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Abstract To address the problem of excessive local secondary stripping between adjacent mining areas in open pit mines caused by internal row raising, a multivariate function was fitted to the model of the main mining seam of Zhundong open pit coal mine in Xinjiang, and the different locations of the end gang of the second mining area were divided into multiple sections at certain step sizes and calculated by integration, resulting in stripping ratios for each section, which were fitted to a stripping ratio curve. The optimal location of the mining area boundary was found to be 55 m westward offset from the mining area boundary in the inner row of the raised section, and numerical simulations based on the strength reduction method were applied to analyse the slope stability of the end gang at this location. The results of the study show that the analysed slope meets the stability requirements and the optimised new boundary avoids the stripping of approximately 65,837,376 m3 of economically unreasonable section.

Abstract Background Burning mouth syndrome (BMS) is an oral-facial pain disorder involving the central and peripheral nervous systems, but the evidence for altered pain sensitivity remains inconclusive. The aim of this study was to investigate pain sensitivity and oral health-related quality of life (OHRQoL) in patients with BMS and to assess the relationship between them. Methods Fifty Chinese patients with BMS (57.82 ± 11.2 years) and fifty age- and gender-matched healthy subjects (55.64 ± 10.1 years) participated in the study. The Pain Sensitivity Questionnaire (PSQ) was used to assess participants’ pain sensitivity. The Oral Health Impact Profile (OHIP-14) was used to evaluate participants’ OHRQoL. Results The PSQ total score (p = 0.009), the PSQ minor score (p = 0.003) and the OHIP-14 score (p

Abstract Background Transplantation of mitochondria is increasingly explored as a novel therapy in central nervous system (CNS) injury and disease. However, there are limitations in safety and efficacy because mitochondria are vulnerable in extracellular environments and damaged mitochondria can induce unfavorable danger signals. Methods Mitochondrial O-GlcNAc-modification was amplified by recombinant O-GlcNAc transferase (OGT) and UDP-GlcNAc. O-GlcNAcylated mitochondrial proteins were identified by mass spectrometry and the antiglycation ability of O-GlcNAcylated DJ1 was determined by loss-of-function via mutagenesis. Therapeutic efficacy of O-GlcNAcylated mitochondria was assessed in a mouse model of transient focal cerebral ischemia-reperfusion. To explore translational potential, we evaluated O-GlcNAcylated DJ1 in CSF collected from patients with subarachnoid hemorrhagic stroke (SAH). Results We show that isolated mitochondria are susceptible to advanced glycation end product (AGE) modification, and these glycated mitochondria induce the receptor for advanced glycation end product (RAGE)-mediated autophagy and oxidative stress when transferred into neurons. However, modifying mitochondria with O-GlcNAcylation counteracts glycation, diminishes RAGE-mediated effects, and improves viability of mitochondria recipient neurons. In a mouse model of stroke, treatment with extracellular mitochondria modified by O-GlcNAcylation reduces neuronal injury and improves neurologic deficits. In cerebrospinal fluid (CSF) samples from SAH patients, levels of O-GlcNAcylation in extracellular mitochondria correlate with better clinical outcomes. Conclusions These findings suggest that AGE-modification in extracellular mitochondria may induce danger signals, but O-GlcNAcylation can prevent glycation and improve the therapeutic efficacy of transplanted mitochondria in the CNS.

With the acceleration of urbanization and profound socioeconomic changes, the influx of people from various social strata into cities has led to the phenomenon of residential segregation. Currently, the international community has accumulated profound theoretical foundations and rich practical experiences in the study of residential segregation. This research, primarily based on the WOS literature database, sorts and summarizes relevant studies on residential segregation in recent years (focusing on publications from 2020 to 2024), emphasizing the following four key aspects: (1) tracing the evolution of the theory of residential segregation and analytical methods; (2) analyzing the main characteristics of urban residential segregation; (3) exploring the driving mechanisms and effects of urban residential segregation; and (4) summarizing research trends and providing future perspectives. This study aids urban planners in more accurately identifying areas and characteristics of residential segregation, optimizing urban layouts, and providing richer and more in-depth theoretical support and practical guidance for the field of urban planning science.

This study was designed to determine the optimal nitrogen application rate for strong-gluten wheat cultivation in the North China Plain. Employing Zhongmai 578, a strong-gluten wheat variety, a field experiment was conducted with the following four nitrogen levels: 0 kg/ha (N0), 150 kg/ha (N1), 210 kg/ha (N2), and 270 kg/ha (N3). The research focused on examining the impact of nitrogen application on the photosynthesis, yield, and quality of strong-gluten wheat. The findings revealed that the N2 treatment (210 kg/ha) yielded the highest results compared to the N0 treatment. Photosynthetic parameters, including chlorophyll content in wheat flag leaves, generally exhibited an increase followed by a decrease, peaking at 7 days after anthesis (except for the transpiration rate, which peaked at 14 days post-anthesis). In the first year, quality indices such as water absorption, capacity, sedimentation value, ductility, protein, and wet gluten initially increased and then decreased with rising nitrogen levels. Conversely, in the second year, these quality indices, including hardness, showed a progressive increase with elevated nitrogen application. These results indicate that enhanced nitrogen application can significantly improve the photosynthetic characteristics of strong-gluten wheat, thereby augmenting both yield and quality. Within the parameters of this experiment, an application of 210 kg/ha of nitrogen emerged as the optimal rate, promoting the superior yield and quality of strong-gluten wheat in the North China Plain.

Abstract Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms (ERBB2, BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.

Abstract Malignant transformation (MT) in recurrent parotid pleomorphic adenomas (PAs) is rare; therefore its occurrence lacks reliable predictive factors. Our goal was to clarify the predictors for MT of recurrent parotid PAs based on preoperative clinical parameters. Patients with a clinical diagnosis of recurrent parotid PA were retrospectively enrolled. The association between clinicopathologic variables and MT of PA was assessed using univariate and multivariate analyses. MT occurred in 11.8% of the 467 patients. In univariate analysis, three or more previous recurrences, newly developed facial nerve paralysis, difficulty in mouth opening, tumors with the largest tumor diameter ≥ 2.4 cm, and abnormal neck lymph node enlargement were associated with MT occurrence. Further, multivariate analysis showed that three or more previous recurrences, newly developed facial nerve paralysis, difficulty in mouth opening, and abnormal neck lymph node enlargement were independently related to MT. MT of recurrent PA was not uncommon. Clinical signs of malignancy included newly developed facial nerve paralysis, difficulty in mouth opening, three or more previous recurrences, and abnormal neck lymph node enlargement.

Although the internal electric field (IEF) of bismuth oxyiodide (BiOI) is acknowledged as a potent driving force for efficient charge separation, enhancing the intensity of IEF remains a challenge. Herein, highly crystalline BiOI nanosheets with I‐rich surface are employed to intensify IEF and direct the charge migration. In comparison to I‐poor BiOI nanosheets, which possess Bi−O layer termination and I‐defects, the I‐rich BiOI demonstrates 62.5‐fold improvement in IEF intensity to its well‐developed high crystalline structure, and its IEF direction is reversed by the surface I‐rich layers. This intensified IEF of I‐rich BiOI induces numerous holes (h+) to migrate to the surface of primary exposed (001) facets and electrons (e−) to the lateral facets efficiently, resulting in efficient charge separation spatially. Additionally, the surface accumulates h+ and superoxide radicals and acts in synergy to enhance the photodegradation of phenol. The photocatalytic activity of the I‐rich BiOI is found to be approximately fivefold and threefold higher than that of I‐poor BiOI under full spectra and visible light, respectively. Herein, the manipulation of IEF through surface and bulk structure regulation of BiOI for efficient charge separation is discussed, expecting to rationally improve photocatalytic performances.

Damaged brains try to repair themselves by producing neurons in areas where neurogenesis does not normally occur. Here, the authors show that brain endothelial cells provide microvesicle-encased signals that convert parenchymal astrocytes into neural progenitors, thus improving outcomes after stroke.

Microplastics are contaminants of emerging concern. In particular, research on the ecological effects of microplastics on microorganisms has attracted widespread attention. In this study, the role of characteristics of microplastics and environmental factors on microorganisms in sediments along the Daihai Lakeshore were investigated. Microscopic identification of microplastics revealed that the most common characteristics of microplastics were fiber, black color and particle size

Drip irrigation is a water-saving and fertilizer-saving application technology used in recent years, with which the frequency of drip irrigation nitrogen application has not yet been determined. In order to investigate the effects of different drip irrigation nitrogen application frequencies on the processing quality of medium-gluten wheat (Jimai22) and strong-gluten wheat (Jimai20 and Shiluan02-1), a two-year field experiment was carried out. Two frequencies of water and N application were set under the same conditions of total N application (210 kg·ha−1) and total irrigation (120 mm): DIF4, consisting of four equal applications of water and N (each of 30 kg·ha−1 of N application and 30 mm of irrigation) and DIF2, consisting of two equal applications of water and N (each of 60 kg·ha−1 of N application and 60 mm of irrigation). The results showed that IF4 significantly increased protein content by 2–8.6%, wet gluten content by 4.5–22.1%, and hardness value (p > 0.05), and PC2 was considered as a protein factor; the sedimentation value was highly significantly correlated with most of the parameters of the flour stretch (p < 0.01). DIF4 improved the stretching quality, and the flour quality of Jima22 was decreased, the flour quality of strong-gluten wheats Jimai20 and Shiluan02-1 was improved, and PC1 was considered to be the dough factor. In conclusion, although the frequency of nitrogen application by drip irrigation increased the protein factor and improved the tensile quality, the flour quality was not necessarily enhanced.

BackgroundCuproptosis is a type of programmed cell death that is involved in multiple physiological and pathological processes, including cancer. We constructed a prognostic cuproptosis-related long non-coding RNA (lncRNA) signature for acute myeloid leukemia (AML).MethodsRNA-seq and clinical data for AML patients were acquired from The Cancer Genome Atlas (TCGA) database. The cuproptosis-related prognostic lncRNAs were identified by co-expression and univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) was performed to construct a cuproptosis-related lncRNA signature, after which the AML patients were classified into two risk groups based on the risk model. Kaplan-Meier, ROC, univariate and multivariate Cox regression, nomogram, and calibration curves analyses were used to evaluate the prognostic value of the model. Then, expression levels of the lncRNAs in the signature were investigated in AML samples by quantitative polymerase chain reaction (qPCR). KEGG functional analysis, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. The sensitivities for potential therapeutic drugs for AML were also investigated.ResultsFive hundred and three lncRNAs related to 19 CRGs in AML samples from the TCGA database were obtained, and 21 differentially expressed lncRNAs were identified based on the 2-year overall survival (OS) outcomes of AML patients. A 4-cuproptosis-related lncRNA signature for survival was constructed by LASSO Cox regression. High-risk AML patients exhibited worse outcomes. Univariate and multivariate Cox regression analyses demonstrated the independent prognostic value of the model. ROC, nomogram, and calibration curves analyses revealed the predictive power of the signature. KEGG pathway and ssGSEA analyses showed that the high-risk group had higher immune activities. Lastly, AML patients from different risk groups showed differential responses to various agents.ConclusionA cuproptosis-related lncRNA signature was established to predict the prognosis and inform on potential therapeutic strategies for AML patients.

ObjectivesTo determine the predictor for occult neck metastases and the role of elective neck dissection (END) in cT3-4N0 parotid adenoid cystic carcinoma (ACC).MethodsPatients with surgically treated parotid ACC were retrospectively enrolled. Predictors of occult neck metastases and the effect of END on disease specific survival (DSS), overall survival (OS), locoregional control survival (LRC), and distant metastasis free survival (DMS) were analyzed.ResultsOccult neck metastases occurred in 35 (19.7%) of the 178 patients undergoing an END. The tumor stage [p=0.011, 4.215 (1.387–10.435)] and intra-parotid lymph node metastasis [p=0.032, 3.671 (1.693–8.775)] were related to the possibility of occult neck metastases independently. The END group had better 10-year LRC than the observation group (56% vs. 43%, p=0.002) and also better 10-year DMS than the observation group (43% vs. 32%, p

Cerebrospinal fluid (CSF) is an important sample source for diagnosing diseases in the central nervous system (CNS), but collecting and injecting CSF in small animals is technically challenging and often results in high mortality rates. Here, we present a cost-effective and efficient method for accessing the CSF in live rodents for fluid collection and infusion purposes. The key element of this protocol is a metal needle tool bent at a unique angle and length, allowing the successful access of the CSF through the foramen magnum. With this method, we can collect 5–10 µL of the CSF from mice and 70–100 µL from rats for downstream analyses, including mass spectrometry. Moreover, our minimally-invasive procedure enables iterative CSF collection from the same animal every few days, representing a significant improvement over prior protocols. Additionally, our method can be used to inject solutions into mice cisterna magna with high success rates and high postoperative recovery rates. In summary, we provide an efficient and minimally-invasive protocol for collecting and infusing reagents into the CSF in live rodents. We envision this protocol will facilitate biomarker discovery and drug development for diseases in the central nervous system.

ObjectivesTo explore the possible risk factors of orocutaneous fistula (OCF) development in free flap reconstruction of the tongue/floor of the mouth (TFOM).MethodsData of patients who underwent free flap reconstruction of the TFOM were retrospectively analyzed. The association between clinicopathologic variables and OCF occurrence was analyzed using univariate and multivariate analyses.ResultsAltogether, 469 patients were enrolled. OCF occurred in 43 patients with a rate of 9.2%. The univariate analysis revealed the negative effects of smoking, preoperative albumin level, cachexia, T4 stage, neck dissection, entire resection of the floor of the mouth (FOM), segmental mandibulectomy, and surgical site infection on OCF occurrence. The multivariate analysis confirmed the independence of cachexia (p

Abstract Charge separation efficiency of photocatalysts is still the key scientific issue for solar‐to‐chemical energy conversion. In this work, an electron donor–acceptor (D‐A) interface with high charge separation between TPPS (tetra(4‐sulfonatophenyl)porphyrin) and PDI (perylene diimide) is successfully constructed for boosting photocatalytic H2 evolution. The TPPS/PDI with D‐A interface shows excellent photocatalytic H2 evolution rate of 546.54 µmol h–1 (30.36 mmol h–1 g–1), which is 9.95 and 9.41 times higher than that of pure TPPS and PDI, respectively. The TPPS/PDI has a markedly stronger internal electric field, which is respectively 3.76 and 3.01 times higher than that of pure PDI and TPPS. The D‐A interface with giant internal electric field efficiently facilitates charge separation and urges TPPS/PDI to have a longer excited state lifetime than single component. The work provides entirely new ideas for designing materials with D‐A interface to realize high photocatalytic activity.

Abstract Background LncRNA LINC00662 is closely related to the occurrence and development of cancer. This study aims to explore the effect of LINC00662 on colon cancer tumor growth and metastasis and its molecular mechanism. Methods CCK8, colony formation, transwell, scratch wound, TUNEL, flow cytometry, RT-PCR, western blotting and immunohistochemistry assays were used to detect the proliferation, apoptosis, invasion and migration of colon cancer cell and mRNA and protein expressions. Luciferase reporter and RNA pull down assays were used to detect the combination of LINC00662 and miR-340-5p or IL22 and the combination of miR-340-5p and CLDN8/IL22. Co-immunoprecipitation were used to detect the co-expression of CLDN8 and IL22 in colon cell lines. The targets of LINC00662 were predicated by Starbase v2.0. The target genes of miR-340-5p were predicated by miRDB and TargetScan. GO and KEGG enrichment analysis were performed by DAVID website. Results LINC00662 was up-regulation in colon cancer tissues and cell lines. Univariate Cox regression analysis showed that the LINC00662 expression level was related to the poor prognosis. LINC00662-WT and miR-340-5p mimics co-transfection depressed luciferase activity and IL22/CLDN8-WT and miR-340-5p inhibitors co-transfection memorably motivated luciferase activity. LINC00662 overexpression promoted cell proliferation, invasion and migration, and inhibited cell apoptosis in colon cancer. In vivo xenograft studies in nude mice manifested that LINC00662 overexpression prominently accelerate tumor growth. There was an opposite reaction in the biological functions of colon cells and tumor growth between LINC00662 overexpression and LINC00662 inhibition in vitro and in vivo. The functions of miR-340-5p mimics regulating the biological functions of colon cells and tumor growth were consistent with those of LINC00662 inhibition. CLDN8 and IL22, as target genes of miR-340-5p, reversed the functions of LINC00662 affecting the biological functions of colon cells and the protein levels of Bax, Bcl-2, XIAP, VEGF, MMP-2, E-cadherin and N-cadherin. Co-immunoprecipitation experiments indicated that CLDN8 directly interact with IL22 in colon cell lines. LINC00662 regulated CLDN8 and IL22 expressions and the activation of ERK signaling pathway via targeting miR-340-5p. Conclusion LINC00662 overexpression promoted the occurrence and development of colon cancer by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway.

Objective. Dysfunction of the enterocyte barrier is associated with the development of ulcerative colitis (UC). This study was aimed at exploring the effect of DNMT3a on enterocyte barrier function in the progression of UC and the underlying mechanism. Method. Mice were given 3.5% dextran sodium sulphate (DSS) in drinking water to induce colitis. The primary intestinal epithelial cells (IECs) were isolated and treated with lipopolysaccharide (LPS) to establish an in vitro inflammatory model. We detected mouse clinical symptoms, histopathological damage, enterocyte barrier function, B cell differentiation, DNA methylation level, and cytokine production. Subsequently, the effect of DNMT3a from IECs on B cell differentiation was explored by a cocultural experiment. Result. DSS treatment significantly reduced the body weight and colonic length, increased disease activity index (DAI), and aggravated histopathological damage. In addition, DSS treatment induced downregulation of tight junction (TJ) protein, anti-inflammatory cytokines (IL-10 and TGF-β), and the number of anti-inflammatory B cells (CD1d+) in intestinal epithelial tissues, while upregulated proinflammatory cytokines (IL-6 and TNF-α), proinflammatory B cells (CD138+), and DNA methylation level. Further in vitro results revealed that DNMT3a silencing or TNFSF13 overexpression in IECs partly abolished the result of LPS-induced epithelial barrier dysfunction, as well as abrogated the effect of IEC-regulated B cell differentiation, while si-TACI transfection reversed these effects. Moreover, DNMT3a silencing decreased TNFSF13 methylation level and induced CD1d+ B cell differentiation, and the si-TNFSF13 transfection reversed the trend of B cell differentiation but did not affect TNFSF13 methylation level. Conclusion. Our study suggests that DNMT3a induces enterocyte barrier dysfunction to aggravate UC progression via TNFSF13-mediated interaction of enterocyte and B cells.

Microvascular failure is one of the key pathogenic factors in the dynamic pathological evolution after traumatic brain injury (TBI). Our laboratory and others previously reported that Annexin A2 functions in blood-brain barrier (BBB) development and cerebral angiogenesis, and recombinant human Annexin A2 (rA2) protected against hypoxia plus IL-1β-induced cerebral trans-endothelial permeability in vitro, and cerebral angiogenesis impairment of AXNA2 knock-out mice in vivo. We thereby hypothesized that ANXA2 might be a cerebrovascular therapy candidate that targets early BBB integrity disruption, and subacute/delayed cerebrovascular remodeling after TBI, ultimately improve neurological outcomes. In a controlled cortex impact (CCI) mice model, we found rA2 treatment (1 mg/kg) significantly reduced early BBB disruption at 24 h after TBI; and rA2 daily treatment for 7 days augmented TBI-induced mRNA levels of pro-angiogenic and endothelial-derived trophic factors in cerebral microvessels. In cultured human brain microvascular endothelial cells (HBMEC), through MAPKs array, we identified that rA2 significantly activated Akt, ERK, and CREB, and the activated CREB might be responsible for the rA2-induced VEGF and BDNF expression. Moreover, rA2 administration significantly increased cerebral angiogenesis examined at 14 days and vessel density at 28 days after TBI in mice. Consistently, our results validated that rA2 significantly induced angiogenesis in vitro, evidenced by tube formation and scratched migration assays in HBMEC. Lastly, we demonstrated that rA2 improved long-term sensorimotor and cognitive function, and reduced brain tissue loss at 28 days after TBI. Our findings suggest that rA2 might be a novel vascular targeting approach for treating TBI.

Background/Aims: IGF2BP2 has been reported to serve as an oncogene in various solid cancers. However, the role of IGF2BP2 in acute myelocytic leukemia (AML) is still unknown. Methods: Public databases Gene Omnibus was used to evaluate the expression of IGF2BP2 in AML patients and healthy controls. In addition, primary cells from these two populations were prepared by Ficoll density centrifugation. Rt-qPCR and western blot were used to detect IGF2BP2 expression in the primary cells from these two populations. Meta-analysis was performed to evaluate the association of IGF2BP2 and prognosis. Lentivirus-based shRNAs were used to knock down IGF2BP2 in AML cell lines KG-1a and Kasumi. Results: We searched the public database Gene Omnibus and analyzed IGF2BP2 expression in both AML and healthy populations. The results showed that IGF2BP2 was overexpressed in AML patients. To verify this phenomenon in fresh human samples, we compared the expression of IGF2BP2 in primary cells from 10 AML patients and 10 healthy controls and found that the expression of IGF2BP2 was upregulated in AML primary cells. More importantly, we observed that IGF2BP2 expression was negatively correlated with the CEBPA mutation status, which is an indicator of good prognosis (RR=0.648, p=0.0001). In addition, IGF2BP2 expression was positively associated with poor prognostic factors, such as the FLT3-ITD mutation (RR=1.198, p=0.0009) and IDH1 mutation (RR=1.354, p=0.0003), as well as intermediate and poor cytogenetic risk (RR=1.214, p=0.0026). To evaluate the prognostic value of IGF2BP2 in AML, we further performed a meta-analysis of 8 studies consisting of 1731 patients and found that IGF2BP2 overexpression was correlated with worse overall survival in AML patients [HR=1.31(1.16-1.49); p = 0.00]. Furthermore, we performed Gene Omnibus and Gene Set Enrichment analyses and found that the genes regulated by IGF2BP2 were mainly enriched in cell proliferation. IGF2BP2 knockdown by 4 different shRNA vectors significantly inhibited the growth of two AML cell lines, KG-1a and Kasumi. Conclusion: Thus, IGF2BP2 may serve as a biomarker to predict the prognosis of AML and as a potential target in AML.

Stress association proteins (SAPs) are A20/AN1 zinc-finger domain proteins, which play important roles in plant adaptation to abiotic stress and plant development. The functions of SAPs in some plants were reported, but little is known about it in wheat (Triticum aestivum L.). In this study, we characterized a novel 2AN1-type stress association protein gene TaSAP7-A, which was mapped to chromosome 5A in wheat. Subcellular localization indicated that TaSAP7-A was distributed in the nucleus and cytoplasm. Unlike previously known A20/AN1-type SAP genes, TaSAP7-A was negatively regulated to abiotic stress tolerance. Overexpressing TaSAP7-A Arabidopsis lines were hypersensitive to ABA, osmotic and salt stress at germination stage and post-germination stage. Overexpression of TaSAP7-A Arabidopsis plants accelerated the detached leaves’ chlorophyll degradation. Association analysis of TaSAP7-A haplotypes and agronomic traits showed that Hap-5A-2 was significantly associated with higher chlorophyll content at jointing stage and grain-filling stage. These results jointly revealed that TaSAP7-A is related to the chlorophyll content in the leaves of Arabidopsis and wheat. Both in vivo and in vitro experiments demonstrated that TaSAP7-A interacted with TaS10B, which was the component of regulatory subunit in 26S proteasome. In general, TaSAP7-A was a regulator of chlorophyll content, and favorable haplotypes should be helpful for improving plant chlorophyll content and grain yield of wheat.

Due to the problems such as the excessive proportion of road transport and extreme carbon emission situation of China’s transport structure adjustment, this paper combines the fourth-party logistics with the bulk cargo green transport. It is advancing the adjustment of China’s bulk cargo transport structure using fourth-party logistics. This paper improves the particle swarm optimization algorithm to compare the integrated cost and carbon emissions of different bulk fourth-party transport networks to verify the benefits of the fourth-party logistics on bulk cargo transport networks’ cost reduction and emission reduction. The results show that using the fourth-party logistics model to promote the transfer of cargoes from road to rail can reduce the integrated cost of the transport network, reduce carbon emissions, and achieve green transport.

Abstract Head and neck squamous cell carcinoma (HNSCC) ranks among the top most common cancers with a poor prognosis. The mechanism of chemoresistance is still not well known. This study is to investigate the programmed death‐ligand 1 (PD‐L1) expression in HNSCC, and test the effect of lactoferricin B (LfcinB) on chemoresistance and its mechanism. We analyzed 510 HNSCC patients in TCGA database and investigated how CD274 expression was related to patient prognosis. PD‐L1 was verified from HNSCC samples at local hospital with immunohistochemistry. PD‐L1 expression in the acquired cisplatin‐resistant HNSCC cells was examined by PCR and WB in order to test PD‐L1‐induced chemoresistance. LfcinB inoculation in cisplatin‐resistant HNSCC cells and in the nude mice was introduced to test the effect of LfcinB on targeting cisplatin resistance and its mechanism. High CD274 mRNA (>125 FPKM) from TCGA database had a significantly reduced 5‐year survival rate, and a lower 5‐year survival rate in the chemotherapy and radiotherapy‐treated patients (P

Abstract Background Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and has a poor prognosis. The epithelial-to-mesenchymal transition (EMT) is crucial for increasing the metastasis of OSCC. Recently, studies have indicated that sirtuin7 (SIRT7) is implicated in tumor genesis; however, the potential role of SIRT7 in the EMT and metastasis of OSCC has not been reported. Methods We investigated the cellular responses to SIRT7 silencing or overexpression in OSCC cell lines by wound healing assay, migration and invasion assay, western blotting, immunofluorescence and immunohistochemistry. Results In the present study, we found that SIRT7 was significantly downregulated in OSCC cell lines and human OSCC/OSCC tissues with lymph node metastasis. Overexpression of SIRT7 decreased the proliferation and invasion of OSCC cells in vitro, whereas SIRT7 knockdown significantly increased OSCC cell growth and invasion. Upregulation of SIRT7 concomitantly increased the expression of E-cadherin, and decreased the expression of mesenchymal markers. SIRT7 overexpression also reduced the level of acetylated SMAD4 in OSCC cells. Moreover, SIRT7 overexpression significantly inhibited OSCC lung metastasis in vivo. Conclusion Together, these findings suggested that SIRT7 suppressed EMT in OSCC metastasis by promoting SMAD4 deacetylation.

Abstract Background Activation of microglia can result in phenotypic and functional diversity. However, the pathways that trigger different states of microglial activation remain to be fully understood. Here, we hypothesized that after injury, astrocytes and endothelium may contribute to a gliovascular switch for microglial activation. Methods Astrocytes or cerebral endothelial cells were subjected to oxygen glucose deprivation, then conditioned media were transferred to microglia. The release of TNFα, IL-1β, IL-10, and IGF-1 was measured using ELISA. Surface markers of CD11b, CD45, CD86, and MHC class II were detected by flow cytometry. mRNA expression of iNOS, CD86, CD206, Arginase1, and transcription factors was measured using real-time PCR. Microglial function including migration and phagocytosis was assessed. Dendritogenesis was determined by counting the number of primary dendrites, secondary dendrites, and dendritic ends in the neurons exposed to either endothelial- or astrocyte-activated microglia. Results Exposure to conditioned media from oxygen-glucose-deprived cerebral endothelial cells or oxygen-glucose-deprived astrocytes activated microglia into different forms. The endothelium converted ramified microglia into amoeboid shapes; increased the release of TNFα, IL-1β, and IL-10; decreased IGF-1; upregulated iNOS expression; and inhibited microglial migration and phagocytosis. In contrast, astrocytes increased microglial production of IGF-1, upregulated CD206 expression, and enhanced microglial phagocytosis. These opposing effects of the endothelium versus astrocyte crosstalk partly mirror potentially deleterious versus potentially beneficial microglial phenotypes. Consistent with this idea, endothelial-activated microglia were neurotoxic, whereas astrocyte-activated microglia did not affect neuronal viability but instead promoted neuronal dendritogenesis. Conclusion These findings provide proof of concept that endothelial cells and astrocytes provide differing signals to microglia that influence their activation states and suggest that a gliovascular switch may be involved in the balance between beneficial versus deleterious microglial properties.

Abstract Orofacial pain impairs a patient's speech, swallowing, eating and interpersonal relations. Thirty-seven patients with a premalignant oral lesion, 124 patients with oral squamous cell carcinoma (OSSC), and 21 patients with a recurrence of OSSC were evaluated for their orofacial pain. The University of California San Francisco Oral Cancer Pain Questionnaire was administered to these patients at their initial visit, before they were prescribed analgesics for pain and before any treatment. Significant differences with respect to orofacial pain between the groups could be evaluatedwere observed. Patients with recurrence had the highest facial pain and patients with precancer had the lowest. Patients with OSSC and recurrence of OSSC reported significant levels of orofacial pain and functional restriction because of pain. Moreover, patients with recurrence of OSSC experienced significantly higher function-related pain, rather than pain qualities. These findings suggest that an important predictor for recurrence of OSSC may be the onset of orofacial pain that is exacerbated during function. The present study examined orofacial pain depending on the disease severity of precancer and oral cancer patients. Earlier recognition of symptoms of OSSC may improve early detection of its recurrence.

Lipocalin-2 (LCN2) is a stress protein, and can be hyper-produced by many kinds of cells after exposure to injury or disease conditions. In this study, we asked whether LCN2 may play a protective role in cerebral endothelium. After focal cerebral ischemia in rats, plasma levels of LCN2 were significantly elevated at 6, 12, and 24 hrs, and persisted until 3 days post-stroke. To assess the vascular mechanisms of LCN2, we used brain endothelial cell cultures to investigate its effects on neutrophil adhesion and endothelial barrier integrity. LCN2 did not affect neutrophil adhesion to endothelial cells either under normal conditions or after TNFα stimulation. TNFα significantly increased endothelial permeability, and LCN2 rescued endothelial permeability. Concomitantly, LCN2 restored the membrane distribution of the tight junction protein ZO-1 and the adherens junction protein VE-cadherin. Our findings suggest that elevated LCN2 in the blood after ischemic stroke might affect endothelial function, in part by reducing damage to endothelial junctional proteins and maintain blood-brain barrier integrity.

Atherosclerosis is the main pathological basis for the occurrence of most cardiovascular diseases, the leading global health threat, and a great burden for society. It has been well established that atherosclerosis is not only a metabolic disorder but also a chronic, sterile, and maladaptive inflammatory process encompassing both innate and adaptive immunity. Macrophages, the major immune cell population in atherosclerotic lesions, have been shown to play critical roles in all stages of atherosclerosis, including the initiation and progression of advanced atherosclerosis. Macrophages have emerged as a novel potential target for antiatherosclerosis therapy. In addition, the macrophage phenotype is greatly influenced by microenvironmental stimuli in the plaques and presents complex heterogeneity. This article reviews the functions of macrophages in different stages of atherosclerosis, as well as the phenotypes and functions of macrophage subsets. New treatment strategies based on macrophage-related inflammation are also discussed.

Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10-100 µmol/l. What's more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.