Activation of the Photosensitive Potential of 2D GaSe by Interfacial Engineering.

Two-dimensional (2D) gallium selenide (GaSe) holds great promise for pioneering advancements in photodetection due to its exceptional electronic and optoelectronic properties. However, in conventional photodetectors, 2D GaSe only functions as a photosensitive layer, failing to fully exploit its inherent photosensitive potential. Herein, we propose an ultrasensitive photodetector based on out-of-plane 2D GaSe/MoSe2 heterostructure. Through interfacial engineering, 2D GaSe serves not only as the photosensitive layer but also as the photoconductive gain and passivation layer, introducing a photogating effect and extending the lifetime of photocarriers. Capitalizing on these features, the device exhibits exceptional photodetection performance, including a responsivity of 28 800 A/W, specific detectivity of 7.1 × 1014 Jones, light on/off ratio of 1.2 × 106, and rise/fall time of 112.4/426.8 µs. Moreover, high-resolution imaging under various wavelengths is successfully demonstrated using this device. Additionally, we showcase the generality of this device design by activating the photosensitive potential of 2D GaSe with other transition metal dichalcogenides (TMDCs) such as WSe2, WS2, and MoS2. This work provides inspiration for future development in high-performance photodetectors, shining a spotlight on the potential of 2D GaSe and its heterostructure.

Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors. AIM: To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients. METHODS: This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA). RESULTS: The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit. CONCLUSION: Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.

Ursolic acid molecules dock MAPK1 to modulate gut microbiota diversity to reduce neuropathic pain.

To investigate the efficacy of Ursolic acid in alleviating neuropathic pain in rats with spinal nerve ligation (SNL), the SNL rat model was surgically induced. Different concentrations of Ursolic acid and manipulated target mitogen-activated protein kinase 1 (MAPK1) were administered to the SNL rats. Fecal samples were collected from each group of rats for 16S rDNA analysis to examine the impact of gut microbiota. Molecular docking experiments were conducted to assess the binding energy between Ursolic acid and MAPK1. In vivo studies were carried out to evaluate the expression of inflammatory factors and signaling pathways in spinal cord and colon tissues. Ursolic acid was found to have a beneficial effect on pain reduction in rats by increasing plantar withdrawal latency (PWL) and paw withdrawal threshold (PWT). Comparing the Ursolic acid group with the control group revealed notable differences in the distribution of Staphylococcus, Allobaculum, Clostridium, Blautia, Bifidobacterium, and Prevotella species. Network pharmacology analysis identified MAPK1 and intercellular adhesion molecule-1 (ICAM1) as common targets for Ursolic acid, SNL, and neuropathic pain. Binding sites between Ursolic acid and these targets were identified. Additionally, immunofluorescent staining showed a decrease in GFAP and IBA1 intensity in the spinal cord along with an increase in NeuN following Ursolic acid treatment. Overexpression of MAPK1 in SNL rats led to an increase in inflammatory factors and a decrease in PWL and PWT. Furthermore, MAPK1 counteracted the pain-relieving effects of Ursolic acid in SNL rats. Ursolic acid was found to alleviate neuropathic pain in SNL rats by targeting MAPK1 and influencing gut microbiota homeostasis.

Fatigue Affects Body Acceleration During Vertical Jumping and Agility Tasks in Elite Young Badminton Players.

BACKGROUND: Badminton is a sport demanding both high aerobic and anaerobic fitness levels, and fatigue can significantly impact game performance. However, relevant studies are limited, and none have employed a wearable inertial measurement unit (IMU) to investigate the effects of fatigue on athletic performance in the field. HYPOTHESIS: Overall performance and body acceleration in both time and frequency domains during the fundamental badminton skills of vertical jumping and changes of direction will be affected by fatigue. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 38 young badminton players competing at the Division I level participated. Body accelerations while performing vertical jump and agility-T tests before and immediately after undergoing a fatigue protocol were measured by an IMU, positioned at the L4 to L5 level. RESULTS: Jumping height decreased significantly by 4 cm (P < 0.01) after fatigue with greater downward acceleration (1.03 m/s2, P < 0.05) during the squatting subphase. Finishing time increased significantly by 50 ms only during the 10-m side-shuffling of the agility-T test (P = 0.02) after fatigue with greater peak and mean accelerations (3.83 m/s2, P = 0.04; 0.43 m/s2, P < 0.01), and higher median and mean frequency (0.38 Hz, P = 0.04, 0.11 Hz, P = 0.01). CONCLUSION: This study using a wearable IMU demonstrates the effects of fatigue on body acceleration in badminton players. The frequency-domain analysis further indicated that fatigue might lead to loss of voluntary control of active muscles and increased impacts on the passive elastic elements. CLINICAL RELEVANCE: The findings imply that fatigue can lead to diminished athletic performance and highlight the potential for an increased risk of sports injuries. Consequently, maintaining precision in monitoring fatigue is crucial for elite young badminton players.

A comprehensive exploration of twist1 to identify a biomarker for tumor immunity and prognosis in pan-cancer.

Twist1 has been identified as a critical gene in tumor, but current study of this gene remains limitative. This study aims to investigate its roles and potential mechanisms across pan-cancer. The study used various databases and computational techniques to analyze twist's RNA expression, clinical data, gene mutations, tumor stemness, tumor microenvironment, immune regulation. Furthermore, the experimental method of fluorescence staining was carried out to identify twist1 expression in various tumor masses. After analyzing the protein-protein interaction of TWIST, enrichment analysis and predictive potential drugs were performed, and molecular docking was conducted to validate. We found that twist1 expression was significantly higher in various types of cancer and associated with tumor stage, grade, and poor prognosis in multiple cancers. Differential expression of twist1 was linked to gene mutation, RNA modifications, and tumor stemness. Additionally, twist1 expression was positively associated with tumor immunoregulation and immune checkpoint. Salinomycin, klugline, isocephaelince, manassantin B, and pimonidazole are predictive potential drugs targeting TWIST1. This study revealed that twist1 plays an important role in tumor, and might be a curial marker in tumor diagnose and prognosis. The study also highlighted twist1 as a promising therapeutic target for cancer treatment and provided a foundation for future research.

Effects of Aging Treatment on the Microstructures and Mechanical Properties of a TC18 Alloy.

In the present work, the effects of aging treatment on the microstructures of a TC18 alloy are studied. The influence of aging treatment on the tensile properties and failure mechanisms is systematically analyzed. It is found that the size and morphology of the primary α (αp) phases are insensitive to aging temperature and time. Furthermore, the aging temperature and time dramatically influence the precipitation of the secondary α (αs) phases. Massive αs phases precipitate and gradually coarsen, and finally weave together by increasing the aging temperature or extending the aging time. The variations in αp and αs phases induced by aging parameters also affect the mechanical properties. Both yield strength (YS) and ultimate tensile strength (UTS) first increase and then decrease by increasing the aging temperature and time, while ductility first decreases and then increases. There is an excellent balance between the strengths and ductility. When the aging temperature is changed from 450 to 550 °C, YS varies from 1238.6 to 1381.6 MPa, UTS varies from 1363.2 to 1516.8 MPa, and the moderate elongation ranges from 9.0% to 10.3%. These results reveal that the thickness of αs phases is responsible for material strengths, while the content of α phases can enhance material ductility. The ductile characteristics of the alloy with coarser αs phases are more obvious than those with thinner αs phases. Therefore, the aging treatment is helpful for the precipitation and homogeneous distribution of αs phases, which are essential for balancing the strengths and ductility of the studied Ti alloy.

A nanomedicine composed of polymer-ss-DOX and polymer-Ce6 prodrugs with monoclonal antibody targeting effect for anti-tumor chemo-photodynamic synergetic therapy.

Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity and uncontrolled drug release due to their lack of targeting. To improve the bioavailability of drugs and reduce side effects, we have developed a mixed micelle of nanomedicine composed of two prodrugs with surface modified monoclonal antibody for cancer therapy. In this system, Nimotuzumab was used as targeting ligands of the mixed micelles (named as DCMMs) that is composed of polymer-doxorubicin prodrug (abbreviated as PEG-b-P(GMA-ss-DOX)) and maleimide polyethylene glycol-chlorin e6 (abbreviated as Mal-PEG-Ce6). The mixed micelles modified with Nimotuzumab (named as NTZ-DCMMs) bind to overexpressed EGFR receptors on Hepatoma-22 (H22) cells. Disulfide bonds in PEG-b-P(GMA-ss-DOX) are disrupted in tumor microenvironment, inducing the reduction-responsive release of DOX and leading to tumor cell apoptosis. Simultaneously, Chlorin e6 (Ce6) produced plenty of singlet oxygen (1O2) under laser irradiation to kill tumor cells. In vivo biological distribution and antineoplastic effect experiments demonstrate that NTZ-DCMMs enhanced drug enrichment at tumor sites through targeting function of antibody, dramatically suppressing tumor growth and mitigating cardiotoxicity of drugs. All results prove that NTZ-DCMMs have the ability to actively target H22 cells and quickly respond to tumor microenvironment, which is expected to become an intelligent and multifunctional drug delivery carrier for efficient chemotherapy and photodynamic therapy of hepatoma. STATEMENT OF SIGNIFICANCE: Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity due to their lack of targeting. Therefore, it's necessary to develop effective, targeted, and collaborative treatment strategies. We construct a mixed micelle of nanomedicine based on two polymer prodrugs and modified with monoclonal antibody on surface for cancer therapy. Under the tumor cell microenvironment, the disulfide bonds of polymer-ss-DOX were broken, effectively triggering DOX release. The photosensitizer Ce6 could generate a large amount of ROS under light, which synergistically promotes tumor cell apoptosis. By coupling antibodies to the hydrophilic segments of polymer micelles, drugs can be specifically delivered. Compared with monotherapy, the combination of chemotherapy and photodynamic therapy can significantly enhance the therapeutic effect of liver cancer.

The Molecular Profile of Soil Microbial Communities Inhabiting a Cambrian Host Rock.

The process of soil genesis unfolds as pioneering microbial communities colonize mineral substrates, enriching them with biomolecules released from bedrock. The resultant intricate surface units emerge from a complex interplay among microbiota and plant communities. Under these conditions, host rocks undergo initial weathering through microbial activity, rendering them far from pristine and challenging the quest for biomarkers in ancient sedimentary rocks. In addressing this challenge, a comprehensive analysis utilizing Gas Chromatography Mass Spectrometry (GC-MS) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was conducted on a 520-Ma-old Cambrian rock. This investigation revealed a diverse molecular assemblage with comprising alkanols, sterols, fatty acids, glycerolipids, wax esters, and nitrogen-bearing compounds. Notably, elevated levels of bacterial C16, C18 and C14 fatty acids, iso and anteiso methyl-branched fatty acids, as well as fungal sterols, long-chained fatty acids, and alcohols, consistently align with a consortium of bacteria and fungi accessing complex organic matter within a soil-type ecosystem. The prominence of bacterial and fungal lipids alongside maturity indicators denotes derivation from heterotrophic activity rather than ancient preservation or marine sources. Moreover, the identification of long-chain (>C22) n-alkanols, even-carbon-numbered long chain (>C20) fatty acids, and campesterol, as well as stigmastanol, provides confirmation of plant residue inputs. Furthermore, findings highlight the ability of contemporary soil microbiota to inhabit rocky substrates actively, requiring strict contamination controls when evaluating ancient molecular biosignatures or extraterrestrial materials collected.

Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD), which includes simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), is a significant contributor to liver disease on a global scale. The change of immunity-related genes (IRGs) expression level leads to different immune infiltrations. However, the expression of IRGs and possible regulatory mechanisms involved in NAFLD remain unclear. The objective of our research is to investigate crucial genes linked to the development of NAFLD and the transition from SS to NASH. Methods: Dataset GSE89632, which includes healthy controls, SS patients, and NASH patients, was obtained using the GEO database. To examine the correlation between sets of genes and clinical characteristics, we employed weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Hub genes were extracted using a network of protein-protein interactions (PPI) and three different machine learning algorithms. To validate the findings, another dataset that is publicly accessible and mice that were subjected to a high-fat diet (HFD) or MCD diet were utilized. Furthermore, the ESTIMATE algorithm and ssGSEA were employed to investigate the immune landscape in the normal versus SS group and SS versus NASH group, additionally, the relationship between immune infiltration and the expression of hub genes was also examined. Results: A total of 28 immune related key genes were selected. Most of these genes expressed reverse patterns in the initial and progressive stages of NAFLD. GO and KEGG analyses showed that they were focused on the cytokine related pathways and immune cell activation and chemotaxis. After screening by various algorithms, we obtained two hub genes, including JUN and CCL20. Validation of these findings was confirmed by analyzing gene expression patterns in both the validation dataset and the mouse model. Ultimately, two hub genes were discovered to have a significant correlation with the infiltration of immune cells. Conclusion: We proposed that there were dynamic changes in the expression levels of IRGs in different stages of NAFLD disease, which led to different immune landscapes in SS and NASH. The findings of our research could serve as a guide for the accurate management of various phases of NAFLD.

A theoretical model for predicting the startup performance of pumps as turbines.

Using the unsteady Bernoulli equation for the piping system and the angular momentum equation for the rotor, derives here a theoretical model to predict the startup performance of a pump as turbine (PAT). This model is effective for predicting the instantaneous evolution characteristics of the main performance parameters of PAT during startup, and these changings are initially faster and then slowly as a whole. The effect of the rotor moment of inertia and the final stabilized rotational speed of PAT on evolution characteristics of parameters is opposite. The rotational speed, head, hydraulic power, and conversion efficiency show a upward rising trend with the startup time, whereas the flow rate and hydraulic head loss display a downward trend.

Telocinobufagin, a PLK1 suppressor that inhibits tumor growth and metastasis by modulating CDC25c and CTCF in HNSCC cells.

BACKGROUND: The high metastasis and mortality rates of head and neck squamous cell carcinoma (HNSCC) urgently require new treatment targets and drugs. A steroidal component of ChanSu, telocinobufagin (TBG), was verified to have anti-cancer effects in various tumors, but its activity and mechanism in anti-HNSCC were still unknown. PURPOSE: This study tried to demonstrate the anti-tumor effect of TBG on HNSCC and verify its potential mechanism. METHODS: The effect of TBG on cell proliferation and metastasis were performed and the TBG changed genes were detected by RNA-seq analysis in HNSCC cells. The GSEA and PPI analysis were used to identify the pathways targeted for TBG-regulated genes. Meanwhile, the mechanism of TBG on anti-proliferative and anti-metastasis were investigated in vitro and in vivo. RESULTS: The in vitro and in vivo experiments confirmed that TBG has favorable anti-tumor effects by induced G2/M phase arrest and suppressed metastasis in HNSCC cells. Further RNA-seq analysis demonstrated the genes regulated by TBG were enriched at the G2/M checkpoint and PLK1 signaling pathway. Then, the bioinformatic analysis of clinical data found that high expressed PLK1 were closely associated with poor overall survival in HNSCC patients. Furthermore, PLK1 directly and indirectly modulated G2/M phase and metastasis (by regulated CTCF) in HNSCC cells, simultaneously. TBG significantly inhibited the protein levels of PLK1 in both phosphorylated and non-phosphorylated forms and then, in one way, inactivated PLK1 failed to activate G2/M phase-related proteins (including CDK1, CDC25c, and cyclin B1). In another way, be inhibited PLK1 unable promote the nuclear translocation of CTCF and thus suppressed HNSC cell metastasis. In contrast, the anti-proliferative and anti-metastasis effects of TBG on HNSCC cell were vanished when cells high-expressed PLK1. CONCLUSION: The present study verified that PLK1 mediated TBG induced anti-tumor effect by modulated G2/M phase and metastasis in HNSCC cells.

Tryptophan metabolism in digestive system tumors: unraveling the pathways and implications.

Tryptophan (Trp) metabolism plays a crucial role in influencing the development of digestive system tumors. Dysregulation of Trp and its metabolites has been identified in various digestive system cancers, including esophageal, gastric, liver, colorectal, and pancreatic cancers. Aberrantly expressed Trp metabolites are associated with diverse clinical features in digestive system tumors. Moreover, the levels of these metabolites can serve as prognostic indicators and predictors of recurrence risk in patients with digestive system tumors. Trp metabolites exert their influence on tumor growth and metastasis through multiple mechanisms, including immune evasion, angiogenesis promotion, and drug resistance enhancement. Suppressing the expression of key enzymes in Trp metabolism can reduce the accumulation of these metabolites, effectively impacting their role in the promotion of tumor progression and metastasis. Strategies targeting Trp metabolism through specific enzyme inhibitors or tailored drugs exhibit considerable promise in enhancing therapeutic outcomes for digestive system tumors. In addition, integrating these approaches with immunotherapy holds the potential to further enhance treatment efficacy.

Anti-ENO1 antibody combined with metformin against tumor resistance: a novel antibody-based platform.

Background: Antibody-based platforms (i.e., ADC) have emerged as one of the most encouraging tools for the cancer resistance caused by cancer stem cells (CSCs) enrichment. Our study might provide a promising therapeutic direction against drug resistance and serve as a potential precursor platform for screening ADC. Methods: The cell migration, invasion, drug resistance, and self-renewal were assessed by the cell invasion and migration assay, wound healing assay, CCK-8 assay, colony formation assay, and sphere formation assay, respectively. The expression profiles of CSCs (ALDH+ and CD44+) subpopulations were screened by flow cytometry. The western blot and cell immunofluorescence assay were used to evaluate pathway-related protein expression in both anti-ENO1 antibody, MET combined with DPP/CTX-treated CSCs. Results: In the present study, western blot and flow cytometry verified that anti-ENO1 antibody target the CD44+ subpopulation by inhibiting the PI3K/AKT pathway, while metformin might target the ALDH+ subpopulation through activation of the AMPK pathway and thus reverse drug resistance to varying degrees. Subsequently, in vitro investigation indicated that anti-ENO1 antibody, metformin combined with cisplatin/cetuximab could simultaneously target ALDH+ and CD44+ subpopulations. The combination also inhibited the CSCs proliferation, migration, invasion, and sphere formation; which may result in overcoming the drug resistance. Then, molecular mechanism exploration verified that the anti-ENO1 antibody, metformin combined with cisplatin/cetuximab inhibited the Wnt/ß-catenin signaling. Conclusions: The study preliminarily revealed anti-ENO1 antibody combined with metformin could overcome drug resistance against CSCs by inhibiting the Wnt//ß-catenin pathway and might serve as a potential precursor platform for screening ADC. More importantly, it is reasonably believed that antibody-based drug combination therapy might function as an encouraging tool for oncotherapy.

Relationship between bleeding sites and clinical data: experience of 646 epistaxis cases in 8 years.

PURPOSE: This study aims to investigate the bleeding sites and their relationship with clinical characteristics in hospitalized epistaxis patients. METHODS: We retrospectively reviewed the data of 646 hospitalized epistaxis patients. RESULTS: The bleeding sites were identified in 395 (61.1%) patients and unidentified in 251 (38.9%). We found that age > 50 years (P = 0.030) and the history of cardiovascular diseases (P = 0.027) were more frequent in patients with unidentified bleeding sites. Among patients with identified sites, inferior meatus (n = 130, 32.9%) was the most common site, followed by the septal surface of the olfactory region (n = 102, 25.8%), nasal septum (n = 80, 20.3%), middle meatus (n = 60, 15.2%), and others (n = 23, 5.8%). After dividing patients into five groups by the area of the bleeding sites, we found significant differences in age (P = 0.026), history of hypertension (P = 0.001), cardiovascular diseases (P = 0.032), and nasal packing (P = 0.011). The logistic regression also revealed that these four factors were predictors for different bleeding sites. CONCLUSION: The bleeding sites can be identified in most epistaxis patients. Age > 50 years and the history of cardiovascular diseases are more frequent in patients with unidentified bleeding sites. In our patients, the most common bleeding site is inferior meatus, followed by the septal surface of the olfactory region, nasal septum, and middle meatus. Age, histories of hypertension, cardiovascular diseases, and nasal packing are factors associated with the bleeding risks of different bleeding sites. According to the different clinical characteristics of patients, the order of the nasal endoscopic examination should be adjusted to develop their treatment plans.

A sterol analog inhibits hedgehog pathway by blocking cholesterylation of smoothened.

The hedgehog (Hh) signaling pathway has long been a hotspot for anti-cancer drug development due to its important role in cell proliferation and tumorigenesis. However, most clinically available Hh pathway inhibitors target the seven-transmembrane region (7TM) of smoothened (SMO), and the acquired drug resistance is an urgent problem in SMO inhibitory therapy. Here, we identify a sterol analog Q29 and show that it can inhibit the Hh pathway through binding to the cysteine-rich domain (CRD) of SMO and blocking its cholesterylation. Q29 suppresses Hh signaling-dependent cell proliferation and arrests Hh-dependent medulloblastoma growth. Q29 exhibits an additive inhibitory effect on medulloblastoma with vismodegib, a clinically used SMO-7TM inhibitor for treating basal cell carcinoma (BCC). Importantly, Q29 overcomes resistance caused by SMO mutants against SMO-7TM inhibitors and inhibits the activity of SMO oncogenic variants. Our work demonstrates that the SMO-CRD inhibitor can be a new way to treat Hh pathway-driven cancers.

CXCL13 promotes TNF-α synthesis in rheumatoid arthritis through activating ERK/p38 pathway and inhibiting miR-330-3p generation.

Rheumatoid arthritis (RA) is a well-known autoimmune disorder associated with joint pain, joint swelling, cartilage and bone degradation as well as deformity. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays a crucial role in multiple cellular pathogenesis processes, including RA. TNF-α is a vital proinflammatory factor in the progression of RA. However, the role of CXCL13 in TNF-α production in RA has not been fully explored. Our analysis of both database and clinical samples revealed higher levels of CXCL13 and TNF-α in RA samples compared to healthy controls. CXCL13 concentration-dependently induces TNF-α synthesis in RA synovial fibroblasts. CXCL13 enhances TNF-α expression by interacting with the CXCR5 receptor, activating the ERK/p38 pathways, and inhibiting miR-330-3p generation. Importantly, treatment with CXCL13 shRNA counteracted the upregulation of TNF-α production induced by collagen-induced arthritis. Our findings support the notion that CXCL13 is a promising target in the treatment of RA.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

In-Ovo Glutamine Administration Enhances Intestinal Development and Functions in Broiler Chickens: Insights from Enteroid Models.

BACKGROUND: Early life events play significant roles in tissue development and animal health in their later life. Early nutrition, through in-ovo delivery, has shown beneficial effects on improving intestinal health in broiler chickens. However, the underlying mechanism is not fully investigated. A recently developed enteroid culture technique allows investigations on intestinal epithelial functions that are close to physiologic conditions. OBJECTIVES: In this study, we evaluated the short- and long-term effects of in-ovo administration of glutamine (Gln) on intestinal epithelial development and functions by using intestinal enteroid culture and tissue electrophysiologic analysis. METHODS: A hundred eggs of commercial Cobb500 broilers were in-ovo injected with 0.2 mL of either phosphate-buffered saline (PBS) or 3% Gln at embryonic day 18 (E18). Chicks were killed on the day of hatch, and at 3- and 14-d posthatch. Enteroids were generated from the small intestine. After 4 d of culture, enteroids were harvested for 5-ethynyl-2'-deoxyuridine proliferation, fluorescein isothiocyanate-4 kDa dextran permeability, and glucose absorption assays. At day 3 (d3) and day 14 (d14), intestinal barrier and nutrient transport functions were measured by the Ussing chamber. The gene expression of epithelial cell markers, nutrient transporters, and tight-junction proteins were analyzed in both intestinal tissues and enteroids. RESULTS: In comparison with the PBS control group, in-ovo Gln increased intestinal villus morphology, epithelial cell proliferation, and differentiation, and altered epithelial cell population toward increased number of enteroendocrine and goblet cells while decreasing Paneth cells. Enteroids gene expression of nutrient transporters (B0AT1, SGLT1, and EAAT3), tight junction (ZO2), glucose absorption, and barrier functions were enhanced on the day of hatch. Long-term increases of intestinal di-peptide and alanine transport were observed at day 14 posthatch. CONCLUSIONS: Together our results suggested that the in-ovo injection of Gln stimulated intestinal epithelium proliferation and programmed the epithelial cell differentiation toward absorptive cells.

SIVA-1 enhances acquired chemotherapeutic drug resistance of gastric cancer in vivo by regulating the ARF/MDM2/p53 pathway.

SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.

Experimental Evaluation of Anticorrosion of a Standard 20# Gathering Pipeline by Injecting Oxygen-Reduced Air into Simulated In-Service Wells.

Oxygen-reduced air flooding (ORAF) can effectively improve oil recovery in low-permeability reservoirs, but oxygen corrosion and CO2 corrosion in downstream gathering pipelines are inevitable due to the existence of oxygen, which limits the popularization and application of ORAF. In this paper, research on the corrosion inhibitor is carried out for the gathering pipeline of an oilfield with ORAF in China. Under the conditions of a simulated onsite gathering pipeline, 6 kinds of anti-CO2 corrosion inhibitors and 6 kinds of antioxygen corrosion inhibitors were selected to evaluate and screen the effects of 20# steel by the dynamic weight loss method. Two antioxygen corrosion inhibitors KY-12 and KY-17 and one anti-CO2 corrosion inhibitor A were selected for the experiment. The corrosion inhibition rates of the three inhibitors reached 83.67, 91.49, and 78.44%, respectively, at a temperature of 40 °C and an inhibitor concentration of 1000 mg/L. Through the experimental evaluation of three primary corrosion inhibitors at different temperatures (25, 40, and 55 °C) and different concentrations (400, 500, 800, 1000, and 2000 mg/L), the KY-17 corrosion inhibitor with the best stability at different temperatures was selected, and the corrosion inhibition effect was the best at different concentrations, with the highest slow release rate reaching 92.7%. This conclusion has a good reference significance for the selection and dosage of corrosion inhibitors for downstream gathering pipelines of the ORAF oilfield.