RNF144A promotes antiviral responses by modulating STING ubiquitination.

Stimulator of interferon (IFN) genes (STING, also named MITA, ERIS, MPYS, or TMEM173) plays an essential role in DNA virus- or cytosolic DNA-triggered innate immune responses. Here, we demonstrate that the RING-in-between RING (RBR) E3 ubiquitin ligase family member RING-finger protein (RNF) 144A interacts with STING and promotes its K6-linked ubiquitination at K236, thereby enhancing STING translocation from the ER to the Golgi and downstream signaling pathways. The K236R mutant of STING displays reduced activity in promoting innate immune signal transduction. Overexpression of RNF144A upregulates HSV-1- or cytosolic DNA-induced immune responses, while knockdown of RNF144A expression has the opposite effect. In addition, Rnf144a-deficient cells exhibit impaired DNA virus- or cytosolic DNA-triggered signaling, and RNF144A protects mice from DNA virus infection. In contrast, RNF144A does not affect RNA virus- or cytosolic RNA-triggered innate immune responses. Taken together, our findings identify a new positive regulator of DNA virus- or cytosolic DNA-triggered signaling pathways and a critical ubiquitination site important for fully functional STING during antiviral responses.

Self-Rectifying All-Optical Modulated Optoelectronic Multistates Memristor Crossbar Array for Neuromorphic Computing.

Researching optoelectronic memristors capable of integrating sensory and processing functions is essential for advancing the development of efficient neuromorphic vision. Here, we experimentally demonstrated an all-optical controlled and self-rectifying optoelectronic memristor (OEM) crossbar array with the function of multilevel storage under light stimuli. The NiO/TiO2 device exhibits an ultrahigh (>104) rectifying ratio (RR) thus overcoming the presence of sneak current. The reversible conductance modulation without electric signal involvement provides a novel way to realize ultrafast information processing. The proposed OEM array realized synaptic functions observed in the human brain, including long-term potentiation (LTP), long-term depression (LTD), paired-pulse facilitation (PPF), the transition from short-term memory (STM) to long-term memory (LTM), and learning experience behaviors successfully. The authors present a novel OEM crossbar that possesses complete light-modulation capabilities, potentially advancing the future development of efficient neuromorphic vision.

Novel Three-Dimensional Artificial Neural Network Based on an Eight-Layer Vertical Memristor with an Ultrahigh Rectify Ratio (>107) and an Ultrahigh Nonlinearity (>105) for Neuromorphic Computing.

In recent years, memristors have successfully demonstrated their significant potential in artificial neural networks (ANNs) and neuromorphic computing. Nonetheless, ANNs constructed by crossbar arrays suffer from cross-talk issues and low integration densities. Here, we propose an eight-layer three-dimensional (3D) vertical crossbar memristor with an ultrahigh rectify ratio (RR > 107) and an ultrahigh nonlinearity (>105) to overcome these limitations, which enables it to reach a >1 Tb array size without reading failure. Furthermore, the proposed 3D RRAM shows advanced endurance (>1010 cycles), retention (>104 s), and uniformity. In addition, several synaptic functions observed in the human brain were mimicked. On the basis of the advanced performance, we constructed a novel 3D ANN, whose learning efficiency and recognition accuracy were enhanced significantly compared with those of conventional single-layer ANNs. These findings hold promise for the development of highly efficient, precise, integrated, and stable VLSI neuromorphic computing systems.

Oculocerebrorenal syndrome of Lowe (OCRL) controls leukemic T-cell survival by preventing excessive PI(4,5)P2 hydrolysis in the plasma membrane.

T-cell acute lymphoblastic leukemia (T-ALL) is one of the deadliest and most aggressive hematological malignancies, but its pathological mechanism in controlling cell survival is not fully understood. Oculocerebrorenal syndrome of Lowe is a rare X-linked recessive disorder characterized by cataracts, intellectual disability, and proteinuria. This disease has been shown to be caused by mutation of oculocerebrorenal syndrome of Lowe 1 (OCRL1; OCRL), encoding a phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] 5-phosphatase involved in regulating membrane trafficking; however, its function in cancer cells is unclear. Here, we uncovered that OCRL1 is overexpressed in T-ALL cells, and knockdown of OCRL1 results in cell death, indicating the essential role of OCRL in controlling T-ALL cell survival. We show OCRL is primarily localized in the Golgi and can translocate to plasma membrane (PM) upon ligand stimulation. We found OCRL interacts with oxysterol-binding protein-related protein 4L, which facilitates OCRL translocation from the Golgi to the PM upon cluster of differentiation 3 stimulation. Thus, OCRL represses the activity of oxysterol-binding protein-related protein 4L to prevent excessive PI(4,5)P2 hydrolysis by phosphoinositide phospholipase C ß3 and uncontrolled Ca2+ release from the endoplasmic reticulum. We propose OCRL1 deletion leads to accumulation of PI(4,5)P2 in the PM, disrupting the normal Ca2+ oscillation pattern in the cytosol and leading to mitochondrial Ca2+ overloading, ultimately causing T-ALL cell mitochondrial dysfunction and cell death. These results highlight a critical role for OCRL in maintaining moderate PI(4,5)P2 availability in T-ALL cells. Our findings also raise the possibility of targeting OCRL1 to treat T-ALL disease.

Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program.

BACKGROUND: Calcific aortic stenosis (CAS) is the most common valvular heart disease in older adults and has no effective preventive therapies. Genome-wide association studies (GWAS) can identify genes influencing disease and may help prioritize therapeutic targets for CAS. METHODS: We performed a GWAS and gene association study of 14 451 patients with CAS and 398 544 controls in the Million Veteran Program. Replication was performed in the Million Veteran Program, Penn Medicine Biobank, Mass General Brigham Biobank, BioVU, and BioMe, totaling 12 889 cases and 348 094 controls. Causal genes were prioritized from genome-wide significant variants using polygenic priority score gene localization, expression quantitative trait locus colocalization, and nearest gene methods. CAS genetic architecture was compared with that of atherosclerotic cardiovascular disease. Causal inference for cardiometabolic biomarkers in CAS was performed using Mendelian randomization and genome-wide significant loci were characterized further through phenome-wide association study. RESULTS: We identified 23 genome-wide significant lead variants in our GWAS representing 17 unique genomic regions. Of the 23 lead variants, 14 were significant in replication, representing 11 unique genomic regions. Five replicated genomic regions were previously known risk loci for CAS (PALMD, TEX41, IL6, LPA, FADS) and 6 were novel (CEP85L, FTO, SLMAP, CELSR2, MECOM, CDAN1). Two novel lead variants were associated in non-White individuals (P<0.05): rs12740374 (CELSR2) in Black and Hispanic individuals and rs1522387 (SLMAP) in Black individuals. Of the 14 replicated lead variants, only 2 (rs10455872 [LPA], rs12740374 [CELSR2]) were also significant in atherosclerotic cardiovascular disease GWAS. In Mendelian randomization, lipoprotein(a) and low-density lipoprotein cholesterol were both associated with CAS, but the association between low-density lipoprotein cholesterol and CAS was attenuated when adjusting for lipoprotein(a). Phenome-wide association study highlighted varying degrees of pleiotropy, including between CAS and obesity at the FTO locus. However, the FTO locus remained associated with CAS after adjusting for body mass index and maintained a significant independent effect on CAS in mediation analysis. CONCLUSIONS: We performed a multiancestry GWAS in CAS and identified 6 novel genomic regions in the disease. Secondary analyses highlighted the roles of lipid metabolism, inflammation, cellular senescence, and adiposity in the pathobiology of CAS and clarified the shared and differential genetic architectures of CAS with atherosclerotic cardiovascular diseases.

Cobalt-Catalyzed Domino Transformations via Enantioselective C-H Activation/Nucleophilic [3 + 2] Annulation toward Chiral Bridged Bicycles.

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

Mitochondria-derived peptide is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1alpha -mediated mitochondrial biogenesis.

Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. Mitochondrial-derived peptide (MOTS-c), a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate the putative underlying mechanisms. We found that endogenous MOTS-c levels in plasma and spinal dorsal horn were significantly lower in STZ-treated mice than in control animals. Accordingly, MOTS-c treatment significantly improves STZ-induced weight loss, elevation of blood glucose, mechanical allodynia, and thermal hyperalgesia; however, these effects were blocked by dorsomorphin, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, MOTS-c treatment significantly enhanced AMPKα1/2 phosphorylation and PGC-1α expression in the lumbar spinal cord of PDN mice. Mechanistic studies indicated that MOTS-c significantly restored mitochondrial biogenesis, inhibited microglia activation, and decreased the production of pro-inflammatory factors, which contributed to the alleviation of pain. Moreover, MOTS-c decreased STZ-induced pain hypersensitivity in PDN mice by activating AMPK/PGC-1α signaling pathway. This provides the pharmacological and biological evidence for developing mitochondrial peptide-based therapeutic agents for PDN.

Small Extracellular Vesicles Derived from Helicobacter Pylori-Infected Gastric Cancer Cells Induce Lymphangiogenesis and Lymphatic Remodeling via Transfer of miR-1246.

Lymph node metastasis (LNM) is a significant barrier to the prognosis of patients with gastric cancer (GC). Helicobacter pylori (H. pylori)-positive GC patients experience a higher rate of LNM than H. pylori-negative GC patients. However, the underlying mechanism remains unclear. Based on the findings of this study, H. pylori-positive GC patients have greater lymphangiogenesis and lymph node immunosuppression than H. pylori-negative GC patients. In addition, miR-1246 is overexpressed in the plasma small extracellular vesicles (sEVs) of H. pylori-positive GC patients, indicating a poor prognosis. Functionally, sEVs derived from GC cells infected with H. pylori deliver miR-1246 to lymphatic endothelial cells (LECs) and promote lymphangiogenesis and lymphatic remodeling. Mechanistically, miR-1246 suppresses GSK3ß expression and promotes ß-Catenin and downstream MMP7 expression in LECs. miR-1246 also stabilizes programmed death ligand-1 (PD-L1) by suppressing GSK3ß and induces the apoptosis of CD8+ T cells. Overall, miR-1246 in plasma sEVs may be a novel biomarker and therapeutic target in GC-LNM.

ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity.

BACKGROUND: The role of Acyl-CoA dehydrogenase long chain (ACADL) in different tumor types had different inhibiting or promoting effect. However, its role in non-small cell lung cancer (NSCLC) carcinogenicity is not clear. METHOD: In this study, we utilized The Cancer Genome Atlas (TCGA) database to analyze ACADL expression in NSCLC and its correlation with overall survival. Furthermore, we investigated the function of ACADL on cellular proliferation, invasion, colony, apoptosis, cell cycle in vitro with NSCLC cells. Mechanistically, we evaluated the regulatory effect of ACADL expression on its downstream factor yes-associated protein (YAP) by assessing YAP phosphorylation levels and its cellular localization. Finally, we verified the tumorigenic effect of ACADL on NSCLC cells through xenograft experiments in vivo. RESULTS: Compared to adjacent non-cancerous samples, ACADL significantly down-regulated in NSCLC. Overexpression of ACADL, effectively reduced the proliferative, colony, and invasive capabilities of NSCLC cells, while promoting apoptosis and inducing cell cycle arrest. Moreover, ACADL overexpression significantly enhanced YAP phosphorylation and hindered its nuclear translocation. However, the inhibitory effect of the overexpression of ACADL in NSCLC cells mentioned above can be partially counteracted by YAP activator XMU-MP-1 application both in vitro and in vivo. CONCLUSION: The findings suggest that ACADL overexpression could suppress NSCLC development by modulating YAP phosphorylation and limiting its nuclear shift. This role of ACADL-YAP axis provided novel insights into NSCLC carcinogenicity and potential therapeutic strategies.

Interlayer-Coupling-Driven High-Temperature Superconductivity in La_{3}Ni_{2}O_{7} under Pressure.

The newly discovered high-temperature superconductivity in La_{3}Ni_{2}O_{7} under pressure has attracted a great deal of attention. The essential ingredient characterizing the electronic properties is the bilayer NiO_{2} planes coupled by the interlayer bonding of 3d_{z^{2}} orbitals through the intermediate oxygen atoms. In the strong coupling limit, the low-energy physics is described by an intralayer antiferromagnetic spin-exchange interaction J_{∥} between 3d_{x^{2}-y^{2}} orbitals and an interlayer one J_{⊥} between 3d_{z^{2}} orbitals. Taking into account Hund's rule on each site and integrating out the 3d_{z^{2}} spin degree of freedom, the system reduces to a single-orbital bilayer t-J model based on the 3d_{x^{2}-y^{2}} orbital. By employing the slave-boson approach, the self-consistent equations for the bonding and pairing order parameters are solved. Near the physically relevant 1/4-filling regime (doping δ=0.3∼0.5), the interlayer coupling J_{⊥} tunes the conventional single-layer d-wave superconducting state to the s-wave one. A strong J_{⊥} could enhance the interlayer superconducting order, leading to a dramatically increased T_{c}. Interestingly, there could exist a finite regime in which an s+id state emerges.

Atypical antipsychotics antagonize GABAA receptors in the ventral tegmental area GABA neurons to relieve psychotic behaviors.

Psychosis is an abnormal mental condition that can cause patients to lose contact with reality. It is a common symptom of schizophrenia, bipolar disorder, sleep deprivation, and other mental disorders. Clinically, antipsychotic medications, such as olanzapine and clozapine, are very effective in treatment for psychosis. To investigate the neural circuit mechanism that is affected by antipsychotics and identify more selective therapeutic targets, we employed a strategy by using these effective antipsychotics to identify antipsychotic neural substrates. We observed that local injection of antipsychotics into the ventral tegmental area (VTA) could reverse the sensorimotor gating defects induced by MK-801 injection in mice. Using in vivo fiber photometry, electrophysiological techniques, and chemogenetics, we found that antipsychotics could activate VTA gamma-aminobutyric acid (GABA) neurons by blocking GABAA receptors. Moreover, we found that the VTAGABA nucleus accumbens (NAc) projection was crucially involved in such antipsychotic effects. In summary, our study identifies a novel therapeutic target for the treatment of psychosis and underscores the utility of a 'bedside-to-bench' approach for identifying neural circuits that influence psychotic disorders.

Suppressing memory associations impacts decision-making preference: Evidence from the think/no-think paradigm.

Recent research has suggested that episodic memory can guide our decision-making. Forgetting is one essential characteristic of memory. If certain memories are suppressed to be forgotten, decisions that rely on such memories should be impacted. So far, little research has examined whether suppression of episodic memory would impact decision-making. In the current pre-registered study, the effect of memory suppression on subsequent reinforcement decision-making was examined by combining the Think/No-think paradigm and a reinforcement decision-making task. We found that suppressing memories of learned associations significantly impaired recollected memories of those associations, and participants' decision bias disappeared after their memory associations were suppressed. Furthermore, the more memory associations participants recalled, the higher decision preferences they exhibited. Our findings provide additional support for the role of episodic memory in reinforcement decision-making, and suggest that suppressing memory associations can lead to behavioral consequences.

The Arabidopsis RTH plays an important role in regulation of iron (Fe) absorption and transport.

KEY MESSAGE: RTH may activate Fe assimilation related genes to promote Fe absorption, transport and accumulation in Arabidopsis. Iron (Fe) is an important nutrient element. The Fe absorption and transport in plants are well investigated over the past decade. Our previous work indicated that RTE1-HOMOLOG (RTH), the homologous gene of reversion-to-ethylene sensitivity 1 (RTE1), plays a role in ethylene signaling pathway. However, its function in Fe absorption and transport is largely unknown. In the present study, we found that RTH was expressed in absorptive tissue and conducting tissue, including root hairs, root vascular bundle, and leaf veins. Under high Fe concentration, the seedling growth of rth-1 mutant was better, while the RTH overexpression lines were retarded compared to the wild type (Col-0). When treated with EDTA-Fe3+ (400 µM), the chlorophyll content and ion leakage rate were higher and lower in rth-1 than those of Col-0, respectively. By contrast, the chlorophyll contents and ion leakage rates of RTH overexpression lines were decreased and hastened compared with Col-0, respectively. Fe measurement indicated that the Fe contents of rth-1 were lower than those of Col-0, whereas those of RTH overexpression lines were comparably higher. Gene expression analysis revealed that Fe absorption and transport genes AHA2, IRT1, FIT, FPN1, and YSL1 decreased in rth-1 but increased in RTH overexpression lines compared with Col-0. Additionally, Y2H (yeast two-hybrid) and BiFC (bimolecular fluorescence complementation) assays showed that RTH can physically interact with hemoglobin 1 (HB1) and HB2. All these findings suggest that RTH may play an important role in regulation of Fe absorption, transport, and accumulation in Arabidopsis.

Exercise Regulates Myokines in Aging-Related Diseases through Muscle-Brain Crosstalk.

BACKGROUND: The related functions of skeletal muscle and brain decrease significantly with age, and muscle-brain-related diseases are primarily associated with each other. Exercise can promote the secretion of myokines in skeletal muscle, showing a beneficial effect on the function of both, reflecting muscle-brain crosstalk. However, the key mechanism of action of exercise-regulated myokines in muscle-brain diseases remains unclear. SUMMARY: This review is intended to sort out and explore the key mechanism of the effect of exercise regulatory myokines on muscle-brain diseases through summarizing the relevant literature on the level of motor regulatory myokines in recent years and pay special attention to the impact of exercise type, intensity, and duration on myokine expression levels. KEY MESSAGES: The mechanism by which exercise regulates myokine levels in muscle-brain diseases is explained, and an effective exercise prescription for myokine expression that is more suitable for the elderly based on relevant literature is proposed. This work may hold certain value for subsequent exercise treatment of chronic diseases in the elderly and for further research on muscle-brain crosstalk.

PEG modification increases thermostability and inhibitor resistance of Bst DNA polymerase.

Polyethylene glycol modification (PEGylation) is a widely used strategy to improve the physicochemical properties of various macromolecules, especially protein drugs. However, its application in enhancing the performance of enzymes for molecular biology remains underexplored. This study explored the PEGylation of Bst DNA polymerase, determining optimal modification reaction conditions. In comparison to the unmodified wild-type counterpart, the modified Bst DNA polymerase exhibited significantly improved activity, thermal stability, and inhibitor tolerance during loop-mediated isothermal amplification. When applied for the detection of Salmonella in crude samples, the modified enzyme demonstrated a notably accelerated reaction rate. Therefore, PEGylation emerges as a viable strategy for refining DNA polymerases, helping in the development of novel molecular diagnostic reagents.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

TEM Investigation on the Dislocation Loops in Zirconium Alloy by Neutron and Kr+ Ion Irradiation Tests.

Neutron irradiation (E ≥ 1 MeV) and 400 keV Kr+ ion irradiation tests were carried out and compared to study the formation and growth mechanism of dislocation loops in zirconium alloys. The results show that, as the irradiation reached 1.9 × 1025 n/m2 and 1.0 × 1020 Kr+/m2, a large number of -type dislocation loops and a small amount of large-sized -type dislocations hundreds of nanometers or even micrometers in size are observed in both samples. EDS results confirmed that the concentrations of Nb and Fe in the -type dislocation loops are higher than that in the matrix. With the increases of the dislocation loop size, part of the loop structure will decompose into the twisted, small-sized dislocation lines. Between two of the small-sized dislocation lines, a cubic structure was observed.

Comparative study of arterial and venous grafting for pedicle lengthening in head and neck microvascular reconstruction.

BACKGROUND: In the field of head and neck microvascular reconstruction, no previous study has compared arterial and venous grafting as methods of anterolateral thigh (ALT) pedicle lengthening. Therefore, we conducted this comparative study to compare the outcomes between the two pedicle lengthening techniques. METHODS: We performed comparative effectiveness research by conducting a retrospective chart review from January 2012 to December 2021 to identify patients who underwent head and neck reconstruction with non-descending branch ALT perforator flaps using either the in situ pedicle lengthening (ISPL) technique or the vein graft (VG) technique. A total of 26 patients were analyzed, including 14 who underwent ISPL, and 12 who underwent VG. The collected data, including patient demographics, surgical indications, history of prior free flap, prior neck dissection, radiation therapy, chemotherapy, graft length, and flap outcomes, were analyzed. The flap outcomes were categorized as total flap loss, partial flap loss, flap compromise that required operating room visits, or minor issues, including infection or dehiscence. The flap characteristics and postoperative outcomes were compared between the two groups. RESULTS: The VG group had two flap losses, whereas the ISPL group had none. Although the failure rate was higher in the VG group than that in the ISPL group, the difference was not statistically significant (0% vs. 16.7%, p = 0.203). Additionally, there were no significant differences in flap take-back (14.3% vs. 16.7%, p = 1) and minor complications between the two groups (35.7% vs. 33.3%, p = 1). CONCLUSIONS: If pedicle lengthening with vessel graft is inevitable in head and neck reconstruction, arterial graft may provide a reliable outcome and may be considered an effective alternative when compared to vein grafts.

Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS.

OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Screening of the shared pathogenic genes of ulcerative colitis and colorectal cancer by integrated bioinformatics analysis.

Ulcerative colitis (UC) is one of the high-risk pathogenic factors for colorectal cancer (CRC). However, the shared gene and signalling mechanisms between UC and CRC remain unclear. The goal of this study was to delve more into the probable causal relationship between UC and CRC. CRC and UC datasets were downloaded from the Gene Expression Omnibus database. Using R software and Perl, differentially expressed genes (DEGs) in both UC and CRC tissues were re-annotated and screened. The biological activities and signalling pathways involved in DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The STRING database and Cytoscape software were used to construct the gene interaction network. A total of 384 DEGs were selected for further investigation, and functional analysis revealed that inflammatory and immunological responses were crucial in the development of the two diseases. Moreover, the top 15 key genes involved in the UC and CRC were screened using cytoHubba, including IL1B, CXCL10, CCL20, MMP9, ICAM1, CCL4, CXCR1, MMP3, TLR2, PTGS2, IL1RN, IL6, COL1A2, TIMP1 and CXCL1. The identification of these genes in the present study may provide a novel perspective for the prediction, prevention and personalized medicine of UC and CRC patients.