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Social contacts play an important role in the development and survival of social animals. Social isolation (SI) at adolescence often induces abnormalities in many kinds of behaviors. This study assessed whether five weeks of continuous SI at adulthood could alter social behaviors and whether dorsal raphe nucleus (DR) to medial prefrontal cortex (mPFC) 5-HT neural projections were involved in this alteration in C57BL/6J adult male mice. The present study found that five weeks chronic social isolation (CSI) at adulthood increased mounting and sniffing behaviors in resident-intruder test, and lengthened duration staying in interaction zone of stranger cage in the three-chamber social preference test. CSI also reduced the release of 5-HT in the mPFC detected by 5-HT 1.0 sensor and measured by in vivo fiber photometry test. Meanwhile, the c-Fos expression indicated that CSI reduced the activity of serotonergic neurons. Chemogenetic activation of DR-mPFC 5-HTergic projection reduced sniffing of CSI mice in the resident-intruder test, but didn’t significantly affect mounting behavior. It also decreased the interaction time during the three-chamber social preference test. Thus, 5-HT neural projections from the DR to the mPFC are involved in changes of social exploration behaviors induced by CSI at adulthood.

Background The burden due to influenza-related hospitalization is heavy in children under 5 years old, a high-risk group of severe influenza, but there is little research on the risk factors for such hospitalizations. Objective To explore the risk factors for influenza A variant virus-related hospitalization in children under 5 years old. Methods A retrospective design was used. Children under five years old (n=1 450) with influenza A virus infection were selected from Emergency Department, Beijing Ditan Hospital Capital Medical University during December 2018 to February 2019. Clinical data were collected, including age, sex, baseline chronic disease, time from onset to first contact, time from onset to initiation of antiviral therapy, main clinical features and prevalence of hospitalization. Multivariate Logistic regression analysis was used to identify the risk factors of hospitalization. Results The median age for the children was 2.5 (1.1, 3.9) years, and males outnumbered females (56.5% vs 43.5%) . Thirty-eight (2.6%) had baseline chronic diseases, and 155 (10.7%) were hospitalized. Stepwise univariate and multivariate Logistic regression analyses showed that: younger than 6 months〔OR=5.808, 95%CI (2.650, 12.730) , P48 h〔OR=4.663, 95%CI (1.712, 12.704) , P48 h〔OR=19.835, 95%CI (9.043, 43.502) , P

Objectives: This study aims to discover the role of lncRNA MIR17HG, referred to as MIR17HG, in cisplatin resistance for cholangiocarcinoma (CCA). Methods: QRT-PCR was conducted to measure the expression of MIR17HG in cisplatin-resistant/sensitive CCA cells and clinical CCA specimens. Log-rank test was used to analyze the survival curve. Cck8-assay and flow cytometry were employed to detect the sensitivity of CCA cells to cisplatin and the apoptosis rate following different treatments, respectively. The next-generation sequencing was carried out to get gene transcripts after silencing MIR17HG in HCCC-9810 cells. The LncBase database was used to predict the target miRNA of MIR17HG, and MS2 RIP assay and dual luciferase assay were conducted to confirm their binding. MiRwalk database and the RNA sequencing data were utilized to screen the key genes regulated by MIR17HG/miR-138-5p axis and a dual luciferase assay was performed to confirm the binding site of miR-138-5p with AKAP9. Immunoblotting was further employed to give assistant evidence. Rescue experiments were performed to observe the function of miR-138-5p and AKAP9 in MIR17HG-induced cisplatin resistance. Results: MIR17HG overexpression predicts cisplatin resistance and poor prognosis in CCA. MIR17HG could bind with miR-138-5p to release AKAP9, thereby inhibiting cisplatin-induced apoptosis and promoting cisplatin resistance in CCA. MIR17HG silencing in CCA cells leads to expression alteration of genes, which are enriched in platinum resistance-related pathways. Conclusions: LncRNA MIR17HG regulates platinum resistance-associated genes and promotes cisplatin resistance partially via the miR-138-5p/AKAP9 axis by inhibiting cisplatin-induced apoptosis in CCA. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cause of cancer-related morbidity and mortality among women worldwide, with bone being the most common site of all metastatic breast cancer. Bone metastases are often associated with pain and skeletal-related events (SREs), indicating poor prognosis and poor quality of life. Most current therapies for breast cancer bone metastasis primarily serve palliative purposes, focusing on pain management, mitigating the risk of bone-related complications, and inhibiting tumor progression. The emergence of nanodelivery systems offers novel insights and potential solutions for the diagnosis and treatment of breast cancer-related bone metastasis. This article reviews the recent advancements and innovative applications of nanodrug delivery systems in the context of breast cancer bone metastasis and explores future directions in nanotheranostics. [ABSTRACT FROM AUTHOR]

Abstract Increased glycolysis is a hallmark of tumor, which can provide tumor cells with energy and building blocks to promote cell proliferation. Recent studies have shown that not only the expression of glycolytic genes but also their subcellular localization undergoes a variety of changes to promote development of different types of tumors. In this study, we performed a comprehensive analysis of glycolysis and gluconeogenesis genes based on data from TCGA to identify those with significant tumor-promoting potential across 14 types of tumors. This analysis not only confirms genes that are known to be involved in tumorigenesis, but also reveals a significant correlation of triosephosphate isomerase 1 (TPI1) with poor prognosis, especially in lung adenocarcinoma (LUAD). TPI1 is a glycolytic enzyme that interconverts dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (GAP). We confirm the upregulation of TPI1 expression in clinical LUAD samples and an inverse correlation with the overall patient survival. Knocking down of TPI1 in lung cancer cells significantly reduced cell migration, colony formation, and xenograft tumor growth. Surprisingly, we found that the oncogenic function of TPI1 depends on its translocation to cell nucleus rather than its catalytic activity. Significant accumulation of TPI1 in cell nucleus was observed in LUAD tumor tissues compared with the cytoplasm localization in adjacent normal tissues. Moreover, nuclear translocation of TPI1 is induced by extracellular stress (such as chemotherapy agents and peroxide), which facilitates the chemoresistance of cancer cells. Our study uncovers a novel function of the glycolytic enzyme TPI1 in the LUAD.

Introduction and Aim. Sentinel lymph node (SLN) mapping has been developed as an alternative to complete lymphadenectomy for the surgical staging of early-stage, uterine-confined endometrial cancer to reduce the morbidity of lymphadenectomy and has been demonstrated as a safe and feasible alternative. We compare the surgical and oncological outcomes between SLN mapping with routine lymphadenectomy in the surgical staging of early-stage endometrial cancer in our centre. Methods. A retrospective single-centre cohort study of patients with early-stage endometrioid endometrial cancer undergoing staging surgery (total hysterectomy, bilateral salpingo-oophorectomy with/without pelvic lymph node, and/or para-aortic lymph node dissection (PLND)) with either SLN mapping or routine lymphadenectomy between July 2017 and December 2018. Results. 203 cases with clinical and radiological International Federation of Gynaecology and Obstetrics (FIGO) stage I endometrioid endometrial cancer were included, out of which 109 cases underwent SLN mapping and 94 cases complete lymphadenectomy. Compared to the PLND group, the SLN group had shorter operative time (129 vs. 162 minutes), less blood loss (100 vs. 300 ml), and decreased length of postoperative hospital stay (3 vs. 4 days) (p

Currently, the treatment for sepsis-induced acute lung injury mainly involves mechanical ventilation with limited use of drugs, highlighting the urgent need for new therapeutic options. As a pivotal aspect of acute lung injury, the pathologic activation and apoptosis of endothelial cells related to oxidative stress play a crucial role in disease progression, with NOX4 and Nrf2 being important targets in regulating ROS production and clearance. Echinacoside, extracted from the traditional Chinese herbal plant Cistanche deserticola, possesses diverse biological activities. However, its role in sepsis-induced acute lung injury remains unexplored. Moreover, although some studies have demonstrated the regulation of NOX4 expression by SIRT1, the specific mechanisms are yet to be elucidated. Therefore, this study aimed to investigate the effects of echinacoside on sepsis-induced acute lung injury and oxidative stress in mice and to explore the intricate regulatory mechanism of SIRT1 on NOX4. We found that echinacoside inhibited sepsis-induced acute lung injury and oxidative stress while preserving endothelial function. In vitro experiments demonstrated that echinacoside activated SIRT1 and promoted its expression. The activated SIRT1 was competitively bound to p22 phox, inhibiting the activation of NOX4 and facilitating the ubiquitination and degradation of NOX4. Additionally, SIRT1 deacetylated Nrf2, promoting the downstream expression of antioxidant enzymes, thus enhancing the NOX4-Nrf2 axis and mitigating oxidative stress-induced endothelial cell pathologic activation and mitochondrial pathway apoptosis. The SIRT1-mediated anti-inflammatory and antioxidant effects of echinacoside were validated in vivo. Consequently, the SIRT1-regulated NOX4-Nrf2 axis may represent a crucial target for echinacoside in the treatment of sepsis-induced acute lung injury.

Abstract Background Differences in genetics and microenvironment of LUAD patients with or without TP53 mutation were analyzed to illustrate the role of TP53 mutation within the carcinogenesis of LUAD, which will provide new concepts for the treatment of LUAD. Methods In this study, we used genetics and clinical info from the TCGA database, including somatic mutations data, RNA-seq, miRNA-seq, and clinical data. More than one bioinformatics tools were used to analyze the unique genomic pattern of TP53-related LUAD. Results According to TP53 gene mutation status, we divided the LUAD patients into two groups, including 265 in the mutant group (MU) and 295 in the wild-type group (WT). 787 significant somatic mutations were detected between the groups, including mutations in titin (TTN), type 2 ryanodine receptor (RYR2) and CUB and Sushi multiple domains 3(CSMD3), which were up-regulated in the MU. However, no significant survival difference was observed. At the RNA level, we obtained 923 significantly differentially expressed genes; in the MU, α-defensin 5(DEFA5), pregnancy-specific glycoprotein 5(PSG5) and neuropeptide Y(NPY) were the most up-regulated genes, glucose-6-phosphatase (G6PC), alpha-fetoprotein (AFP) and carry gametocidal (GC) were the most down-regulated genes. GSVA analysis revealed 30 significant pathways. Compared with the WT, the expression of 12 pathways in the mutant group was up-regulated, most of which pointed to cell division. There were significant differences in tumor immune infiltrating cells, such as Macrophages M1, T cells CD4 memory activated, Mast cells resting, and Dendritic cells resting. In terms of immune genes, a total of 35 immune-related genes were screened, of which VGF (VGF nerve growth factor inducible) and PGC (peroxisome proliferator-activated receptor gamma coactivator) were the most significant up-regulated and down-regulated genes, respectively. Research on the expression pattern of immunomodulators found that 9 immune checkpoint molecules and 6 immune costimulatory molecules were considerably wholly different between the two groups. Conclusions Taking the mutant group as a reference, LUAD patients in the mutant group had significant differences in somatic mutations, mRNA-seq, miRNA-seq, immune infiltration, and immunomodulators, indicating that TP53 mutation plays a crucial role in the occurrence and development of LUAD.

Abstract Background Trimetazidine (TMZ) pretreatment protects cardiomyocytes during cardiac surgery. TMZ may protect elderly patients with ischaemic heart disease (IHD) undergoing non-cardiac surgery. Methods This was a randomized, double-blind, placebo-controlled trial (registration #ChiCTR1900025018) of patients with IHD scheduled to undergo non-cardiac surgery at Shenzhen People’s Hospital (Shenzhen, Guangdong Province, China) between June 2014 and September 2015, randomized to 60 mg TMZ or placebo 12 h before surgery. The primary endpoint was the occurrence of in-hospital cardiovascular events. The secondary endpoints were myocardial ischaemia on five-lead electrocardiogram (cECG), cardiac troponin I (cTnI) elevation, cardiac death, acute coronary events, heart failure, and arrhythmia requiring treatments. Results Compared with the placebo group, the TMZ group showed a lower occurrence of in-hospital cardiovascular events (primary endpoint, 20.0% vs. 37.5%, P = 0.02), myocardial ischaemia (15.0% vs. 32.5%, P

【Objective】 Water balance in a region is jointly controlled by land usage, precipitation and evapotranspiration. All these are modulated by soil texture. Taking the sandy areas in Horqin of Inner Mongolia as an example, this paper analyzes how land usage affects evapotranspiration and its consequence for water balance. 【Method】 The analysis was based on MODIS and meteorological data, and the evapotranspiration during crop growth season in Naiman Banner was retrieved by the SEBAL model. Using these data, we calculated the response of water balance to land usage across the region. 【Result】 The maximum daily evapotranspiration was 3.74 mm/d occurring in July, and the least was 2.35 mm/d occurring in September. Spatially, the evapotranspiration was high in the south and low in the center of the region. It was found that the evapotranspiration was negatively correlated with land surface temperature and reflectance with R2=0.94 and 0.44, respectively, while positively correlated with the normalized vegetation index with R2=0.4. Daily evapotranspiration from different land usage was ranked in the order: land for construction> woodland > cultivated land > grassland > bare soil. On average, the water deficit in the sandy region is 121 mm but varies spatially with land usage. Water deficit in the woodland and the cultivated land in the south was more than 100 mm. In some areas, part of the evapotranspiration emanated from groundwater or runoff; and the water deficit in some woodland could be as high as 204.7 mm. The water surplus in areas with bare soil was 16.8 mm, indicating that regions with bare soil functioned as the water source discharging to groundwater. 【Conclusion】 Large-scale afforestation in this region is not recommended because of its high demand for water. It is beneficial to keep soil surface in some areas bare to maintain stability of ecological functions in Horqin while in the meantime ensuring its productivity.

Abstract There has been interest in the use of nonintubated techniques for video-assisted thoracoscopic surgery (VATS) in both awake and sedated patients. The authors’ centre developed a nonintubated technique with spontaneous ventilation for use in a patient under general anaesthesia using a phrenic nerve block. This treatment was compared with a case-matched control group. The authors believe that this technique is beneficial for optimizing anaesthesia for patients undergoing VATS. The patients were randomly allocated (1:1) to the phrenic nerve block (PNB) group and the control group. Both groups of patients received a laryngeal mask airway (LMA) that was inserted after anaesthetic induction, which permitted spontaneous ventilation and local anaesthesia in the forms of a paravertebral nerve block, a PNB and a vagal nerve block. However, the patients in the PNB group underwent procedures with 2% lidocaine, whereas saline was used in the control group. The primary outcome included the propofol doses. Secondary outcomes included the number of propofol boluses, systolic blood pressure (SBP), pH values of arterial blood gas and lactate (LAC), length of LMA pulled out, length of hospital stay (length of time from the operation to the time of discharge) and complications after 1 month. Intraoperatively, there were increases in lactate (F = 12.31, P = 0.001) in the PNB group. There was less propofol (49.20 ± 8.73 vs. 57.20 ± 4.12, P = 0.000), fewer propofol boluses (P = 0.002), a lower pH of arterial blood gas (F = 7.98, P = 0.006) and shorter hospital stays (4.10 ± 1.39 vs. 5.40 ± 1.22, P = 0.000) in the PNB group. There were no statistically significant differences in the length of the LMA pulled out, SBP or complications after 1 month between the groups. PNB optimizes the anaesthesia of nonintubated VATS.

Excessive lipid mobilization will snatch cell membrane lipids in postpartum dairy cows, which may impair the function of immune cells, including peripheral mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs). Acetate, as a precursor and the energy source of milk fat synthesis, plays a key role in lipid synthesis and the energy supply of dairy cows. However, there is little information about the effect of sodium acetate (NaAc) on the immune function of PBMC and PMN in postpartum dairy cows. Therefore, this study aimed to evaluate the effects of NaAc on the immune functions of PBMCs and PMNs in postpartum dairy cows. In this experiment, twenty-four postpartum multiparous Holstein cows were randomly selected and divided into a NaAc treatment group and a control group. Our results demonstrated that the dietary addition of NaAc increased (p < 0.05) the number of monocytes and the monocyte ratio, suggesting that these postpartum cows fed with NaAc may have better immunity. These expressions of genes (LAP, XBP1, and TAP) involved in the antimicrobial activity in PBMCs were elevated (p < 0.05), suggesting that postpartum dairy cows supplemented with NaAc had the ability of antimicrobial activity. In addition, the mRNA expression of the monocarboxylate transporters MCT1 and MCT4 in PBMCs was increased (p < 0.05) in diets supplemented with NaAc in comparison to the control. Notably, the expression of the XBP1 gene related to antimicrobial activity in PMN was upregulated with the addition of NaAc. The mRNA expression of genes (TLN1, ITGB2, and SELL) involved in adhesion was profoundly increased (p < 0.05) in the NaAc groups. In conclusion, our study provided a novel resolution strategy in which the use of NaAc can contribute to immunity in postpartum dairy cows by enhancing the ability of antimicrobial and adhesion in PBMCs and PMNs.

This study aimed to assess the effects of partially substituting soybean meal in the diet with slow-release urea (SRU) on the lactation performance, heat shock signal molecules, and environmental sustainability of heat-stressed lactating cows in the middle stage of lactation. In this study, 30 healthy Holstein lactating dairy cattle with a similar milk yield of 22.8 ± 3.3 kg, days in milk of 191.14 ± 27.24 days, and 2.2 ± 1.5 parity were selected and randomly allocated into two groups. The constituents of the two treatments were (1) basic diet plus 500 g soybean meal (SM) for the SM group and (2) basic diet plus 100 g slow-release urea and 400 g corn silage for the SRU group. The average temperature humidity index (THI) during the experiment was 84.47, with an average THI of >78 from day 1 to day 28, indicating the cow experienced moderate heat stress conditions. Compared with the SM group, the SRU group showed decreasing body temperature and respiratory rate trends at 20:00 (p < 0.1). The substitution of SM with SRU resulted in an increasing trend in milk yield, with a significant increase of 7.36% compared to the SM group (p < 0.1). Compared to the SM group, AST, ALT, and γ-GT content levels were significantly increased (p < 0.05). Notably, the levels of HSP-70 and HSP-90α were significantly reduced (p < 0.05). The SRU group showed significantly increased acetate and isovalerate concentrations compared with the SM group (p < 0.05). The prediction results indicate that the SRU group exhibits a significant decrease in methane (CH4) emissions when producing 1 L of milk compared to the SM group (p < 0.05). In summary, dietary supplementation with SRU tended to increase the milk yield and rumen fermentation and reduce plasma heat shock molecules in mid-lactation, heat-stressed dairy cows. In the hot summer, using SRU instead of some soybean meal in the diet alleviates the heat stress of dairy cows and reduces the production of CH4.

In local quasi-geoid modeling, the residual terrain modeling (RTM) method is often used to remove short-wavelength gravity field signals from the measured gravity on the ground in order to obtain a regularized and smooth gravity field that is suited for field interpolation and modeling. Accurate computation of RTM corrections plays a crucial role in computing an accurate local quasi-geoid, and it requires a set of fine-tuned parameters, including the combination of DEMs with different resolutions for suitably representing the real topography, the choice of integration radius for properly defining the extent of the computation zone, and the determination of reference topography to properly describe the RTM-reduced Earth’s surface. To our knowledge, this has not been systematically documented, despite its obvious importance. This study aims to systematically investigate the impact of these factors on RTM correction computation and, consequently, on local quasi-geoid modeling to provide practical guidelines for real-world applications. The tesseroid-based gravity forward modeling technique is employed to investigate the following issues existing in the practical use of the RTM method: ① Can the combination of a high-resolution DEM and a DEM with a lower resolution replace the single use of the high-resolution DEM for RTM correction computation while maintaining accuracy and improving efficiency? If it does, how do I properly choose the resolution of this coarse DEM as well as the integration radius r1 for the inner zone and r2 for the outer zone? ② How large would the differences between the RTM corrections computed by three types of reference topographies, which are obtained from the direct averaging (DA) approach, the moving averaging (MA) approach, and the spherical harmonic (SH) approach, be, and how large would their impact on quasi-geoid modeling be? To obtain objective findings, two research regions were selected for this investigation. One is the Colorado test area (USA) with rugged terrain, and the other is the Auvergne test area (France) with moderate terrain. The main numerical findings are: (1) the combination of the 3” resolution DEM (inner zone) and the 30″ resolution DEM (outer zone) is sufficient for accurate and efficient RTM correction computation; (2) if the resolution of the reference topography is 5′ or slightly lower, all three types of reference topographies are able to obtain local quasi-geoid models at a similar accuracy level, while the values of r1 and r2 are preferred to be at least 20 km and 111 km, respectively; (3) if the reference topography has a resolution of 30′ or lower, the MA or SH reference topography is recommended, especially for the latter one, and the values of r1 and r2 are suggested to be at least 20 km and 222 km, respectively. The above numerical findings can be taken as a reference for local quasi-geoid determination in areas with different topographic regimes than the two selected test areas.