A national-scale assessment of land subsidence in China's major cities.

China's massive wave of urbanization may be threatened by land subsidence. Using a spaceborne synthetic aperture radar interferometry technique, we provided a systematic assessment of land subsidence in all of China's major cities from 2015 to 2022. Of the examined urban lands, 45% are subsiding faster than 3 millimeters per year, and 16% are subsiding faster than 10 millimeters per year, affecting 29 and 7% of the urban population, respectively. The subsidence appears to be associated with a range of factors such as groundwater withdrawal and the weight of buildings. By 2120, 22 to 26% of China's coastal lands will have a relative elevation lower than sea level, hosting 9 to 11% of the coastal population, because of the combined effect of city subsidence and sea-level rise. Our results underscore the necessity of enhancing protective measures to mitigate potential damages from subsidence.

Short- and medium-chain chlorinated paraffins in breast milk in Shanghai, China: Occurrence, characteristics, and risk assessment.

As novel contaminants, short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) have been of great concern in the past several years. Shanghai was one of the provinces with the largest chlorinated paraffins (CPs) emission in China; nevertheless, there is currently little information on the human exposure to SCCPs and MCCPs, particularly MCCPs. In this study, 25 breast milk samples were collected in Shanghai from 2016 to 2017. The concentrations of SCCPs and MCCPs were determined using two-dimensional gas chromatography coupled with orbitrap high-resolution mass spectrometry (GC × GC-orbitrap-HRMS) to investigate their characteristics and assess the associated health risks for breast-fed infants. Compared with the previous studies in other areas, the current study presented the higher CPs concentrations, with median concentrations of SCCPs and MCCPs up to 771 and 125 ng/g lipid weight (lw), respectively. The exposure profiles of the CPs were characterized by C10 and Cl6-7 as the predominant congeners of SCCPs, while C14 and Cl7-9 were identified as the dominant groups of MCCPs. CP-42 and CP-52 were identified as potential sources of CPs found in breast milk samples collected in Shanghai. The concentrations of MCCPs exhibited a positive correlation (p value < 0.05) with the dietary consumption of meat and poultry. No significant positive correlations were observed for SCCPs and MCCPs with polychlorinated dibenzodioxins/furans (PCDD/Fs) congeners. A preliminary exposure assessment showed that SCCPs in breast milk potentially posed high risks to the breast-fed infants in Shanghai.

Preventing Subsidence Reoccurrence in Tianjin: New Preconsolidation Head and Safe Pumping Buffer.

Tianjin, a coastal metropolis in north China, has grappled with land subsidence for nearly a century. Yet, emerging evidence suggests a notable decrease in subsidence rates across Tianjin since 2019. This trend is primarily attributed to the importation of surface water from the Yangtze River system via the South-to-North Water Diversion Project, initiated in December 2014. Utilizing Sentinel-1A Interferometric Synthetic Aperture Radar (InSAR) data (2014-2023), this study reveals that one-third of the Tianjin plain has either halted subsidence or experienced land rebound. As a result, the deep aquifer system (~-200 to -450 m) beneath one third of the Tianjin plain has completed a consolidation cycle, leading to the establishment of new, locally specific preconsolidation heads. The identification of the newly established preconsolidation head seeks to answer a crucial question: How can we prevent the reoccurrence of subsidence in areas where it has already ceased? In essence, subsidence will stop when the local hydraulic head elevates to the new preconsolidation head (NPCH), and permanent subsidence will not be reinitiated as long as hydraulic head remains above the NPCH. The difference of the depth between current hydraulic head and the NPCH defines the safe pumping buffer (SPB). This study outlines detailed methods for identifying the NPCHs in the deep aquifer system from long-term InSAR and groundwater-level datasets. Determining NPCHs and ascertaining SPBs are crucial for estimating how much groundwater can be safely extracted without inducing permanent subsidence, and for developing sustainable strategies for long-term groundwater management and conservation.

Ion imprinted differential modulation system based on enhanced optic-fiber evanescent wave for sensitive and label-free detection of trace nickel ions.

An optical system with low cost monitoring, high sensitivity, strong selectivity and much lower nickel ion (Ni2+) content in tap water than the World Health Organization (WHO) standard (1.19 µM) has been prepared by a simple strategy. This proposed ion-imprinted differential modulation system is based on the Bragg grating (FBG) and microfiber interferometer structure, and the interferometer sensing surface is coated with a polydopamine (PDA)/graphene oxide (GO) film to enhance its sensitivity. Combined with the ion imprinting technique, the microfiber interferometer sensor sensitivity can reach 0.32 nm/nM with the detection limit of 0.66 nM in the low concentration range (Ni2+ concentration range is 0 nM-100 nM). The experiment not only studies the principle of microfiber interferometer and FBG and their refractive index and temperature performance, but also shows that the FBG power change has a good fitting relationship with wavelength change. In addition, this system performance by the amount of power difference rather than the amount of wavelength shift, which significantly saves on the high cost weight, and size associated with the use of spectral analyzers in traditional inspection systems. This study provides a novel and easy method to develop new sensors with higher comprehensive performance.

Suspect, Nontarget Screening, and Toxicity Prediction of Per- and Polyfluoroalkyl Substances in the Landfill Leachate.

Landfills are the final stage of urban wastes containing perfluoroalkyl and polyfluoroalkyl substances (PFASs). PFASs in the landfill leachate may contaminate the surrounding groundwater. As major environmental pollutants, emerging PFASs have raised global concern. Besides the widely reported legacy PFASs, the distribution and potential toxic effects of numerous emerging PFASs remain unclear, and unknown PFASs still need discovery and characterization. This study proposed a comprehensive method for PFAS screening in leachate samples using suspect and nontarget analysis. A total of 48 PFASs from 10 classes were identified; nine novel PFASs including eight chloroperfluoropolyether carboxylates (Cl-PFPECAs) and bistriflimide (HNTf2) were reported for the first time in the leachate, where Cl-PFPECA-3,1 and Cl-PFPECA-2,2 were first reported in environmental media. Optimized molecular docking models were established for prioritizing the PFASs with potential activity against peroxisome proliferator-activated receptor α and estrogen receptor α. Our results indicated that several emerging PFASs of N-methyl perfluoroalkyl sulfonamido acetic acids (N-MeFASAAs), n:3 fluorotelomer carboxylic acid (n:3 FTCA), and n:2 fluorotelomer sulfonate (n:2 FTSA) have potential health risks that cannot be ignored.

Base editing of the HBG promoter induces potent fetal hemoglobin expression with no detectable off-target mutations in human HSCs.

Reactivating silenced γ-globin expression through the disruption of repressive regulatory domains offers a therapeutic strategy for treating ß-hemoglobinopathies. Here, we used transformer base editor (tBE), a recently developed cytosine base editor with no detectable off-target mutations, to disrupt transcription-factor-binding motifs in hematopoietic stem cells. By performing functional screening of six motifs with tBE, we found that directly disrupting the BCL11A-binding motif in HBG1/2 promoters triggered the highest γ-globin expression. Via a side-by-side comparison with other clinical and preclinical strategies using Cas9 nuclease or conventional BEs (ABE8e and hA3A-BE3), we found that tBE-mediated disruption of the BCL11A-binding motif at the HBG1/2 promoters triggered the highest fetal hemoglobin in healthy and ß-thalassemia patient hematopoietic stem/progenitor cells while exhibiting no detectable DNA or RNA off-target mutations. Durable therapeutic editing by tBE persisted in repopulating hematopoietic stem cells, demonstrating that tBE-mediated editing in HBG1/2 promoters is a safe and effective strategy for treating ß-hemoglobinopathies.

A nonenzymic microfiber optic-biosensor modified phenylboric acid for sensitively and specifically detecting low glucose concentration.

A microfiber interferometer coated with sensitive films formed by amide bond between 3-Carboxy-4-fluorophenylboronic acid (FPBA) and polydopamine (PDA) for the detection of trace glucose concentration is designed and demonstrated. Due to a huge evanescent field, this microfiber interferometer has a very sensitive response to the refractive index (RI) of the surrounding environment, which has excellent sensing performance including RI sensitivity response of 1825.83 nm/RIU and low temperature response of -0.04 nm/°C. Due to the good film-forming performance of PDA, whose the amino group coupled with the carboxyl molecule on FPBA to form an amide bond, PDA/FPBA can be attached to the microfiber interferometer for detecting different concentrations of glucose. The concentration range of glucose detection is 0.1-20 mM with a sensitivity of 1.71 nm/mM and a limit of detection of 12.6 ppm. Finally, the sensor is tested in actual samples of human urine to detect different concentrations of glucose and proved to be responsive and reproducible in urine. We can estimate the concentration of glucose in urine by wavelength shift. The sensor has the advantages of simple manufacture, low cost, high sensitivity, and specific recognition glucose in urine. In addition, the success of this sensor shows that the combination of ultrafine fiber and organic chemical materials has broad prospects in the field of optical detection.

Retrograde type A aortic dissection during or after thoracic endovascular aortic repair: a single center 16-year experience.

Objective: This article aims to investigate the incidence rate of retrograde type A aortic dissection (RTAD) and the risk factors of RTAD in relation to thoracic endovascular aortic repair (TEVAR). Methods: Patients with thoracic aortic disease who underwent TEVAR at Henan Provincial People's Hospital from January 2004 to December 2019 were enrolled in the present research. The risk factors associated with RTAD following TEVAR using univariate and multiple logistic regression analyses. Results: During the study period, A total of 1,688 TEVAR patients were included in this study, and of these, 1,592 cases were included in the type B aortic dissection (TBAD) group, and 96 cases were included in the non-TBAD group. There were 1,230 cases of aortic dissection and 362 cases of aortic intramural hematoma and/or penetrating ulcer in the TBAD group. The non-TBAD group included 68 cases of thoracic aortic aneurysm, 21 cases of thoracic aortic pseudoaneurysm, and seven cases of congenital aortic coarctation. The overall incidence rate of RTAD was 1.1% (18/1,688) in patients, all of which occurred in the TBAD group. The cohort comprised 18 RTAD patients with an average age of 56.78, consisting of 13 males and 5 females. Among them, 13 individuals exhibited hypertension. Ten instances happened within the TEVAR perioperative period, including two cases during the surgery, six cases occurred within three months, two cases occurred after one year, and the longest interval was 72 months following TEVAR. TEVAR was successfully implemented in 17 patients, while the operation technique was temporarily altered in one case. The new entry position for RTAD was identified as the proximal region of the stent graft (SG) in 13 patients, while in five cases, the entry site was more than 2 cm away from the proximal region of the SG. 17 cases were at the greater curvature of the aorta, and one case was at the lesser curvature. Multivariate logistic regression analysis revealed that the SG oversizing ratio is a relevant risk factor for RTAD. However, ascending aortic diameter, aortic arch type, SG type, and anchored region were not directly related to the occurrence of RTAD. Conclusion: RTAD is a rare yet catastrophic complication. It could occur both during the procedure, early and late postoperative periods. Maintaining an appropriate SG oversizing ratio is crucial to minimize the risk of RTAD.

First records of the crane fly genus Helius Lepeletier & Serville (Diptera, Limoniidae) in Guangxi, China with description of one new species.

The genus Helius Lepeletier & Serville, 1828 is recorded in Guangxi, China for the first time with the following three species belonging to the subgenus H. (Helius): H. (H.) damingshanussp. nov., H. (H.) nipponensis (Alexander, 1913) and H. (H.) stenorhynchus stenorhynchus Alexander, 1954. Among them, H. (H.) stenorhynchus stenorhynchus is also a new record in China. Their descriptions and illustrations, as well as the first key to Chinese H. (Helius) crane flies, are presented.

Identification and validation of novel signature associated with hepatocellular carcinoma prognosis using Single-cell and WGCNA analysis.

Background: Hepatocellular carcinoma is a rapidly advancing malignancy with a poor prognosis. Therefore, further research is needed on its potential pathogenesis and therapeutic targets. Methods: In this study, the relevant datasets were downloaded from the TCGA database and the key modules were identified using WGCNA in the necroptosis-related gene set, while single-cell datasets were scored using the necroptosis gene set. Differential genes in the high- and low-expression groups were determined using the WGCNA module genes as intersection sets to identify key genes involved in necroptosis in liver cancer. Then, prognostic models were constructed using LASSO COX regression followed by multi-faceted validation. Finally, model genes were found to be correlated with key proteins of the necroptosis pathway and used to identify the most relevant genes, followed by their experimental validation. Subsequently, on the basis of the analysis results, the most relevant SFPQ was selected for cell-level verification. Results: We constructed a prognosis model that included five necroptosis-related genes (EHD1, RAC1, SFPQ, DAB2 and PABPC4) to predict the prognosis and survival of HCC patients. The results showed that the prognosis was more unfavorable in the high-risk group compared to the low-risk group, which was corroborated using ROC curves and risk factor plots. In addition, we further checked the differential genes using GO and KEGG analyses and found that they were predominantly enriched in the neuroactive ligand-receptor interaction pathway. The results of the GSVA analysis demonstrated that the high-risk group was mainly enriched in DNA replication, regulation of the mitotic cycle, and regulation of various cancer pathways, while the low-risk group was predominantly enriched in the metabolism of drugs and xenobiotics using cytochrome P450. SFPQ was found to be the main gene that affects the prognosis and SFPQ expression was positively correlated with the expression of RIPK1, RIPK3 and MLKL. Furthermore, the suppression of SFPQ could inhibit hyper-malignant phenotype HCC cells, while the WB results showed that inhibition of SFPQ expression also resulted in lower expression of necroptosis proteins, compared to the sh-NC group. Conclusions: Our prognostic model could accurately predict the prognosis of patients with HCC to further identify novel molecular candidates and interventions that can be used as alternative methods of treatment for HCC.

Contribution to the Knowledge of Dicranoptychini (Diptera, Tipuloidea, Limoniidae) in China, with the First Mitochondrial Genome of the Tribe and Its Phylogenetic Implications.

Dicranoptychini is a tribe in the subfamily Limoniinae (Diptera, Tipuloidea, and Limoniidae) and includes only the genus Dicranoptycha Osten Sacken, 1860. However, the species diversity of the tribe in China was seriously underestimated, and the taxonomic status of Dicranoptycha has long been controversial. In this study, types of Chinese Dicranoptycha species and specimens collected from several localities in China were examined, and the first mitochondrial (mt) genome of the tribe Dicranoptychini is presented. Two Dicranoptycha species, D. jiufengshana sp. nov. and D. shandongensis sp. nov., from China, are described and illustrated as new to science. A Palaearctic species, D. prolongata Alexander, 1938, is recorded in China for the first time. In addition, the complete mt genome of D. shandongensis sp. nov. is sequenced and annotated, indicating that it is a typical circular DNA molecule with a length of 16,157 bp and shows a similar gene order, nucleotide composition, and codon usage to mt genomes of other Tipuloidea species. The two pairs of repeat elements are found in its control region. Phylogenetic results confirm the sister-group relationship between Cylindrotomidae and Tipulidae, question the position of the genus Epiphragma Osten Sacken, 1860 in Limoniidae, and indicate that Dicranoptychini may be a basal lineage within Limoniinae.

Research progress of extracellular vesicles as biomarkers in immunotherapy for non-small cell lung cancer.

Lung cancer is one of the most severe forms of malignancy and a leading cause of cancer-related death worldwide, of which non-small cell lung cancer (NSCLC) is the most primary type observed in the clinic. NSCLC is mainly treated with surgery, radiotherapy, and chemotherapy. Additionally, targeted therapy and immunotherapy have also shown promising results. Several immunotherapies, including immune checkpoint inhibitors, have been developed for clinical use and have benefited patients with NSCLC. However, immunotherapy faces several challenges like poor response and unknown effective population. It is essential to identify novel predictive markers to further advance precision immunotherapy for NSCLC. Extracellular vesicles (EVs) present an important research direction. In this review, we focus on the role of EVs as a biomarker in NSCLC immunotherapy considering various perspectives, including the definition and properties of EVs, their role as biomarkers in current NSCLC immunotherapy, and different EV components as biomarkers in NSCLC immunotherapy research. We describe the cross-talk between the role of EVs as biomarkers and novel technical approaches or research concepts in NSCLC immunotherapy, such as neoadjuvants, multi-omics analysis, and the tumour microenvironment. This review will provide a reference for future research to improve the benefits of immunotherapy for patients with NSCLC.

A neural circuit for gastric motility disorders driven by gastric dilation in mice.

Introduction: Symptoms of gastric motility disorders are common clinical manifestations of functional gastrointestinal disorders (FGIDs), and are triggered and exacerbated by stress, but the neural pathways underpinning them remain unclear. Methods: We set-up a mouse model by gastric dilation (GD) in which the gastric dynamics were assessed by installing strain gauges on the surface of the stomach. The neural pathway associated with gastric motility disorders was investigated by behavioral tests, electrophysiology, neural circuit tracing, and optogenetics and chemogenetics involving projections of the corticotropin-releasing hormone (CRH) from the paraventricular nucleus of the hypothalamus (PVN) to acetylcholine (ChAT) neurons in the dorsal motor nucleus of the vagus (DMV). Results: We found that GD induced gastric motility disorders were accompanied by activation of PVN CRH neurons, which could be alleviated by strategies that inhibits the activity of PVN CRH neurons. In addition, we identified a neural pathway in which PVN CRH neurons project into DMV ChAT neurons, modulated activity of the PVN CRH →DMV ChAT pathway to alleviate gastric motility disorders induced by GD. Discussion: These findings indicate that the PVN CRH →DMV ChAT pathway may mediate at least some aspects of GD related gastric motility, and provide new insights into the mechanisms by which somatic stimulation modulates the physiological functions of internal organs and systems.

Room-temperature ultrasonic-assisted self-assembled synthesis of silkworm cocoon-like COFs@GCNTs composite for sensitive detection of diuron in food samples.

Diuron (DU) exhibits good weed control effect but possesses strong hazard to human health, thereby designing a fast and sensitive method to detect DU is highly urgent. Herein, we report the ultrasonic-assisted self-assembly synthesis of porous covalent organic frameworks (COFs) spheres@graphitized multi-walled carbon nanotubes (GCNTs) composite based on π-π conjugation effect at room temperature, which was employed for DU determination. For the COFs@GCNTs composite, COFs with ultrahigh specific surface area shows strong adsorption ability towards DU, whereas GCNTs with favorable conductivity help to form the 3D interconnected conductive network around COFs spheres, thereby effectively compensating for the poor conductivity of COFs. Because of the synergistic effect between COFs and GCNTs, the developed sensor presented a low detection limit of 0.08 µM in the concentration range of 0.30-18.00 µM. Moreover, the actual sample analysis in the tomato and cucumber yielded satisfactory recoveries (96.40%-103.20%), proving reliable practicability of the developed sensor.

New Preconsolidation Heads Following the Long-Term Hydraulic-Head Decline and Recovery in Houston, Texas.

The Houston area in Texas, United States, has been experiencing land subsidence for a century from the 1920s to 2010s. A substantial portion of the Houston area had finished a consolidation cycle following the long-term hydraulic head decline and recovery. A new "maximum effective stress" (preconsolidation stress) was preserved in the memory of the aquitards. For an aquifer system comprising aquifers and aquitards, the preconsolidation stress is corresponding to the lowest hydraulic head in the aquitards, not in the aquifers. Preconsolidation head is generally regarded as a groundwater-level threshold below which inelastic compaction begins. The preconsolidation head finalized after the long-term hydraulic head decline and recovery is called new preconsolidation head. This study has developed an empirical equation for projecting the new preconsolidation head. According to this study, the new preconsolidation heads in the primary aquifers (lower Chicot and Evangeline) are local specific: varying from about 30 m below land surface (-30 m) in the south to -50 m in the north of the Harris-Galveston Subsidence District (HGSD) Regulatory Area 1, from -60 m in the east to -80 m in the west of Area 2, and from -70 m in the south to -100 m in the center of Area 3. In Areas 1 and 2, the current hydraulic heads are about 10 m to 20 m higher than the local new preconsolidation heads; thus, remarkable land subsidence (>1 cm/year) would not be reinitiated unless the hydraulic heads are to fall below the local new preconsolidation head.

Long Noncoding RNA DSCAM-AS1 Facilitates Proliferation and Migration of Hemangioma Endothelial Cells by Targeting miR-411-5p/TPD52 Axis.

Background: Diagnosed as a kind of vascular neoplasm of infancy, hemangioma (HA) occurs mainly due to the aberrant proliferation of endothelial cells. Existing evidence has manifested the close relationship of long noncoding RNAs (lncRNAs) with the pathogenesis of HA. Although lncRNA DSCAM antisense RNA 1 (DSCAM-AS1) has been revealed to be implicated in the progression of human diseases, the underlying mechanism DSCAM-AS1 exerts in HA formation is unclear. Aims: To figure out how DSCAM-AS1 may regulate the progression of human hemangioma endothelial cells (HemECs). Methods: DSCAM-AS1 expression was verified through RT-qPCR detection. Functional assays including EdU assay, colony formation assay, flow cytometry analysis, TUNEL assay, and transwell assay were applied to evaluate cell proliferation, apoptosis, and migration upon DSCAM-AS1 knockdown. Moreover, RNA pull-down assay, luciferase reporter assay, RIP assay, and other mechanism experiments were utilized for evaluating the correlation of DSCAM-AS1 and RNAs in HemECs. Results: DSCAM-AS1 knockdown inhibited proliferative capability and migratory capability of HemECs whereas expedited apoptosis. Molecular mechanism results testified DSCAM-AS1 could function as a ceRNA to bind miR-411-5p in HemECs. Besides, it was confirmed that tumor protein D52 (TPD52) served as a downstream target of miR-411-5p in HemECs. More importantly, related rescue assays uncovered that elevated expression of TPD52 or inhibited expression of miR-411-5p reversed the repressive progression of HemECs mediated by DSCAM-AS1 depletion. Conclusion: DSCAM-AS1 expedited HA progression via miR-411-5p/TPD52 pathway, which provided a novel therapeutic option for HA treatment.

Infant Exposure to PCBs and PBDEs Revealed by Hair and Human Milk Analysis: Evaluation of Hair as an Alternative Biomatrix.

Human hair, as an emerging biological monitoring matrix, has begun to be used in various human exposure studies, but little research has been done on persistent organic pollutants (POPs), especially for the body burden of POPs in infants. In this study, 36 breast-fed infants in Shanghai were recruited for a study to determine their exposure to POPs, including 12 dioxin-like polychlorinated biphenyls (dl-PCBs), 6 indicator PCBs, and 8 polybrominated diphenyl ethers (PBDEs) in the inner layer (internal) and outer layer (external) of infant hair and human milk. The similarity or difference of the POP distribution pattern or concentration among these matrices was investigated, and only weak correlations (r < 0.4) were observed between the POP concentration in human milk and infant hair (internal or external). POPs in human milk have a different profile than those in infant hair, while they have stable concentration ratios (0.58-2.72), similar distribution patterns, fine Spearman's rank correlations, and tangled principal component analysis (PCA) plots in each POP family between external and internal hair samples. The result suggested that POPs in internal hair can be easily affected by those in external hair, but POPs in human milk seem to have little contribution to the POP profile in internal hair. Although infant hair cannot reflect the POPs from diet or from body burden, it can be an ideal biomatrix that estimates infant exposure to POPs from exogenous sources like house dust when considering the similar pattern of POPs and their proper accumulation period in hair.

Review and contribution to the stoneflies (Insecta: Plecoptera) of Guangxi Zhuang Autonomous Region, China, with new species and new records from South China.

Three new species of the genus Nemoura Latreille, 1796: Nemoura alticalcaneum Mo, Wang Li, sp. n., Nemoura ganeum Mo, Yang Li, sp. n. and Nemoura tauripitis Mo, Li Murnyi, sp. n., are described from Guangxi Zhuang Autonomous Region of China. Eight new province records from Guangxi, two new province records from Guangdong and one new province record from Hunan are given, among them one new for China as well. The newly recorded species are depicted and complementary descriptions provided, including the first female description of seven species and first egg description of two species. The paper is completed with an updated checklist of Guangxi stoneflies, distribution of species richness across prefectural cities in Guangxi, with distribution maps for each species.

Two new species and a new record of eriophyoid mites (Acari: Eriophyodea) from Guangxi, China.

Two new species of eriophyoid mites are described and illustrated from Guangxi, China: Acaphylla quercus sp. nov. collected on Quercus glauca Thunb. (Fagaceae), Rhyncaphytoptus miliusius sp. nov. collected on Miliusa sinensis Finet Gagnep. (Annonaceae). We further report Cecidodectes euzonus Nalepa, 1917, collected on Trema tomentosa (Roxb.) H.Hara (Cannabaceae), for the first time from China. All the species are vagrants on lower leaf surface causing no apparent damage to their host plants.

Genistein attenuates memory impairment in Alzheimer's disease via ERS-mediated apoptotic pathway in vivo and in vitro.

Genistein (GS), an isoflavone compound found in soybean, plays a neuroprotective role in Alzheimer's disease (AD). However, the mechanism of its action remains unclear. Herein, binding ability between GS and GRP78 was predicted by molecular docking, and the effect of GS in vivo and vitro were further studied. In this study, the effects of GS on learning and memory ability, changes of hippocampal neurons and ultrastructure of hippocampal CA3 region in AD rats were investigated. Besides, the protein or mRNA levels of the related proteins were detected. The results showed GS could effectively improve the learning and the memory ability, reduce the damage of hippocampal neurons, and decrease the protein or mRNA expression levels of GRP78, CHOP, Caspase-12, Cle-Caspase-9, Cle-Caspase-3, PERK, and p-PERK. Taken together, our data reveal GS has a neuroprotective effect by inhibiting the ERS-mediated apoptotic pathway, which may be a new therapeutic target for the treatment of AD.