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ObjectivesThis study aimed to examine whether China’s Targeted Poverty Alleviation (TPA) program mitigates depression and explores the mechanisms through which the TPA program affects individuals’ depression.MethodsUsing the data from the China Family Panel Studies (CFPS) survey from 2012 to 2020, we employ a Difference-in-Difference model to analyze the effect of the TPA program on individuals’ depression levels.ResultsOur findings indicate that the TPA program reduces depression scores by 0.116 points, accounting for 6.82% of the standard deviation of depression scores. Further analyses indicate that these effects are mediated through improvements in local medical conditions, reductions in household healthcare spending, increases in household entertainment expenditures, and greater likelihood of living in family.ConclusionThis study showed that the TPA program significantly mitigates individuals’ depression levels. The possible channels include (1) improving local medical conditions, (2) cutting down household healthcare spending, (3) increasing household entertainment expenses, and (4) increasing the likelihood of living in family.

1. Abstract: Objective: Bladder cancer is one of the most prominent malignancies affecting the urinary tract, characterized by a poor prognosis. Our previous research has underscored the pivotal role of m6A methylation in the progression of bladder cancer. Nevertheless, the precise relationship between N6-methyladenosine (m6A) regulation of long non-coding RNA (lncRNA) and bladder cancer remains elusive. Methods: This study harnessed sequencing data and clinical records from 408 bladder cancer patients in the TCGA database. Employing R software, we conducted bioinformatics analysis to establish an m6A-lncRNA co-expression network. Analyzing the differences between high and low-risk groups, particularly at the immunological level, and subsequently investigating the primary regulatory factors of these lncRNA, validating the findings through experiments, and exploring their specific cellular functions. Results: We identified 50 m6A-related lncRNA with prognostic significance through univariate Cox regression analysis. In parallel, we employed a LASSO-Cox regression model to pinpoint 11 lncRNA and calculate risk scores for bladder cancer patients. Based on the median risk score, patients were categorized into low-risk and high-risk groups. The high-risk cohort exhibited notably lower survival rates than their low-risk counterparts. Further analysis pointed to RBM15 and METTL3 as potential master regulators of these m6A-lncRNA. Experimental findings also shed light on the upregulated expression of METTlL3 and RBM15 in bladder cancer, where they contributed to the malignant progression of tumors. The experimental findings demonstrated a significant upregulation of METTL3 and RBM15 in bladder cancer specimens, implicating their contributory role in the oncogenic progression. Knockdown of METTL3 and RBM15 resulted in a marked attenuation of tumor cell proliferation, invasion, and migration, which was concomitant with a downregulation in the cellular m6A methylation status. Moreover, these results revealed that RBM15 and METTL3 function in a synergistic capacity, positing their involvement in cancer promotion via the upregulation of m6A modifications in long non-coding RNAs. Additionally, this study successfully developed an N-methyl-N-nitrosourea (MNU)-induced rat model of in situ bladder carcinoma, confirming the elevated expression of RBM15 and METTL3, which paralleled the overexpression of m6A-related- lncRNAs observed in bladder cancer cell lines. This congruence underscores the potential utility of these molecular markers in in vivo models that mirror human malignancies. Conclusion: This study not only offers novel molecular targets,but also enriches the research on m6A modification in bladder cancer, thereby facilitating its clinical translation.

Abstract Background Laparoscopic hepatectomy under low central venous pressure (LCVP) is associated with intraoperative organ hypoperfusion, including cerebral hypoperfusion. We hypothesized that a ventilation strategy designed to achieve targeted mild hypercapnia (TMH) (end-tidal carbon dioxide partial pressure [PetCO2] of 45 ± 5 mmHg) rather than targeted normocapnia (TN) (PetCO2 of 30 ± 5 mmHg) would increase regional cerebral oxygen saturation (rSO2) during laparoscopic hepatectomy under LCVP. Methods Eighty patients undergoing laparoscopic hepatectomy under LCVP were randomly divided into the TMH group (n = 40) and the TN group (n = 40). Mechanical ventilation was adjusted to maintain the PetCO2 within the relevant range. Cerebral oxygenation was monitored continuously using the FORE-SIGHT system before anesthetic induction until the patient left the operating room. Patient and surgical characteristics, rSO2, intraoperative hemodynamic parameters (CVP, mean artery blood pressure [MAP], and heart rate), PetCO2, intraoperative blood gas analysis results, and postoperative complications were recorded. Results No significant differences were observed in CVP, MAP, and heart rate between the two groups during surgery. The rSO2 was significantly lower in the TN group on both the left and right sides during the intraoperative period (P 0.05). Conclusion Our findings demonstrate that rSO2 is better maintained during laparoscopic hepatectomy under LCVP when patients are ventilated to a PetCO2 of 45 ± 5 mmHg (TMH) than a PetCO2 of 30 ± 5 mmHg (TN). Trial registration ChiCTR2100051130(14/9/2021).

Accurate estimation of the State of Health (SOH) of lithium-ion batteries is crucial for ensuring their safe and reliable operation. Data-driven methods have shown excellent performance in estimating SOH, but obtaining high-quality and strongly correlated features remains a major challenge for these methods. Moreover, different features have varying importance in both spatial and temporal scales, and single data-driven models are unable to capture this information, leading to issues with attention dispersion. In this paper, we propose a data-driven method for SOH estimation leveraging the Bi-directional Long Short-Term Memory (Bi-LSTM) that uses the Differential Thermal Voltammetry (DTV) analysis to extract features, and incorporates attention mechanisms (AM) at both temporal and spatial scales to enable the model focusing on important information in the features. The proposed method is validated using the Oxford Battery degradation Dataset, and the results show that it achieves high accuracy and robustness in SOH estimation. The Root Mean Squared Error (RMSE) and Mean Absolute Error (MAE) are around 0.4% and 0.3%, respectively, indicating the potential for online application of the proposed method in the cyber hierarchy and interactional network (CHAIN) framework.

Uneven soil moisture and nutrient distribution before and after intercropping limits apple cropping system productivity in the western Shanxi–Loess Plateau area. To address this issue, a field trial was conducted between 2020 and 2021 to study the effects of different water and fertilizer management practices on soil moisture, nutrients, and root distribution, as well as the overall effectiveness of the apple–maize and apple–soybean intercropping systems during crop replacement. The experiment involved two irrigation methods: drip (D) and flood (M) irrigation. Three irrigation levels included rain-fed without irrigation (W0), and 50% (W1) and 80% (W2) of field capacity (Fc). Three fertilizer treatments included no additional fertilizer application (F0), 375 kg∙hm−2 (F1), and 750 kg∙hm−2 (F2), in addition to a control (CK) without irrigation or fertilization. The soil water content (SWC) decreased after the crop replacement. Additionally, nitrate nitrogen (NN), ammonium nitrogen (AN), and organic matter (OM) content levels in all treatments increased, whereas total phosphorus (TP) content decreased. The soil layer with crop roots moved downward after crop replacement, and partial fertilizer productivity (PFP), irrigation water use efficiency (IWUE), and water use efficiency (WUE) were decreased under both irrigation treatments. Principal component analysis showed that the W2F2 treatment had the highest benefit from crop combination across both irrigation treatments during the crop replacement period. According to our results, to optimize the benefits of apple-crop intercropping, drip irrigation with complete water supply and flood irrigation with incomplete water supply are recommended during crop replacement. In addition, an upper irrigation limit of 80% Fc with 750 kg∙hm−2 fertilization is recommended for optimal water and fertilizer regulation.

Intercropping systems reduce ineffective evaporation between trees but also intensify interspecific competition and reduce productivity. To improve the water-use efficiency and the economic benefits of an intercropping system on the Loess Plateau, China, where rainfall is limited and evaporation intense, an apple–soybean intercropping system with micro-irrigation water control was adopted to analyze the soil water, root density, water-use efficiency, yield, and economic benefits of intercropping under different micro-irrigation methods. Subsurface seepage irrigation, bubbler irrigation, and drip irrigation under mulching were used with irrigation upper limit levels of three maximum irrigation levels [60% (W1), 75% (W2), and 90% (W3) of field capacity (FC)]. Rainwater harvesting from ridges and furrows (GL) without irrigation was the control. Bubbler irrigation increased the soil water content, optimized the vertical soil water distribution, and promoted root growth. Except for the control treatment (GL), the other micro-irrigation treatments increased with the irrigation amount, but the water-use efficiency decreased. Drip irrigation under mulch combined with W2 (75% Fc) irrigation could obtain the maximum intercropping yield, which was increased by 71.1% compared with the GL treatment. Drip irrigation under a mulch combined with W2 produced the maximum intercropping yield; the economic benefits were higher under drip irrigation with mulching combined with W1; and all three micro-irrigation methods combined with W2 improved the economic benefits by 52.1–115.5% compared to GL. Drip irrigation under mulching or bubbler irrigation combined with W2 should be used when there are sufficient water resources, but drip irrigation under a mulch combined with W1 when there is a water shortage.

Abstract Background Ovarian cancer typically is diagnosed late because insensitivity and lack of specificity of current biomarkers prior to its clinical detection. Ribosomal protein S6 (RPS6) is a ribosomal protein involved in the ribosomal 40S subunit, but its biological role in epithelial ovarian cancer (EOC) is still unknown. Results RPS6 was elevated in EOC compared to normal ovarian tissues and adenomas. Higher expression of RPS6 predicted worse prognosis in EOC. The level of RPS6 was correlated with clinical stage, histological type and pathological grade. Knockdown of RPS6 reduced the proliferation of ovarian cancer cell lines SKOV-3 and HO8910, and inhibit the migration and invasion ability. It revealed that cells arrested at G0G1 phase after knockdown of RPS6, and the expressions of CyclinD1, Cyclin E, CDK2, CDK4, CDK6 and pRb were also reduced. Conclusions RPS6 is involved in EOC and knockdown of RPS6 could inhibit the proliferation, invasion and migration ability of EOC in vitro by inducing G0/G1 phase arrest. RPS6 is expected to be a novel biomarker and molecular target to the EOC.

Based on three-dimensional seismic interpretation, structural and sedimentary feature analysis, and examination of fluid properties and production dynamics, the regularity and main controlling factors of hydrocarbon accumulation in the Tazhong uplift, Tarim Basin are investigated. The results show that the oil and gas in the Tazhong uplift has the characteristics of complex accumulation mainly controlled by faults, and more than 80% of the oil and gas reserves are enriched along fault zones. There are large thrust and strike-slip faults in the Tazhong uplift, and the coupling relationship between the formation and evolution of the faults and accumulation determine the difference in complex oil and gas accumulations. The active scale and stage of faults determine the fullness of the traps and the balance of the phase, that is, the blocking of the transport system, the insufficient filling of oil and gas, and the unsteady state of fluid accumulation are dependent on the faults. The multi-period tectonic sedimentary evolution controls the differences of trap conditions in the fault zones, and the multi-phase hydrocarbon migration and accumulation causes the differences of fluid distribution in the fault zones. The theory of differential oil and gas accumulation controlled by fault is the key to the overall evaluation, three-dimensional development and discovery of new reserves in the Tazhong uplift. Key words: Tarim Basin, Tazhong uplift, fault zone, complex oil and gas accumulation, oil and gas distribution, difference, main controlling factor

Background/purpose: The aim of this study was to evaluate the efficacy and safety of Tripterygium Wilfordii Hook F (TWHF) in DN patients with overt proteinuria and normal eGFR. Methods: 124 eligible DN patients were randomly assigned into two groups to receive either valsartan 160 mg/d treatment (control group) or TWHF 60 mg/d plus valsartan 160 mg/d treatments (TWHF group) for 24 weeks. The changes of clinical, biochemical data and adverse events during observation period were all analyzed. The primary endpoint was a reduction in 24-h urine protein excretion between baseline and the end of study, the secondary endpoint was to observe the change in estimated glomerular filtration rate (eGFR) between two groups. Results: After treatment, there was a more significant decrease in proteinuria in patients who received TWHF treatment (from 4.95 ± 1.27 g/24 h to 3.36 ± 0.83 g/24 h) compared to valsartan monotherapy (from 5.21 ± 1.59 g/24 h to 4.52 ± 1.06 g/24 h). The percentage change in urine protein excretion was −32.12% in TWHF group and −13.24% in valsartan group. Patients’ plasma albumin in TWHF group (from 32.53 ± 5.24 g/L to 36.91 ± 4.42 g/L) was higher than that in control group (from 33.18 ± 4.87 g/L to 34.67 ± 4.75 g/L). No significant change in blood pressure, blood glucose, eGFR, and serum potassium was observed. But the adverse events in TWHF group were higher than those in control group. Conclusion: TWHF is more effective than valsartan monotherapy in reduction of proteinuria in DN patients with overt proteinuria and normal eGFR, but with more adverse effects. Keywords: Diabetes mellitus, Diabetic nephropathy, Tripterygium wilfordii hook F, Valsartan

The packet loss during transmission of load control commands can lead to regulation errors in the smart grid and increase the cost of utility agencies due to the purchase of additional automatic generation control (AGC) services. In this paper, a two-layer cooperative communication network between the utility company and relays is presented. The utility company rents the relay to assist with the downlink transmission to improve the reliability of communication and reduce the data transmission cost due to packet loss. Furthermore, the uncertainty of channel gain is considered, and a two-tier game model is established. A distributed robust power control algorithm based on the continuous convex approximation method is proposed to obtain the optimal relay power allocation and price. Through the simulation analysis of the proposed scheme and the two comparison schemes, the cost of the utility company was reduced by 6% and 21%, and the standard deviation of income value between the relays was reduced by 40% and 48%, respectively.

In this study, a typical apple–soybean intercropping system was used to analyze the effects of different soil water and heat regulation modes on the spatial distribution of the soil water content (SWC), photosynthetic physiological characteristics, and growth. Three maximum irrigation levels [50% (W1), 65% (W2), and 80% (W3) of field capacity (FC)] and two mulching intervals [from seedling to podding stage (M1) and during the full stage (M2) of soybeans] were tested. The results showed that the SWC of W3M2 was the highest, while the W2M1 and W1M2 treatments used more deep soil water. Irrigation increased the chlorophyll content, net photosynthesis, and transpiration rate of leaves in the agroforestry system. In addition, the net photosynthetic rate of leaves under the W2 irrigation level increased after mulch removal in the later growth stage. At W1 and W2 irrigation levels, the soybean yield of half-stage mulching was 0.85–15.49% higher than that of full-stage mulching. Multiple regression analysis showed that grain yield under the W3M2 treatment reached the maximum value of the fitting equation. The photosynthetic rate, water use efficiency, and grain yield under W2M1 reached 71–86% of the maximum value of the fitting equation, with the largest soil plant analysis development value. To effectively alleviate water competition in the apple–soybean intercropping system, our results suggest adoption of the 80% FC upper irrigation limit (W3) combined with soybean M2 treatment in young apple trees–soybean intercropping system during water abundant years. In addition, adoption of the 65% FC upper irrigation limit (W2) combined with the soybean M1 treatment in water deficit years could effectively improve soil water, heat environment, and promote growth.

BackgroundOf gynecologic malignancies, ovarian cancer is the leading cause of death, mainly due to the lack of sensitive tumor markers, which means it almost always presents at an advanced stage. Exosome Component 4 (EXOSC4) is involved in RNA degradation, but its role in epithelial ovarian cancer (EOC) is unclear.MethodsThe expression levels of EXOSC4 in EOC and normal ovarian tissue specimens were determined by immunohistochemical staining. The overall survival (OS) and progression-free survival (PFS) of patients with EOC were evaluated after patients were classified into high and low EXOSC4 expression groups, and the Cox regression model was established to identify independent predictors of patient prognosis. The effects of EXOSC4 on proliferation, colony formation, migration, and invasion were examined in the SKOV-3 and HO8910 cell lines by lentivirus-mediated shRNA knockdown. Flow cytometry was used to detect cell cycle changes. The mRNA levels of cyclin D1, CDK4, and c-myc were detected by RT-PCR. The protein expression levels of β-catenin, cyclin D1, CDK4, c-myc, vimentin, N-cadherin, and E-cadherin were assessed by western blot. Wnt/β-catenin activation was measured by TCF/LEF reporter assay.ResultsEXOSC4 was significantly elevated in EOC tissues and cell lines. High EXOSC4 expression was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and pathological grade, and identified as an independent predictor of shorter OS and PFS. EXOSC4 knockdown suppressed proliferation, migration, and invasion in EOC cell lines. Cells were arrested at G0/G1 phase after EXOSC4 knockdown. The mRNA levels of cyclin D1, CDK4, and c-myc were decreased. β-catenin, cyclin D1, CDK4, c-myc, vimentin, and N-cadherin protein expression levels were reduced, while those of E-cadherin was increased. Wnt/β-catenin activity was suppressed after the EXOSC4 knockdown.ConclusionsEXOSC4 is involved in EOC. Knockdown of EXOSC4 can inhibit the proliferation, migration, and invasion ability of EOC by suppressing the Wnt pathway. EXOSC4 is expected to be a novel biomarker and molecular target in EOC.

Background/Purpose: Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP. Methods: A phase 3, multicenter, randomized (2:1) controlled trial was conducted in adult CAP patients receiving nemonoxacin 500 mg or levofloxacin 500 mg orally once daily for 7–10 days. Clinical, microbiological response and adverse events were assessed. Non-inferiority was determined in terms of clinical cure rate of nemonoxacin compared with that of levofloxacin in a modified intention-to-treat (mITT) population. NCT registration number: NCT01529476. Results: A total of 527 patients were randomized and treated with nemonoxacin (n = 356) or levofloxacin (n = 171). The clinical cure rate at test-of-cure visit was 94.3% (300/318) for nemonoxacin and 93.5% (143/153) for levofloxacin in the mITT population [difference (95% CI), 0.9% (−3.8%, 5.5%)]. The microbiological success rate was 92.1% (105/114) for nemonoxacin and 91.7% (55/60) for levofloxacin in the bacteriological mITT population [difference (95% CI), 0.4% (−8.1%, 9.0%)]. The incidence of adverse events (AEs) was comparable between nemonoxacin (33.1%, 118/356) and levofloxacin (33.3%, 57/171) (P > 0.05). Conclusion: Nemonoxacin 500 mg once daily for 7–10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile.ClinicalTrials.gov identifier: NCT01529476. Keywords: Clinical outcome, Community-acquired pneumonia, Levofloxacin, Nemonoxacin, Randomized controlled trial, Safety

Background: Cesarean scar pregnancy (CSP) involves a rare form of placental attachment that often leads to life-threatening conditions. The best treatment for CSP has been debated for decades. We aimed to evaluate the different treatments for CSP and analyzed the risk factors for intraoperative hemorrhage.Methods: CSP patients treated at the Affiliated Hospital of Jiangnan University were reviewed retrospectively from January 2014 to 2020. CSP was classified into three types based on the location and shape of gestational tissue, blood flow features, and thickness of the myometrium at the incision site. The clinical characteristics, types, approaches of treatment, and clinical outcomes of CSP were analyzed.Results: A total of 55 patients were included in this study, 29 (52.7%) of whom underwent transvaginal curettage after uterine artery embolization (UAE) and 22 (40%) of whom underwent transabdominal ultrasound-guided hysteroscopic curettage (USHC) in type I and II. Four patients (7.3%) classified as type III underwent laparoscopic cesarean scar resection (LCSR). Intraoperative blood loss, blood transfusion rate, and scar diverticulum were significantly higher in type II than in type I (P < 0.05). Even though USHC showed no differences in intraoperative blood loss, length of stay, and scar diverticulum compared with curettage after UAE (P > 0.05), superiority was found in surgical time and hospitalization cost (P < 0.05). Furthermore, the type of CSP (OR = 10.53, 95% CI: 1.69–65.57; P = 0.012) and diameter of the gestational sac (OR = 25.76, 95% CI: 2.67–248.20; P = 0.005) were found to be risk factors for intraoperative hemorrhage.Conclusions: Transabdominal ultrasound-guided hysteroscopic curettage is an effective and relatively safe treatment option for patients with CSP. Type of CSP and diameter of the gestational sac were found to be associated with excessive intraoperative hemorrhage.

BackgroundParavertebral block (PVB) is the most recognized regional anesthesia technique after thoracic epidural anesthesia for postoperative analgesia in thoracic and breast surgery. Erector spinae plane block (ESPB) is a recently discovered blocking technique, and it has evidenced excellent postoperative analgesia for breast and thoracic surgery with fewer adverse reactions. However, there are controversies about the postoperative analgesic effects of the two analgesic techniques.ObjectiveTo assess the analgesic effects of PVB versus ESPB in postoperative thoracic and breast surgery.MethodsWe systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to April 5, 2021. The primary outcome was postoperative pain scores. Secondary outcomes included: opioid consumption, additional analgesia, postoperative nausea and vomiting (PONV) 24 hours post-operation, and the time required for completing block procedure. This study was registered in PROSPERO, number CRD42021246160.ResultsAfter screening relevant, full-text articles, ten randomized controlled trials (RCTs) that met the inclusion criteria were retrieved for this meta-analysis. Six studies involved thoracic surgery patients, and four included breast surgery patients. Thoracic surgery studies included all of the outcomes involved in this meta-analysis while breast surgery did not report pain scores at movement and additional analgesia in 24 hours post-operation. For thoracic surgery, PVB resulted in significant reduction in the following pain scores: 0-1 hours (MD = -0.79, 95% CI: -1.54 to -0.03, P = 0.04), 4-6 hours (MD = -0.31, 95% CI: -0.57 to -0.05, P = 0.02), and 24 hours (MD = -0.42, 95% CI: -0.81 to -0.02, P = 0.04) at rest; significant reduction in pain scores at 4-6 hours (MD = -0.47, 95% CI: -0.93 to -0.01, P = 0.04), 8-12 hours (MD = -1.09, 95% CI: -2.13 to -0.04, P = 0.04), and 24 hours (MD = -0.31, 95% CI: -0.57 to -0.06, P = 0.01) at movement. Moreover, the opioid consumption at 24 hours post-operation (MD = -2.74, 95% CI: -5.41 to -0.07, P = 0.04) and the incidence of additional analgesia in 24 hours of the postoperative course (RR: 0.53, 95% CI: 0.29 to 0.97, P = 0.04) were significantly lower in the PVB group than in the ESPB group for thoracic surgery. However, no significant differences were found in pain scores at rest at various time points postoperatively, and opioid consumption at 24 hours post-operation for breast surgery. The time required for completing block procedure was longer in the PVB group than in the ESPB group for thoracic and breast surgery, and the incidence of PONV between the two groups showed no significant difference.ConclusionThe postoperative analgesic effects of PVB versus ESPB are distinguished by the surgical site. For thoracic surgery, the postoperative analgesic effect of PVB is better than that of ESPB. For breast surgery, the postoperative analgesic effects of PVB and ESPB are similar.

X-ray sources based on pulsed electron accelerators stimulate the development of bremsstrahlung converter designs. The numerical optimization of transmission-type X-ray targets for maximum X-ray output by pulsed electron beams was carried out in the present work. The targets featured a combination of a heavy element (tungsten or molybdenum) X-ray conversion layer and a titanium membrane that served as the vacuum window, thermal shielding for converter heat, and an electron dump. The energy spectrum of the electron beam generated via explosive emission was analyzed via the space-charge effect, and was utilized for the source sampling algorithm for electron transportation simulation with a Monte Carlo method for X-ray emission analysis. It was revealed that the transmission photon intensity of a mono-material target is primarily affected by the thickness of the target, and there exists an optimal target thickness within which the photon fluence is restricted by insufficient electron stopping; when exceeded, the extra thickness of the X-ray converter target imposes absorption and attenuates the generated X-ray. Analysis on dual-layer targets proved that this optimized converter target thickness, combined with a proper titanium window, produces the highest X-ray photon emissions.

Modeling the relationship between precipitation and water level is of great significance in the prevention of flood disaster. In recent years, the use of machine learning algorithms for precipitation–water level prediction has attracted wide attention in flood forecasting and other fields; however, a clear method to model the relationship of precipitation and water level using grid precipitation products with a neural network model is lacking. The issues of the method include how to select a neural network model, as well as how to influence the modeling results with different types and resolutions of remote sensing data. The purpose of this paper is to provide some findings for the issues. We used the back-propagation (BP) neural network and a nonlinear autoregressive exogenous model (NARX) time series network to model the relationship between precipitation and water level, respectively. The water level of Pingshan hydrographic station at a catchment area in the Jinsha River Basin was simulated by the two network models using three different grid precipitation products. The results showed that when the ground station data are missing, the grid precipitation product is a good alternative to construct the precipitation–water level relationship. In addition, using the NARX network as a model fitting network using extra inputs was better than using the BP neural network; the Nash efficiency coefficients of the former were all higher than 97%, while the latter were all lower than 94%. Furthermore, the input of grid products with different spatial resolutions has little significant effect on the modeling results of the model.

Abstract Background The major dose-limiting toxicity of paclitaxel, one of the most commonly used drugs to treat solid tumor, is painful neuropathy. However, the molecular mechanisms underlying paclitaxel-induced painful neuropathy are largely unclarified. Methods Paw withdrawal threshold was measured in the rats following intraperitoneal injection of paclitaxel. The qPCR, western blotting, protein or chromatin immunoprecipitation, ChIP-seq identification of NFATc2 binding sites, and microarray analysis were performed to explore the molecular mechanism. Results We found that paclitaxel treatment increased the nuclear expression of NFATc2 in the spinal dorsal horn, and knockdown of NFATc2 with NFATc2 siRNA significantly attenuated the mechanical allodynia induced by paclitaxel. Further binding site analysis utilizing ChIP-seq assay combining with gene expression profile revealed a shift of NFATc2 binding site closer to TTS of target genes in dorsal horn after paclitaxel treatment. We further found that NFATc2 occupancy may directly upregulate the chemokine CXCL14 expression in dorsal horn, which was mediated by enhanced interaction between NFATc2 and p300 and consequently increased acetylation of histone H4 in CXCL14 promoter region. Also, knockdown of CXCL14 in dorsal horn significantly attenuated mechanical allodynia induced by paclitaxel. Conclusion These results suggested that enhanced interaction between p300 and NFATc2 mediated the epigenetic upregulation of CXCL14 in the spinal dorsal horn, which contributed to the chemotherapeutic paclitaxel-induced chronic pain.

Abstract Background Cyclosporin A (CsA) is a promising therapeutic drug for myocardial ischemia reperfusion injury (MI/RI) because of its definite inhibition to the opening of mitochondrial permeability transition pore (mPTP). However, the application of cyclosporin A to treat MI/RI is limited due to its immunosuppressive effect to other normal organ and tissues. SS31 represents a novel mitochondria-targeted peptide which can guide drug to accumulate into mitochondria. In this paper, mitochondria-targeted nanoparticles (CsA@PLGA-PEG-SS31) were prepared to precisely deliver cyclosporin A into mitochondria of ischemic cardiomyocytes to treat MI/RI. Results CsA@PLGA-PEG-SS31 was prepared by nanoprecipitation. CsA@PLGA-PEG-SS31 showed small particle size (~ 50 nm) and positive charge due to the modification of SS31 on the surface of nanoparticles. CsA@PLGA-PEG-SS31 was stable for more than 30 days and displayed a biphasic drug release pattern. The in vitro results showed that the intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced in hypoxia reoxygenation (H/R) injured H9c2 cells. CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species. In vivo results showed that CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium of MI/RI rat heart. Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function. Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats. Conclusion CsA@PLGA-PEG-SS31 exhibited significant cardioprotective effects against MI/RI in rats hearts through protecting mitochondrial integrity, decreasing apoptosis of cardiomyocytes and myocardial infract area. Thus, CsA@PLGA-PEG-SS31 offered a promising therapeutic method for patients with acute myocardial infarction.