A rapid nucleic acid detection platform based on phosphorothioate-DNA and sulfur binding domain.

Nucleic acid detection plays a key role in diverse diagnosis and disease control. Currently available nucleic acid detection techniques are challenged by trade-offs among speed, simplicity, precision and cost. Here, we described a novel method, designated SENSOR (Sulfur DNA mediated nucleic acid sensing platform), for rapid nucleic acid detection. SENSOR was developed from phosphorothioate (PT)-DNA and sulfur binding domain (SBD) which specifically binds double-stranded PT-modified DNA. SENSOR utilizes PT-DNA oligo and SBD as targeting module, which is linked with split luciferase reporter to generate luminescence signal within 10 min. We tested detection on synthesized nucleic acid and COVID-19 pseudovirus, achieving attomolar sensitivity combined with an amplification procedure. Single nucleotide polymorphisms (SNP) could also be discriminated. Indicating SENSOR a new promising nucleic acid detection technique.

Regulation of chloroplast protein degradation.

Chloroplasts are unique organelles that not only provide sites for photosynthesis and many metabolic processes, but also are sensitive to various environmental stresses. Chloroplast proteins are encoded by genes from both nuclear and chloroplast genomes. During chloroplast development and responses to stresses, the robust protein quality control systems are essential for regulation of protein homeostasis and the integrity of chloroplast proteome. In this review, we summarize the regulatory mechanisms of chloroplast protein degradation refer to protease system, ubiquitin-proteasome system, and the chloroplast autophagy. These mechanisms symbiotically play a vital role in chloroplast development and photosynthesis under both normal or stress conditions.

Mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation for ferroptosis after spinal cord injury.

Spinal cord injury is characterized by different aetiologies, complex pathogenesis, and diverse pathological changes. Current treatments are not ideal, and prognosis is generally poor. After spinal cord injury, neurons die due to various forms of cell death. Among them, ferroptosis causes dysfunction after spinal cord injury, and no existing traditional treatments have been indicated to block its occurrence. Meanwhile, emerging therapies using mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation therapy are promising for reversing spinal cord neuronal ferroptosis after spinal cord injury. However, no definitive studies have demonstrated the effectiveness of these approaches. This review summarizes the existing research on the mechanisms of ferroptosis; ferroptosis after spinal cord injury; treatment of spinal cord injury with mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation; and treatment of ferroptosis using mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation. Inhibiting ferroptosis can promote the reversal of neurological dysfunction after spinal cord injury. In addition, mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation can reverse adverse outcomes of spinal cord injury and regulate ferroptosis-related factors. Thus, it can be inferred that mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation have the potential to inhibit ferroptosis after spinal cord injury. This review serves as a reference for future research to confirm these conclusions.

A New Uniaxial Tensile Model for Foam Metal/Epoxy Interpenetrated Phase Composites.

Foam metal/epoxy interpenetrating phase composite is a new type of composite material with interpenetrating continuity in composition, which exhibits different intrinsic relationships under different stress states in tension and compression, and it is necessary to study the intrinsic relationships in the tensile state in depth. A mesoscopic damage-based tensile intrinsic model is developed, and the elasto-plastic tensile intrinsic equations of the representative volume element are derived based on small deformation theory and total strain theory, as well as the assumptions of equal stress and equal strain. The tensile strengths of nickel-iron foam/epoxy interpenetrated phase composites in three different sizes and their constituent phases were measured, and it was shown in the results that the composite of three-dimensional network interpenetration with high-strength foam metal and epoxy resin formed a weak surface inside the material, and did not significantly improve the tensile strength of the composites. The tensile instantonal equations and damage instantonal equations of nickel-iron foam/epoxy interpenetrated phase composites were predicted by the method of inversion, and the applicability and high accuracy of the tensile intrinsic model were verified in comparison with the measured results.

Targeting SHP2 reverses BRAF inhibitor tolerance in anaplastic thyroid carcinoma.

PURPOSE: To explore the possibility of a combination of dabrafenib and SHP2 inhibitor in the treatment of anaplastic thyroid carcinoma and to provide a new therapeutic strategy for the treatment of anaplastic thyroid cancer. PATIENTS AND METHODS: Firstly, a drug resistance model was established, and the expression levels of related RTK were detected by qPCR. Western blot was used to detect the protein expression levels of Akt and MAPK signaling pathways in the control group, single-drug group and two-drug combination group. The gene silencing of SHP2 was achieved by transfection of siRNA and verified by Western blot. CCK8 kit and clone formation assay were used to detect cell proliferation activity. In vivo model of mutant thyroid cancer cells was established by subcutaneous injection of mice and then divided into four groups. Tumor diameter was measured every two days. Immunohistochemistry was used to evaluate the expression of p-ERK, p-AKT and Ki67 in mouse tumors. RESULTS: In this study, dabrafenib-resistant ATC cells were first constructed, and the response of RTKs in drug-resistant cells was upregulated to activate Akt and MER/ERK pathways. The activation of Akt and MEK/ERK pathways in the combination group was significantly inhibited, and the proliferation ability of tumor cells was significantly reduced compared with Dabrafenib, SHP099 group and DMSO group. To verify that SHP099 was not off-target, we also silenced SHP2 expression by transfection with siRNA and obtained the same results. Finally, by building a mouse drug resistance model, we confirmed that dabrafenib and SHP099 can also play a powerful anti-cancer effect in vivo. CONCLUSION: The SHP2 inhibitor SHP099 can effectively reverse the drug resistance of dabrafenib through inhibiting the reactivated RAS signaling pathway in anaplastic thyroid cancer.The combination of dabrafenib with SHP2 inhibitor has shown significant tumor suppressive effects for dabrafenib-resistant cells and it may be a new therapeutic strategy with longer lasting therapeutic benefits.

Access to functionalized 2-pyrones through cascade reactions of α-halothioesters involving DBU-derived ammonium ylides.

Facile access to 4-aryl-6-oxycarbonyl-2-pyrones from α-halothioesters with ß,γ-unsaturated α-keto esters is achieved via a DBU-promoted Michael addition/lactonization/elimination cascade reaction. The reaction mechanism is tentatively elucidated by performing control experiments and high-resolution mass spectrometry analysis, which indicates that the cascade sequence may involve DBU-derived ammonium ylides.

Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer.

Ovarian cancer (OC) is the most lethal gynecological malignancy with a 5-year survival rate of 49.1% on average. In clinical practice, cytoreduction and chemotherapy remain the conventional treatment for advanced OC. However, the overall prognosis remains poor, which urges oncologists to develop new treatments. Chimeric antigen receptor (CAR)-T therapy as a branch of immunotherapy had gained a success in treating hematological malignancies. TM4SF1, a potential biomarker in many tumors, was validated highly expressed in ovarian cancer. Here we constructed a 3rd generation CAR-T agent targeting TM4SF1 to treat ovarian cancer. CAR-T cells showed a specific cytotoxicity against TM4SF1 positive tumor cell lines in vitro and repressed SKOV3-derived tumor growth in vivo. This is the first time reporting a CAR-T therapy targeting TM4SF1 in ovarian cancer. Our results suggested that TM4SF1 could be a very promising target in curing OC and showed the possibility of TM4SF1-based immunotherapy.

Circ-calm4 regulates hypoxia-induced pulmonary artery smooth muscle autophagy by binding Purb.

Pulmonary hypertension (PH) is a serious and fatal disease characterized by pulmonary vasoconstriction and pulmonary vascular remodeling. The excessive autophagy of pulmonary artery smooth muscle cells (PASMCs) is one of the important factors of pulmonary vascular remodeling. A number of studies have shown that circular RNA (circRNA) can participate in the onset of PH. Our previous studies have shown that circRNA calmodulin 4 (circ-calm4) is involved in the progression of hypoxic PH. However, the role of circ-calm4 on regulation of hypoxic PH autophagy has not been reported. In this study, we demonstrated for the first time that hypoxia-mediated upregulated circ-calm4 expression has a key regulatory effect on autophagy in hypoxia-induced PASMCs and hypoxic PH mouse models. Knockdown of circ-calm4 both in vivo and in vitro can inhibit the autophagy in PASMCs induced by hypoxia. We also performed bioinformatics predictions and conducted experiments to verify that circ-calm4 bound to the purine-rich binding protein (Purb) to promote its expression in the nucleus, thereby initiating the transcription of autophagy-related protein Beclin1. Interestingly, we found that Beclin1 transcription initiated by Purb was accompanied by a modification of Beclin1 super-enhancer to improve transcription activity and efficiency. Overall, our results confirm that the circ-calm4/Purb/Beclin1 signal axis is involved in the occurrence of hypoxia-induced PASMCs autophagy, and the novel regulatory mechanisms and signals transduction pathways in PASMC autophagy induced by hypoxia.

Increased serum pannexin-1 concentrations reflect illness severity and predict a poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study.

BACKGROUND: Pannexin-1 is a nonselective, large pore and voltage gated channel protein, whose activation may aggravate acute brain injury. We ascertained the clinical significance of serum pannexin-1 as a prognostic biomarker of acute intracerebral hemorrhage (ICH). METHODS: In this prospective, observational study of 124 acute supratentorial ICH patients and 124 healthy controls, serum pannexin-1 concentrations were determined. Admission National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used for assessment of hemorrhagic severity, post-stroke 6-month modified Rankin scale (mRS) score was registered to reflect clinical outcome and early neurologic deterioration (END) and 6-month poor outcome (mRS score of 3-6) were regarded as the 2 prognostic parameters. Their associations with serum pannexin-1 concentrations were investigated using multivariate analysis. The predictive performance was evaluated in terms of area under receiver operating characteristic curve (AUC). RESULTS: In comparison to controls, significantly increased serum pannexin-1 concentrations after ICH (median, 6.8 vs. 2.7 mg/ml) were independently correlative with NIHSS score (ß, 0.193; 95% CI: 0.086-0.300), hematoma volume (ß, 0.641; 95% CI: 0.423-0.859) and mRS score (ß, 0.199; 95% CI: 0.065-0.174), were independently predictive of END (OR, 1.176; 95% CI: 1.081-1.280) and poor outcome (odds ratio, 1.218; 95% CI: 1.059-1.400), as well as were efficiently discriminative of END (AUC, 0.764; 95% CI: 0.663-0.864) and poor 6-month outcome (AUC, 0.790; 95% CI: 0.711-0.870). Serum pannexin-1 combined with NIHSS score and hematoma volume (AUC, 0.908; 95% CI: 0.857-0.960) displayed significantly higher predictive ability for poor 6-month outcome than NIHSS score and hematoma volume alone (both P < 0.05). CONCLUSION: Rising serum pannexin-1 concentrations following ICH, in strong correlation with hemorrhagic severity, independently distinguish the risk of END and 90-day poor outcome. Assumably, serum pannexin-1 may represent a valuable prognostic biomarker of ICH.

Conjugative RP4 Plasmid-Mediated Transfer of Antibiotic Resistance Genes to Commensal and Multidrug-Resistant Enteric Bacteria In Vitro.

Many antibiotic-resistant bacteria carry resistance genes on conjugative plasmids that are transferable to commensals and pathogens. We determined the ability of multiple enteric bacteria to acquire and retransfer a broad-host-range plasmid RP4. We used human-derived commensal Escherichia coli LM715-1 carrying a chromosomal red fluorescent protein gene and green fluorescent protein (GFP)-labeled broad-host-range RP4 plasmid with ampR, tetR, and kanR in in vitro matings to rifampicin-resistant recipients, including Escherichia coli MG1655, Dec5α, Vibrio cholerae, Pseudomonas putida, Pseudomonas aeruginosa, Klebsiella pneumoniae, Citrobacter rodentium, and Salmonella Typhimurium. Transconjugants were quantified on selective media and confirmed using fluorescence microscopy and PCR for the GFP gene. The plasmid was transferred from E. coli LM715-1 to all tested recipients except P. aeruginosa. Transfer frequencies differed between specific donor-recipient pairings (10-2 to 10-8). Secondary retransfer of plasmid from transconjugants to E. coli LM715-1 occurred at frequencies from 10-2 to 10-7. A serial passage plasmid persistence assay showed plasmid loss over time in the absence of antibiotics, indicating that the plasmid imposed a fitness cost to its host, although some plasmid-bearing cells persisted for at least ten transfers. Thus, the RP4 plasmid can transfer to multiple clinically relevant bacterial species without antibiotic selection pressure.

A Novel Whole-Cell Biosensor for Bioavailable Antimonite in Water and Sediments.

Antimony (Sb) is an emerging contaminant, and its on-site speciation analysis is central to the accurate evaluation of its bioavailability and toxicity. The whole-cell biosensors (WCBs) for Sb(III) are promising but challenging due to the lack of Sb(III)-specific recognition components. Here, we constructed a novel Sb(III)-specific WCB using an Sb(III) transcriptional regulator (antR) and its cognate promoter (Pant). To prevent the promoter leakage of Pant, an additional regulatory gene, antR, was inserted downstream of the Sb(III)-inducible promoter, improving the sensitivity of the WCB by an order of magnitude and reaching the detection limit at 0.009 µM, which is lower than the WHO drinking water standard of Sb. Moreover, the WCB with double antR showed a high specificity toward Sb(III) compared with interfering ions at 3 orders of magnitude higher concentrations. This WCB was capable of measuring Sb(III) bioavailability in natural waters and sediments on-site, and its results were not statistically different from the chemical analysis. The insights gained from this work demonstrate that the addition of regulatory genes prevents promoter leakage and improves the sensitivity of WCBs in field applications. IMPORTANCE Antimony (Sb) is a redox-sensitive pollutant ubiquitous in the environment. Sb(III) is dominant in the subsurface and is readily oxidized to less toxic Sb(V) upon exposure to air, and therefore, on-site Sb speciation analysis is essential to evaluate its bioavailability and toxicity. Dissolved Sb concentration and speciation can be determined accurately using on-site chemical sensors, but chemical sensors have difficulty determining the bioavailable Sb(III) that is taken up by the cells. Here, we constructed an Sb(III)-specific whole-cell biosensor (WCB) using double Sb(III) transcriptional regulators (antR) downstream of its cognate promoter Pant. With an additional antR, the sensitivity of the WCB was improved by approximately 10 times, and the promoter leakage commonly found in WCBs was inhibited. Integrated with a tea-bag design, the WCB is able to measure Sb(III) bioavailability in natural water and sediments on-site. This study demonstrates the importance of inserting one more regulatory gene to improve sensitivity.

Reconstitution and expression of mcy gene cluster in the model cyanobacterium Synechococcus 7942 reveals a role of MC-LR in cell division.

Cyanobacterial blooms pose a serious threat to public health due to the presence of cyanotoxins. Microcystin-LR (MC-LR) produced by Microcystis aeruginosa is the most common cyanotoxins. Due to the limitation of isolation, purification, and genetic manipulation techniques, it is difficult to study and verify in situ the biosynthetic pathways and molecular mechanisms of MC-LR. We reassembled the biosynthetic gene cluster (mcy cluster) of MC-LR in vitro by synthetic biology, designed and constructed the strong bidirectional promoter biPpsbA2 , transformed it into Synechococcus 7942, and successfully expressed MC-LR at a level of 0.006-0.018 fg cell-1 d-1 . We found the expression of MC-LR led to abnormal cell division and cellular filamentation, further using various methods proved that by irreversibly competing its GTP-binding site, MC-LR inhibits assembly of the cell division protein FtsZ. The study represents the first reconstitution and expression of the mcy cluster and the autotrophic production of MC-LR in model cyanobacterium, which lays the foundation for resolving the microcystins biosynthesis pathway. The discovered role of MC-LR in cell division reveals a mechanism of how blooming cyanobacteria gain a competitive edge over their nonblooming counterparts.

Novel Self-Assembled Multifunctional Nanoprobes for Second-Near-Infrared-Fluorescence-Image-Guided Breast Cancer Surgery and Enhanced Radiotherapy Efficacy.

Breast-conserving surgery (BCS) is the predominant treatment approach for initial breast cancer. However, due to a lack of effective methods evaluating BCS margins, local recurrence caused by positive margins remains an issue. Accordingly, radiation therapy (RT) is a common modality in patients with advanced breast cancer. However, while RT also protects normal tissue and enhances tumor bed doses to improve therapeutic effects, current radiosensitizers cannot meet these urgent clinical needs. To address this, a novel self-assembled multifunctional nanoprobe (NP) gadolinium (Gd)-diethylenetriaminepentaacetic acid-human serum albumin (HSA)@indocyanine green-Bevacizumab (NPs-Bev) is synthesized to improve the efficacy of fluorescence-image-guided BCS and RT. Fluorescence image guidance of the second near infrared NP improves complete resection in tumor-bearing mice and accurately discriminates between benign and malignant mammary tissue in transgenic mice. Moreover, targeting tumors with NPs induces more reactive oxygen species under X-ray radiation therapy, which not only increases RT sensitivity, but also reduces tumor progression in mice. Interestingly, self-assembled NPs-Bev using HSA, the magnetic resonance contrast agent and Bevacizumab-targeting vascular growth factor A, which are clinically safe reagents, are safe in vitro and in vivo. Therefore, the novel self-assembled NPs provide a solid precision therapy platform to treat breast cancer.

Predictive Value of HBsAg for Off-treatment Response in HBeAg-negative Chronic Hepatitis B Patients.

OBJECTIVE: To investigate the virological relapse (VR) rate and prognostic value of the HBsAg level at treatment completion for predicting sustained off-treatment response in HBeAg-negative patients after neucleos(t)ide analog (NA) therapy. STUDY DESIGN: Prospective observational cohort study. PLACE AND DURATION OF STUDY: The Second Hospital of Shandong University, Ji'nan, China, between December 2001 and January 2020. METHODOLOGY: Eighty-one HBeAg-negative chronic hepatitis B patients who stopped NA treatment were included. Factors associated with the VR were identified using univariate and multivariate Cox regression models. RESULTS: Of the 81 patients, 42 had sustained off-treatment response with a median follow-up of 60.0 months (interquartile range [IQR] 33.0-111.0 months). Thirty-nine patients relapsed and 32 relapsed within the first year. The cumulative VR rates were 34.6%, 41.0%, 42.5%, 48.1%, and 55.8% at 1, 2, 3, 5, and 10 years off-therapy, respectively. For patients with end-of-treatment (EOT) HBsAg <250 IU/mL, the 10-year cumulative VR rate was 26.0%. Time to HBV DNA negativity (median, 2 months [IQR 1.0-3.0 months]) and age at EOT were also independent predictors of sustained off-treatment response. CONCLUSION: Discontinuing long-term NA treatment is a feasible option for HBeAg-negative chronic hepatitis B patients whose HBsAg levels are low, and HBsAg <250 IU/mL may be an acceptable cut-off value. Younger age at EOT and shorter time to HBV DNA negativity are also independent factors associated with sustained off-treatment response. KEY WORDS: Hepatitis B surface antigen, Nucleos(t)ide analogs, Cessation, Relapse.

Application of next-generation sequencing technology in the detection of pathogenic bacteria of the periprosthetic joint infection after arthroplasty.

To investigate the application value of next-generation sequencing (NGS) technology in the detection of pathogenic bacteria in the periprosthetic joint infection after arthroplasty. Twenty-two cases of patients with joint infection after arthroplasty in our hospital from March 2020 to March 2021 were selected, with 11 cases of knee and 11 cases of hip, including 8 cases of male and 14 cases of female, and an average age of 63.55 ± 13.11 years old (range from 28 to 85). Microbiological culture results of synovial fluid and periprosthetic joint tissue and NGS results of periprosthetic joint tissue were collected. The detection rate of NGS and microbiological culture were calculated and statistically analysed by paired χ2 test. Among the 22 patients with joint infection after arthroplasty, the positive rate of NGS was 90.91% (20/22), whereas the positive rate of bacterial culture was 50.00% (11/22). Paired chi-square test showed a statistically significant difference in the detection rate between the two groups (P = .0029). In the detection of pathogenic microorganism, NGS detected 12 kinds of bacteria, Staphylococcus aureus in 3 patients, Staphylococcus epidermidis in 5 cases, Streptococcus 1 case, Streptococcus dysgalactiae 1 case, Xanthomonas campestris 3 cases, Escherichia coli 2 cases, Bacillus cereus 2 cases, Klebsiella pneumoniae 1 case, Finegoldia magna 1 case, Corynebacterium klopensteriella in 1 case, Brucella 1 case, and Aspergillus flavus 1 case. Bacterial culture detected 6 kinds of bacteria, included 5 cases of Staphylococcus epidermis (including 3 cases of Methicillin-resistant coagulase-negative Staphylococcus, (MRSCoN)), 2 cases of Staphylococcus aureus (both Methicillin-resistant Staphylococcus aureus, (MRSA)), 1 case of Klebsiella pneumoniae, 1 case of Staphylococcus hominis (MRSCoN), 1 case of G+ bacillus, and 1 case of Brucella. Compared with bacterial culture, NGS technology has some advantages in the detection efficiency, detection rate, and comprehensiveness, which might be greater diagnostic value in the joint fluid of infection after arthroplasty.

Thermal-Driven Optimization of the Strong Metal-Support Interaction of a Platinum-Manganese Oxide Octahedral Molecular Sieve to Promote Toluene Oxidation: Effect of the Interface Pt2+-Ov-Mnδ.

Strong metal-support interactions (SMSIs) have a significant effect on the performance of supported noble-metal catalysts for volatile organic compound (VOC) elimination. Herein, the strength of the SMSI of Pt/OMS-2 between Pt and the OMS-2 support is regulated by simply changing calcination temperatures, and the catalyst calcined at 300 °C (Pt/OMS-2-300) performs the best in the catalytic combustion of toluene. Through systematic structural characterizations, it is revealed that much more Pt2+-Ov-Mnδ+ species are formed in Pt/OMS-2-300, which can help facilitate the generation of more reactive oxygen species and promote lattice oxygen mobility. Moreover, the results of in situ DRIFTS experiments further confirm that abundant Pt2+-Ov-Mnδ+ species at the Pt-MnO2 interface on Pt/OMS-2-300 can better enhance the adsorption and activation of toluene, thus boosting the catalytic performance in toluene combustion. This newly developed strategy of thermal-driven regulation of the SMSI provides a novel perspective for constructing highly efficient catalysts for VOC emission control.

Characterization of the gut microbiome and resistome of Galapagos marine iguanas (Amblyrhynchus cristatus) from uninhabited islands.

BACKGROUND: Understanding the natural microbiome and resistome of wildlife from remote places is necessary to monitor the human footprint on the environment including antimicrobial use (AU). Marine iguanas are endemic species from the Galapagos Islands where they are highly affected by anthropogenic factors that can alter their microbiota as well as their abundance and diversity of antimicrobial-resistant genes (ARGs). Thus, this study aims to apply culture-independent approaches to characterize the marine iguana's gut metagenomic composition of samples collected from the uninhabited islands Rabida (n = 8) and Fernandina (Cabo Douglas, n = 30; Punta Espinoza, n = 30). Fresh feces from marine iguanas were analyzed through SmartChip RT-PCR, 16S rRNA, and metagenomic next-generation sequencing (mNGS) to identify their microbiome, microbial-metabolic pathways, resistome, mobilome, and virulome. RESULTS: The marine iguana's gut microbiome composition was highly conserved despite differences in ecological niches, where 86% of taxa were shared in the three locations. However, site-specific differences were mainly identified in resistome, mobilome, virulorome, and metabolic pathway composition, highlighting the existence of factors that induce microbial adaptations in each location. Functional gut microbiome analyses revealed its role in the biosynthesis and degradation of vitamins, cofactors, proteinogenic amino acids, carbohydrates, nucleosides and nucleotides, fatty acids, lipids, and other compounds necessary for the marine iguanas. The overall bacterial ARG abundance was relatively low (0.006%); nevertheless, the presence of genes encoding resistance to 22 drug classes was identified in the iguana's gut metagenome. ARG-carrying contig and co-occurrence network analyses revealed that commensal bacteria are the main hosts of ARGs. Taxa of public health interest such as Salmonella, Vibrio, and Klebsiella also carried multidrug-resistance genes associated with MGEs which can influence the dissemination of ARGs through horizontal gene transfer. CONCLUSION: Marine iguanas depend on the gut microbiome for the biosynthesis and degradation of several compounds through a symbiotic relationship. Niche-specific adaptations were evidenced in the pool of microbial accessory genes (i.e., ARGs, MGEs, and virulence) and metabolic pathways, but not in the microbiome composition. Culture-independent approaches outlined the presence of a diverse resistome composition in the Galapagos marine iguanas from remote islands. The presence of AR pathogens in marine iguanas raises concerns about the dispersion of microbial-resistant threats in pristine areas, highlighting wildlife as sentinel species to identify the impact of AU.

Potential role of serum hypoxia-inducible factor 1alpha as a biomarker of delayed cerebral ischemia and poor clinical outcome after human aneurysmal subarachnoid hemorrhage: A prospective, longitudinal, multicenter, and observational study.

Objective: Hypoxia-inducible factor 1alpha (HIF-1α) functions as a crucial transcriptional mediator in hypoxic and ischemic brain response. We endeavored to assess the prognostic significance of serum HIF-1α in human aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this prospective, longitudinal, multicenter, and observational study of 257 patients with aSAH and 100 healthy controls, serum HIF-1α levels were quantified. Univariate analyses, followed by multivariate analyses, were performed to discern the relationship between serum HIF-1α levels and severity and delayed cerebral ischemia (DCI) plus poststroke 6-month poor outcome [extended Glasgow outcome scale (GOSE) scores of 1-4]. Predictive efficiency was determined under the receiver operating characteristic (ROC) curve. Results: There were significantly increased serum HIF-lα levels after aSAH, in comparison to controls (median, 288.0 vs. 102.6 pg/ml; P < 0.001). Serum HIF-lα levels were independently correlated with Hunt-Hess scores [ß, 78.376; 95% confidence interval (CI): 56.446-100.305; P = 0.001] and modified Fisher scores (ß, 52.037; 95% CI: 23.461-80.614; P = 0.002). Serum HIF-lα levels displayed significant efficiency for discriminating DCI risk [area under ROC curve (AUC), 0.751; 95% CI: 0.687-0.815; P < 0.001] and poor outcome (AUC, 0.791; 95% CI: 0.736-0.846; P < 0.001). Using the Youden method, serum HIF-1α levels >229.3 pg/ml predicted the development of DCI with 92.3% sensitivity and 48.4% specificity and serum HIF-1α levels >384.0 pg/ml differentiated the risk of a poor prognosis with 71.4% sensitivity and 81.1% specificity. Serum HIF-1α levels >229.3 pg/ml were independently predictive of DCI [odds ratio (OR), 3.061; 95% CI: 1.045-8.965; P = 0.041] and serum HIF-1α levels >384.0 pg/ml were independently associated with a poor outcome (OR, 2.907; 95% CI: 1.403-6.024; P = 0.004). The DCI predictive ability of their combination was significantly superior to those of Hunt-Hess scores (AUC, 0.800; 95% CI: 0.745-0.855; P = 0.039) and modified Fisher scores (AUC, 0.784; 95% CI: 0.726-0.843; P = 0.004). The prognostic predictive ability of their combination substantially exceeded those of Hunt-Hess scores (AUC, 0.839; 95% CI: 0.791-0.886; P < 0.001) and modified Fisher scores (AUC, 0.844; 95% CI: 0.799-0.890; P < 0.001). Conclusion: Elevated serum HIF-lα levels after aSAH, in independent correlation with stroke severity, were independently associated with DCI and 6-month poor outcome, substantializing serum HIF-lα as a potential prognostic biomarker of aSAH.

Revealing the synergy between zinc and aluminum in Cu/ZnO/Al2O3 industrial catalyst.

The active sites in Cu/ZnO/Al2O3 industrial catalyst for CO2 hydrogenation to methanol need to be fully clarified. In this work, we reveal two types of active sites at the nano-sized Cu/ZnO interface, of which only one type is efficient. The efficient active site is characterized by isolated and under-coordinated Zn atoms located at the vertices of the supported ZnO island, thus the density of which is so limited. To anchor such Zn atoms onto other islands on Cu with high density is the key to enhancing the catalytic activity. To replace ZnO with Al2O3 islands on Cu is not favored energetically. However, under reduction condition, Zn single atoms can stably decorate the edges of the Al2O3 islands, resulting in the enhancement of the efficient active sites at the Cu/oxide interface. This could be the mechanism of the synergy effects taking place in the Cu/ZnO/Al2O3 catalyst.