Tumor-colonized Streptococcus mutans metabolically reprograms tumor microenvironment and promotes oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) remains a major death cause in head and neck cancers, but the exact pathogenesis mechanisms of OSCC are largely unclear. RESULTS: Saliva derived from OSCC patients but not healthy controls (HCs) significantly promotes OSCC development and progression in rat models, and metabolomic analyses reveal saliva of OSCC patients but not HCs and OSCC tissues but not adjacent non-tumor tissues contain higher levels of kynurenic acid (KYNA). Furthermore, large amounts of Streptococcus mutans (S. mutans) colonize in OSCC tumor tissues, and such intratumoral S. mutans mediates KYNA overproductions via utilizing its protein antigen c (PAc). KYNA shifts the cellular types in the tumor microenvironment (TME) of OSCC and predominantly expedites the expansions of S100a8highS100a9high neutrophils to produce more interleukin 1ß (IL-1ß), which further expands neutrophils and induces CD8 + T cell exhaustion in TME and therefore promotes OSCC. Also, KYNA compromises the therapeutic effects of programmed cell death ligand 1 (PD-L1) and IL-1ß blockades in oral carcinogenesis model. Moreover, KYNA-mediated immunosuppressive program and aryl hydrocarbon receptor (AHR) expression correlate with impaired anti-tumor immunity and poorer survival of OSCC patients. CONCLUSIONS: Thus, aberration of oral microbiota and intratumoral colonization of specific oral bacterium such as S. mutans may increase the production of onco-metabolites, exacerbate the oral mucosal carcinogenesis, reprogram a highly immunosuppressive TME, and promote OSCC, highlighting the potential of interfering with oral microbiota and microbial metabolism for OSCC preventions and therapeutics. Video Abstract.

Association of procalcitonin with voriconazole concentrations: a retrospective cohort study.

Inflammation is a potential risk factor of voriconazole (VCZ) overdose, procalcitonin (PCT) is reported to act as a diagnostic marker for bacterial infections. However, the association of PCT with VCZ trough serum concentrations (VCZ-Cmin) is not fully clear. Our study aims to investigate the associations between PCT and VCZ-Cmin. In this retrospective cohort study, we collected the clinical data of 147 patients who received VCZ and monitored the VCZ concentration of them in our hospital from August 2017 to August 2021. All patients underwent routine clinical examinations on the day or the day before VCZ administration. General information and clinical symptoms of these patients were recorded. Multivariate liner analysis showed that PCT was significantly associated with VCZ-Cmin (p < 0.001). Overall, it was shown that VCZ-Cmin was significantly increased by 0.32 µg/mL for each fold increment in PCT in crude model. In the minor adjusted model (Model 1, adjustment for sex, age, albumin, direct bi1irubin, WBC) and fully adjusted model (Model 2, adjustment for sex, age, albumin, direct bilirubin, WBC, AST and ALT), VCZ-Cmin was significantly increased by 0.23 µg/mL and 0.21 µg/mL, respectively, for each fold increment in PCT. In conclusion, this research reveals the correlation between PCT and VCZ-Cmin, indicating that PCT has the potential to serve as a valuable biomarker for drug monitoring in the treatment of VCZ.

3D genome contributes to MHC-II neoantigen prediction.

Reliable and ultra-fast DNA and RNA sequencing have been achieved with the emergence of high-throughput sequencing technology. When combining the results of DNA and RNA sequencing for tumor cells of cancer patients, neoantigens that potentially stimulate the immune response of either CD4+ or CD8+ T cells can be identified. However, due to the abundance of somatic mutations and the high polymorphic nature of human leukocyte antigen (HLA) it is challenging to accurately predict the neoantigens. Moreover, comparing to HLA-I presented peptides, the HLA-II presented peptides are more variable in length, making the prediction of HLA-II loaded neoantigens even harder. A number of computational approaches have been proposed to address this issue but none of them considers the DNA origin of the neoantigens from the perspective of 3D genome. Here we investigate the DNA origins of the immune-positive and non-negative HLA-II neoantigens in the context of 3D genome and discovered that the chromatin 3D architecture plays an important role in more effective HLA-II neoantigen prediction. We believe that the 3D genome information will help to increase the precision of HLA-II neoantigen discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

Discovery of candidate genes involved in ethylene biosynthesis and signal transduction pathways related to peach bud cold resistance.

Background: Low temperature pose significant challenges to peach cultivation, causing severe damage to peach buds and restricting production and distribution. Ethylene, an important phytohormone, plays a critical role in enhancing plant cold resistance. Structural genes and transcription factors involved in ethylene biosynthesis and signal transduction pathways are associated with cold resistance. However, no research has specifically addressed their roles in peach cold resistance. Methods: In this study, we aimed for cold-resistance gene discovery in cold-sensitive peach cultivar "21Shiji" (21SJ) and cold-resistance cultivar "Shijizhixing" (SJZX) using RNA-seq and gas chromatography. Results: The findings revealed that under cold stress conditions, ethylene biosynthesis in "SJZX" was significantly induced. Subsequently, a structural gene, PpACO1-1, involved in ethylene biosynthesis in peach buds was significantly upregulated and showed a higher correlation with ethylene release rate. To identify potential transcription factors associated with PpACO1-1 expression and ethylene signal transduction, weighted gene co-expression network analysis was conducted using RNA-seq data. Four transcription factors: PpERF2, PpNAC078, PpWRKY65 and PpbHLH112, were identified. Conclusion: These findings provide valuable theoretical insights for investigating the regulatory mechanisms of peach cold resistance and guiding breeding strategies.

Three new Melanogaster species (Boletales, Paxillaceae) from southwestern China based on morphological and molecular evidence.

Three newly discovered Melanogaster species, namely M.cyaneus, M.diqingensis, and M.truncatisporus, are introduced and illustrated based on both morphological and molecular data from Sichuan and Yunnan provinces in China. A multigene phylogenetic analysis (nrITS, nrLSU, and rpb2) was performed mainly to verify the placement of the new species in Melanogaster. A second, nrITS-only phylogenetic analysis comprising more Melanogaster species for which only ITS sequences were available, was used to infer the relationship between the new species and as many known Melanogaster species as possible. Specimens of M.cyaneus, M.diqingensis, and M.truncatisporus formed three independent clades in a phylogenetic tree inferred from the ITS data set. The robust support from ITS for these clades and genetic similarity with other species being lower than 93.2% suggest that these three species are indeed distinct from the other Melanogaster species in the phylogeny. Morphologically, M.cyaneus is characterized by its blue or bluish gleba, light brown to yellowish brown peridium, and subglobose to globose basidiospores, 6.2-15 × 4.6-9.0 µm. Melanogasterdiqingensis is distinguished from other Melanogaster species by its pale yellow to brown-yellow peridium and obovate to subglobose basidiospores, 3.0-5.1 × 2.0-4.0 µm. Melanogastertruncatisporus is diagnosed by its subglobose to globose or irregularly elongate-pyriform basidiomata, pale yellow to deeply orange-yellow peridium, and subglobose to globose or pyriform, truncate basidiospores. Additionally, infrageneric classification based on the number of peridium layers, the average thickness of the peridium, and the average length and width of basidiospores was tested with M.cyaneus, M.diqingensis, and M.truncatisporus. Orthogonal partial least squares discriminant (OPLS-DA) analysis placed the three new species within the Melanogaster, Rivulares, and Variegati sections, respectively. However, the morphologically circumscribed sections were not monophyletic in the phylogenetic tree. Therefore, the current infrageneric classification should be abandoned.

NTSR1 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma through the Wnt/ß-catenin pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) patients are implicated in poor prognoses and increased mortality rates. Metastasis, as a leading cause of LUAD-related deaths, requires further investigation. Highly metastatic cancer cells often exhibit extensive characteristics of epithelial-mesenchymal transition (EMT). This study attempted to identify novel targets associated with LUAD metastasis and validate their specific molecular mechanisms. METHODS: Bioinformatics was conducted to determine NTSR1 expression in LUAD and the enriched pathways. Immunohistochemical analysis was used to assess NTSR1 expression in LUAD tissue. qRT-PCR examined expressions of NTSR1 and Wnt/ß-Catenin pathway-related genes in LUAD cells. Transwell assayed cell migration and invasion. Cell adhesion experiments were conducted to evaluate cell adhesion capacity. Western blot analysis was employed to examine expression of EMT, Wnt/ß-Catenin pathway, and cell adhesion markers. RESULTS: NTSR1 was upregulated in LUAD tissues and cells, and enriched in EMT pathway. Knockdown of NTSR1 reduced migration, invasion, and adhesion abilities in LUAD cells, and inhibited EMT progression and Wnt/ß-Catenin pathway. Rescue experiments demonstrated that ß-Catenin activator SKL2001 reversed repressive influence of NTSR1 knockdown on LUAD cell malignant phenotypes and EMT progression. CONCLUSION: The data obtained in this study suggested that NTSR1 stimulated EMT and metastasis in LUAD via Wnt/ß-Catenin pathway. This finding may provide options for overcoming LUAD metastasis.

A novel approach for large-scale characterization of residential cooking-generated PM with computer vision and low-cost sensors.

Cooking is one of the major sources of indoor particulate matter (PM), which poses significant health risks and is a severe health hazard. Current studies lack an economical and effective analytical framework for quantifying inhalable particles (PM10) and fine particulate matter (PM2.5) from residential cooking activities on a large scale under real-world scenarios. This study bridges this gap by employing computer vision (CV) technology and readily available sensors. We collected data over a month in real-world settings, including cooking videos and air quality data (indoor PM10, PM2.5, CO2, temperature, relative humidity, and outdoor PM10 and PM2.5 concentrations). To classify high-emission (pan-frying, stir-frying, deep-frying) and low-emission (stewing, steaming, boiling, non-cooking) activities, we developed and validated a robust CV model named "Cooking-I3D." This model leverages a pre-trained Two-Stream Inflated 3D ConvNet (I3D) architecture. We then assessed the efficacy of the CV-predicted cooking method in PM characterization using a first-order multivariate autoregressive model, controlling for environmental factors. The Cooking-I3D model achieved exceptional performance, boasting an accuracy of 95 % and an Area Under the Curve (AUC) of 0.98. Our results indicate that a single 6-minute high-emission cooking event triggers a 21-25 % increase in indoor PM concentrations and a 23-24 % increase in the indoor/outdoor ratio, with relative errors in these estimates ranging from 10 to 21 %. This innovative method offers a powerful tool for long-term assessment of cooking-related indoor air pollution and facilitates precision exposure assessment in human health studies.

Poly(p-coumaric acid) nanoparticles alleviate temporomandibular joint osteoarthritis by inhibiting chondrocyte ferroptosis.

Oxidative stress and inflammation are key drivers of osteoarthritis (OA) pathogenesis and disease progression. Herein we report the synthesis of poly(p-coumaric) nanoparticles (PCA NPs) from p-courmaic acid (p-CA), a naturally occurring phytophenolic acid, to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis (TMJOA). Compared to hyaluronic acid (HA) that is clinically given as viscosupplementation, PCA NPs exhibited long-term efficacy, superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA. Notably, TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis, while reducing inflammation, oxidative stress, matrix degradation, and chondrocyte ferroptosis. Overall, our study demonstrates a multifunctional nanoparticle, synthesized from natural p-coumaric acid, that is stable and possess potent antioxidant, anti-inflammatory properties and ferroptosis inhibition, beneficial for treatment of TMJOA.

Stable and Fast Ion Transport Electrolyte Interfaces Modified with Novel Fluorine- and Nitrogen-Containing Solvents for Ni-Rich Cathode Materials.

Ternary nickel-rich layered oxide LiNi0.8Co0.1Mn0.1O2 (NCM811) is recognized as a cathode material with a promising future, attributed to its high energy density. However, the pulverization of cathode particles, structural collapse, and electrolyte decomposition are closely associated with the fragile cathode-electrolyte interphases (CEI), which seriously affect the electrochemical performances of ternary high-nickel materials. In this paper, fluorine- and nitrogen-containing methyl-2-nitro-4-(trifluoromethyl)benzoate (MNTB) was selected, which was synergistically regulated with fluoroethylene carbonate (FEC) to generate a robust CEI film. The preferential decomposition of MNTB/FEC results in the formation of an inorganic-rich (Li3N, LiF, and Li2O) CEI film with uniformly dense and stable characteristics, which is conducive to the migration of Li+ and the stability of the NCM811 structure and enhances the cycling stability of the battery system. Simultaneously, MNTB effectively suppresses the adverse reaction associated with increased polarization caused by higher interface impedance due to conventional single FEC additives, further improving the rate capability of the battery. Moreover, MNTB/FEC can effectively eliminate HF, preventing its corrosion on the NCM811 cathode. Under the synergistic effect of MNTB/FEC, after 300 discharge cycles at a high cutoff voltage of 4.3 V and a current density of 1 C (2 mA cm-2), the discharge capacity of the NCM811||Li battery was 150.12 mA h g-1 with a capacity retention of 81.10%, while it was only 32.8% for the standard electrolyte (STD). The discharged capacity of the MNTB/FEC-containing battery was about 115.43 mA h g-1 at the high rate of 7 C, which was considerably higher than that of the STD (93.34 mA h g-1). In this study, the designed MNTB as a novel solvent synergistically regulated with FEC will contribute to the enhanced stability of NCM811 materials at high cutoff voltages and at the same time provide an effective modified strategy to enhance the stability of commercial electrodes.

Time synchronization between parietal-frontocentral connectivity with MRCP and gait in post-stroke bipedal tasks.

BACKGROUND: In post-stroke rehabilitation, functional connectivity (FC), motor-related cortical potential (MRCP), and gait activities are common measures related to recovery outcomes. However, the interrelationship between FC, MRCP, gait activities, and bipedal distinguishability have yet to be investigated. METHODS: Ten participants were equipped with EEG devices and inertial measurement units (IMUs) while performing lower limb motor preparation (MP) and motor execution (ME) tasks. MRCP, FCs, and bipedal distinguishability were extracted from the EEG signals, while the change in knee degree during the ME phase was calculated from the gait data. FCs were analyzed with pairwise Pearson's correlation, and the brain-wide FC was fed into support vector machine (SVM) for bipedal classification. RESULTS: Parietal-frontocentral connectivity (PFCC) dysconnection and MRCP desynchronization were related to the MP and ME phases, respectively. Hemiplegic limb movement exhibited higher PFCC strength than nonhemiplegic limb movement. Bipedal classification had a short-lived peak of 75.1% in the pre-movement phase. These results contribute to a better understanding of the neurophysiological functions during motor tasks, with respect to localized MRCP and nonlocalized FC activities. The difference in PFCCs between both limbs could be a marker to understand the motor function of the brain of post-stroke patients. CONCLUSIONS: In this study, we discovered that PFCCs are temporally dependent on lower limb gait movement and MRCP. The PFCCs are also related to the lower limb motor performance of post-stroke patients. The detection of motor intentions allows the development of bipedal brain-controlled exoskeletons for lower limb active rehabilitation.

[Effects of Fly Ash on the Efficiency and Bacterial Community Structure of Urban Multi-source Organic Solid Waste].

To achieve efficient resource utilization of fly ash and multi-source organic waste, a composting experiment was carried out to investigate the effects of fly ash on co-aerobic composting using kitchens, chicken manure, and sawdust (15:5:2). The effects of different application doses (5 % and 10 %, calculated in total wet weight of organic solid waste) of fly ash on physical and chemical properties, nutrient elements, and bacterial community structure during co-composting were evaluated. The results showed that the addition dose of 5 % and 10 % fly ash significantly increased the highest temperature (56.6 ℃ and 56.9 ℃) and extended the thermophilic period to nine days. Compared with that in the control, the total nutrient content of compost products in the treatments of 5 % FA and 10 % FA was increased by 4.09 % and 13.55 %, respectively. The bacterial community structure changed greatly throughout the composting, and the bacterial diversity of all treatments increased obviously. In the initial stage of composting, Proteobacteria was the dominant phylum of bacteria, with a relative abundance ranging from 35.26 % to 39.40 %. In the thermophilic period, Firmicutes dominated; its relative abundance peaked at 52.46 % in the 5 % FA treatment and 67.72 % in the 10 % FA treatment. Bacillus and Thermobifida were the predominant groups in the thermophilic period of composting. The relative abundance of Bacillus and Thermobifida in the 5 % FA and 10 % FA treatments were 33.41 % and 62.89 %(Bacillus) and 33.06 % and 12.23 %(Thermobifida), respectively. The results of the redundancy analysis (RDA) revealed that different physicochemical indicators had varying degrees of influence on bacteria, with organic matter, pH, available phosphorus, and available potassium being the main environmental factors influencing bacterial community structure. In summary, the addition of fly ash promoted the harmlessness and maturation of co- aerobic composting of urban multi-source organic waste, while optimizing microbial community structure and improving the quality and efficiency of composting.

Oregano Essential Oil in Livestock and Veterinary Medicine.

With a growing global concern over food safety and animal welfare issues, the livestock and veterinary industries are undergoing unprecedented changes. These changes have not only brought challenges within each industry, but also brought unprecedented opportunities for development. In this context, the search for natural and safe products that can effectively replace traditional veterinary drugs has become an important research direction in the fields of animal husbandry and veterinary medicine. Oregano essential oil (OEO), as a natural extract, is gradually emerging in the fields of animal husbandry and veterinary medicine with its unique antibacterial, antioxidant, and multiple other biological activities. OEO not only has a wide antibacterial spectrum, effectively fighting against a variety of pathogenic microorganisms, but also, because of its natural properties, helps us to avoid traditional veterinary drugs that may bring drug residues or cause drug resistance problems. This indicates OEO has great application potential in animal disease treatment, animal growth promotion, and animal welfare improvement. At present, the application of OEO in the fields of animal husbandry and veterinary medicine has achieved preliminary results. Studies have shown that adding OEO to animal feed can significantly improve the growth performance and health status of animals and reduce the occurrence of disease. At the same time, pharmacokinetic studies in animals show that the absorption, distribution, metabolism, and excretion processes of OEO in animals shows good bioavailability. In summary, oregano essential oil (OEO), as a substitute for natural veterinary drugs with broad application prospects, is gradually becoming a research hotspot in the field of animal husbandry and veterinary medicine. In the future, we look forward to further tapping the potential of OEO through more research and practice and making greater contributions to the sustainable development of the livestock and veterinary industries.

Water quality evaluation based on water quality index and multiple linear regression: A research on Hanyuan Lake in southern Sichuan Province, China.

This study aims to understand the changes in the water quality of Hanyuan Lake and to show these changes over time. In this study, monthly sampling was conducted at three sampling sites in Hanyuan Lake, and water samples were measured for water quality indicators in the laboratory according to the methods specified in the Environmental Quality Standards for Surface Water (GB3838-2002). Based on the monitoring data from January to December 2019, the WQI comprehensive evaluation method was used to conduct multiple linear stepwise regression analysis, extract key indicators, and establish the WQImin model. The results show that according to the WQI comprehensive evaluation method, the WQI values of Hanyuan Lake are all above 90, and the grade is excellent. The overall water quality of Hanyuan Lake is excellent, and most of the water quality indexes reach the Class I standard in the Environmental Quality Standards for Surface Water (GB3838-2002). WQImin1 (R2 = 0.86, p < 0.001, PE = 4.28) as the best WQImin model. In this study, a model with fewer parameters was established by multiple linear regression method, which is conducive to better monitoring of water quality at monitoring stations while saving costs. PRACTITIONER POINTS: According to the WQI comprehensive evaluation method, the WQI values of Hanyuan Lake are all above 90, the rating is excellent. From January 2019 to September 2020, the monthly change trend of each section is roughly the same, showing a trend of first decreasing, then rising, then decreasing, and finally rising and flattening. The WQImin model was developed to completely describe the change in the water body.

Research on sensitized Fiber Bragg Grating temperature sensor based on bimetal three-substrates.

Temperature is one of the most important physical quantities in the field of earthquake precursor observation. Aiming at the problem of low sensitivity in the Fiber Bragg Grating (FBG) temperature sensor, the sensitized FBG temperature sensor based on bimetal three-substrates is proposed. Through theoretical analysis of the bimetallic model, the structural parameters of the sensor are optimized, and the sensor is simulated and analyzed with ANSYS. Then, the sensor is developed according to the simulation results, and the temperature test system is built to test the performance of the sensor. The results show that the sensitivity of the temperature sensor is 49.3 pm/°C, which is about 4.9 times that of the bare FBG sensor, and the linearity is over 0.999. The research results provide a reference for developing the same type of sensors and further improving the sensitivity of FBG temperature sensors.

Metabolomic profile of muscles from tilapia cultured in recirculating aquaculture systems and traditional aquaculture in ponds and protein stability during freeze-thaw cycles.

Muscle protein stability during freeze-thaw (F-T) cycles was investigated with tilapia cultured in recirculating aquaculture systems (RAS) and traditional aquaculture in ponds (TAP). This study found that fatty acids (eg., palmitic acid) were enriched in TAP, while antioxidants (eg., glutathione) were enriched in RAS. Generally, proteins in the RAS group exhibited greater stability against denaturation during the F-T cycle, suggested by a less decrease in haem protein content (77% in RAS and 86% in TAP) and a less increase in surface hydrophobicity of sarcoplasmic protein (63% in RAS and 101% in TAP). There was no significant difference in oxidative stability of myofibrillar protein between the two groups. This study provides a theoretical guide for the quality control of tilapia cultured in RAS during frozen storage.

Novel Isoalantolactone-Based Derivatives as Potent NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.

The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized. Among them, compound 49 emerged as the optimal lead, displaying the most potent inhibitory efficacy on nigericin-induced IL-1ß release in THP-1 cells, with an IC50 value of 0.29 µM, approximately 27-fold more potent than that of IAL (IC50: 7.86 µM), and exhibiting higher metabolic stability. Importantly, 49 remarkably improved DSS-induced ulcerative colitis in vivo. Mechanistically, we demonstrated that 49 covalently bound to cysteine 279 in the NACHT domain of NLRP3, thereby inhibiting the assembly and activation of NLRP3 inflammasome. These results provided compelling evidence to further advance the development of more potent NLRP3 inhibitors based on this scaffold.

Mechanisms influencing spatiotemporal differentiation of tourist towns based on geographic detector: A case study of Fujian Province.

The construction of tourist towns is an important aspect of new-type urbanization construction. In this study, 155 tourist towns in Fujian Province were selected as samples to analyze spatiotemporal differentiation using the geographical concentration index, nearest neighbor index, and local correlation index. Then, a geographic detector model was used to detect the factors that influence the spatiotemporal differentiation of tourist towns and to analyze the explanatory power and interaction of these detection factors. Finally, the mechanisms underlying the detection factors were discussed. Factors affecting the spatiotemporal differentiation of tourist towns in Fujian Province were core factors of traffic network, level of urbanization and population distribution; important factors of industrial structure and socioeconomic basis; and a fundamental factor of policy guidance. These six factors interacted to jointly affect the spatiotemporal differentiation of tourist towns in Fujian Province. The results of this study can provide a basis for the development of tourist towns in other similar regions and have reference value for better optimizing the pattern of urban and town systems and coordinating the synergistic development of urban and rural areas.

Effect of electroacupuncture on proBDNF/mBDNF and synaptic plasticity in rats with learning and memory impairment after cerebral ischemia-reperfusion. / ç”µé’ˆå¯¹è„‘ç¼ºè¡€å†çŒæ³¨å­¦ä¹ è®°å¿†éšœç¢å¤§é¼ æµ·é©¬è„‘æºæ€§ç¥žç»è¥å »å› å­è½¬åŒ–å’Œçªè§¦å¯å¡‘æ€§çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the rats' behavior and the transforming precursor of brain-derived neurotrophic factor (proBDNF) into mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia-reperfusion (IR), so as to explore its mechanisms underlying improvement of learning and memory ability. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 6 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (1 Hz/20 Hz) was applied to GV24 and GV20 for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria 24 h after modeling and after intervention. Morris water maze test was used to detect the learning and memory function of the rats. TTC staining was used to evaluate the cerebral infarction volume on the affected side. The protein expression levels of proBDNF, mBDNF, tissue plasminogen activator (tPA), tyrosine kinase receptor B (TrkB) and p75 neurotrophin receptor (p75NTR) in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score, the percentage of cerebral infarction volume and the expression levels of proBDNF and p75NTR protein in hippocampus were increased (P<0.01), while the times of crossing the original platform and the total distance in the target quadrant, the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were decreased (P<0.01, P<0.05) in the model group. Compared with the model group, the neurological function score, the percentage of cerebral infarction volume, and the expression levels of proBDNF and p75NTR protein in hippocampus were decreased (P<0.01, P<0.05), while the times of crossing the original platform, the total distance in the target quadrant, and the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were increased (P<0.05, P<0.01) in the EA group. CONCLUSIONS: EA can alleviate learning and memory impairment in IR rats, which may be related to its function in up-regulating the expression of tPA protein and promoting the transformation of proBDNF to mBDNF, thus improving the synaptic plasticity.

Associations of maternal and personal smoking with all-cause and cause-specific mortality risk and life expectancy: a prospective cohort study.

OBJECTIVES: The aim of this study was to evaluate the individual and combined effects of maternal smoking during pregnancy (MSDP) and personal smoking on mortality and life expectancy. STUDY DESIGN: A prospective cohort study based on the UK Biobank, with a median follow-up of 12.47 years. METHODS: This study employed multivariate Cox regression to determine the relative risks of mortality from all causes and specific diseases according to maternal and/or personal smoking status and pack-years of smoking (0, 1-20, 21-30, >30). Additionally, this study estimated the additive interaction between the two exposures. Life table analyses were performed using the estimated age-specific mortality rates to forecast life expectancy. RESULTS: Results indicated that MSDP elevated the risk of all-cause mortality (HR = 1.12, 95% CI: 1.09-1.15) and mortality due to neoplasms (HR = 1.10, 95% CI: 1.06-1.12), circulatory (HR = 1.13, 95% CI: 1.06-1.19), respiratory (HR = 1.27, 95% CI: 1.16-1.40) and digestive system diseases (HR = 1.22, 95% CI: 1.08-1.38). Notably, both multiplicative and additive interactions were observed between maternal and personal smoking, with Relative Excess Risk due to Interaction (RERI) values for mortality from all causes, neoplasms, circulatory, and respiratory diseases being 0.21, 0.22, 0.16, and 0.76, respectively. This study also found a trend towards shorter gained life expectancy when maternal smoking and increasing pack-years of personal smoking were combined. CONCLUSIONS: In this cohort study of UK Biobank, MSDP was associated with an increased risk of all-cause mortality and reduced life expectancy, suggesting that quitting smoking during pregnancy might have health and longevity benefits for both generations.