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Rheumatoid arthritis (RA) is an inflammatory disease accompanied by abnormal synovial microenvironment (SM). Sesquiterpene lactones (SLs) are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment. α-Methylene-γ-butyrolactone (α-M-γ-B) is a core moiety that widely exists in natural SLs. This study was designed to investigate the anti-arthritic potential of α-M-γ-B as an independent small molecule in vitro and in vivo. α-M-γ-B exhibited stronger electrophilicity and anti-inflammatory effects than the other six analogs. α-M-γ-B inhibited the production of pro-inflammatory mediators via repolarizing M1 macrophages into M2 macrophages. The transcriptome sequencing suggested that α-M-γ-B regulated the immune system pathway. Consistently, α-M-γ-B attenuated collagen type II-induced arthritic (CIA) phenotype, restored the balance of Tregs-macrophages and remodeled SM via repolarizing the synovial-associated macrophages in CIA mice. Mechanistically, although α-M-γ-B did not prevent the trans-nucleus of NF-κB it interfered with the DNA binding activity of NF-κB via direct interaction with the sulfhydryl in cysteine residue of NF-κB p65, which blocked the activation of NF-κB. Inhibition of NF-κB reduced the M1 polarization of macrophage and suppressed the synovial hyperplasia and angiogenesis. α-M-γ-B failed to ameliorate CIA in the presence of N-acetylcysteine or when the mice were subjected to the macrophage-specific deficiency of Rela. In conclusion, α-M-γ-B significantly attenuated the CIA phenotype by directly targeting NF-κB p65 and inhibiting its DNA binding ability. These results suggest that α-M-γ-B has the potential to serve as an alternative candidate for treating RA. The greater electrophilicity of α-M-γ-B, the basis for triggering strong anti-inflammatory activity, accounts for the reason why α-M-γ-B is evolutionarily conserved in the SLs by medical plants.

It is known that load forecasting plays an important role for the smart grids and mostly, the users have the combinational load forecast demands with different time-scales. However, due to various internal or external factors, such as poor management, the available load data set is limited. Therefore, the problem becomes as the high-precision combinational load forecast at different time-scales but with limited valid datasets. In this paper, taking the work in a city power company of China as an example, an empirical study for this problem is considered and then a robust forecasting system is built. The forecasting models are designed and screened and then constructed a model library for the system. In order to improve the robustness of the designed system, a mean absolute percentage error (MAPE) based dynamic model selection method is proposed and finally the performance of the system is verified on the State Grid Chongqing Company of China. The results indicate that our designed multi-temporal-spatial-scales load forecast system can dynamically select the best model for different demands, which demonstrates that the build system is an effective and reliable system-level solution. In particular, for the annual based load forecast, 80% of the industries in the considered city have a MAPE less than 5%, while the MAPE of the whole city is less than 2.160%; for the monthly based load forecast, 87% of the industries in the considered city have a MAPE less than 10%, while the MAPE for the whole city is less than 3.755%. In addition, for the annual based forecast, GM(1,1) is mostly used for the industry-based forecasts, but the model with the highest average forecast accuracy is LR-ER. While for region-based forecasts, the mostly selected models are GM(1,n) and AR. For the monthly based forecast, GM(1,1)-SI and FOA-HW have a higher average accuracy than other models for both industries- and region-based forecasts, respectively.

The Al–Zn–Mg–Cu 7055 aluminum alloy was meticulously fabricated through spray forming (SF) technology, followed by hot extrusion and T76 treatment. This comprehensive process allowed for a thorough investigation of its microstructural characteristics, mechanical properties, and fatigue behavior. Post-treatment analysis revealed that the SF-7055 aluminum alloy exhibited no notable segregation or porosity defects, ensuring its exceptional quality and reliability. The microstructural analysis revealed a uniform distribution of refined grains and dispersed precipitates, contributing to the material's strength. Mechanical testing demonstrated that the hot extruded SF-7055 aluminum alloy exhibits superior tensile strength and elongation, with significant anisotropy in mechanical properties favoring the extrusion direction (ED) over the transverse direction (TD). Fatigue testing under varying cyclic stresses revealed an extended fatigue life in the ED-oriented specimens, attributed to the texture-induced resistance to crack initiation and propagation. The study underscores the effectiveness of SF and hot extrusion in enhancing the SF-7055 aluminum alloy's performance, making it a viable candidate for critical aerospace applications. The findings provide valuable insights into the relationship between processing, microstructure, and properties, offering a pathway to the design and fabrication of high-performance aluminum alloys.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

Summary: Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids.For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the outbreak of COVID-19 in Wuhan, China. As a highly infectious epidemic, SARS-CoV-2 rapidly evolves. Presently, COVID-19 coexists with humans, mainly with mild or moderate disease. The latest Guidelines for the Diagnosis and Treatment of COVID-19 (trial version of the 10th Edition) recommend several oral traditional Chinese medicines (TCMs) for treatment. This study aims to evaluate the evidence-based benefits of these TCMs as adjunctive therapies to conventional western medicine (CWM) for patients with mild or moderate COVID-19. Methods: We conducted a systematic review and meta-analysis adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing the PRISMA checklist. We searched PubMed, Cochrane Library, Embase, CNKI, and Wan-Fang databases to retrieve randomized controlled trials and retrospective cohort studies of TCM in combination with CWM on the treatment of mild or moderate COVID-19 that were published as of December 25, 2023. A network meta-analysis using the frequency model was employed to evaluate the benefits of different interventions. Results: A total of 30 eligible studies, enrolling 4144 participants, utilized 7 marketed oral TCMs in China. Compared with CWM alone, the integration of TCMs with CWM can significantly reduce severe conversion rate. This combined approach also enhances the clinical effective rate, shortens the negative conversion time of nucleic acid, and improves both symptoms and blood biochemical markers in patients. The network meta-analysis provided preliminary evidence of the superiority of specific TCMs for various outcomes: Qingfei Paidu for raising the CT improvement rate and clinical effective rate, and shortening the negative conversion time of nucleic acid; Huashi Baidu for reducing severe conversion and improving cough; Xuanfei Baidu for improving fatigue; Jinhua Qinggan for improving fever; Lianhua Qingwen for shortening the recovery time of fatigue and cough; and Shufeng Jiedu for shortening the recovery time of fever. Conclusions: TCM in combination with CWM may be beneficial for patients with mild or moderate COVID-19. Each TCM may have distinct benefits in COVID-19.

Objectives: Individuals diagnosed with schizophrenia have a high incidence and fatality rates due to pneumonia. Sarcopenia is a contributing factor to the development of pneumonia in patients with schizophrenia. In this study, we examine the effectiveness of three simple screening questionnaires, namely SARC-F, SARC-CalF, and SARC-F + EBM, in predicting the occurrence of pneumonia in stable patients with schizophrenia who are experiencing sarcopenia. Design: A prospective study. Setting: Patients with stable schizophrenia patients aged ≥50 years in two psychiatric hospitals in western China. Methods: Medical data from patients were collected from September 1 to September 30, 2020. Data specifically from patients diagnosed with pneumonia were collected for a period of one year, from October 2020 to October 2021. Three hundred thirty-five stable schizophrenia patients, among whom 229 were males (68.36 %.), were enrolled in the prospective study. The risk of sarcopenia was evaluated using the SARC-F, SARC-CalF, and SARC-F + EBM scores, with values of ≥4, 11, and 12 indicating an elevated risk of sarcopenia. The collected data were analyzed using logistic regression analysis to establish the association between the scores of these screening tools and the risk of pneumonia in individuals with stable schizophrenia. Results: The rate of pneumonia in stable schizophrenia individuals was 24.48 %. Among the included stable schizophrenia patients, the incidence of pneumonia in individuals with SARC-CalF scores ≥11 was higher than in those with SARC-CalF scores less than 11 (29.91 % vs 14.88 %, P = 0.002). In individuals with SARC-F + EBM scores ≥12, the pneumonia occurrence was higher than that in those with SARC-F + EBM scores less than 12 (37.33 % vs 20.77 %, P = 0.003). However, this pattern was not found in patients with stable schizophrenia who had SARC-F scores of 4 or above and less than 4. Following the implementation of logistic regression data analysis, it has been discovered that persons with SARC-CalF scores greater than or equal to 11 were at a significantly increased risk of having pneumonia compared to patients with SARC-CalF scores less than 11 (OR = 2.441, 95 % CI: 1.367–4.36). After adjusting the possible confounders, patients with SARC-CalF scores ≥11 had a greater danger of pneumonia (OR = 2.518, 95%CI: 1.36–4.665). As a result, it was found that individuals with SACR-F+EBM scores ≥12 were more likely to acquire pneumonia (OR = 2.273, 95%CI: 1.304–3.961) when compared to those with scores

The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis. We found here that PFOS caused NASH in mice, and lipid accumulation and inflammatory response in the L-02 cells. PFOS induced hepatic ferroptosis in vivo and in vitro, as evidenced by the decrease in glutathione peroxidase 4 (GPX4), and the increases in cytosolic iron, acyl-CoA synthetase long-chain family member 4 (ACSL4) and lipid peroxidation. In the PFOS-treated cells, the increases in the inflammatory factors and lipid contents were reversed by ferroptosis inhibitor. PFOS-induced ferroptosis was relieved by autophagy inhibitor. The expression of mitochondrial calcium uniporter (MCU) was accelerated by PFOS, leading to subsequent mitochondrial calcium accumulation, and inhibiting autophagy reversed the increase in MCU. Inhibiting mitochondrial calcium reversed the variations in GPX4 and cytosolic iron, without influencing the change in ACSL4, induced by PFOS. MCU interacted with ACSL4 and the siRNA against MCU reversed the changes in ACSL4，GPX4 and cytosolic iron systemically. This study put forward the involvement of hepatic ferroptosis in PFOS-induced NASH and identified MCU as the mediator of the autophagy-dependent ferroptosis.

Failure to obtain timely fire services will lead to thermal runaway phenomenon, which will seriously threaten the lives of people and property safety. In this study, a dynamic method was proposed to estimate fire service accessibility based on real-time traffic. To validate the method, a total of 110,055 POls extracted from online maps and existing 12 fire stations in Yiyang were used as fire service demand points and supply points. Travel times of fire trucks from supply points to demand points were calculated based on real-time traffic, and a total of 550,275 valid samples were obtained. The results showed that the ≥10 min fire service coverage rate in Yiyang is only 71.60 %. Based on the distribution area of demand points ≥10 min, the locations of three optimization solutions of new fire stations are proposed. By calculating the total average time (TAT) of the three optimization solutions of proposed new fire stations, it is concluded that TAT decreases by 743.99 s, 99.72 s, 92.59 s, respectively. From perspectives of safety and economy, the construction of the 10 fire stations of optimized solution I will effectively improve the regional fire service level.

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five different stages of R. roxburghii fruit development. Flavonoids and the genes related to their biosynthesis were found to undergo significant changes in abundance across different developmental stages, and numerous quercetin derivatives were identified. We found three gene expression modules that were significantly associated with the abundances of the different flavonoids in R. roxburghii and identified three structural UDP-glycosyltransferase genes directly involved in the synthesis of quercetin derivatives within these modules. In addition, we found that RrBEH4, RrLBD1 and RrPIF8 could significantly increase the expression of downstream quercetin derivative biosynthesis genes. Taken together, these results provide new insights into the metabolism of flavonoids and the accumulation of quercetin derivatives in R. roxburghii.

Residual stress is an important surface integrity index to evaluate the crack initiation and failure of die surface. The efficient prediction of cutting residual stress can guide the high-quality machining of die and improve its service life. The existing cutting residual stress prediction models are complex, time-consuming and inefficient. In this paper, a hybrid prediction method of cutting residual stress based on finite element-analytical-neural network is proposed. Firstly, the stress, strain and temperature of the cutting surface are obtained based on the orthogonal cutting finite element model. Then, the stress relaxation analytical algorithm considering the elastic-plastic state of the material is used to replace the stress release process of the finite element, and the residual stress distribution data were obtained based on the joint model of finite element and analytical algorithm. Secondly, the surrogate model of BP neural network (SSA-BP) is improved based on SSA algorithm to realize the rapid prediction of characteristic value of residual stress. The effectiveness of the finite element-analytical-neural network hybrid model was verified by the cutting residual stress test of H13 steel. Finally, the effects of tool structure parameters and cutting parameters on the residual stress distribution and the maximum compressive stress and maximum tensile stress of H13 steel were studied. This method can provide a flexible and efficient basic model for obtaining the optimal cutting conditions for controlling the residual stress of H13 steel and other metals.

Summary: Nucleic acid therapeutics offer tremendous promise for addressing a wide range of common public health conditions. However, the in vivo nucleic acids delivery faces significant biological challenges. Lipid nanoparticles (LNPs) possess several advantages, such as simple preparation, high stability, efficient cellular uptake, endosome escape capabilities, etc., making them suitable for delivery vectors. However, the extensive hepatic accumulation of LNPs poses a challenge for successful development of LNPs-based nucleic acid therapeutics for extrahepatic diseases. To overcome this hurdle, researchers have been focusing on modifying the surface properties of LNPs to achieve precise delivery. The review aims to provide current insights into strategies for LNPs-based organ-selective nucleic acid delivery. In addition, it delves into the general design principles, targeting mechanisms, and clinical development of organ-selective LNPs. In conclusion, this review provides a comprehensive overview to provide guidance and valuable insights for further research and development of organ-selective nucleic acid delivery systems.

Rice cake is a common traditional food in China. In this study, the effect of Polygonatum cyrtonema (PC) on the qualities and characteristics of rice cake was investigated. The incorporation of PC powder in rice cakes endowed a light-yellow color and increased the water content and water absorption of products. Rheological analysis showed that the rice cake containing PC exhibited weak-gel properties. Additionally, PC (40%) inhibited the rice cake aging and lowered the hardness of rice cakes to 13.86 N after 4 h storage. In vitro starch digestion analysis showed that PC (40%) reduced the digestibility of rice cakes by decreasing the starch hydrolysis rate from 88.70 to 58.95%, displaying a low estimated glycemic index (eGI) of 52.14. The findings mentioned above indicated that the inclusion of PC powder in rice cakes enhanced their characteristics and attributes, which also provided an approach for the development of PC products.

Background: Auditory Verbal Hallucinations (AVH) constitute a prominent feature of schizophrenia. Although low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic benefits in ameliorating AVH, the underlying mechanisms of its efficacy necessitate further elucidation. Objective: This study investigated the cortical gradient characteristics and their associations with clinical responses in schizophrenia patients with AVH, mediated through 1 Hz rTMS targeting the left temporoparietal junction. Method: Functional gradient metrics were employed to examine the hierarchy patterns of cortical organization, capturing whole-brain functional connectivity profiles in patients and controls. Results: The 1 Hz rTMS treatment effectively ameliorated the positive symptoms in patients, specifically targeting AVH. Initial evaluations revealed expanded global gradient distribution patterns and specific principal gradient variations in certain brain regions in patients at baseline compared to a control cohort. Following treatment, these divergent global and local patterns showed signs of normalizing. Furthermore, there was observed a closer alignment in between-network dispersion among various networks after treatment, including the somatomotor, attention, and limbic networks, indicating a potential harmonization of brain functionality. Conclusion: Low-frequency rTMS induces alternations in principal functional gradient patterns, may serve as imaging markers to elucidate the mechanisms underpinning the therapeutic efficacy of rTMS on AVH in schizophrenia.

Synergistic regional emission reduction (SRER) is an important part of the strategy to achieve carbon neutrality. In this paper, a system efficiency value-added model is proposed to measure the strength of SRER network relationships for 40,186 sets of city pairs and the SRER levels of 284 cities in China from 2011 to 2021. Subsequently, the evolution characteristics of the SRER network, the spatial and temporal characteristics of urban SRER levels, and the driving factors of the SRER network evolution are further analyzed. The results are as follows: SRER network is shifting from a fan-shaped network pattern of “three-region clustering and sporadic coverage” to a shuttle-shaped nested network pattern of “east-west linkage and multi-region support”. Time series analysis found that urban SRER level in China showed fluctuating growth characteristics during the study period. Spatial analysis reveals that the spatial autocorrelation of urban SRER level is decreasing, and the spatial distribution range is expanding towards the southwest. Emission reduction comparative advantages (CAER), green innovation division of labor (GIDL) and urban economic linkages (LCEL) are driver factors of SRER network evolution. This study proposes an evaluation method for the urban SRER level from network relationships perspective. Subsequently, network evolution characterization, spatial and temporal characterization, and driving factor analysis were conducted. The results of the study provide important theoretical guidance and inspiration for grasping the current status and enhancement paths of China's urban SRER level.

We aimed to investigate the effects of quercetin and taxifolin on gut health in the Chinese sucker (Myxocyprinus asiaticus). Short-term exposure (96 h) was conducted by exposing Chinese sucker to 2.5 mg/L of quercetin (Q2.5), 5 mg/L of quercetin (Q5), 10 mg/L of quercetin (Q10), 2.5 mg/L of taxifolin (T2.5), 5 mg/L of taxifolin (T5), 10 mg/L of taxifolin (T10), and their combination (quercetin and taxifolin: 5 mg/L+5 mg/L, QT). Then, we analyzed intestinal microorganisms, fat composition, digestive enzyme activities, and antioxidant and inflammatory-related gene expression. Both quercetin and taxifolin had an inhibitory effect on the intestinal flora, and the higher the quercetin concentration, the better the inhibitory effect. When compared to quercetin, taxifolin inhibited harmful bacteria more efficiently and maintained the abundance of probiotics. T5 and QT reduced the content of total cholesterol (T-CHO), and QT reduced the content of triglycerides (TG) in intestinal tissues. Q5 inhibited trypsin activity, while T5 increased amylase (AMS) activity in intestinal tissues. Q5, T5, and QT increased the expression of GST, GPx4, SOD1 and CAT in the intestine. The expression levels of GST and CAT in T5 were higher than in the Q5 and QT groups. Q5, T5, and QT inhibited the expression of IL1β, IL6, IL8, TNF-α, and TNF-β, and increased the expression levels of IL10. In summary, using taxifolin alone would be more beneficial with regards to maintaining homeostasis of the intestinal flora and increasing the antioxidant and anti-inflammatory capacity of the intestinal tract. The optimal application rate of taxifolin was 5 mg/L.

Objective: Pathologic cardiac hypertrophy (PCH) is a precursor to heart failure. Amydrium sinense (Engl.) H. Li (AS), a traditional Chinese medicinal plant, has been extensively utilized to treat chronic inflammatory diseases. However, the therapeutic effect of ASWE on PCH and its underlying mechanisms are still not fully understood. Methods: A cardiac hypertrophy model was established by treating C57BL/6 J mice and neonatal rat cardiomyocytes (NRCMs) in vitro with isoprenaline (ISO) in this study. The antihypertrophic effects of AS water extract (ASWE) on cardiac function, histopathologic manifestations, cell surface area and expression levels of hypertrophic biomarkers were examined. Subsequently, the impact of ASWE on inflammatory factors, p65 nuclear translocation and NF-κB activation was investigated to elucidate the underlying mechanisms. Results: In the present study, we observed that oral administration of ASWE effectively improved ISO-induced cardiac hypertrophy in mice, as evidenced by histopathological manifestations and the expression levels of hypertrophic markers. Furthermore, the in vitro experiments demonstrated that ASWE treatment inhibited cardiac hypertrophy and suppressed inflammation response in ISO-treated NRCMs. Mechanically, our findings provided evidence that ASWE suppressed inflammation response by repressing p65 nuclear translocation and NF-κB activation. ASWE was found to possess the capability of inhibiting inflammation response and cardiac hypertrophy induced by ISO. Conclusion: To sum up, ASWE treatment was shown to attenuate ISO-induced cardiac hypertrophy by inhibiting cardiac inflammation via preventing the activation of the NF-kB signaling pathway. These findings provided scientific evidence for the development of ASWE as a novel therapeutic drug for PCH treatment.

Summary: The spontaneous migration of bone marrow neutrophils (BMNs) is typically induced by distant tumor cells during the early stage of the tumor and critically controls tumor progression and metastases. Therefore, identifying the key molecule that prevents this process is extremely important for suppressing tumors. Interleukin-37 (IL-37) can suppress pro-inflammatory cytokine generation via an IL-1R8- or Smad3-mediated pathway. Here, we demonstrate that human neutrophil IL-37 is responsively reduced by tumor cells and the recombinant IL-37 isoform d (IL-37d) significantly inhibits spontaneous BMN migration and tumor lesion formation in the lung by negatively modulating CCAAT/enhancer binding protein beta (C/EBPβ) in a Lewis lung carcinoma (LLC)-inducing lung cancer mouse model. Mechanistically, IL-37d promotes C/EBPβ ubiquitination degradation by facilitating ubiquitin ligase COP1 recruitment and disrupts C/EBPβ DNA binding abilities, thereby reducing neutrophil ATP generation and migration. Our work reveals an anti-tumor mechanism for IL-37 via destabilization of C/EBPβ to prevent spontaneous BMN migration and tumor progression.

Background: Gastric cancer (GC) is the fourth most common cause of cancer-related death and the fifth most frequent malignant cancer, especially advanced GC. Carboxypeptidase X member 1 (CPXM1) is an epigenetic factor involved in many physiological processes, including osteoclast differentiation and adipogenesis. Several studies have shown the association of CPXM1 with multiple tumors; however, the mechanism of CPXM1 involvement in the progression of GC is yet to be characterized. Method: CPXM1 expression data were obtained from the Tumor Immune Estimation Resource. The Cancer Genome Atlas and the Gene Expression Omnibus databases were used to obtain patient-matched clinicopathological information, and the Kaplan–Meier plot database was utilized for the prognosis analysis of GC patients. The Catalog of Somatic Mutations in Cancer and cBioportal databases were adopted to study CPXM1 mutations in tumors. Next, we utilized the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis for mechanism research. Furthermore, we performed tumor microenvironment and immune infiltration analysis based on CPXM1. Finally, we predicted sensitivity to several targeted drugs in GC patients based on CPXM1.CPXM1 is upregulated in GC and is correlated with poor prognosis, gender, and tumor stage in GC patients. Gene enrichment analysis suggested that CPXM1 may regulate the occurrence and progression of GC via the PI3K–AKT and TGF-β pathway. Moreover, CPXM1 expression results in an increase in the proportion of immune and stromal cells. Additionally, the proportion of plasma cells was inversely related to the expression of CPXM1, whereas macrophage M2 expression was proportionate to CPXM1 expression. Finally, six small-molecule drugs that showed notable variations in IC50 between two groups were screened. Conclusion: These results suggested that CPXM1 regulates the progression of GC and may represent a novel target for the detection and treatment of GC.

Purpose: Eukaryotic translation elongation factor 1α2 (eEF1A2) promotes tumour progression in various cancers. We performed a pan-cancer analysis of eEF1A2 and explored its role in thyroid carcinoma (THCA). Methods: Databases from The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and the Human Protein Atlas (HPA) were used to investigate the differential expression of eEF1A2 in pan-cancer. The pathological stage, prognostic characteristics, tumour microenvironment (TME), tumour mutational burden (TMB), and microsatellite instability (MSI) were analysed in diverse tumours with different expression levels of eEF1A2. The expression levels in papillary thyroid carcinoma (PTC) and its specific role in cell proliferation, migration, invasion, and cell glycolysis in PTC cells were verified by quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry, cell counting kit-8, colony formation, wound healing, Transwell assay, and lactate acid and glucose assays.Results:eEF1A2 was differentially expressed in various malignant tumour tissues compared to control tissues and was associated with poor pathological stage and prognosis in most types of tumours. Moreover, eEF1A2 expression closely correlated with the infiltration of immunosuppressive cells, TMB, and MSI in some tumour types. Expression of eEF1A2 in PTC is higher than the para-carcinoma, and eEF1A2 downregulation suppressed TPC-1 and BCPAP cell proliferation, migration, invasion, and glycolysis. Conclusion: Our study suggests that the expression of eEF1A2 is related to the prognosis and immune infiltration of some tumours and may be a predictor of prognosis and immunotherapy. eEF1A2 could promote malignant behaviour of PTC cells.

Aluminum ammonium sulfate dodecahydrate (AASD) is a promising hydrated salt-type phase change material. However, its application is severely hindered by its large undercooling and low thermal conductivity. Herein, Al2O3 nanoparticles and xanthan gum are utilized as additives to prepare the modified AASD and improve its supercooling. The modified AASD is adsorbed into the porous modified expanded graphite to prepare a shape-stable composite phase change material (CPCM). Differential scanning calorimeter, thermal constant analyzer, X-ray diffractometer, and scanning electron microscopy are used to characterize the CPCM. Results show that the supercooling of CPCM decreases from 48 to 10 °C, and the latent heat and thermal conductivity of CPCM are 235.40 kJ/kg and 4.086 W/(m·K), respectively. Compared with pure AASD, the CPCM loses around 10.7 % latent heat, while the thermal conductivity is boosted for more than eight times. After 300 melting-solidification cycles, the latent heat of CPCM only decreases by 5.9 %. Besides, the 600-h corrosion test demonstrates that the 316 L stainless steel is suitable for manufacturing containers for the CPCM. In sum, the developed CPCM owns low supercooling, high thermal conductivity, high cycle stability, and good material compatibility, and hence has a great potential in the field of building and domestic heating.

In the context of carbon neutrality and urbanization, there is a notable research gap regarding the carbon sequestration benefits of urban forests and the identification of suitable tree species for achieving sustainable carbon sequestration. In this study, we examined the dynamics and drivers of urban forest carbon sequestration in Shanghai, one of the most urbanized cities in China. First, we compiled a comprehensive field inventory data set spanning 20 years for the Shanghai Green Belt. Second, we quantified and compared the total carbon accumulation and growth rates of six monoculture forests and two mixed forest types consisting of six common tree species. Third, we conducted drivers analysis of the effects of stand-related and anthropogenic factors on carbon accumulation and growth rates. Overall, our results revealed that each forest type exhibited a unique growth pattern of tree biomass carbon (TBC), with the Chapman–Richards growth function providing an accurate representation of carbon dynamics. During the early stages of development (within 20 years), the carbon accumulation rate of Populus L. reached 4.13 Mg ha−1 yr−1, which was approximately 127 % higher than that of broadleaf mixed forests. In late stages, the potential tree biomass carbon accumulation of broadleaf mixed forests reached 172.8 Mg ha−1, which was 34 % higher than that of Populus L. over the entire growth cycle. Forest types, stand age, canopy density class, ownership, closure management, strongly influence the accumulation rates of TBC. Overall, these findings contribute to the understanding of the advantages of mixed and monoculture plantations for carbon sequestration, and these results can be used to predict future patterns of carbon storage in urban forests in Shanghai.

Phytosterol organic acid esters are important food resources and the components of biomembrane structure. Due to the lack of extraction and synthesis techniques, more research has been focused on phytosterols, and the research on phytosterol acid esters have encountered a bottleneck, but phytosterol acid esters confer substantial benefits to human health. In this study, stigmasteryl vanillate (VAN), stigmasteryl protocatechuate (PRO) and stigmasteryl sinapate (SIN) were prepared through the Steglich reaction. The processes are promotable and the products reach up to 95% purity. In addition, their stability was evaluated by differential scanning calorimetry and thermogravimetric analysis. HPLC analysis revealed an enhancement in water solubility after esterification with phenolic acid. In an in vitro digestion model, the bioaccessibility of stigmasteryl phenolates was significantly higher than that of stigmasterols (STIs). Regarding the anti-inflammatory properties, VAN, PRO, and SIN exhibit superior effects against TNF-α induced pro-inflammatory responses compared to STI. All stigmasteryl phenolates supplementation increased the ATP production, the basal, and maximal oxygen consumption rate in mitochondrial stress test. Overall, we present a synthesis method for stigmasteryl phenolates. It will contribute to the development and research of phytosterol acid ester analysis, functions and utilization in food. Moreover, the nutrient-stigmasterol hybrids tactic we have constructed is practical and can become a targeted mitochondrial delivery strategy with enhanced anti-inflammatory effects.

Gastrointestinal diseases exert a profound impact on global health, leading to millions of healthcare interventions and a significant number of fatalities annually. This, coupled with escalating healthcare expenditures, underscores the need for identifying and addressing potential exacerbating factors. One emerging concern is the pervasive presence of microplastics and nano-plastics in the environment, largely attributed to the indiscriminate usage of disposable plastic items. These nano-plastics, having infiltrated our food chain, pose a potential threat to gastrointestinal health. To understand this better, we co-cultured human gastric fibroblasts (HGF) with polystyrene nano-plastics (PS-NPs) of diverse sizes (80, 500, 650 nm) and meticulously investigated their cellular responses over a 24-hour period. Our findings revealed PS particles were ingested by the cells, with a notable increase in ingestion as the particle size decreased. The cellular death induced by these PS particles, encompassing both apoptosis and necrosis, showcased a clear dependence on both the particle size and its concentration. Notably, the larger PS particles manifested more potent cytotoxic effects. Further analysis indicated a concerning reduction in cellular membrane potential, alongside a marked increase in ROS levels upon PS particles exposure. This suggests a significant disruption of mitochondrial function and heightened oxidative stress. The larger PS particles were especially detrimental in causing mitochondrial dysfunction. In-depth exploration into the PS particles impact on genes linked with the permeability transition pore (PTP) elucidated that these PS particles instigated an internal calcium rush. This surge led to a compromise in the mitochondrial membrane potential, which in tandem with raised ROS levels, further catalyzed DNA damage and initiated cell death pathways. In essence, this study unveils the intricate mechanisms underpinning cell death caused by PS particles in gastric epithelial cells and highlighting the implications of PS particles on gastrointestinal health. The revelations from this research bear significant potential to shape future healthcare strategies and inform pertinent environmental policies.

Objective: In recent decades, thyroid cancer (TC) has exhibited a rising incidence pattern. Elevated levels of the transcription factor FOXP4 have been strongly linked to the progression of diverse tumors; nevertheless, its specific role in thyroid cancer remains underexplored. The primary objective of this study was to elucidate the functions of FOXP4 and its associated target gene, FBXW7, in the context of thyroid cancer. Methods: FOXP4 and FBXW7 expression levels in TC tissues and cell lines were assessed through immunohistochemistry and RT-qPCR analyses. The functional aspects of FOXP4, including its effects on cell proliferation, migration capabilities, cell cycle regulation, and epithelial-mesenchymal transition (EMT), were investigated. Furthermore, the interaction between FOXP4 and FBXW7 was confirmed using chromatin immunoprecipitation (ChIP) assays. The impact of FBXW7 on FOXP4-mediated cellular phenotypes was subsequently examined. Additionally, the in vivo role of FOXP4 and FBXW7 in tumor growth was elucidated through the establishment of a murine tumor model. Results: Elevated levels of FOXP4 were observed in papillary carcinoma tissues, and patients exhibiting high FBXW7 levels showed a more favorable prognosis. KTC-1 cells displayed a concomitant increase in FOXP4 expression and decrease in FBXW7 expression. FOXP4 overexpression in these cells enhanced cell proliferation, migration capabilities, and EMT. The interaction between the FOXP4 protein and the FBXW7 promoter was confirmed, and the effects of FOXP4 were mitigated upon overexpression of FBXW7. Furthermore, knockdown of FOXP4 led to decelerated growth of transplanted tumors and increased FBXW7 levels within the tumors. Conclusion: The findings of the current study underscore the regulatory role of FOXP4 in the transcription of FBXW7 and establish a clear link between aberrations in FBXW7 expression and the manifestation of malignant phenotypes in highly aggressive TC cells.

Background: Autism is a severe neurodevelopmental disorder characterized by social interaction deficits, impairments in communication, and restricted and repetitive stereotyped behavior and activities. Family and twin studies suggested an essential role of genetic factors in the etiology of autism spectrum disorder (ASD). Also, other studies found SORCS3 and GSDME (DFNA5) might be involved in brain development and susceptible to ASD. Methods: In this study, 17 genome-wide significant SNPs reported in previous ASD genome-wide association studies (GWAS) and 7 SNPs in strong linkage disequilibrium with known ASD GWAS hits were selected to investigate the association between these SNPs and autism in the Han Chinese population. Then, 10 tagSNPs in SORCS3 and 11 tagSNPs in GSDME were selected to analyze the association between these SNPs and autism. The selected 24 SNPs and tagSNPs were genotyped using the Agena MassARRAY SNP genotyping assay in 757 Han Chinese autism trios. Results: Rs1484144 in NAA11 was significantly associated with autism; significance remained after the Bonferroni correction (P

SET and MYND domain protein 2 (SMYD2) can methylate histone H3 at lysine36 (H3K36) and some non-histone substrates to play a role in tumorigenesis. However, It is unclear how SMYD2 contributes to chronic kidney disease (CKD). Here, AZ505 or LLY507, which could inhibit SMYD2, were used in cisplatin-induced CKD to investigate the effects and possible mechanisms by which they might act. We found that high expression of SMYD2 in cisplatin-induced CKD. However, AZ505 or LLY507 can significantly inhibit its expression, improve renal function injury and fibrosis induced by cisplatin, inhibit the transition of epithelial cells to a fibrogenic phenotype and fibrosis-related proteins, inhibit the expression of Inflammatory Cytokines (such as IL-6 and TNF-α), And inhibit the phosphorylation of pro-fibrosis molecule Smad3 and signal transduction and transcription activator-3 (STAT3) and up-regulated the expression of renal protective factor Smad7. In cultured tubular epithelial cells, AZ505 also can inhibit the expression of EMT, fibrosis-related proteins, and inflammatory cytokines in cisplatin-induced tubular epithelial cells. Based on these findings, SMYD2 may be a critical regulator of cisplatin-induced CKD and targeted pharmacological inhibition of SMYD2 may prevent cisplatin-induced CKD through Smad3 or STAT3-related signaling pathways.

Sensing and understanding large-scale dynamic scenes require a high-performance imaging system. Conventional imaging systems pursue higher capability by simply increasing the pixel resolution via stitching cameras at the expense of a bulky system. Moreover, they strictly follow the feedforward pathway: That is, their pixel-level sensing is independent of semantic understanding. Differently, a human visual system owns superiority with both feedforward and feedback pathways: The feedforward pathway extracts object representation (referred to as memory engram) from visual inputs, while, in the feedback pathway, the associated engram is reactivated to generate hypotheses about an object. Inspired by this, we propose a dual-pathway imaging mechanism, called engram-driven videography. We start by abstracting the holistic representation of the scene, which is associated bidirectionally with local details, driven by an instance-level engram. Technically, the entire system works by alternating between the excitation–inhibition and association states. In the former state, pixel-level details become dynamically consolidated or inhibited to strengthen the instance-level engram. In the association state, the spatially and temporally consistent content becomes synthesized driven by its engram for outstanding videography quality of future scenes. The association state serves as the imaging of future scenes by synthesizing spatially and temporally consistent content driven by its engram. Results of extensive simulations and experiments demonstrate that the proposed system revolutionizes the conventional videography paradigm and shows great potential for videography of large-scale scenes with multi-objects.

Objective: To compare the effects of oral intake and nasogastric tube (NG) feeding on nutritional status, complications and survival during neoadjuvant chemoradiotherapy for esophageal squamous-cell carcinoma (ESCC) patients. Methods: A total of 61 ​ESCC cases treated with neoadjuvant chemoradiotherapy from December 2018 to March 2020 were enrolled, including (38 in oral intake group, and 22 in NG feeding group. Disease characteristics and baseline nutritional markers were collected in both groups. Nutritional status, complication and completion rate of chemoradiotherapy in both groups were evaluated. Results: Compared with the oral intake group, patients in the NG feeding group had a later T stage (P ​= ​0.027) and clinical stage (P ​= ​0.014). The levels of energy intake (P ​= ​0.033), serum prealbumin (P ​ ​0.05). Conclusions: As a safe and effective enteral nutrition approach to improving nutrition, nasogastric tube feeding could increase treatment completion rate and reduce the incidence of ≥ grade 2 esophagitis reaction during neoadjuvant chemoradiotherapy.

Unprogrammed macrophage polarization, especially prolonged activation of proinflammatory macrophages, is associated with delayed wound healing in diabetic objectives. Macrophage-derived exosomes cargo a variety of microRNAs (miRNAs), participating in different stages in wound healing. Here, exosomes were isolated from naive bone marrow–derived macrophages (BMDMs) (M0-Exos), interferon-γ plus lipopolysaccharide-polarized BMDMs (M1-Exos), and interleukin-4-polarized BMDMs (M2-Exos). M1-Exos impaired migration and tube formation in human umbilical vein endothelial cells (HUVECs) compared to M0-Exos, whereas M2-Exos exhibited the opposite effects. High-throughput sequencing was performed to decipher the miRNA expression profiles in M0-Exos, M1-Exos, and M2-Exos. A total of 63 miRNAs were identified to be differentially expressed in exosomes derived from polarized BMDMs. Among them, miRNA-155-5p is highly expressed in M1-Exos, which interrupted angiogenesis in HUVECs. Furthermore, miRNA-155-5p directly binds to the 3′ UTR of growth differentiation factor 6 (GDF6) mRNA to suppress its protein expression. Lastly, local administration of a temperature-sensitive hydrogel Pluronic F-127 loading miRNA-155-5p antagomiR promoted angiogenesis and accelerated wound healing in diabetic db/db mice via enhancing GDF6. In summary, this study deciphered the miRNA expression profiles in exosomes from polarized macrophages. M2-like macrophage-derived exosomes and miRNA-155-5p inhibitors could be promising therapeutics against diabetic foot ulcers.

Studying the intrinsic properties of concrete is essential for addressing various aspects of concrete structure design, material selection, and sustainability. In this study, a suspended strong magnetic torsion balance device was designed and constructed to investigate the ferromagnetic properties of concrete specimens and their constituent materials. It was found that sand and cement generally exhibit ferromagnetic properties, while aggregates do not possess ferromagnetic properties. Analysis using powder X-ray diffraction (XRD) and chemical experiments confirmed that the ferromagnetic material in sand and cement is elemental iron. A simplified calculation formula for the magnetic force between concrete specimens and an external magnetic field was derived. Three sets of specimens were designed and fabricated for experimental exploration of ferromagnetic properties and magnetic force measurements. The experimental results demonstrate that plain concrete possesses measurable ferromagnetic properties. The magnetic force of concrete initially experiences a rapid decay followed by a gradual leveling off as the distance (from the magnetic field source to the concrete surface) increases. The decay rate approximately follows a fourth-power relationship with distance. Under a loading condition with an applied magnetic field intensity of 0.2 T, the optimal measurement range for ferromagnetic force in concrete is between 0.02 m and 0.05 m.

Background: Orthodontic tooth movement (OTM) is a typical treatment that corrects malaligned teeth by applying mechanical forces. However, mechanical overload often leads to damage of PDL fibroblasts. Sanhuang decoction (SHD) is commonly used to inhibit inflammation and oxidative stress. However, the mechanism of SHD for OTM treatment is still unclear. Therefore, this study attempts to explore the underlying mechanism through relevant experiments. Methods: In the present paper, we established a OTM rat model and further explored the effects of SHD on the PDL of OTM rats. The OTM model and effects of SHD were determined by micro-CT, and the PDL pathological changes, PDL width and capillaries in PDL were observed by H&E staining. Subsequently, the ROS levels in PDL was determined using flow cytometry analysis with DCFH-DA staining, MDA contents and antioxidative enzymes activities were also measured using commercial kits. Furthermore, the autophagy of PDL fibroblasts and proteins in the PI3K/Akt/mTOR pathway were detected using immunoluminescence, qPCR and western blotting assays. Results: The results showed SHD treatment can alleviate the decrease of PDL cells and capillaries induced by OTM, and improve the MDA and ROS levels in PDL, as well as enhance the activities of SOD and GSH-Px. Further experiments indicated SHD decreased the autophagy levels of PDL fibroblasts via promoting the phosphorylation levels of mTOR, PI3K and Akt proteins. Conclusion: SHD inhibited autophagy of periodontal ligament fibroblasts during orthodontic tooth movement by inhibiting oxidative stress via activating PI3K-Akt-mTOR pathway. Our present findings suggested SHD treatment would be useful for management of the possible disorders occurs in orthodontic tooth movement therapy.

Background and purpose: To evaluate the efficiency and safety of immunotherapy combined with or without radiotherapy (RT) for metastatic or recurrent esophageal squamous cell carcinoma (ESCC). Methods: We retrospectively reviewed data of 127 patients with metastatic or recurrent ESCC, who received immunotherapy with or without RT at Tianjin Medical University Cancer Institute between 2017 and 2021. Results: The median follow-up time was 15.7 months (95 % confidence interval (CI): 12.42–18.99). The median PFS of the RT and NRT groups was 5.45 months (95 % CI: 2.89–8.28) and 4.60 months (95 % CI: 3.75–7.06), respectively (P = 0.660). The median OS was 11.9 (95 % CI: 8.61–19.2) and 10.3 (95 % CI: 7.56–15.8) months, respectively (P = 0.890). The median PFS of locoregional recurrence patients in the RT and NRT groups was 11.27 months (95 % CI: 2.45–20.09) and 4.17 months (95 % CI: 2.64–5.71), respectively (P = 0.081). The median OS of locoregional recurrent patients in the RT and NRT groups was 19.48 months (95 % CI: 8.37–30.60) and 7.69 months (95 % CI: 3.45–11.93), respectively (P = 0.026). 64 % of patients in the RT group and 30 % of patients in the NRT group experienced an improvement in dysphagia (P = 0.033). No significant increase in treatment-related toxicity was observed in the RT group compared with the NRT group, except for some hematological complications. Conclusions: Locoregional recurrent patients gained survival benefits from immunotherapy combined with RT. The combination of immunotherapy and RT was safe in metastatic/recurrent ESCC patients. RT for the esophagus leads to the improvement of dysphagia compared to immunotherapy alone.

Summary: Drug-target interactions (DTIs) prediction is an important step in drug discovery. As traditional biological experiments or high-throughput screening are high cost and time-consuming, many deep learning models have been developed. Overfitting must be avoided when training deep learning models. We propose a simple framework, called OverfitDTI, for DTI prediction. In OverfitDTI, a deep neural network (DNN) model is overfit to sufficiently learn the features of the chemical space of drugs and the biological space of targets. The weights of trained DNN model form an implicit representation of the nonlinear relationship between drugs and targets. Performance of OverfitDTI on three public datasets showed that the overfit DNN models fit the nonlinear relationship with high accuracy. We identified fifteen compounds that interacted with TEK, a receptor tyrosine kinase contributing to vascular homeostasis, and the predicted AT9283 and dorsomorphin were experimentally demonstrated as inhibitors of TEK in human umbilical vein endothelial cells (HUVECs).

Cadmium (Cd) exposure is a risk factor for endothelial dysfunction and cardiovascular disease. Ferroptosis is a type of cell death that relies on lipid peroxidation. Whether ferroptosis acts in Cd-induced vascular endothelial damage and the underlying mechanisms remain unclear. Herein, we found that Cd resulted in ferroptosis of vascular endothelial cells (ECs) in vivo and in vitro. In the visualized zebrafish embryos, Cd accumulated in vascular ECs, ROS and lipid peroxidation levels were increased, and the oxidoreductase system was disturbed after exposure. Moreover, Cd decreased Gpx4 in ECs and caused smaller mitochondria with increased membrane density. Accompanied by ferroptosis, the number of ECs and the area of the caudal venous plexus in zebrafish embryos were reduced, and the survival rate of HUVECs decreased. These effects were partially reversed by ferrostatin-1 and aggravated by erastin. Mechanistically, an excessive increase in Heat Shock Protein 70 (Hsp70) was identified by transcriptomics after Cd exposure. Inhibition of Hsp70 by VER-155008 or siRNA ameliorated Cd-induced ferroptosis, thereby alleviating endothelial injury. Furthermore, Hsp70 regulated Cd-induced ferroptosis by targeting multiple targets, including Gpx4, Fth1, Nrf2 and Acsl4. Our findings provide a new approach to investigating the endothelial damage of Cd and indicate that regulation of Hsp70 is an important target for alleviating this process.

As the additive manufacturing provides an advanced method for fabricating polymeric composite components in thermal engineering applications, the thermal contact conductance (TCC) between the contact composites can become an important problem. In order to understand the interfacial heat transfer mechanism between thermoplastic composites, TCC between additively manufactured carbon fiber reinforced polyamide 12 (CF/PA12) composites was experimentally studied with steady-state measurements in this work. By considering the material surface microstructure, thermal and mechanical properties, the effects of interface temperature, contact pressure, surface morphology, carbon fiber (CF) content and orientation in composites on TCC were analyzed. The results show that the TCC is dependent on the actual contact area and the thermal conduction path inside the material. In general, high surface roughness decreases the TCC because of the reduction of contact area; while it is the opposite of temperature and pressure. The CF distribution affects the internal thermal conduction path and surface roughness, leading to the variations in TCC.

Agricultural drought seriously threatens the food and ecological security of most of the world’s developing countries. Data-driven integrated agricultural drought index with remote sensing provides an effective tool to monitor, evaluate, and predict the agricultural drought. However, there is still a lack of comprehensive analytical work on taking the most effective machine learning (ML) and deep learning (DL) methods to construct such integrated drought index. In other words, it is still unclear whether the recent DL methods can improve integrated drought monitoring as compared with the currently widely used ML methods. Therefore, we critically evaluated the performances of four representative DL methods (represents the four currently popular DL network types) i.e., Entity Embedding Deep Neural Network (EEDNN), One-dimensional Convolutional Neural Network (1D-CNN), Gated Recurrent Unit (GRU), and Self-Attention Mechanism (SAM) and three widely used tree-based ML methods i.e., Cubist, Random Forest (RF), and Light Gradient Boosting Machine (LGBM), through constructing a QuickDRI like integrated drought index (abbreviated as QuickDRI-China). About 30 years of meteorological data, 14 years of remote sensing data, and various biophysical variables in China such as land use/land cover, available water capacity, irrigated agriculture, elevation, and ecoregion were employed in this study. Results showed that the EEDNN performed best, followed by the RF and LGBM, and then the other methods including the currently wide used Cubist, according to the station accuracy evaluations, spatial description evaluations, and responses to specific drought event. The tree-based ML methods such as RF and LGBM are still competitive in constructing the integrated agricultural drought index at the current stage. However, the higher accuracy, the smoother spatial description, and the more responsive ability of the EEDNN demonstrate great potential of DL methods. The future integrated agricultural drought monitoring with remote sensing should develop a specialized DL network for heterogeneous agricultural drought features.

Preservation and microorganism control of fresh-cut fruit pose a persistent challenge in the food industry. To address this issue, we prepared a β-cyclodextrin (β-CD) inclusion complex containing carvacrol using a coprecipitation method and employed it for the non-contact fumigation of fresh-cut Shatangju mandarin slices. This biodegradable and safe preservative offers an effective means to combat spoilage and ensure product quality. We confirmed the formation of the encapsulated structure of the inclusion complex through various characterization methods, including scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential thermal analysis (DTA). We also demonstrated the inhibitory effect of this preservative on Penicillium digitatum and its associated spoilage both in vitro and in vivo. The incidence and severity were significant lower in the inclusion complex-treated group (75.0% and 46.7%, respectively) compared to the group treated with pure carvacrol (100% and 69.2%, respectively). In addition, fruit freshness parameters and sensory evaluation showed that the inclusion complex treatment effectively maintained the overall quality of the fruit and achieved the highest consumer acceptance.

With the decrease in energy storage costs and the popularization of the shared economy principle, shared energy storage (SES) has been gradually deployed in the residential community to reduce energy costs. However, centralized trading platforms for SES trading are rare in the residential community, so it is difficult for users with the trading demands to search for appropriate trading partners and make a deal. To address the above problem, a decentralized trading mechanism of SES considering the preference of trading subjects is proposed to enable the users in the residential community to trade in the absence of centralized trading platforms. The cost-based price models are built to determine the acceptable price ranges for SES users, DG users and power consumers, which will be used as the basis for the quotation in the process of decentralized trading. Moreover, based on a multinomial logit model and an improved Rubinstein model, the trading partner selection method and the negotiation strategy are proposed to be adopted in the decentralized trading mechanism. Through the autonomous selection of trading partners and multiple rounds of negotiation and quotation, the trading probability of the users can be improved. Numerical simulation studies show that the proposed decentralized trading mechanism can achieve a higher sale rate of SES trading. All types of users can obtain revenue or reduce energy costs through SES trading.

The overwhelming impact of complex-phase microstructures to mechanical response in multiphase steels requires accurate constitutive properties of the individual phases. However, precise prediction of individual phase properties to their mechanical response is critical and sophisticated, and commonly requires multiscale characterizations and numerous approximations. In this work, by employing full phase information and semi-empirical analytical models, we accurately predict the yield strength of deformed variants of Ce-modified SAF2507 super duplex stainless steel (SDSS). High energy synchrotron X-ray diffraction (HE-SXRD) reveals the phase fractions of major phases along with secondary phases of Cr2N and eutectic CexFey. Average lattice strain/crystallite size of the austenite and ferrite/martensite phases from the measured volume is estimated through the Williamson-Hall method. A unique composite strengthening type analytical model is used to estimate yield strength by taking individual strengthening contributions from all phases, their grain sizes, stored dislocation densities, solid solution, and precipitates. Close agreement between reconstructed and experimental yield strength is observed for several cold and cryogenic rolled SDSS. A combination of HE-SXRD and analytical model offers a time-effective virtual design pathway to engineer high-strength steel.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Exosomes, small extracellular vesicles that function as a key regulator of cell-to-cell communication, are emerging as a promising candidate for bone regeneration. Here, we aimed to investigate the effect of exosomes from pre-differentiated human alveolar bone-derived bone marrow mesenchymal stromal cells (AB-BMSCs) carrying specific microRNAs on bone regeneration. Exosomes secreted from AB-BMSCs pre-differentiated for 0 and 7 days were cocultured with BMSCs in vitro to investigate their effect on the differentiation of the BMSCs. MiRNAs from AB-BMSCs at different stages of osteogenic differentiation were analyzed. BMSCs seeded on poly-L-lactic acid(PLLA) scaffolds were treated with miRNA antagonist-decorated exosomes to verify their effect on new bone regeneration. Exosomes pre-differentiated for 7 days effectively promoted the differentiation of BMSCs. Bioinformatic analysis revealed that miRNAs within the exosomes were differentially expressed, including the upregulation of osteogenic miRNAs (miR-3182, miR-1468) and downregulation of anti-osteogenic miRNAs (miR-182–5p, miR-335–3p, miR-382–5p), causing activation of the PI3K/Akt signaling pathway. The treatment of BMSC-seeded scaffolds with anti-miR-182–5p decorated exosomes demonstrated enhanced osteogenic differentiation and efficient formation of new bone. In conclusion, Osteogenic exosomes secreted from pre-differentiated AB-BMSCs were identified and the gene modification of exosomes provides great potential as a bone regeneration strategy. Data Availability Statement: Data generated or analyzed in this paper partly are available in the GEO public data repository(http://www.ncbi.nlm.nih.gov/geo).

Biological diversity is a concept that contains multiple facets, of which functional diversity is considered to be more integrative to describe the relationship between biodiversity and ecosystem functioning. In recent decades, functional diversity patterns have been assessed along elevational gradients in plants and birds. However, few empirical studies have been conducted to reveal amphibian functional diversity patterns between elevational zonations on mountains. In the present study, we investigated amphibian ecomorphologically functional diversity patterns in different elevational zonations of Nepal Himalaya. Our results indicated that functional space occupied by amphibian assemblages differed in size between elevational zonations, with assemblages in zonation-2 (500–1300 m) occupying the highest proportion. In terms of the position in functional space, assemblages in low elevational zonations (zonation 1 & 2) differed significantly from those in high elevational zonations (zonation 3–5). Distribution of individuals in the five assemblages along the six axes of the functional space was significantly different between most pairs of comparisons, while the difference varied between assemblages along axes. Interestingly, despite morphologically extreme amphibians accounted for small proportions of the total number of amphibians, they filled a large proportion of the six dimensional functional space. More importantly, most of the extreme amphibians were also the most functional uniqueness individuals, and they were widely distributed in all the zonations. Therefore, functional vulnerability of amphibian assemblages exists throughout all the elevational zonations. Accordingly, extreme amphibians with most functional uniqueness should be in particular well protected to maintain amphibian functional diversity. Further research can explore the mechanism underlying the unique amphibian functional diversity patterns in Nepal Himalaya.

Klotho (KL) is a renal protein with aging-suppression properties that mediates its regulatory effect during cardiac fibroblast aging. However, to determine whether KL can protect aged myocardial cells by attenuating ferroptosis, this study aimed to investigate the protective effect of KL on aged cells and to explore its potential mechanism. Cell injury of H9C2 cells was induced with D-galactose (D-gal) and treated with KL in vitro. This study demonstrated that D-gal induces aging in H9C2 cells. D-gal treatment increased β-GAL(β-galactosidase) activity, decreased cell viability, enhanced oxidative stress, reduced mitochondrial cristae, and decreased the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase-4 (GPx4), and P53, which are primary regulators of ferroptosis. The results showed that KL can eliminate D-gal-induced aging in H9C2 cells, likely due to its ability to increase the expression of the ferroptosis-associated proteins SLC7A11 and GPx4. Moreover, pifithrin-α, a P53-specific inhibitor, enhanced the expression of SLC7A11 and GPx4. These results suggest that KL may be involved in D-gal-induced H9C2 cellular aging during ferroptosis, mainly through the P53/SLC7A11/GPx4 signaling pathway.

Purpose: The underlying mechanism for radiation as a potentiator of immune checkpoint inhibition (ICI) is unclear. We developed a novel murine model to investigate the effects of post-irradiation intratumoral heterogeneity (ITH) on response to ICI. Experimental design: Parental mouse melanoma B16F10 cells were irradiated in vitro (5Gy x 3 fractions), then an a priori determined number of resulting colonies were implanted in C57BL/6J immunocompetent mice creating syngeneic models of unirradiated (parental) and irradiated tumors with low (irradiated-L) and high (irradiated-H) ITH. Mice were treated with placebo, α-PD-L1, α-CTLA-4 or dual ICI. Murine tumors underwent whole exome sequencing (WES). Clinically correlated paired pre- and post-irradiation patient rectal adenocarcinoma samples underwent WES. Results: Irradiated-L tumors showed increased tumor mutational burden (TMB) and a sustained decrease in ITH. Irradiated-L tumors were predicted to express five neoantigens with high variant allele frequency/clonal distribution. Mice with irradiated-L and irradiated-H versus parental B16F10 tumors demonstrated longer overall survival with dual ICI. Only mice with irradiated-L tumors experienced an overall survival benefit with single agent ICI. Clinically correlated rectal adenocarcinoma samples showed similarly increased TMB and decreased ITH following irradiation. Conclusions: Post-irradiation ITH modulates ICI response in a murine melanoma model. Irradiation may offer a mechanism to widen the therapeutic window of ICI.

Understanding the spatial patterns and the maintenance of biodiversity is a central target in ecology and biogeography, which provide important insights into community assembly processes. Mountain ecosystems provide informative systems for examining how biodiversity is distributed and identifying the mechanisms underlying those patterns. However, most of the existed studies only focused on plants, birds, and microbes, while little attention has been paid on amphibians, especially tadpoles. In the present study, we explored the elevational patterns of multiple facets of tadpole diversity and the community assembly mechanisms in temperate montane streams of Mount Emei, China. The taxonomic, functional, and phylogenetic diversity of tadpole assemblages in montane streams were quantified. Their elevational patterns were investigated using first and second-order polynomial regression analyses. The microhabitat determinants of these patterns were assessed by ordinary least squares models and hierarchical partitioning analyses. The phylogenetic tree of tadpoles and the Eucliden distance of traits between tadpoles were constructed. They were subsequently used to calculate the standardized effect size of mean pairwise phylogenetic and functional distances, and to speculate the tadpole assembly rules. Our results indicated that the Faith’s PD and the standardized effect size of Faith’s PD had hump-shaped responses to elevation, while the relationships between elevation and observed taxonomic diversity, observed functional diversity, and the standardized effect size of functional diversity were not significant. Interestingly, these patterns were determined by microhabitat variables, such as water conductivity, river width, water depth, and substrate type. Mean pairwise phylogenetic distance also showed hump-shaped correlations with the elevational gradient. Tadpole functional and phylogenetic structures were more clustered in low and high elevational streams, suggesting that environmental filtering was the main driver. At mid-elevations, functional and phylogenetic structures were overdispersal, indicating that limiting similarity plays a dominant role in shaping the tadpole assemblages.

Cotton boll count is an important phenotypic trait that aids in a better understanding of the genetic and physiological mechanisms of cotton growth. Several computer vision technologies are available for cotton boll segmentation. However, estimating the number of cotton bolls in a segmented cluster of cotton bolls is a challenging task due to the complex shapes of cotton bolls. This study proposed a combination of spectral-spatial and supervised machine learning based methods for cotton boll candidate recognition and counting from high resolution RGB images obtained from unmanned aerial vehicles (UAVs). An algorithm consisting of machine vision, band-mean filter, Otsu thresholding, red/blue band ratio filter, and geometrical characteristics-based error removal techniques, was employed to detect open cotton boll pixels under several environmental settings. In addition, a support vector machine (SVM) based encoding method was developed using geometric features of cotton boll candidates to predict the number of cotton bolls from the segmented cotton boll candidates. This algorithm was implemented over three experiment sites with three cotton varieties, two tillage practices, seven cover crop treatments, two irrigation regimes (irrigated and rainfed), 26 irrigation levels, and two sensors (DJI FC6310 RGB and MicaSense Rededge) capturing images at two spatial resolutions (0.75 cm and 1.07 cm) over two growing seasons (2019 and 2021). These different experimental settings allowed the proposed approaches to be validated against a variety of complex backgrounds. A visual inspection of 1000 randomly selected pixels revealed that the proposed cotton boll candidate recognition approach was highly effective in segmenting cotton bolls and background pixels, with high classification accuracy (> 95%) and a low number of falsely classified pixels (precision > 0.96; recall > 0.93). A high correlation between ground truth observations and predicted cotton boll count indicated that the use of geometric features of segmented candidates as predictors in association with the SVM model demonstrated a good performance in estimating boll count from recognized cotton boll candidates. Furthermore, linear regression analyses revealed that both boll count and candidate area are potential predictors of lint yield, with boll count being a better predictor than candidate area. Overall, the study demonstrated that machine vision/learning techniques can be potentially used on UAV images to count the number of cotton bolls and predict lint yield over large acreages with reasonable accuracy.