-Gide membrane) by performing the subcutaneous implantation models in mice.Methods:For in vivo studies, we stablished membrane implantation models using 6-8 week-old male C57BL/6 mice. The degradation rates were explored through HE staining analysis at different time points (1, 3, 5, 7, 14 and 28 d, 3 mice/group/time point). The influences of the two membranes on local macrophages and neovasculum were evaluated by immunofluorescence detection of F4/80 and CD31, and the mobilization effects of the two membranes on local stem cells were evaluated by immunohistochemical detection of Ki67 and CD146. For in vitro studies, mice periodontal ligament stem cells (mPDLSCs) were co-cultured with these two membrane materials, and the cell morphologies were observed by scanning electron microscopy. In addition, the gene expressions of Ki67, Cxcl1, Ccl1, Tnfa were investigated by real-time fluorescence quantitative PCR (RT-qPCR). Results:The results of in vivo studies showed that by day 28, there was no significant difference in degradation rate between these two membrane materials [SIS degradation rate: (16.84±4.00) %, Bio-Gide degradation rate: (24.07±3.97) %, P=0.090], illustrating that both of them could maintain the barrier effects for more than one month. In addition, there was no significant difference in the infiltration number of local F4/80 positive macrophages between these two groups by the day 3 after implantation [SIS: (20.67±5.69) cells/visual field, Bio-Gide: (25.33±2.52) cells/visual field, P=0.292]. However, compared with the Bio-Gide membrane, SIS membrane significantly promoted local CD31 +vascular regeneration [SIS: (4.67±1.15) cells/visual field, Bio-Gide: (1.00±1.00) cells/visual field, P=0.015] and CD146 +stem cell recruitment [SIS: (22.33±4.16) cells/visual field, Bio-Gide: (11.33±2.52) cells/visual field, P=0.025]. The RT-qPCR results also showed that SIS membrane promoted the gene expression of Cxcl1 (SIS vs Bio-Gide P<0.001) in mPDLSCs, but had no effect on the gene expression of Tnfa (SIS vs Bio-Gide P=0.885). Conclusions:SIS membrane showed a similar degradation rate compared with Bio-Gide membrane, and there was no significant difference in the effects of these two membranes on local inflammation or macrophages. Therefore, both of these membranes could meet the barrier effects required by guided tissue regeneration.

Objective To assess the effects of low-dose esketamine on the median effective dose(ED50)of ciprofol for anesthesia induction in painless gastrointestinal endoscopy.Methods Fifty-nine pa-tients underwent elective painless gastrointestinal endoscopy,26 males and 33 females,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups by random number table method:esketamine combined with ciprofol group(group EC,n = 29)and ciprofol group(group C,n = 30).Group EC received intravenous injection of esketamine 0.3 mg/kg and group C received the same amount of normal saline 2 minutes before administration of ciprofol.The initial anesthesia induction dose of ciprofol was 0.4 mg/kg.If a positive reaction occurs during the examination,the next patient will receive an increase dose of propofol 0.04 mg/kg,otherwise will decrease by propofol 0.04 mg/kg.The positive reaction was defined that the patient's BIS can not be decreased to 60 2 minutes after anesthesia induction,or the cough or body movement reaction occur at level 2 or above when entering the mirror.The dosage of ciprofol,recovery time,discharge time,the occurrence of intraoperative and postoperative adverse reactions were recorded.The ED50,95%effective dose(ED95)and 95%confidence interval(CI)of the two groups were calculated by Probit probability regression analysis.Results Compared with group C,the dosage of ciprofol,the incidence of hypotension and frequency of administration of vasoactive drugs during the exami-nation process in group EC were significantly reduced(P＜0.05).The ED50 of ciprofol for anesthesia in-duction in painless gastrointestinal endoscopy in group EC was 0.21 mg/kg(95%CI 0.12-0.25 mg/kg)and the ED95 was 0.32 mg/kg(95%CI 0.26-0.39 mg/kg).The ED50 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group C was 0.37 mg/kg(95%CI 0.32-0.40 mg/kg)and the ED95 was 0.48 mg/kg(95%CI 0.43-0.54 mg/kg).The ED50 and ED95 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group EC was significantly lower than that in group C(P＜0.05).There was no significant difference in other frequency of adverse events between the two groups.Conclusion Esketamine 0.3 mg/kg can reduce the ED50 of ciprofol in painless gastrointestinal endoscopy and reduce the dosage of ciprofol during the examination process,which is safe for painless gastrointestinal endoscopy with stable intraoperative circulation.

Anaplastic thyroid carcinoma(ATC)is the most aggressive malignancy with poor prognosis.The pathogenesis of ATC is complex,and there is no effective treatment at present.In recent years,with the deep understanding of the genetic(such as BRAF V600E,TP53,TERT,PIK3CA mutations,etc.)and epigenetic(such as histone methylation,histone deacetylation,microRNA regulatory pathways,etc.)changes driving ATC,molecular targeted therapy has brought new hope to ATC patients.This article reviews the molecular mechanisms of ATC and the latest achievements in targeted therapy and other therapies.