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Chronic cancer pain is very common symptom in cancer patients, but this issue has not been satisfactorily resolved by the conventional three-step analgesic therapy. There are multiple non-pharmacological interventions for managing chronic cancer pain, but we haven't reached a consensus on which non pharmacological treatment is the best and these treatments are lack of high-quality evidence. In order to identify the most effective non-pharmaceutical therapy alternatives and investigate further possible medication interventions, this study will use network meta-analysis to assess the therapeutic effects of pharmacological and non-pharmacological treatments on chronic cancer pain patients and support clinical decision-making by prioritizing therapies according to the most valuable clinical outcomes for these patients. We will carry out a systematic search of published randomized controlled trials (group, crossover, and parallel) in the PubMed, Web of Science, Cochrane Library, MEDLINE, Embase, and CINAHL databases, without language or date restrictions, in accordance with the PRISMA for Network Meta-Analyses (PRISMA-NMA) guidelines. Included studies must evaluate the effects of pharmacological and non-pharmacological treatments in patients with chronic cancer pain. Adult chronic cancer pain patients (≥ 18 years old) receiving pharmacological or non-pharmacological treatment will be our target participants. Our primary outcomes will be pain intensity, total effective rate of treatment, onset time, and quality of Life (QoL); Adverse reaction will be our secondary outcome. We'll utilize the mean difference (MD) for continuous variables, the odds ratio (OR) for binary variables, and the 95% confidence interval (CI) for interval estimates. The Cochrane Bias Risk Tool (RoB2.0) will be used to assess the bias risk of every RCT trial included in NMA. We will use Review Manager 5.3 software to conduct heterogeneity testing and meta-analysis. The network meta-analysis will be performed by ADDIS1.16.8 software. The Confidence in Network Meta-analysis (CINeMA) framework will be used to evaluate the level of confidence in the NMA results. Besides, we will use SUCRA for ranking the network meta-analysis results, and we will also apply normalized entropy to verify the accuracy of the SUCRA ranking outcomes. This network meta-analysis will compare the efficacy of pharmacological versus non-pharmacological treatments for pain intensity in chronic cancer pain patients. The final analysis results may be significantly heterogeneous, because the population with cancerous pain suffers from different types of cancers. Owing to the databases primary reliance on our listed databases for inclusion, potentially valuable research will be overlooked. This study has been registered in the PROSPERO database (CRD42024505214).

In a modern power system, reducing carbon emissions has become a significant goal in mitigating the impact of global warming. Therefore, renewable energy sources, particularly wind-power generation, have been extensively implemented in the system. Despite the advantages of wind power, its uncertainty and randomness lead to critical security, stability, and economic issues in the power system. Recently, multi-microgrid systems (MMGSs) have been considered as a suitable wind-power deployment candidate. Although wind power can be efficiently utilized by MMGSs, uncertainty and randomness still have a significant impact on the dispatching and operation of the system. Therefore, to address the wind power uncertainty issue and achieve an optimal dispatching strategy for MMGSs, this paper presents an adjustable robust optimization (ARO) model based on meteorological clustering. Firstly, the maximum relevance minimum redundancy (MRMR) method and the CURE clustering algorithm are employed for meteorological classification in order to better identify wind patterns. Secondly, a conditional generative adversarial network (CGAN) is adopted to enrich the wind-power datasets with different meteorological patterns, resulting in the construction of ambiguity sets. Thirdly, the uncertainty sets that are finally employed by the ARO framework to establish a two-stage cooperative dispatching model for MMGS can be derived from the ambiguity sets. Additionally, stepped carbon trading is introduced to control the carbon emissions of MMGSs. Finally, the alternative direction method of multipliers (ADMM) and the column and constraint generation (C&CG) algorithm are adopted to achieve a decentralized solution for the dispatching model of MMGSs. Case studies indicate that the presented model has a great performance in improving the wind-power description accuracy, increasing cost efficiency, and reducing system carbon emissions. However, the case studies also report that the approach consumes a relative long running time. Therefore, in future research, the solution algorithm will be further improved for the purpose of raising the efficiency of the solution.

Myocardial injury triggers intense oxidative stress, inflammatory response, and cytokine release, which are essential for myocardial repair and remodeling. Excess reactive oxygen species (ROS) scavenging and inflammation elimination have long been considered to reverse myocardial injuries. However, the efficacy of traditional treatments (antioxidant, anti-inflammatory drugs and natural enzymes) is still poor due to their intrinsic defects such as unfavorable pharmacokinetics and bioavailability, low biological stability, and potential side effects. Nanozyme represents a candidate to effectively modulate redox homeostasis for the treatment of ROS related inflammation diseases. We develop an integrated bimetallic nanozyme derived from metal-organic framework (MOF) to eliminate ROS and alleviate inflammation. The bimetallic nanozyme (Cu-TCPP-Mn) is synthesized by embedding manganese and copper into the porphyrin followed by sonication, which could mimic the cascade activities of superoxide dismutase (SOD) and catalase (CAT) to transform oxygen radicals to hydrogen peroxide, followed by the catalysis of hydrogen peroxide into oxygen and water. Enzyme kinetic analysis and oxygen-production velocities analysis were performed to evaluate the enzymatic activities of Cu-TCPP-Mn. We also established myocardial infarction (MI) and myocardial ischemia-reperfusion (I/R) injury animal models to verify the ROS scavenging and anti-inflammation effect of Cu-TCPP-Mn. As demonstrated by kinetic analysis and oxygen-production velocities analysis, Cu-TCPP-Mn nanozyme possesses good performance in both SOD- and CAT-like activities to achieve synergistic ROS scavenging effect and provide protection for myocardial injury. In both MI and I/R injury animal models, this bimetallic nanozyme represents a promising and reliable technology to protect the heart tissue from oxidative stress and inflammation-induced injury, and enables the myocardial function to recover from otherwise severe damage. This research provides a facile and applicable method to develop a bimetallic MOF nanozyme, which represents a promising alternative to the treatment of myocardial injuries.

‘Yuluxiang’ pear ( Pyrus sinkiangensis ) commonly develop a greasy coating and yellowing during storage. In this study, 1.0 μL L –1 1-methylcyclopropene (1-MCP) was applied to ‘Yuluxiang’ pear to investigate its effects on fruit quality, peel wax composition, greasiness index, chlorophyll content, and the expression pattern of related genes during storage at ambient temperature (25°C). The results showed that 1-MCP treatment maintained higher fruit firmness and chlorophyll content, decreased respiration rate, and postponed the peak of ethylene production rate, lowered the greasy index of the peel. The main wax components of peel accumulated during storage, the principal ones being alkenes (C23, C25, and C29), fatty acids (C16, C18:1, and C28), aldehydes (C24:1, C26:1, and C28:1), and esters (C22:1 fatty alcohol-C16 fatty acid, C22:1 fatty alcohol-C18:1 fatty acid, C22 fatty alcohol-C16 fatty acid, C22 fatty alcohol-C18:1 fatty acid, C24:1 fatty alcohol-C18:1 fatty acid, and C24 fatty alcohol-C18:1 fatty acid), and were reduced by 1-MCP. 1-MCP also decreased the expression of genes associated with ethylene biosynthesis and signal transduction ( ACS1 , ACO1 , ERS1 , ETR2 , and ERF1 ), chlorophyll breakdown ( NYC1 , NOL , PAO , PPH , and SGR ), and wax accumulation ( LACS1 , LACS6 , KCS1 , KCS2 , KCS4 , KCS10L , KCS11L , KCS20 , FDH , CER10 , KCR1 , ABCG11L , ABCG12 , ABCG21L , LTPG1 , LTP4 , CAC3 , CAC3L , and DGAT1L ). There were close relationships among wax components (alkanes, alkenes, fatty acids, esters, and aldehydes), chlorophyll content, greasiness index, and level of expression of genes associated with wax synthesis and chlorophyll breakdown. These results suggest that 1-MCP treatment decreased the wax content of ‘Yuluxiang’ pear and delayed the development of peel greasiness and yellowing by inhibiting the expression of genes related to the ethylene synthesis, signal transduction, wax synthesis, and chlorophyll degradation.

Arctigenin (ATG) is a major component of Fructus Arctii , a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically provides renoprotection in DKD is not known. Here we report that ATG administration is sufficient to attenuate proteinuria and podocyte injury in mouse models of diabetes. Transcriptomic analysis of diabetic mouse glomeruli showed that cell adhesion and inflammation are two key pathways affected by ATG treatment, and mass spectrometry analysis identified protein phosphatase 2 A (PP2A) as one of the top ATG-interacting proteins in renal cells. Enhanced PP2A activity by ATG reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results demonstrate a renoprotective mechanism of ATG via PP2A activation and establish PP2A as a potential target for DKD progression. Arctigenin (ATG) is the major active component of a Chinese herbal remedy known to reduce proteinuria in patients with diabetic kidney disease (DKD). Here, Zhong et al. identify PP2A as a pharmacological target of ATG in podocytes, and find that PP2A is responsible for some of the beneficial effects of ATG in mouse models of DKD.

Background Flesh is prone to accumulate more anthocyanin in postharvest ‘Friar’ plum ( Prunus salicina Lindl.) fruit stored at an intermediate temperature. However, little is known about the molecular mechanism of anthocyanin accumulation regulated by storage temperature in postharvest plum fruit. Results To reveal the potential molecular regulation mechanism of anthocyanin accumulation in postharvest ‘Friar’ plum fruit stored at different temperatures (0 °C, 10 °C and 25 °C), the fruit quality, metabolite profile and transcriptome of its flesh were investigated. Compared to the plum fruit stored at 0 °C and 25 °C, the fruit stored at 10 °C showed lower fruit firmness after 14 days and reduced the soluble solids content after 21 days of storage. The metabolite analysis indicated that the fruit stored at 10 °C had higher contents of anthocyanins (pelargonidin-3-O-glucoside, cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside and quercetin-3-O-rutinose), quercetin and sucrose in the flesh. According to the results of weighted gene coexpression correlation network analysis (WGCNA), the turquoise module was positively correlated with the content of anthocyanin components, and flavanone 3-hydroxylase ( F3H ) and chalcone synthase ( CHS ) were considered hub genes. Moreover, MYB family transcription factor APL ( APL ), MYB10 transcription factor ( MYB10 ), ethylene-responsive transcription factor WIN1 ( WIN1 ), basic leucine zipper 43-like ( bZIP43 ) and transcription factor bHLH111-like isoform X2 ( bHLH111 ) were closely related to these hub genes. Further qRT–PCR analysis verified that these transcription factors were specifically more highly expressed in plum flesh stored at 10 °C, and their expression profiles were significantly positively correlated with the structural genes of anthocyanin synthesis as well as the content of anthocyanin components. In addition, the sucrose biosynthesis-associated gene sucrose synthase ( SS ) was upregulated at 10 °C, which was also closely related to the anthocyanin content of plum fruit stored at 10 °C. Conclusions The present results suggest that the transcription factors APL, MYB10, WIN1, bZIP43 and bHLH111 may participate in the accumulation of anthocyanin in ‘Friar’ plum flesh during intermediate storage temperatures by regulating the expression of anthocyanin biosynthetic structural genes. In addition, the SS gene may play a role in anthocyanin accumulation in plum flesh by regulating sucrose biosynthesis.

Metastatic colorectal cancer is commonly treated with oxaliplatin. However, patients may develop resistance to treatment over time, and currently, there are no validated predictive biomarkers for this resistance. A differential analysis of the transcriptome and DNA methylome of colorectal cancer cell lines, classified by their varying IC50 values for oxaliplatin, revealed that genes associated with resistance were enriched for interferon regulatory factor pathways. In contrast, sensitive genes showed enrichment for transcription, amino acid metabolism, development, and binding motifs of c-MyC:Max, AP1 and others. In univariate Cox’s proportional hazard model analysis, it was found that UBE2H expression is linked to shorter survival time in the TCGA dataset and was further validated across five GEO datasets of colorectal cancer. The transcription of UBE2H, along with its gene body methylation, and copy number variation was found to be higher in resistant cell lines compared to sensitive ones. Additionally, UBE2H levels were higher in cancer samples than in control samples, while the promoter methylation is lower in cancer samples than in control samples. In groups with high UBE2H, there was an increased infiltration of eight cell types, including CD8 + T cells and type 2 T helper cells. Conversely, only T helper 17 cells showed reduced infiltration. Moreover, UBE2H expression was positively correlated with checkpoint inhibitors, CTLA4 and PDCD1, along with immune regulatory genes, such as FOXP3, IL10, IGFB1, CD274, and LAG3, etc. Analysis of single cell RNA-sequencing data revealed that UBE2H expression is elevated in undifferentiated and proliferative cells located at the base of intestinal crypts in normal colon tissue. Our findings suggest that UBE2H could serve as a resistance marker to oxaliplatin, as it is associated with methylation, the presence of proliferative and undifferentiated cancer cells, and immune exhaustion. The proposed analytical pipeline may also be applicable to other cancers and diseases.

Estimated glomerular filtration rate (eGFR) is usually calculated based on serum creatinine (eGFR ) or cystatin C (eGFR ). This study aimed to investigate the association between cystatin C-creatinine eGFR discordance (ΔeGFR ) and new-onset hypertension and to assess the mediating role of triglyceride glucose (TyG) index based on the China Health and Retirement Longitudinal Study. The ΔeGFR was calculated by eGFR - eGFR . A Cox proportional risk model was used to assess the association between ΔeGFR and risk of new-onset hypertension. The mediating role of TyG was assessed using mediation analysis, and thresholds were obtained Receiver Operating Characteristic curve. A total of 4,644 participants (median age 59 years, 55.5% female) were finally included. During a mean follow-up period of 5.0 years, 613 new cases of hypertension occurred. Multivariable analysis showed that, individuals in negative-ΔeGFR group (< -15) had a 24% increase risk of hypertension (Hazard ratio [HR] = 1.24; 95% confidence interval [95% CI]: 0.99, 1.56), while positive-ΔeGFR group (≥15) had a 20% decrease risk of hypertension (HR = 0.80; 95% CI: 0.63, 1.02), compared with those in the reference group (-15 ≤ ΔeGFR < 15 mL/min/1.73 m ). In addition, each 15 mL/min/1.73m increase in ΔeGFR was associated with a 13.4% reduction in the risk of new-onset hypertension (HR= 0.87; 95% CI: 0.79, 0.95). TyG acted as a partial mediator, explaining 9.3% of the total effect. The present study demonstrates an association between ΔeGFR and the risk of new-onset hypertension and reveals the important mediating role of TyG in this association.

Purpose The aim of this study was to evaluate the effect of hydrofluoric acid (HF) etching duration on the shear bond strength between zirconia-enhanced lithium silicate (ZLS) and enamel. Methods Ninety-six extracted human third molars and premolars were used and randomly divided into six groups (n=16). The teeth were sectioned to produce specimens from the buccal and lingual surfaces, polished to achieve smooth bonding areas of 3×3 mm. The ceramic materials used (Celtra Duo, IPS e.max Press) were prepared into 3×3×3 mm blocks, with surfaces treated with or without 4.9% HF for varying durations. Representative specimens from each group were analyzed using field-emission scanning electron microscopy (SEM) to assess etching-induced surface morphology. Silane coupling agent and luting resin (RelyX TM Veneer) were then applied to bond the ceramics to the enamel, forming the bonding specimens. These specimens were stored in distilled water at 37°C for either 24 hours or 6 months before shear bond strength testing, which was conducted using a universal testing machine at a crosshead speed of 1.0 mm/min. Failure modes were evaluated under a stereomicroscope. Data were analyzed using two-way ANOVA and Post hoc Tukey tests test (α=.05) as well as Weibull distributions. Results As etching time increases, the dissolution of ceramic components on the ZLS surface also rises. After 24 hours or 6 months of storage in water at 37°C, the shear bond strength of ZLS etched with 4.9% HF for 40 seconds was significantly greater than that of Lithium disilicate (LS 2 ) etched with 4.9% HF for 20 seconds ( P <.05), accompanied by a higher Weibull modulus. Aging resulted in a reduction of bond strength across all groups, approximately 20%, alongside lower characteristic strength, and a higher incidence of adhesive failures at the bonding interface. Conclusion HF etching duration has a significant effect on the surface morphology of ZLS and the shear bond strength with enamel. ZLS etched with 4.9% HF for 40 seconds demonstrated the highest shear bond strength, highlighting the importance of optimal etching time for enhancing bonding performance.