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In this article, we aim to verify the relationship between ESG disclosure quality and stock liquidity of listed companies and to provide a detailed analysis of its mechanisms. Based on the theories of information asymmetry, signal transmission, reputation, and stakeholder, we summarize and analyze the theoretical and logical framework of how ESG information disclosure can impact stock liquidity. Following the fixed effect (considering individual, year, and industry), panel model was applied to empirically test the relationship between ESG disclosure score and stock liquidity with data ranging from 2012 to 2021. The research findings indicate that improving the quality of ESG disclosure by companies can significantly enhance the level of stock liquidity. Furthermore, we analyze and verify through mechanism tests that ESG disclosure can influence stock liquidity by increasing analyst attention and media coverage (information effect) and enhancing reputation (reputation effect). From a theoretical perspective, the paper enriches the research related to the economic impact of ESG information disclosure and factors affecting stock liquidity. Also, we validate theories connected to information and reputation. From a practical perspective, the research has specific reference value for policymakers, enterprise managers, and investors.

Abstract Background In recent years, the research on the relationship between sarcopenia before and after the treatment of esophageal cancer, as well as its impact on prognosis of esophageal cancer, has increased rapidly, which has aroused people’s attention to the disease of patients with esophageal cancer complicated with sarcopenia. This review examines the prevalence of sarcopenia in patients with esophageal cancer, as well as the relationship between sarcopenia (before and after surgery or chemotherapy) and prognosis in patients with esophageal cancer. Moreover, we summarized the potential pathogenesis of sarcopenia and pharmacologic and non-pharmacologic therapies. Methods A narrative review was performed in PubMed and Web of Science using the keywords (“esophageal cancer” or “esophageal neoplasm” or “neoplasm, esophageal” or “esophagus neoplasm” or “esophagus neoplasms” or “neoplasm, esophagus” or “neoplasms, esophagus” or “neoplasms, esophageal” or “cancer of esophagus” or “cancer of the esophagus” or “esophagus cancer” or “cancer, esophagus” or “cancers, esophagus” or “esophagus cancers” or “esophageal cancer” or “cancer, esophageal” or “cancers, esophageal” or “esophageal cancers”) and (“sarcopenia” or “muscular atrophy” or “aging” or “senescence” or “biological aging” or “aging, biological” or “atrophies, muscular” or “atrophy, muscular” or “muscular atrophies” or “atrophy, muscle” or “atrophies, muscle” or “muscle atrophies”). Studies reporting relationship between sarcopenia and esophageal cancer were analyzed. Results The results of the review suggest that the average prevalence of sarcopenia in esophageal cancer was 46.3% ± 19.6% ranging from 14.4 to 81% and sarcopenia can be an important predictor of poor prognosis in patients with esophageal cancer. Patients with esophageal cancer can suffer from sarcopenia due to their nutritional deficiencies, reduced physical activity, chemotherapy, and the effects of certain inflammatory factors and pathways. When classic diagnostic values for sarcopenia such as skeletal muscle index (SMI) are not available clinically, it is also feasible to predict esophageal cancer prognosis using simpler metrics, such as calf circumference (CC), five-count sit-up test (5-CST), and six-minute walk distance (6MWD). Conclusions Identifying the potential mechanism of sarcopenia in patients with esophageal cancer and implementing appropriate interventions may hold the key to improving the prognosis of these patients.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Abstract Background Glioblastoma (GBM), the most common primary malignant brain tumor, has a poor prognosis, with a median survival of only 14.6 months. The Warburg effect is an abnormal energy metabolism, which is the main cause of the acidic tumor microenvironment. This study explored the role of the Warburg effect in the prognosis and immune microenvironment of GBM. Methods A prognostic risk score model of Warburg effect‐related genes (Warburg effect signature) was constructed using GBM cohort data from The Cancer Genome Atlas. Cox analysis was performed to identify independent prognostic factors. Next, the nomogram was built to predict the prognosis for GBM patients. Finally, the drug sensitivity analysis was utilized to find the drugs that specifically target Warburg effect‐related genes. Results Age, radiotherapy, chemotherapy, and WRGs score were confirmed as independent prognostic factors for GBM by Cox analyses. The C‐index (0.633 for the training set and 0.696 for the validation set) and area under curve (>0.7) indicated that the nomogram exhibited excellent performance. The calibration curve also indicates excellent consistency of the nomogram between predictions and actual observations. In addition, immune microenvironment analysis revealed that patients with high WRGs scores had high immunosuppressive scores, a high abundance of immunosuppressive cells, and a low response to immunotherapy. The Cell Counting Kit‐8 assays showed that the drugs targeting Warburg effect‐related genes could inhibit the GBM cells growth in vitro. Conclusion Our research showed that the Warburg effect is connected with the prognosis and immune microenvironment of GBM. Therefore, targeting Warburg effect‐related genes may provide novel therapeutic options.

Abstract Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

Abstract Glioblastoma (GBM) is the most common primary central nervous system tumor, whose prognosis remains poor under the sequential standard of care, such as neurosurgery followed by concurrent temozolomide radiochemotherapy and adjuvant temozolomide chemotherapy in the presence or absence of tumor treating fields. Accordingly, the advent of molecular targeted therapy and immunotherapy has opened a new era of tumor management. A diverse range of targeted drugs have been tested in patients with GBM in phase III clinical trials. However, these drugs are ineffective for all patients, as evidenced by the fact that only a minority of patients in these trials showed prolonged survival. Furthermore, there are several published phase III clinical trials that involve immune checkpoint inhibitors, peptide vaccines, dendritic cell vaccines, and virotherapy. Accordingly, this review comprehensively overviews existing studies of targeted drugs and immunotherapy for glioma and discusses the challenge and perspective of targeted drugs and immunotherapy for glioma to clarify future directions.

Abstract Background Balanced reciprocal translocation (BRT) is one of the most common chromosomal abnormalities that causes infertility, recurrent miscarriage, and birth defects. Preimplantation genetic testing (PGT) is widely used to select euploid embryos for BRT carriers to increase the chance of a healthy live birth. Several strategies can be used to distinguish reciprocal translocation carrier embryos from those with a normal karyotype; however, these techniques are time-consuming and difficult to implement in clinical laboratories. In this study, nanopore sequencing was performed in two reciprocal translocation carriers, and the results were validated using the next-generation sequencing-based method named, “Mapping Allele with Resolved Carrier Status” (MaReCs). Results The translocation breakpoints in both reciprocal translocation carriers were accurately identified by nanopore sequencing and were in accordance with the results obtained using MaReCs. More than one euploid non-balanced translocation carrier embryo was identified in both patients. Amniocentesis results revealed normal karyotypes, consistent with the findings by MaReCs and nanopore sequencing. Conclusion Our results suggest that nanopore sequencing is a powerful strategy for accurately distinguishing non-translocation embryos from translocation carrier embryos and precisely localizing translocation breakpoints, which is essential for PGT and aids in reducing the propagation of reciprocal translocation in the population.

Abstract Brain tumors, although rare, contribute to distinct mortality and morbidity at all ages. Although there are few therapeutic options for brain tumors, enhanced biological understanding and unexampled innovations in targeted therapies and immunotherapies have considerably improved patients’ prognoses. Nonetheless, the reduced response rates and unavoidable drug resistance of currently available treatment approaches have become a barrier to further improvement in brain tumor (glioma, meningioma, CNS germ cell tumors, and CNS lymphoma) treatment. Previous literature data revealed that several different signaling pathways are dysregulated in brain tumor. Importantly, a better understanding of targeting signaling pathways that influences malignant behavior of brain tumor cells might open the way for the development of novel targeted therapies. Thus, there is an urgent need for a more comprehensive understanding of the pathogenesis of these brain tumors, which might result in greater progress in therapeutic approaches. This paper began with a brief description of the epidemiology, incidence, risk factors, as well as survival of brain tumors. Next, the major signaling pathways underlying these brain tumors’ pathogenesis and current progress in therapies, including clinical trials, targeted therapies, immunotherapies, and system therapies, have been systemically reviewed and discussed. Finally, future perspective and challenges of development of novel therapeutic strategies in brain tumor were emphasized.

Abstract In this field study of the labor process of food delivery workers, we examine the new rules of time and new forms of labor time control in the food delivery industry. Food delivery platforms attract laborers with the flexibility of working time and place but simultaneously strictly surveil the labor process of delivery workers, thus establishing a multidimensional body of control consisting of the platform and customers. At the same time, platform mechanisms of “grab the order” and “wait for the order” help platforms subtly control delivery workers’ experience, thoughts, and emotions. These mechanisms create a sense of time characterized by “punctuality” and “speed,” making delivery workers “all-day workers.” Delivery workers come to delivery platforms in search of work freedom, but in the end, they become constrained by platforms. Helpless, they voluntarily subject themselves to the time control of the platform, while the latter obtains profit under the guise of freedom.

Plant photosynthetic capacity directly determines crop yield. Light quality regulates photosynthetic capacity. This review discusses plant responses to far-red light from the phenotypic to the molecular level, focusing specifically on the improvement of photosynthetic capacity by adjustment of photosynthetic electron transport and the path of light energy. Far-red light can also regulate leaf angle and increase plant height and leaf area, via expression of associated genes, to capture more light energy. Thus, far-red light regulates plant morphology and photosynthetic capacity. Identifying the mechanism of this regulation may lead to increased crop yields.

BackgroundDietary antioxidants have long been thought to be likely to prevent the development of gliomas. Previous studies have reported vitamin A, C, and E protective effects against gliomas. B vitamins, one of the main vitamins in the diet, are closely related to human health, but the association with gliomas has rarely been reported.ObjectiveThis study aimed to evaluate the relationship between five B vitamins and glioma.MethodsIn this Chinese population-based case–control study, 506 glioma cases and 506 matched (age and sex) controls were included. The dietary intake of study participants was assessed using a valid 111-item food frequency questionnaire. The intake of five B vitamins was calculated based on participants’ dietary information from the food frequency questionnaire. The logistic regression model was used to examine the association between B vitamins and glioma, and the restriction cubic spline evaluated the dose–response relationship between the two.ResultsAfter adjusting for confounding factors, thiamine (OR = 0.09, 95%CI: 0.05–0.20), riboflavin (OR = 0.12, 95%CI: 0.06–0.25), nicotinic acid (OR = 0.24, 95%CI: 0.12–0.47), folate (OR = 0.07, 95%CI: 0.03–0.15) and biotin (OR = 0.14, 95%CI: 0.07–0.30) in the highest tertile were associated with a significantly decreased risk of glioma compared with the lowest tertile. The results of thiamine and biotin in glioma with different pathological types and grades were different. The restricted cubic spline function showed significant dose–response relationships between the intake of five B vitamins and the risk of glioma. When B vitamins exceeded a specific intake, the risk of glioma did not change.ConclusionOur study suggests that higher dietary intake of thiamine, riboflavin, nicotinic acid, and folate are associated with a decreased risk of glioma, but the results of biotin are not consistent among different populations. In the future, prospective studies should be conducted better to validate the effects of B vitamins on gliomas.

Olfactory neuroblastoma is a rare neoplasm that usually presents in the upper nasal cavity. Although its prognosis is highly unfavorable, effective treatment options are still lacking. Moreover, there is no standard treatment for patients with olfactory neuroblastoma that progressed to leptomeningeal carcinomatosis. Here we report an uncommon case of a 59-year-old woman who was diagnosed with olfactory neuroblastoma and leptomeningeal carcinomatosis. For a direct delivery of the drugs to the tumor, and to avoid the impact of lumbar puncture on the patient’s quality of life, the intravenous chemotherapy plus intrathecal administration of MTX via an Ommaya reservoir was chosen. The results were striking, with the disappearance of tumor cells in the cerebrospinal fluid and the relief of the patient’s symptoms with PR. Our result indicates that chemotherapy via an Ommaya reservoir offers a new potential therapy for patients with meningeal metastases.

Medulloblastoma, a common pediatric malignant tumor, has been recognized to have four molecular subgroups [wingless (WNT), sonic hedgehog (SHH), group 3, group 4], which are defined by the characteristic gene transcriptomic and DNA methylomic profiles, and has distinct clinical features within each subgroup. The tumor immune microenvironment is integral in tumor initiation and progression and might be associated with therapeutic responses. However, to date, the immune infiltrative landscape of medulloblastoma has not yet been elucidated. Thus, we proposed MethylCIBERSORT to estimate the degree of immune cell infiltration and weighted correlation network analysis (WGCNA) to find modules of highly correlated genes. Synthesizing the hub genes in the protein–protein interaction (PPI) network and modules of the co-expression network, we identify three candidate biomarkers [GRB2-associated-binding protein 1 (GAB1), Abelson 1 (ABL1), and CXC motif chemokine receptor type 4 (CXCR4)] via the molecular profiles of medulloblastoma. Given this, we investigated the correlation between these three immune hub genes and immune checkpoint blockade response and the potential of drug prediction further. In addition, this study demonstrated a higher presence of endothelial cells and infiltrating immune cells in Group 3 tumor bulk. The above results will be conducive to better comprehending the immune-related pathogenesis and treatment of medulloblastoma.

Plants have evolved multiple strategies to survive and adapt when confronting the changing climate, including elevated CO2 concentration (e[CO2]) and intensified drought stress. To explore the role of abscisic acid (ABA) in modulating the response of plant water relation characteristics to progressive drought under ambient (a[CO2], 400 ppm) and e[CO2] (800 ppm) growth environments, two tomato (Solanum lycopersicum) genotypes, Ailsa Craig (AC) and its ABA-deficient mutant (flacca), were grown in pots, treated with or without exogenous ABA, and exposed to progressive soil drying until all plant available water in the pot was depleted. The results showed that exogenous ABA application improved leaf water potential, osmotic potential, and leaf turgor and increased leaf ABA concentrations ([ABA]leaf) in AC and flacca. In both genotypes, exogenous ABA application decreased stomatal pore aperture and stomatal conductance (gs), though these effects were less pronounced in e[CO2]-grown AC and gs of ABA-treated flacca was gradually increased until a soil water threshold after which gs started to decline. In addition, ABA-treated flacca showed a partly restored stomatal drought response even when the accumulation of [ABA]leaf was vanished, implying [ABA]leaf might be not directly responsible for the decreased gs. During soil drying, [ABA]leaf remained higher in e[CO2]-grown plants compared with those under a[CO2], and a high xylem sap ABA concentration was also noticed in the ABA-treated flacca especially under e[CO2], suggesting that e[CO2] might exert an effect on ABA degradation and/or redistribution. Collectively, a fine-tune ABA homeostasis under combined e[CO2] and drought stress allowed plants to optimize leaf gas exchange and plant water relations, yet more detailed research regarding ABA metabolism is still needed to fully explore the role of ABA in mediating plant physiological response to future drier and CO2-enriched climate.

Blue and red light are essential light signals used to regulate stomatal development and leaf structure. In the present study, stomatal and leaf traits that respond to blue and red light were studied at two light intensities (400 and 100 µmol m−2 s−1) in soybeans. The stomatal traits and leaf characteristics were determined. Furthermore, their contribution to the operational maximum stomatal conductance (gopmax) was evaluated using the rdacca.hp R package. With the light intensity significantly reduced, the stomatal size (SZ) under blue light did not change. Similarly, the decrease in light intensity did not influence the stomatal density (SD), specific leaf weight (SLW) or gopmax under red light. These results implied that the regulation of SD and SLW depended on blue light and that SZ was highly sensitive to red light. In addition, SLW was strongly correlated with SD. The SLW and SD had the highest contribution rates (19.43% and 19.5%, respectively) to gopmax, as compared with the other parameters. In conclusion, these results suggested that in long-term exposure to blue light, the enhancements in gopmax were primarily due to the synergistic promotion of SLW and SD.

High mating value is believed to correspond with high mating opportunities. On that premise, this study explores three cues that are linked to women of high long-term mating value, namely a “beautiful” facial appearance, “sexually attractive” body shape, and “virtuous” behavior. With exclusive attention focused on the above cues, this study examines what kind of human attributes would make a contribution to women’s mating opportunities. The results reveal that both “beautiful” women and “virtuous” women were assessed (in this study) as having greater mating opportunities than “sexually attractive” women. In regard to the human attributes, only the “beautiful” woman was assessed as having high levels of human uniqueness and human nature. Meanwhile, “virtuous” women were assessed as having higher levels of human uniqueness but lower levels of human nature. In contrast, “sexually attractive” women were assessed as having lower levels of human uniqueness but higher levels of human nature. In addition, the results of a mediation analysis show that the trait of human uniqueness, and not human nature, was the mediator between the three types of women and women’s mating opportunities. This finding means that, when women have higher levels of human uniqueness, they can acquire more mating opportunities. These findings contribute an improved understanding to why and how “beauty” or “virtue” increases the opportunity for woman to be selected as a spouse.

Abstract Elevated CO2 concentration in the air (e[CO2]) decreases stomatal density (SD) and stomatal conductance (g s) where abscisic acid (ABA) may play a role, yet the underlying mechanism remains largely elusive. We investigated the effects of e[CO2] (800 ppm) on leaf gas exchange and water relations of two tomato (Solanum lycopersicum) genotypes, Ailsa Craig (WT) and its ABA-deficient mutant (flacca). Compared to plants grown at ambient CO2 (400 ppm), e[CO2] stimulated photosynthetic rate in both genotypes, while depressed the g s only in WT. SD showed a similar response to e[CO2] as g s, although the change was not significant. e[CO2] increased leaf and xylem ABA concentrations and xylem sap pH, where the increases were larger in WT than in flacca. Although leaf water potential was unaffected by CO2 growth environment, e[CO2] lowered osmotic potential, hence tended to increase turgor pressure particularly for WT. e[CO2] reduced hydraulic conductance of leaf and root in WT but not in flacca, which was associated with downregulation of gene expression of aquaporins. It is concluded that ABA-mediated regulation of g s, SD, and gene expression of aquaporins coordinates the whole-plant hydraulics of tomato grown at different CO2 environments.

Abstract Background and aims Glutathione S-transferase A3 (GSTA3) is known as an antioxidative protease, however, the crucial role of GSTA3 in liver fibrosis remains unclear. As a recently we developed water-soluble pyridone agent with antifibrotic features, fluorofenidone (AKF-PD) can attenuate liver fibrosis, present studies were designed to explore the role of GSTA3 in liver fibrosis and its modulation by AKF-PD in vivo and in vitro. Methods Rats liver fibrosis models were induced by dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4). The two activated hepatic stellate cells (HSCs) lines, rat CFSC-2G and human LX2 were treated with AKF-PD respectively. The lipid peroxidation byproduct malondialdehyde (MDA) in rat serum was determined by ELISA. The accumulation of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescein fluorescence analysis. The expression of α-smooth muscle actin (α-SMA), fibronectin (FN), and phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK) and glycogen synthase kinase 3 beta (GSK-3β) were detected by western blotting (WB). Results GSTA3 was substantially reduced in the experimental fibrotic livers and transdifferentiated HSCs. AKF-PD alleviated rat hepatic fibrosis and potently inhibited HSCs activation correlated with restoring GSTA3. Moreover, GSTA3 overexpression prevented HSCs activation and fibrogenesis, while GSTA3 knockdown enhanced HSCs activation and fibrogenesis resulted from increasing accumulation of ROS and subsequent amplified MAPK signaling and GSK-3β phosphorylation. Conclusions We demonstrated firstly that GSTA3 inhibited HSCs activation and liver fibrosis through suppression of the MAPK and GSK-3β signaling pathways. GSTA3 may represent a promising target for potential therapeutic intervention in liver fibrotic diseases.

Abstract Background Intercropping and close planting are important cultivation methods that increase soybean yield in agricultural production. However, plant shading is a major abiotic stress factor that influences soybean growth and development. Although shade affects leaf morphological parameters and decreases leaf photosynthesis capacity, information on the responses of soybean leaf photosynthesis to shading at proteomic level is still lacking. Results Compared with leaves under normal light (CK) treatment, leaves under shading treatment exhibited decreased palisade and spongy tissue thicknesses but significantly increased cell gap. Although shade increased the number of the chloroplast, the thickness of the grana lamella and the photosynthetic pigments per unit mass, but the size of the chloroplast and starch grains and the rate of net photosynthesis decreased compared with those of under CK treatment. A total of 248 differentially expressed proteins, among which 138 were upregulated, and 110 were downregulated, in soybean leaves under shading and CK treatments were detected via isobaric tags for relative and absolute quantification labeling in the three biological repeats. Differentially expressed proteins were classified into 3 large and 20 small groups. Most proteins involved in porphyrin and chlorophyll metabolism, photosynthesis-antenna proteins and carbon fixation in photosynthetic organisms were upregulated. By contrast, proteins involved in photosynthesis were downregulated. The gene family members corresponding to differentially expressed proteins, including protochlorophyllide reductase (Glyma06g247100), geranylgeranyl hydrogenase (Ggh), LHCB1 (Lhcb1) and ferredoxin (N/A) involved in the porphyrin and chlorophyll metabolism, photosynthesis-antenna proteins and photosynthesis pathway were verified with real-time qPCR. The results showed that the expression patterns of the genes were consistent with the expression patterns of the corresponding proteins. Conclusions This study combined the variation of the soybean leaf structure and differentially expressed proteins of soybean leaves under shading. These results demonstrated that shade condition increased the light capture efficiency of photosystem II (PSII) in soybean leaves but decreased the capacity from PSII transmitted to photosystem II (PSI). This maybe the major reason that the photosynthetic capacity was decreased in shading.

Locomotor function after spinal cord injury (SCI) is critical for assessing recovery. Currently, available means to improve locomotor function include surgery, physical therapy rehabilitation and exoskeleton. Stem cell therapy with neural progenitor cells (NPCs) transplantation is a promising reparative strategy. Along this line, patient-specific induced pluripotent stem cells (iPSCs) are a remarkable autologous cell source, which offer many advantages including: great potential to generate isografts avoiding immunosuppression; the availability of a variety of somatic cells without ethical controversy related to embryo use; and vast differentiation. In this current work, to realize the therapeutic potential of iPSC-NPCs for the treatment of SCI, we transplanted purified iPSCs-derived NPCs into a cervical contusion SCI rat model. Our results showed that the iPSC-NPCs were able to survive and differentiate into both neurons and astrocytes and, importantly, improve forelimb locomotor function as assessed by the grooming task and horizontal ladder test. Purified iPSC-NPCs represent a promising cell type that could be further tested and developed into a clinically useful cell source for targeted cell therapy for cervical SCI patients.

PurposeGlioma is a classical type of primary brain tumors that is most common seen in adults, and its high heterogeneity used to be a reference standard for subgroup classification. Glioma has been diagnosed based on histopathology, grade, and molecular markers including IDH mutation, chromosome 1p/19q loss, and H3K27M mutation. This subgroup classification cannot fully meet the current needs of clinicians and researchers. We, therefore, present a new subgroup classification for glioma based on the expression levels of Gβ and Gγ genes to complement studies on glioma and Gβγ subunits, and to support clinicians to assess a patient’s tumor status.MethodsGlioma samples retrieved from the CGGA database and the TCGA database. We clustered the gliomas into different groups by using expression values of Gβ and Gγ genes extracted from RNA sequencing data. The Kaplan–Meier method with a two-sided log-rank test was adopted to compare the OS of the patients between GNB2 group and non-GNB2 group. Univariate Cox regression analysis was referred to in order to investigate the prognostic role of each Gβ and Gγ genes. KEGG and ssGSEA analysis were applied to identify highly activated pathways. The “estimate” package, “GSVA” package, and the online analytical tools CIBERSORTx were employed to evaluate immune cell infiltration in glioma samples.ResultsThree subgroups were identified. Each subgroup had its own specific pathway activation pattern and other biological characteristics. High M2 cell infiltration was observed in the GNB2 subgroup. Different subgroups displayed different sensitivities to chemotherapeutics. GNB2 subgroup predicted poor survival in patients with gliomas, especially in patients with LGG with mutation IDH and non-codeleted 1p19q.ConclusionThe subgroup classification we proposed has great application value. It can be used to select chemotherapeutic drugs and the prognosis of patients with target gliomas. The unique relationships between subgroups and tumor-related pathways are worthy of further investigation to identify therapeutic Gβγ heterodimer targets.

Increasing atmospheric CO2 concentrations accompanied by abiotic stresses challenge food production worldwide. Elevated CO2 (e[CO2]) affects plant water relations via multiple mechanisms involving abscisic acid (ABA). Here, two tomato (Solanum lycopersicum) genotypes, Ailsa Craig (AC) and its ABA-deficient mutant (flacca), were used to investigate the responses of plant hydraulic conductance to e[CO2] and drought stress. Results showed that e[CO2] decreased transpiration rate (E) increased plant water use efficiency only in AC, whereas it increased daily plant water consumption and osmotic adjustment in both genotypes. Compared to growth at ambient [CO2], AC leaf and root hydraulic conductance (Kleaf and Kroot) decreased at e[CO2], which coincided with the transcriptional regulations of genes of plasma membrane intrinsic proteins (PIPs) and OPEN STOMATA 1 (OST1), and these effects were attenuated in flacca during soil drying. Severe drought stress could override the effects of e[CO2] on plant water relation characteristics. In both genotypes, drought stress resulted in decreased E, Kleaf, and Kroot accompanied by transcriptional responses of PIPs and OST1. However, under conditions combining e[CO2] and drought, some PIPs were not responsive to drought in AC, indicating that e[CO2] might disturb ABA-mediated drought responses. These results provide some new insights into mechanisms of plant hydraulic response to drought stress in a future CO2-enriched environment.

The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment.

Leaf veins constitute the transport network for water and photosynthetic assimilates in vascular plants. The class III homeodomain-leucine zipper (HD-Zip III) gene family is central to the regulation of vascular development. In this research, we performed an overall analysis of the HD-Zip III genes in soybean (Glycine max L. Merr.). Our analysis included the phylogeny, conservation domains and cis-elements in the promoters of these genes. We used the quantitative reverse transcription-polymerase chain reaction to characterize the expression patterns of HD-Zip III genes in leaf vein development and analyze the effects of exogenous hormone treatments. In this study, twelve HD-Zip III genes were identified from the soybean genome and named. All soybean HD-Zip III proteins contained four highly conserved domains. GmHB15-L-1 transcripts showed steadily increasing accumulation during all stages of leaf vein development and were highly expressed in cambium cells. GmREV-L-1 and GmHB14-L-2 had nearly identical expression patterns in soybean leaf vein tissues. GmREV-L-1 and GmHB14-L-2 transcripts remained at stable high levels at all xylem developmental stages. GmREV-L-1 and GmHB14-L-2 were expressed at high levels in the vascular cambium and xylem cells. Overall, GmHB15-L-1 may be an essential regulator that is responsible for the formation or maintenance of soybean vein cambial cells. GmREV-L-1 and GmHB14-L-2 were correlated with xylem differentiation in soybean leaf veins. This study will pave the way for identifying the molecular mechanism of leaf vein development.

Drought stress often occurs concurrently with heat stress, yet the interacting effect of high vapor pressure deficit (VPD) and soil drying on the physiology of potato plants remains poorly understood. This study aimed to investigate the physiological and growth responses of potatoes to progressive soil drying under varied VPDs. Potato plants were grown either in four separate climate-controlled greenhouse cells with different VPD levels (viz., 0.70, 1.06, 1.40, and 2.12 kPa, respectively) or under a rainout shelter in the field. The VPD of each greenhouse cell was caused by two air temperature levels (23 and 30 °C) combined with two relative humidity levels (50 and 70%), and the VPD of the field was natural conditions. Irrigation treatments were commenced three or four weeks after planting in greenhouse cells or fields, respectively. The results indicated that soil water deficits limited leaf gas exchange and shoot dry matter (DMshoot) of plants while increasing the concentration of abscisic acid (ABA) in the leaf and xylem, as well as water use efficiency (WUE) across all VPD levels. High VPD decreased stomatal conductance (gs) but increased transpiration rate (Tr). High VPD increased the threshold of soil water for Tr began to decrease, while the soil water threshold for gs depended on temperature due to the varied ABA response to temperature. High VPD decreased leaf water potential, leaf area, and DMshoot, which exacerbated the inhibition of soil drying to plant growth. Across the well-watered plants in both experiments, negative linear relationships of gs and WUE to VPD and positive linear relations between Tr and VPD were found. The results provide some novel information for developing mechanistic models simulating crop WUE and improving irrigation scheduling in future arid climates.

Neural cell fate is determined by a tightly controlled transcription regulatory network during development. The ability to manipulate the expression of multiple transcription factors simultaneously is required to delineate the complex picture of neural cell development. Because of the limited carrying capacity of the commonly used viral vectors, such as lentiviral or retroviral vectors, it is often challenging to perform perturbation experiments on multiple transcription factors. Here we have developed a piggyBac (PB) transposon-based CRISPR activation (CRISPRa) all-in-one system, which allows for simultaneous and stable endogenous transactivation of multiple transcription factors and long non-coding RNAs. As a proof of principle, we showed that the PB-CRISPRa system could accelerate the differentiation of human induced pluripotent stem cells into neurons and astrocytes by triggering endogenous expression of different sets of transcription factors. The PB-CRISPRa system has the potential to become a convenient and robust tool in neuroscience, which can meet the needs of a variety of in vitro and in vivo gain-of-function applications. Keywords: CRISPR, gene activation, human induced pluripotent stem cells, piggyBac, transposon

As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome. In this study, we developed a safe and cost-effective pipeline to generate clinically relevant NPCs. We first isolated cells from patients' urine and reprogrammed them into iPSCs by non-integrating Sendai viral vectors, and carried out experiments on neural differentiation. NPCs were purified by A2B5, an antibody specifically recognizing a glycoganglioside on the cell surface of neural lineage cells, via fluorescence activated cell sorting. Upon further in vitro induction, NPCs were able to give rise to neurons, oligodendrocytes and astrocytes. To test the functionality of the A2B5+ NPCs, we grafted them into the contused mouse thoracic spinal cord. Eight weeks after transplantation, the grafted cells survived, integrated into the injured spinal cord, and differentiated into neurons and glia. Our specific focus on cell source, reprogramming, differentiation and purification method purposely addresses timing and safety issues of transplantation to SCI models. It is our belief that this work takes one step closer on using human iPSC derivatives to SCI clinical settings.

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Propofol is an intravenous anesthetic that has been widely used in clinics. Besides its anesthetic effects, propofol has also been reported to influence the regulation of the autonomic system. Controversies exist with regard to whether propofol exposure is safe for pregnant women and young children. In this work, human-induced pluripotent stem cell- (hiPSC-) derived neural progenitor cells (NPCs) were treated with propofol at 20, 50, 100, or 300 μM for 6 h or 24 h, and acute and subacute cell injury, cell proliferation, and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for treated and control iPSC-NPCs. Propofol treatment for 6 h at the clinically relevant concentration (20 or 50 μM) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300 μM) decreased NPC viability and induced apoptosis. In addition, 20 μM propofol treatment for 6 h did not alter global gene expression. In summary, propofol treatment at commonly practiced clinical doses for 6 h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration could decrease NPC viability and induce apoptosis.

Abstract Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial in the metastatic cascade. Among these, super-enhancers (SEs), emerging as new epigenetic regulators, consist of large clusters of regulatory elements that drive the high-level expression of genes essential for the oncogenic process, upon which cancer cells develop a profound dependency. These SE-driven oncogenes play an important role in regulating various facets of metastasis, including the promotion of tumor proliferation in primary and distal metastatic organs, facilitating cellular migration and invasion into the vasculature, triggering epithelial-mesenchymal transition, enhancing cancer stem cell-like properties, circumventing immune detection, and adapting to the heterogeneity of metastatic niches. This heavy reliance on SE-mediated transcription delineates a vulnerable target for therapeutic intervention in cancer cells. In this article, we review current insights into the characteristics, identification methodologies, formation, and activation mechanisms of SEs. We also elaborate the oncogenic roles and regulatory functions of SEs in the context of cancer metastasis. Ultimately, we discuss the potential of SEs as novel therapeutic targets and their implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

To provide new insights into the development and utilization of Douchi artificial starters, three common strains (Aspergillus oryzae, Mucor racemosus, and Rhizopus oligosporus) were used to study their influence on the fermentation of Douchi. The results showed that the biogenic amine contents of the three types of Douchi were all within the safe range and far lower than those of traditional fermented Douchi. Aspergillus-type Douchi produced more free amino acids than the other two types of Douchi, and its umami taste was more prominent in sensory evaluation (P < 0.01), while Mucor-type and Rhizopus-type Douchi produced more esters and pyrazines, making the aroma, sauce, and Douchi flavor more abundant. According to the Pearson and PLS analyses results, sweetness was significantly negatively correlated with phenylalanine, cysteine, and acetic acid (P < 0.05), bitterness was significantly negatively correlated with malic acid (P < 0.05), the sour taste was significantly positively correlated with citric acid and most free amino acids (P < 0.05), while astringency was significantly negatively correlated with glucose (P < 0.001). Thirteen volatile compounds such as furfuryl alcohol, phenethyl alcohol, and benzaldehyde caused the flavor difference of three types of Douchi. This study provides theoretical basis for the selection of starting strains for commercial Douchi production.

With the rise of the concept of gender equality and the emphasis on computational thinking, more and more research on computational thinking is being placed in the context of gender differences to promote gender equality. This systematic review examines and analyzes 23 articles that focus on gender differences in computational thinking skills among primary and secondary school students, providing a comprehensive overview of the existing literature while also providing direction and framework for future research. The results show that (1) the current research is imbalanced across regions and age groups, and the research on inherent gender differences in computational thinking skills remains insufficient; (2) the development of a clearer and more specific definition of computational thinking and corresponding assessment instrument is required for a more specific identification of gender differences; (3) under the existing educational environments, gender differences in computational thinking skills among students in different regions exhibit different pattern; and (4) interventional factors contributing to gender effects in interventions have also been identified.

Abstract Human body expressions convey emotional shifts and intentions of action and, in some cases, are even more effective than other emotion models. Despite many datasets of body expressions incorporating motion capture available, there is a lack of more widely distributed datasets regarding naturalized body expressions based on the 2D video. In this paper, therefore, we report the multi-view emotional expressions dataset (MEED) using 2D pose estimation. Twenty-two actors presented six emotional (anger, disgust, fear, happiness, sadness, surprise) and neutral body movements from three viewpoints (left, front, right). A total of 4102 videos were captured. The MEED consists of the corresponding pose estimation results (i.e., 397,809 PNG files and 397,809 JSON files). The size of MEED exceeds 150 GB. We believe this dataset will benefit the research in various fields, including affective computing, human-computer interaction, social neuroscience, and psychiatry.

Abstract Background Colorectal cancer (CRC) is one of the most prevalent types of malignant tumours. Metastasis is the leading cause of cancer-related mortality, with lung metastases accounting for 32.9% of all metastatic CRCs. However, since the biological mechanism of lung metastatic CRC is poorly understood, limited therapeutic targets are available. In the present study, we aimed to identify the key genes and molecular processes involved in CRC lung metastasis. Methods The differentially expressed genes (DEGs) between primary and lung metastatic CRC patients were obtained from the Gene Expression Omnibus (GEO) database via the GEO2R tool. The enriched biological processes and pathways modulated by the DEGs were determined with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome Gene Sets analyses. The search tool Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct a protein–protein interaction (PPI) network among DEGs. Results The DEGs were enriched in surfactant metabolism, cell–cell communication and chemokine signaling pathways. The defined hub genes were included CLU, SFTPD, CCL18, SPP1, APOE, BGN and MMP3. Among them, CLU, SFTPD and CCL18 might be associated with the specific lung tropism metastasis in CRC. In addition, the expression and prognostic values of the hub genes in CRC patients were verified in database of The Cancer Genome Atlas (TCGA) and GEO. Moreover, the protein levels of the hub genes were detected in primary and lung metastatic CRC cells, serum or tissues. Furthermore, SFTPD was confirmed to facilitate cellular proliferation and lung metastasis in CRC. Conclusion This bioinformatics study may provide a better understanding of the candidate therapeutic targets and molecular mechanisms for CRC lung metastasis.

In this study, a novel series of histone deacetylases 6 (HDAC6) inhibitors containing polycyclic aromatic rings were discovered and evaluated for their pharmacological activities. The most potent compound 10c exhibited high HDAC6 inhibitory activity (IC50 = 261 nM) and excellent HDAC6 selectivity (SI = 109 for HDAC6 over HDAC3). 10c also showed decent antiproliferative activity in vitro with IC50 of 7.37–21.84 μM against four cancer cell lines, comparable to that of tubastatin A (average IC50 = 6.10 μM). Further mechanism studies revealed that 10c efficiently induced apoptosis and S-phase arrest in B16-F10 cells. In addition, 10c markedly increased the expression of acetylated-α-tubulin both in vitro and in vivo, without affecting the levels of acetylated-H3 (marker of HDAC1 inhibition). Furthermore, 10c (80 mg/kg) exhibited moderate antitumor efficacy in a melanoma tumour model with a tumour growth inhibition (TGI) of 32.9%, comparable to that (TGI = 31.3%) of tubastatin A. Importantly, the combination of 10c with NP19 (a small molecule PD-L1 inhibitor discovered by us before) decreased tumour burden substantially (TGI% = 60.1%) as compared to monotherapy groups. Moreover, the combination of 10c with NP19 enhanced the anti-tumour immune response, mediated by a decrease of PD-L1 expression levels and increased infiltration of anti-tumour CD8+ T cells in tumour tissues. Collectively, 10c represents a novel HDAC6 inhibitor deserving further investigation as a potential anti-cancer agent.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of approximately 121.4 nM against PC-3 and DU-145 cells, primarily through the PI3K/Akt/mTOR, NF-κB, MAPK, and JAK/STAT signaling pathways. Additionally, they manifest anti-inflammatory and analgesic effects predominantly via the NF-κB, MAPK, and Nrf2 signaling pathways. Utilized in treating rheumatic arthritis, these alkaloids also play a significant role in cardiovascular and cerebrovascular protection, as well as organ protection through the NF-κB, Nrf2, MAPK, and PI3K/Akt/mTOR signaling pathways. This review concludes with perspectives and insights on this topic, highlighting the potential of sinomenine-related compounds in clinical applications and the development of medications derived from natural products.

The development of 3D sensors encourages researchers to process point cloud data directly. Point cloud data requires less memory but conveys more detailed 3D shape information. However, because of occlusion, sensing distance and other reasons, sensors usually cannot get a complete 3D shape. In this paper, we propose a Dynamic and Folding Network (DF-Net) to address the precise point cloud completion problem. Existing completion networks generate the overall shape of a point cloud from an incomplete point cloud. In this paper, we complete the missing part based on the existing part instead. We use a dynamic graph network to better extract local features of points in the neighborhood points. A FoldBlock is used to refine the prediction of the missing part. We validate our method with two benchmarks, ShapeNet-13 and ShapeNet-55. Both qualitative and quantitative experimental results show the proposed method achieves improvement over some state-of-the-art methods. Code is available at https://github.com/yiqisetian/DF-Net.

Abstract Background Hepatic metastasis is the primary and direct cause of death in individuals with colorectal cancer (CRC) attribute to lack of effective therapeutic targets. The present study aimed to identify potential druggable candidate targets for patients with liver metastatic CRC. Methods The transcriptional profiles of super‐enhancers (SEs) in primary and liver metastatic CRC were evaluated in publicly accessible CRC datasets. Immunohistochemistry of human CRC tissues was conducted to determine the expression level of CDK12. Cellular proliferation, survival and stemness were examined upon CDK12 inhibition by shCDK12 or a selective CDK12 inhibitor named SR‐4835 with multiple in vitro and in vivo assays. RNA sequencing and bioinformatics analyses were carried out to investigate the mechanisms of CDK12 inhibition in CRC cells. Results We identified CDK12 as a driver gene for direct hepatic metastasis in CRC. Suppression of CDK12 led to robust inhibition of proliferation, survival and stemness. Mechanistically, CDK12 intervention preferentially repressed the transcription of SE‐associated genes. Integration of the SE landscape and RNA sequencing, BCL2L1 and CCDC137 were identified as SE‐associated oncogenic genes to strengthen the abilities of cellular survival, proliferation and stemness, eventually increasing liver metastasis of CRC. Conclusions Our data highlight the potential of CDK12 and SE‐associated oncogenic transcripts as therapeutic targets for patients with liver metastatic CRC.

Abstract Colonization is believed a rate-limiting step of metastasis cascade. However, its underlying mechanism is not well understood. Uveal melanoma (UM), which is featured with single organ liver metastasis, may provide a simplified model for realizing the complicated colonization process. Because DDR1 was identified to be overexpressed in UM cell lines and specimens, and abundant pathological deposition of extracellular matrix collagen, a type of DDR1 ligand, was noted in the microenvironment of liver in metastatic patients with UM, we postulated the hypothesis that DDR1 and its ligand might ignite the interaction between UM cells and their surrounding niche of liver thereby conferring strengthened survival, proliferation, stemness and eventually promoting metastatic colonization in liver. We tested this hypothesis and found that DDR1 promoted these malignant cellular phenotypes and facilitated metastatic colonization of UM in liver. Mechanistically, UM cells secreted TGF-β1 which induced quiescent hepatic stellate cells (qHSCs) into activated HSCs (aHSCs) which secreted collagen type I. Such a remodeling of extracellular matrix, in turn, activated DDR1, strengthening survival through upregulating STAT3-dependent Mcl-1 expression, enhancing stemness via upregulating STAT3-dependent SOX2, and promoting clonogenicity in cancer cells. Targeting DDR1 by using 7rh, a specific inhibitor, repressed proliferation and survival in vitro and in vivo outgrowth. More importantly, targeting cancer cells by pharmacological inactivation of DDR1 or targeting microenvironmental TGF-β1-collagen I loop exhibited a prominent anti-metastasis effect in mice. In conclusion, targeting DDR1 signaling and TGF-β signaling may be a novel approach to diminish hepatic metastasis in UM.

Skeleton-based action recognition is a typical classification problem which plays a significant role in human-computer interaction and video understanding. Since a human skeleton has natural graphic features, methods based on graph convolutional networks (GCN) are widely applied in skeleton-based action recognition. Previous studies mainly focus on structural links in GCN to generate high-level features of human skeleton. However, low-level features are also important in many applications. For instance, low-level edge gradient and color information are important for image classification. This paper introduces a multi-branches structure to capture different low-level features of human skeleton. We combine both high-level and low-level features to recognize human action. We validate our method in action recognition with two skeleton datasets, NTU-RGB+D and Kinetics. Experiment results indicate that the proposed method achieves considerable improvement over some state-of-the-art methods.

Abstract Background Uveal melanoma (UM) is the most common primary intraocular tumor. Hepatic metastasis is the major and direct death-related reason in UM patients. Given that cancer stem-like cells (CSCs) are roots of metastasis, targeting CSCs may be a promising strategy to overcome hepatic metastasis in UM. Salinomycin, which has been identified as a selective inhibitor of CSCs in multiple types of cancer, may be an attractive agent against CSCs thereby restrain hepatic metastasis in UM. The objective of the study is to explore the antitumor activity of salinomycin against UM and clarify its underlying mechanism. Methods UM cells were treated with salinomycin, and its effects on cell proliferation, apoptosis, migration, invasion, CSCs population, and the related signal transduction pathways were determined. The in vivo antitumor activity of salinomycin was evaluated in the NOD/SCID UM xenograft model and intrasplenic transplantation liver metastasis mouse model. Results We found that salinomycin remarkably obviated growth and survival in UM cell lines and in a UM xenograft mouse model. Meanwhile, salinomycin significantly eliminated CSCs and efficiently hampered hepatic metastasis in UM liver metastasis mouse model. Mechanistically, Twist1 was fundamental for the salinomycin-enabled CSCs elimination and migration/invasion blockage in UM cells. Conclusions Our findings suggest that targeting UM CSCs by salinomycin is a promising therapeutic strategy to hamper hepatic metastasis in UM. These results provide the first pre-clinical evidence for further testing of salinomycin for its antitumor efficacy in UM patients with hepatic metastasis.

Abstract Background Life of patients with uveal melanoma (UM) is largely threatened by liver metastasis. Little is known about the drivers of liver organotropic metastasis in UM. The elevated activity of transcription of oncogenes is presumably to drive aspects of tumors. We hypothesized that inhibition of transcription by cyclin-dependent kinase 7/9 (CDK7/9) inhibitor SNS-032 diminished liver metastasis by abrogating the putative oncogenes in charge of colonization, stemness, cell motility of UM cells in host liver microenvironment. Methods The effects of SNS-032 on the expression of the relevant oncogenes were examined by qRT-PCR and Western blotting analysis. Proliferative activity, frequency of CSCs and liver metastasis were evaluated by using NOD-SCID mouse xenograft model and NOG mouse model, respectively. Results The results showed that CDK7/9 were highly expressed in UM cells, and SNS-032 significantly suppressed the cellular proliferation, induced apoptosis, and inhibited the outgrowth of xenografted UM cells and PDX tumors in NOD-SCID mice, repressed the cancer stem-like cell (CSC) properties through transcriptional inhibition of stemness-related protein Krüppel-like factor 4 (KLF4), inhibited the invasive phonotypes of UM cells through matrix metalloproteinase 9 (MMP9). Mechanistically, SNS-032 repressed the c-Myc-dependent transcription of RhoA gene, and thereby lowered the RhoA GTPase activity and actin polymerization, and subsequently inhibited cell motility and liver metastasis. Conclusions In conclusion, we validate a set of transcription factors which confer metastatic traits (e.g., KLF4 for CSCs, c-Myc for cell motility) in UM cells. Our results identify SNS-032 as a promising therapeutic agent, and warrant a clinical trial in patients with metastatic UM.

In this study, hollow SiO2 microspheres were synthesized by the hydrolysis of tetraethyl orthosilicate (TEOS) according to the Stober process, in which Pichia pastoris GS 115 cells were served as biological templates. The influence of the preprocessing method, the TEOS concentration, the ratio of water to ethanol, and the aging time on the morphology of microspheres was investigated and the optimal conditions were identified. Based on this, TiO2-SiO2 microspheres were prepared by the hydrothermal process. The structures and physicochemical properties of TiO2-SiO2 photocatalysts were systematically characterized and discussed. The photocatalytic activity for the degradation of methyl orange (MO) at room temperature under Xe arc lamp acting as simulated sunlight was explored. The result showed that the as-prepared TiO2-SiO2 microspheres exhibited a good photocatalytic performance.

Structural health monitoring (SHM) is of great significance for post-earthquake damage assessment. Smartphone-based monitoring techniques provide the possibility to perform crowdsensing for all buildings in urban regions after an earthquake. However, this idea still faces many difficulties and is hard to realize. Fortunately, the development of game engines provides the opportunity for simulating this kind of experiment. The main objective of this study was to use Unity to simulate the whole process when a city is struck by an earthquake that consists of one main shock and one aftershock. During the emergency response, the citizens and the “city brain” in Unity, named Ground Eye, cooperate to finish the task of taking refuge and collecting data for regional damage assessment. Some basic assumptions were made first. Then the city model was established in Unity, and the behaviors of the citizens were directed by the behavior tree artificial intelligence (AI). OpenSees was utilized to determine the monitoring demand and simulate the monitoring results. A GUI was built to exhibit the data during the whole process. The results show that the evacuation and monitoring plan is feasible. The simulation framework presented in this paper can be used in other SHM application scenarios.