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With the continuous transformation and upgrading of China's industry, higher requirements have been put forward for the quality and efficiency of the industry, and the service of the industrial cleaning. The traditional cleaning method has been unable to meet the application needs in the industrial field due to its high pollution and high energy consumption. Laser cleaning, as a green, environmental protection, non-destructive new cleaning method, has quickly become a hot technology in the field of industrial cleaning. This paper will focus on this argument for laser rust removal.

Transient sexual experiences can have long-lasting effects on behavioral decisions, but the neural coding that accounts for this change is unclear. We found that the ejaculation experience selectively activated estrogen receptor 2 ( Esr2 )–expressing neurons in the bed nucleus of the stria terminalis (BNST)—BNST Esr2 —and led to persistent decreases in firing threshold for days, during which time the mice displayed sexual satiety. Inhibition of hyperexcited BNST Esr2 elicited fast mating recovery in satiated mice of both sexes. In males, such hyperexcitability reduced mating motivation and was partially mediated by larger HCN (hyperpolarization-activated cyclic nucleotide-gated) currents. Thus, BNST Esr2 not only encode a specific mating action but also represent a persistent state of sexual satiety, and alterations in a neuronal ion channel contribute to sexual experience–dependent long-term changes to mating drive.

This project is the use of Internet of Things technology how to better serve people's home life, which is a wide range of application prospects, social and economic benefits of the research direction. The system is mainly designed based on the planning of multiple detection points of the home environment, so as to provide personal intelligent housekeeping services from temperature, humidity, purification, cleaning, audio and visual for home life. Provide a set of solutions for smart homes, continuously optimize the comfort and services of the home environment, so as to improve people's home life.

Melanoma-associated Ag (MAGE)-C2, an immunogenic cancer germline (testis) Ag, is highly expressed by various tumor cells, thymic medullary epithelial cells, and germ cells. In this study, we aimed to explore the immunologic properties of MAGE-C2–specific CD8+ T cells and the relationship of its TCR β-chain V region (TCR vβ) subfamily distribution to prognosis of patients with esophageal cancer. PBMCs and tumor-infiltrating lymphocytes expanded by CD3/CD28 Dynabeads and MAGE-C2 peptides in vitro resulted in the induction of lysosome-associated membrane protein-1 (LAMP-1 or CD107a) on the cell surface and the production of IFN-γ by MAGE-C2–specific CD8+ T cells. We found differential TCR vβ subfamily distribution among flow-sorted CD107a+IFN-γ+ and CD107a−IFN-γ− CD8+ T cells. The proportion of CD107a+ and/or IFN-γ+ tetramer+ CD8+ T cells was lower in patients with lymph node metastasis, late tumor stage, and poorly differentiated state (p < 0.05). T-box transcription factor was positively correlated with CD107a and IFN-γ. Kaplan–Meier analysis showed that patients whose MAGE-C2–specific CD8+ T cells expressed high CD107a and/or IFN-γ had a longer survival time when compared with patients whose MAGE-C2–specific CD8+ T cells expressed low levels of CD107a and/or IFN-γ. Moreover, analysis of TCR vβ subfamily distribution revealed that a higher frequency of TCR vβ16 in MAGE-C2–specific CD8+ T cells was positively correlated with a better prognosis. These results suggest that the presence of functional MAGE-C2–specific CD8+ T cells had an independent prognostic impact on the survival of patients with esophageal cancer.

Immunotherapy has achieved significant breakthroughs in patients with hematological diseases and various cancers. The adoptive transfer of T cells, especially gene-modified T cells such as chimeric antigen receptor T (CAR-T) cells and T cell receptor-engineered T (TCR-T) cells, is developing rapidly. Since 2017, eight CAR-T cell products have been approved for the treatment of hematological diseases, such as refractory or relapsed acute B lymphoblastic leukemia, specific subtypes of B cell lymphoma, and multiple myeloma. The first TCR-T cell product, Kimmtrak, was approved for the treatment of unresectable or metastatic uveal melanoma in March 2022. However, there are still many problems, including side effects, relapse, high demand for individualization, and expensive cost in hematological diseases, tumor heterogeneity, antigen escape, poor immune cell infiltration ability, immunosuppressive microenvironment, and low response in solid tumors. With the in-depth exploration of tumor immunology and the development of genetic engineering technology, many novel strategies for improving the anti-tumor effect and safety of gene-modified T cell immunotherapy have been attempted. This paper presents a systematic review of the literature on CAR-T cell and TCR-T cell therapy, focusing on applications, clinical trials, problems, and potential solutions.

Clear cell renal cell carcinoma (ccRCC) is a main subtype of renal cancer, and advanced ccRCC frequently has poor prognosis. Many studies have found that lipid metabolism influences tumor development and treatment. This study was to examine the prognostic and functional significance of genes associated with lipid metabolism in individuals with ccRCC. Using the database TCGA, differentially expressed genes (DEGs) associated with fatty acid metabolism (FAM) were identified. Prognostic risk score models for genes related to FAM were created using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Our findings demonstrate that the prognosis of patients with ccRCC correlate highly with the profiles of FAM-related lncRNAs (AC009166.1, LINC00605, LINC01615, HOXA-AS2, AC103706.1, AC009686.2, AL590094.1, AC093278.2). The prognostic signature can serve as an independent predictive predictor for patients with ccRCC. The predictive signature's diagnostic effectiveness was superior to individual clinicopathological factors. Between the low- and high-risk groups, immunity research revealed a startling difference in terms of cells, function, and checkpoint scores. Chemotherapeutic medications such lapatinib, AZD8055, and WIKI4 had better outcomes for patients in the high-risk group. Overall, the predictive signature can help with clinical selection of immunotherapeutic regimens and chemotherapeutic drugs, improving prognosis prediction for ccRCC patients.

TGF-b,secreted by MDSCs,could regulate MAEL through Smad2/Smad3.

Primer sequences were used in our study.

The construct and primer sequences of MAEL used in the study.

Overexpression or knockdown of MAEL increased or decreased tumorigenesis in ESCC cells.

IL-8 played a role in tumor microenvironment.

Correlation analysis between the expression of MAEL and clinicopathological parameters in ESCC patients.

Maelstrom (MAEL) is a novel cancer/testis-associated gene, which is not only expressed in the male testicular germ cells among human normal tissues, but is also aberrantly expressed in various cancer tissues. In our study, MAEL was characterized as a tumor-promoting gene and was significantly associated with esophageal squamous cell carcinoma (ESCC) recurrence and unfavorable prognosis. Kaplan–Meier analysis showed that patients with high MAEL expression had a shorter survival time. Functional experiments showed that MAEL promoted tumor cell growth and inhibited cell apoptosis. These results prompted us to investigate the factors affecting the tumorigenicity of MAEL. Further experimentation demonstrated that MAEL enhanced the expression of phosphorylated Akt1, with subsequent phosphorylation of nuclear factor kappa B (NF-κB) subunit RelA in tumor cells, and chemoattracted myeloid-derived suppressor cells (MDSCs) by upregulating interleukin-8 (IL8) to accelerate tumor progression in the tumor microenvironment. We also found that TGFβ secreted by MDSCs could upregulate MAEL by inducing Smad2/Smad3 phosphorylation. In summary, this study revealed a mechanism by which MAEL could upregulate IL8 through Akt1/RelA to direct MDSCs homing into the tumor, suggesting that MAEL could be an attractive therapeutic target and a prognostic marker against ESCC. Cancer Immunol Res; 6(10); 1246–59. ©2018 AACR.

The effect of MAEL,Reparixin and MDSCs on tumor growth.

Supplementary Fig.1.Increased MDSCs levels in peripheral blood and tumor from OC patients.Supplementary Fig.2.Characterization of phenotype and immunosuppressive activity of MDSCs in OC patients.Supplementary Fig.3.Phenotypic analysis of MDSCs following metformin treatment.

Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells. Cancer Res; 78(7); 1779–91. ©2018 AACR.

Supplementary Table1.Characteristic of antibodies used in the flow cytometry evaluation.Supplementary Table2.Primer sequence and product size for PCR amplification.Supplementary Table3.Clinical and baseline clinical characteristics of OC patients with diabetes

The purpose of this study was to investigate differences in the pharmacodynamic, pharmacokinetic, and kidney distribution between Ligustri Lucidi Fructus (LLF) and wine-steamed Ligustri Lucidi Fructus (WLL) extracts in diabetic nephropathy (DN) rats. The DN rats were induced by high-fat-sugar diet (HFSD)/streptozotocin (STZ) regimen. For pharmacodynamics, the DN rats were treated with LLF and WLL extracts to assess the anti-diabetic nephropathy effects. For pharmacokinetics and kidney distribution, the concentrations of drugs (hydroxytyrosol, salidroside, nuezhenidic acid, oleoside-11-methyl ester, specnuezhenide, 1‴-O-β-d-glucosylformoside, G13, and oleonuezhenide) were determined. Regarding the pharmacodynamics, LLF and WLL extracts decreased the levels of blood glucose, serum creatinine (SCr), blood urea nitrogen (BUN), and 24-h urinary protein (24-h Upro) in DN rats. Furthermore, LLF and WLL extracts increased the level of high-density lipoprotein cholesterol (HDL-C); decreased the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C); and reduced levels of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) in DN rats. The anti-diabetic nephropathy effect of the WLL extract was better than that of the LLF extract. Regarding the pharmacokinetic and kidney tissue distribution, there were obvious differences in the eight ingredients between LLF and WLL extracts in DN rats. LLF and WLL extracts had protective effects on DN rats, while the WLL extract was better than the LLF extract regarding anti-diabetic nephropathy effects. The pharmacokinetic parameters and kidney distribution showed that wine-steaming could affect the absorption and distribution of the eight ingredients. The results provided a reasonable basis for the study of the clinical application and processing mechanism of LLF.

Organolead halide materials have shown promising optoelectronic properties that are suitable for light-emitting diodes (e.g., strong photoluminescence, narrow emission width, and high charge carrier mobility). However, the vast majority of them have no open porosity or open metal sites for host-guest interactions and are therefore not widely applicable in intrinsic fluorescent sensing of small molecules. Herein, we report a lead chloride-based metal-organic framework (MOF) with high porosity and stability and promising photoluminescent characteristics, performing as a sensitive, selective, and long-term stable fluorescence probe for NH3. For the first time, a homemade dynamic real-time photoluminescence monitoring system was developed, which showed that our haloplumbate-based MOF has an immediate response and an extremely low limit of detection (12 ppm) toward NH3. A variety of experimental characterization and theoretical calculations evidenced that the photoluminescence quenching was ascribed to the coordination between NH3 guests and exposed Pb2+ centers in MOFs. Moreover, a portable on-site smart NH3 detector was designed based on this haloplumbate-MOF using a 3D printer, and the quantitative recovery experiment demonstrated the effective detection of NH3 in the range of 15-150 ppm. This study opens a new pathway to design organolead halide-based MOFs to perform on-site chemical sensing of small molecules and shows their high potential to monitor safety concentrations of NH3 in different industrial sites.

Very long-chain fatty acids (VLCFAs) are important industrial raw materials and can be produced by genetically modified oil plants. For a long time, class A lysophosphatidic acid acyltransferase (LPAT) was considered unable to promote the accumulation of VLCFA in oil crops. The bottlenecks that the transgenic high VLCFA lines have an oil content penalty and the low amount of VLCFA in phosphatidylcholine remains intractable. In the present study, a class A LPAT2 from Camelina sativa (CsaLPAT2) promoting VLCFAs accumulation in phospholipid was found. Overexpression of CsaLPAT2 alone in Arabidopsis seeds significantly increased the VLCFA content in triacylglycerol, including C20:0, C20:2, C20:3, C22:0, and C22:1. The proportion of phosphatidic acid molecules containing VLCFAs in transgenic seeds reached up to 45%, which was 2.8-fold greater than that in wild type. The proportion of phosphatidylcholine and diacylglycerol molecules containing VLCFAs also increased significantly. Seed size in CsaLPAT2 transgenic lines showed a slight increase without an oil content penalty. The total phospholipid content in the seed of the CsaLPAT2 transgenic line was significantly increased. Furthermore, the function of class A LPAT in promoting the accumulation of VLCFAs is conserved in the representative oil crops of Brassicaceae, such as C. sativa, Arabidopsis thaliana, Brassica napus, Brassica rapa, and Brassica oleracea. The findings of this study provide a promising gene resource for the production of VLCFAs.

Objective: Esophageal squamous cell carcinoma (ESCC) has high morbidity and mortality rates worldwide. Cancer stem cells (CSCs) may cause tumor initiation, metastasis, and recurrence and are also responsible for chemotherapy and radiotherapy failures. Myeloid-derived suppressor cells (MDSCs), in contrast, are known to be involved in mediating immunosuppression. Here, we aimed to investigate the mechanisms of interaction of CSCs and MDSCs in the tumor microenvironment. Methods: ESCC tissues and cell lines were evaluated. Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) was knocked down and overexpressed by lentiviral transfection. Quantitative PCR, Western blot, immunohistochemistry, cell invasion, flow cytometry, cell sorting, multiplex chemokine profiling, and tumor growth analyses were performed. Results: Microarray analysis revealed 10 upregulated genes in esophageal CSCs. Only NEDD9 was upregulated in CSCs using the sphere-forming method. NEDD9 expression was correlated with tumor invasion (P = 0.0218), differentiation (P = 0.0153), and poor prognosis (P = 0.0373). Additionally, NEDD9 was required to maintain the stem-like phenotype. Screening of chemokine expression in ESCC cells with NEDD9 overexpression and knockdown showed that NEDD9 regulated C-X-C motif chemokine ligand 8 (CXCL8) expression via the ERK pathway. CXCL8 mediated the recruitment of MDSCs induced by NEDD9 in vitro and in vivo. MDSCs promoted the stemness of ESCC cells through NEDD9 via the Notch pathway. Conclusions: As a marker of ESCC, NEDD9 maintained the stemness of ESCC cells and regulated CXCL8 through the ERK pathway to recruit MDSCs into the tumor, suggesting NEDD9 as a therapeutic target and novel prognostic marker for ESCC.

Background Tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) was initially considered an immunity guard; however, its function remains controversial. Besides immune cells, lung and colon cancer cells have also been reported to express TRAIL, which can promote tumor invasion and metastasis. However, the biological function and underlying mechanism of action of TRAIL in esophageal squamous cell carcinoma (ESCC) remain poorly elucidated. Methods The ESCC cells stemness, migration, and proliferation ability was assessed by sphere formation, Transwell, and CCK8 assay. The stemness- and epithelial-mesenchymal transition (EMT)- related genes expression levels were analyzed by Western blot and RT-qPCR. The signal activation was conducted by Western blot. The xenograft mouse experiments and lung metastasis model were performed to confirm our findings in vitro. Results Herein, we found that TRAIL is a negative predictor in patients with ESCC. To further investigate the biological function of TRAIL, we established TRAIL knockdown and overexpression ESCC cell lines and found that TRAIL induced EMT and promoted tumor aggressiveness. Furthermore, we demonstrated that TRAIL- overexpressing cells upregulated PD-L1 expression, which was dependent on the p-ERK/STAT3 signaling pathway. We obtained similar results when using recombinant human TRAIL. Finally, we validated the biological role and mechanism of action of TRAIL in vivo. Conclusions These findings demonstrate that TRAIL promotes ESCC progression by enhancing PD-L1 expression, which induces EMT. This may explain the failure of TRAIL preclinical trials.

Online adaptive replanning (OLAR) is generally labor-intensive and time-consuming during MRI-guided adaptive radiation therapy (MRgART). This work aims to develop a method to determine OLAR necessity during MRgART.A machine learning classifier was developed to predict OLAR necessity based on wavelet multiscale texture features extracted from daily MRIs and was trained and tested with data from 119 daily MRI datasets acquired during MRgART for 24 pancreatic cancer patients treated on a 1.5 T MR-Linac. Spearman correlations, interclass correlation (ICC), coefficient of variance (COV), t-test (p 0.05), self-organized map (SOM) and maximum stable extremal region (MSER) algorithm were used to determine candidate features, which were used to build the prediction models using Bayesian classifiers. The model performance was judged using the AUC of the ROC curve.Spearman correlation identified 123 features that were not redundant (r 0.9). Of them 82 showed high ICC for repositioning 0.6, 67 had a COV greater than 9% for OLAR. Among the 38 features passed the t-test, 25 passed the SOM and 12 passed the MSER. These final 12 features were used to build the classifier model. The combination of 2-3 features at a time was used to build the classifier models. The best performing model was a 3-feature combination, which can predict OLAR necessity with a CV-AUC of 0.98.A machine learning classifier model based on the wavelet features extracted from daily MRI for pancreatic cancer was developed to automatically and objectively determine if OLAR is necessary for a treatment fraction avoiding unnecessary effort during MRgART.

The emergence of chimeric antigen receptor (CAR) T cell therapy has shifted the paradigm of malignant tumor treatment, especially the advent of CD19-directed CAR-T cell therapy for the treatment of relapsed/refractory (R/R) B-cell malignancies. Although CAR-T cell therapy has promising effects, some patients are resistant to this treatment, leaving them with limited options. Therefore, strategies to overcome resistance to CAR-T cell therapy are needed. We retrospectively studied three R/R diffuse large B-cell lymphoma patients who were resistant to CAR-T cell therapy and whose disease was controlled after receiving pembrolizumab, 21D4 CAR-T cells, or ibrutinib and venetoclax. Some promising prevention and treatment strategies to overcome treatment resistance are also discussed.

Organolead halide hybrids have many promising attributes for photocatalysis, e.g. tunable bandgaps and excellent carrier transport, but their instability constraints render them vulnerable to polar molecules and limit their photocatalysis in moisture. Herein, we report the construction of metal–organic frameworks based on [Pb2X]3+ (X = Br–/I–) chains as secondary building units and 2-amino-terephthalate as organic linkers, and extend their applications in photocatalytic CO2 reduction with water vapor as the reductant. Hall effect measurement and ultrafast transient absorption spectroscopy demonstrate the bromo/iodo-bridged frameworks have substantially enhanced photocarrier transport, which results in photocatalytic performances superior to conventional metal-oxo metal-organic frameworks. Moreover, in contrast to lead perovskites, the [Pb2X]3+-based frameworks have accessible porosity and high moisture stability for gas-phase photocatalytic reaction between CO2 and H2O. This work significantly advances the excellent carrier transport of lead perovskites into the field of metal-organic frameworks.

The lateral habenula (LHb) is implicated in emotional processing, especially depression. Recent studies indicate that the basal forebrain (BF) transmits reward or aversive signals to the LHb. However, the contribution of the BF-LHb circuit to the pathophysiology of depression still needs to be determined. Here, we find that the excitatory projection to the LHb from the substantia innominata (SI), a BF subregion, is activated by aversive stimuli and inhibited by reward stimuli. Furthermore, chronic activation of the SI-LHb circuit is sufficient to induce depressive-like behaviors, whereas inhibition of the circuit alleviates chronic stress–induced depressive-like phenotype. We also find that reward consumption buffers depressive-like behaviors induced by chronic activation of the SI-LHb circuit. In summary, we systematically define the function and mechanism of the SI-LHb circuit in modulating depressive-like behaviors, thus providing important insights to better decipher LHb processing in the pathophysiology of depression.

Objective: Esophageal squamous cell carcinoma (ESCC) has high morbidity and mortality rates worldwide. Cancer stem cells(CSCs) may cause tumor initiation, metastasis, and recurrence and are also responsible for chemotherapy and radiotherapy failures.Myeloid-derived suppressor cells (MDSCs), in contrast, are known to be involved in mediating immunosuppression. Here, we aimedto investigate the mechanisms of interaction of CSCs and MDSCs in the tumor microenvironment. Methods: ESCC tissues and cell lines were evaluated. Neural precursor cell expressed, developmentally downregulated 9 (NEDD9)was knocked down and overexpressed by lentiviral transfection. Quantitative PCR, Western blot, immunohistochemistry, cellinvasion, flow cytometry, cell sorting, multiplex chemokine profiling, and tumor growth analyses were performed. Results: Microarray analysis revealed 10 upregulated genes in esophageal CSCs. Only NEDD9 was upregulated in CSCs using thesphere-forming method. NEDD9 expression was correlated with tumor invasion (P = 0.0218), differentiation (P = 0.0153), andpoor prognosis (P = 0.0373). Additionally, NEDD9 was required to maintain the stem-like phenotype. Screening of chemokineexpression in ESCC cells with NEDD9 overexpression and knockdown showed that NEDD9 regulated C-X-C motif chemokineligand 8 (CXCL8) expression via the ERK pathway. CXCL8 mediated the recruitment of MDSCs induced by NEDD9 in vitro andin vivo. MDSCs promoted the stemness of ESCC cells through NEDD9 via the Notch pathway. Conclusions: As a marker of ESCC, NEDD9 maintained the stemness of ESCC cells and regulated CXCL8 through the ERK pathwayto recruit MDSCs into the tumor, suggesting NEDD9 as a therapeutic target and novel prognostic marker for ESCC.

Objective: L1 cell adhesion molecule (L1CAM) exhibits oncogenic activity in tumors. However, the link between L1CAM and the tumor microenvironment remains poorly understood in patients with esophageal squamous cell carcinoma (ESCC). In this study, we investigated how L1CAM expression in ESCC affects the oncogenic characteristics of tumor cells and the tumor microenvironment. Methods: Human ESCC samples were collected, and the mRNA and protein levels of L1CAM were examined by real-time PCR and immunohistochemistry. Overexpression and knockdown gene expression assays were used for mechanistic studies. The cell proliferation and cell cycle were measured with CCK-8 assays and flow cytometry. Cell migration and invasion ability were measured with Transwell assays. Multiplex bead-based assays were performed to identity the factors downstream of L1CAM. Xenograft studies were performed in nude mice to evaluate the effects of L1CAM on tumor growth and regulatory T cell (Treg) recruitment. Results: L1CAM expression was significantly elevated in ESCC tissues (P < 0.001) and correlated with poorer prognosis (P < 0.05). Ablation of L1CAM in ESCC cells inhibited tumor growth and migration, and increased tumor cell apoptosis (P < 0.05). In the tumor microenvironment, L1CAM expression correlated with Treg infiltration in ESCC by affecting CCL22 secretion. Mechanistically, L1CAM facilitated CCL22 expression by activating the PI3K/Akt/NF-κB signaling pathway. Furthermore, CCL22 promoted Treg recruitment to the tumor site; the Tregs then secreted TGF-β, which in turn promoted L1CAM expression via Smad2/3 in a positive feedback loop. Conclusions: Our findings provide new insight into the mechanism of immune evasion mediated by L1CAM, suggesting that targeting L1CAM-CCL22-TGF-β crosstalk between tumor cells and Tregs may offer a unique means to improve treatment of patients with ESCC.

Lonicerae Japonicae Flos (LJF) is commonly used in Chinese herbal medicines and exhibits anti-viral, anti-oxidative, and anti-inflammatory properties. The reciprocal relationship between sleep, the immune system and the central nervous system is well-established in the animal models. In this study, we used the mouse model to analyze the beneficial effects of the LJF on the dysregulated sleep-wakefulness cycle in response to acute sleep deprivation and lipopolysaccharide (LPS)-induced inflammation and the potential underlying mechanisms. Polysomnography data showed that LJF increased the time spent in non-rapid eye movement (NREM) sleep during the day under basal conditions. Furthermore, latency to sleep was reduced and the time spent in rapid eye movement (REM) sleep was increased during recovery from acute sleep deprivation. Furthermore, LJF-treated mice showed increased REM sleep and altered electroencephalogram (EEG) power spectrum in response to intra-peritoneal injection of LPS. LJF significantly reduced the levels of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β in the blood serum as well as hippocampus, and medial prefrontal cortex (mPFC) tissues in the LPS-challenged mice by inhibiting microglial activation. Moreover, LJF increased the time spent in REM sleep in the LPS-challenged mice compared to the control mice. These results suggested that LJF stimulated the sleep drive in response to acute sleep deprivation and LPS-induced inflammation, thereby increasing REM sleep for recovery and neuroprotection. In conclusion, our findings demonstrate that the clinical potential of LJF in treating sleep disorders related to sleep deprivation and neuro-inflammation.

Organolead halide hybrids have many promising attributes for photocatalysis, e.g. tunable bandgaps and excellent carrier transport, but their instability constraints render them vulnerable to polar molecules and limit their photocatalysis in moisture. Herein, we report the construction of metal-organic frameworks based on [Pb

Background Circadian differences in the induction, maintenance, or emergence from volatile anaesthesia have not been well studied. Methods The minimal alveolar concentration (MAC) for preventing movement in response to a painful stimulus, MAC for loss of righting reflex (MACLORR), and MAC for recovery of righting reflex (MACRORR) in C57BL/6J male mice with isoflurane or sevoflurane exposure were measured during either the light or dark phase. Time to onset of loss of righting reflex (TimeLORR) and recovery of righting reflex (TimeRORR) upon exposure to 1 MAC of isoflurane or sevoflurane were determined. EEG was also monitored in the light and dark phase under isoflurane or sevoflurane exposure. The noradrenergic toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was used to deplete noradrenergic neurones in the locus coeruleus to explore the impact of norepinephrine on these measurements. Results MACLORR, TimeLORR, and MAC did not show light- or dark-phase-dependent variations for either isoflurane or sevoflurane exposure. However, MACRORR was higher and TimeRORR was shorter in the dark phase than in the light phase for both isoflurane and sevoflurane exposure. The EEG delta wave power was higher but theta wave power was lower in the light phase than that in the dark phase during the rest state and emergence of anaesthesia. These light- and dark-phase-dependent changes in emergence were abolished in DSP-4-treated mice. Conclusion Our data show that circadian differences exist during emergence but not during induction or maintenance of sevoflurane or isoflurane anaesthesia. The locus coeruleus noradrenergic system may contribute to these differences.

For decades, genetic engineering approaches to produce unusual fatty acids (UFAs) in crops has reached a bottleneck, including reduced seed oil production and seed vigor. Currently, plant models in the field of research are primarily used to investigate defects in oil production and seedling development, while the role of UFAs in embryonic developmental defects remains unknown. In this study, we developed a transgenic Arabidopsis plant model, in which the embryo exhibits severely wrinkled appearance owing to α-linolenic acid (ALA) accumulation. RNA-seq analysis in the defective embryo suggested that brassinosteroid synthesis, fatty acid (FA) synthesis, and photosynthesis were inhibited, while FA degradation, endoplasmic reticulum (ER) stress, and oxidative stress were activated. Lipidomics analysis showed that ultra-accumulated ALA is released from Phosphatidylcholine (PC) as a free fatty acid (FFA) in cell, inducing severe ER and oxidative stress. Furthermore, we identified that overexpression of lysophosphatidic acid acyltransferase 2 (LPAT2) rescued the defective phenotype. In the rescue line, the pool capacity of the Kennedy pathway was increased, and the esterification of ALA indirectly to triacylglycerol (TAG) was enhanced to avoid stress. This study provides a plant model that aids in understanding the molecular mechanism of embryonic developmental defects, and generate strategies to produce higher levels of UFAs.

Highlights • This is the first clinical use of 4D-MRI in an online radiation therapy workflow. • Eleven patients received SBRT on an Elekta MR-Linac using ATP and ATS workflows. • A parallel contour editing approach was successfully utilized in the ATS workflow., Background and purpose In this report, we describe our implementation and initial clinical experience using 4D-MRI driven MR-guided online adaptive radiotherapy (MRgOART) for abdominal stereotactic body radiotherapy (SBRT) on the Elekta Unity MR-Linac. Materials and methods Eleven patients with abdominal malignancies were treated with free-breathing SBRT in three to five fractions on a 1.5 T MR-Linac. Online adaptive plans were generated using Adapt-To-Position (ATP) or Adapt-To-Shape (ATS) workflows based on motion averaged or mid-position images derived from a pre-beam 4D-MRI. A high performance server positioned on the local MR-Linac machine network was utilized for 4D-MR image reconstruction. A parallel contour editing approach was employed in the ATS workflow. Intravoxel incoherent motion (IVIM) and T2 mapping sequences were acquired during adaptive planning in both ATP and ATS workflows for treatment response monitoring. Adaptive plans were delivered under real-time cine image motion monitoring. Results The shortest 4D-MRI time-to-image was the motion averaged image, followed by mid position and respiratory binned images. In this cohert of patients, 50% of treatments utilized the ATS workflow; the remaining treatments utilized the ATP workflow. Mid-position images were utilized as daily planning images for two of the eleven patients. The mean daily adaptive plan secondary dose calculation and ArcCheck 3D Gamma passing rates were 97.5% (92.1–100.0%) and 99.3% (96.2–100.0%), respectively. The median overall treatment times for abdominal SBRT was 46 and 62 min for ATP and ATS workflows, respectively. Conclusion We have successfully implemented and utilized a 4D-MRI driven MRgOART process with ATP and ATS workflows for free-breathing abdominal SBRT on a 1.5 T Elekta Unity MR-Linac.

Background CD8+ T cell trafficking to the tumor site is essential for effective colorectal cancer (CRC) immunotherapy. However, the mechanism underlying CD8+ T cell infiltration in colorectal tumor tissues is not fully understood. In the present study, we investigated CD8+ T cell infiltration in CRC tissues and the role of chemokine–chemokine receptor signaling in regulation of T cell recruitment. Methods We screened chemokines and cytokines in healthy donor and CRC tissues from early- and advanced-stage patients using multiplex assays and PCR screening. We also utilized transcription factor activation profiling arrays and established a xenograft mouse model. Results Compared with tumor tissues of early-stage CRC patients, CD8+ T cell density was lower in advanced-stage tumor tissues. PCR screening showed that CXCL10 levels were significantly increased in advanced-stage tumor tissues. CXCR3 (the receptor of CXCL10) expression on CD8+ T cells was lower in the peripheral blood of advanced-stage patients. The migratory ability of CD8+ T cells to CXCL10 depended on CXCR3 expression. Multiplex arrays showed that IL-17A was increased in advanced-stage patient sera, which markedly downregulated CXCR3 expression via activating STAT3 signaling and reduced CD8+ T cell migration. Similar results were found after CD8+ T cells were treated with Th17 cell supernatant. Adding anti-IL-17A or the STAT3 inhibitor, Stattic, rescued these effects in vitro and in vivo. Moreover, survival analysis showed that patients with low CD8 and CXCR3 expression and high IL-17A levels had significantly worse prognosis. Conclusions CD8+ T cell infiltration in advanced-stage tumor was systematically inhibited by Th17 cells via IL-17A/STAT3/CXCR3 axis. Our findings indicate that the T cell infiltration in the tumor microenvironment may be improved by inhibiting STAT3 signaling.

Objective. Auto-delineation of air regions on daily MRI for MR-guided online adaptive radiotherapy (MRgOART) of abdominal tumors is challenging since the air packets occur randomly and their MR intensities can be similar to some other tissue types. This work reports a new method to auto-delineate air regions on MRI. Approach. The proposed method (named DIFF method) consists of (1) generating a combined volume V comb , which is a union of the air-containing organs on a reference MR image offline, (2) transferring V comb from the reference MR to a daily MR via DIR, (3) combining the transferred V comb with a region of high DIR inaccuracy, and (4) applying a threshold to the obtained final combined volume to generate the air volumes. The high DIR inaccuracy region was calculated from the absolute difference between the deformed daily and the reference images. This method was tested on 36 abdominal daily MRI sets acquired from 7 patients on a 1.5 T MR-Linac. The performance of DIFF was compared with alternative auto-air generation methods that (1) does not account for DIR inaccuracies, and (2) uses rigid registration instead of DIR. Main results. The results show that the proposed DIFF method can be fully automated and can be executed within 25 s. The Dice similarity coefficient of manual and DIFF auto-generated air contours was >92% for all cases, while it was 90% for the alternative auto-delineation methods. Dosimetrically, the auto-generated air regions using DIFF resulted in practically identical DVHs as those generated by using manual air contours. Significance. The DIFF method is robust and accurate and can be implemented to automatically consider the inter- and intra- fractional air volume variations during MRgOART for abdominal tumors. The use of DIFF method improves dosimetric accuracy as compared to other methods, especially beneficial for the patients with large daily abdominal air volume variations.

Melanoma-associated Ag (MAGE)-C2, an immunogenic cancer germline (testis) Ag, is highly expressed by various tumor cells, thymic medullary epithelial cells, and germ cells. In this study, we aimed to explore the immunologic properties of MAGE-C2-specific CD8

A unique method for the synthesis of cyclopentenes and cyclohexenes has been achieved by the coupling of diketones and alkenes under cobalt(II) catalysis and dimethyl sulfoxide involvement. Under optimal conditions, the formation of five- and six-membered rings can be readily controlled by the α-position substitution of styrenes. This process is proposed to proceed through a reaction sequence of oxidative coupling (mediated by K2S2O8), regioselective alkene insertion (promoted by cobalt), and intramolecular attack of the resulting allylcobalt species on the carbonyl group or methyl group in the reactive methylene process.

Organolead halide materials have shown promising optoelectronic properties that are suitable for light-emitting diodes (e.g., strong photoluminescence, narrow emission width, and high charge carrier mobility). However, the vast majority of them have no open porosity or open metal sites for host-guest interactions and are therefore not widely applicable in intrinsic fluorescent sensing of small molecules. Herein, we report a lead chloride-based metal-organic framework (MOF) with high porosity and stability and promising photoluminescent characteristics, performing as a sensitive, selective, and long-term stable fluorescence probe for NH

Ground risk, as one of the key parameters for assessing risk before an operation, plays an important role in the safety management of unmanned aircraft systems. However, how to correctly identify ground risk and to predict risk accurately remains challenging due to uncertainty in relevant parameters (people density, ground impact, etc.). Therefore, we propose a dynamic model based on a deep learning approach to assess the ground risk. First, the parameters that affect ground risk (people density, ground impact, sheltered, etc.) are defined and analyzed. Second, a kinetic-theory-based model is applied to assess the extent of ground impact. Third, a joint convolutional neural network–deep neural network model (C-Snet model) is built to predict the density of people on the ground and to calculate the shelter factor for different degrees of ground impact. Last, a dynamic model combining a deep learning and a kinetic model is established to predict ground risk. We performed simulations to validate the effectiveness and efficiency of the model. The results indicate that ground risk has spatial-temporal characteristics and that our model can predict risk accurately by capturing these characteristics.