Comparison of indocyanine green and blue-stained glue for preoperative localization for pulmonary nodules.

Background: In patients with pulmonary nodules undergoing computed tomography (CT)-guided localization procedures, a range of liquid-based materials have been employed to date in an effort to guide video-assisted thoracoscopic surgery (VATS) procedures to resect target nodules. However, the relative performance of these different liquid-based localization strategies has yet to be systematically evaluated. Accordingly, this study was developed with the aim of examining the relative safety and efficacy of CT-guided indocyanine green (IG) and blue-stained glue (BSG) PN localization. Methods: Consecutive patients with PNs undergoing CT-guided localization prior to VATS from November 2021 - April 2022 were enrolled in this study. Safety and efficacy outcomes were compared between patients in which different localization materials were used. Results: In total, localization procedures were performed with IG for 121 patients (140 PNs), while BSG was used for localization procedures for 113 patients (153 PNs). Both of these materials achieved 100% technical success rates for localization, with no significant differences between groups with respect to the duration of localization (P = 0.074) or visual analog scale scores (P = 0.787). Pneumothorax affected 8 (6.6%) and 8 (7.1%) patients in the respective IG and BSG groups (P = 0.887), while 12 (9.9%) and 10 (8.8%) patients of these patients experienced pulmonary hemorrhage. IG was less expensive than BSG ($17.2 vs. $165). VATS sublobar resection procedure technical success rates were also 100% in both groups, with no instances of conversion to thoracotomy. Conclusions: IG and BSG both offer similarly high levels of clinical safety and efficacy when applied for preoperative CT-guided PN localization, with IG being less expensive than BSG.

Phage defence system CBASS is regulated by a prokaryotic E2 enzyme that imitates the ubiquitin pathway.

The cyclic-oligonucleotide-based anti-phage signalling system (CBASS) is a type of innate prokaryotic immune system. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS uses cyclic oligonucleotides to activate antiviral immunity. One major class of CBASS contains a homologue of eukaryotic ubiquitin-conjugating enzymes, which is either an E1-E2 fusion or a single E2. However, the functions of single E2s in CBASS remain elusive. Here, using biochemical, genetic, cryo-electron microscopy and mass spectrometry investigations, we discover that the E2 enzyme from Serratia marcescens regulates cGAS by imitating the ubiquitination cascade. This includes the processing of the cGAS C terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond and poly-cGASylation. The poly-cGASylation activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Thus, our findings reveal a unique regulatory role of E2 in CBASS.

Regulating Protein-RNA Interactions: Advances in Targeting the LIN28/Let-7 Pathway.

Originally discovered in C. elegans, LIN28 is an evolutionarily conserved zinc finger RNA-binding protein (RBP) that post-transcriptionally regulates genes involved in developmental timing, stem cell programming, and oncogenesis. LIN28 acts via two distinct mechanisms. It blocks the biogenesis of the lethal-7 (let-7) microRNA (miRNA) family, and also directly binds messenger RNA (mRNA) targets, such as IGF-2 mRNA, and alters downstream splicing and translation events. This review focuses on the molecular mechanism of LIN28 repression of let-7 and current strategies to overcome this blockade for the purpose of cancer therapy. We highlight the value of the LIN28/let-7 pathway as a drug target, as multiple oncogenic proteins that the pathway regulates are considered undruggable due to their inaccessible cellular location and lack of cavities for small molecule binding.

FL% is associated with the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk and total arch replacement.

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement. Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection. Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe.

Prediction of microbial activity and abundance using interpretable machine learning models in the hyporheic zone of effluent-dominated receiving rivers.

Serving as a vital linkage between surface water and groundwater, the hyporheic zone (HZ) plays a fundamental role in improving water quality and maintaining ecological security. In arid or semi-arid areas, effluent discharge from wastewater treatment facilities could occupy a predominant proportion of the total base flow of receiving rivers. Nonetheless the relationship between microbial activity, abundance and environmental factors in the HZ of effluent-receiving rivers appear to be rarely addressed. In this study, a spatiotemporal field study was performed in two representative effluent-dominated receiving rivers in Xi'an, China. Land use data, physical and chemical water quality parameters of surface and subsurface water were used as predictive variables, while the microbial respiratory electron transport system activity (ETSA), the Chao1 and Shannon index of total microbial community, as well as the Chao1 and Shannon index of denitrifying bacteria community were used as response variables, while ETSA was used as response variables indicating ecological processes and Shannon and Chao1 were utilized as parameters indicating microbial diversity. Two machine learning models were utilized to provide evidence-based information on how environmental factors interact and drive microbial activity and abundance in the HZ at variable depths. The models with Chao1 and Shannon as response variables exhibited excellent predictive performances (R2: 0.754-0.81 and 0.783-0.839). Dissolved organic nitrogen (DON) was the most important factor affecting the microbial functions, and an obvious threshold value of ∼2 mg/L was observed. Credible predictions of models with Chao1 and Shannon index of denitrifying bacteria community as response variables were detected (R2: 0.484-0.624 and 0.567-0.638), with soluble reactive phosphorus (SRP) being the key influencing factor. Fe (Ⅱ) was favorable in predicting denitrifying bacteria community. The ESTA model highlighted the importance of total nitrogen in the ecological health monitoring in HZ. These findings provide novel insights in predicting microbial activity and abundance in highly-impacted areas such as the HZ of effluent-dominated receiving rivers.

Stress analysis of a large diameter aspheric plastic lens in the variable temperature assisted injection molding process.

The technology known as precision injection molding (PIM) has shown great promise in the large-scale manufacturing of optical plastic lenses. The primary challenge with the PIM process is accurately predicting and reducing residual stress in optical plastic lenses. In this work, the finite element method (FEM) was used to analyze the residual stress distribution in plastic lenses. A three-dimensional model was created using COMSOL software to investigate how residual stress and temperature varied in optical plastic lenses during the packing and cooling stages. Based on the results, variable temperature assisted injection molding experiments were conducted. The results show that the average residual stress in the optical plastic lenses has decreased by 56%, while the minimum and maximum residual stress levels have decreased by 60% and 61%, respectively. Since this method does not require the extra heat treatment of the optical lenses, it offers considerable cost and efficiency benefits.

Structures and activation mechanism of the Gabija anti-phage system.

Prokaryotes have evolved intricate innate immune systems against phage infection1-7. Gabija is a highly widespread prokaryotic defence system that consists of two components, GajA and GajB8. GajA functions as a DNA endonuclease that is inactive in the presence of ATP9. Here, to explore how the Gabija system is activated for anti-phage defence, we report its cryo-electron microscopy structures in five states, including apo GajA, GajA in complex with DNA, GajA bound by ATP, apo GajA-GajB, and GajA-GajB in complex with ATP and Mg2+. GajA is a rhombus-shaped tetramer with its ATPase domain clustered at the centre and the topoisomerase-primase (Toprim) domain located peripherally. ATP binding at the ATPase domain stabilizes the insertion region within the ATPase domain, keeping the Toprim domain in a closed state. Upon ATP depletion by phages, the Toprim domain opens to bind and cleave the DNA substrate. GajB, which docks on GajA, is activated by the cleaved DNA, ultimately leading to prokaryotic cell death. Our study presents a mechanistic landscape of Gabija activation.

Bolus administration of remimazolam was superior to midazolam for deep sedation in elderly patients undergoing diagnostic bronchoscopy: A randomized, double-blind, controlled trial.

BACKGROUND: To date, there is no standardized practice for the use of pharmacological sedatives during flexible bronchoscopy, particularly for elderly patients. This exploratory study aimed to assess the efficacy and safety of remimazolam at a single induced dose for deep sedation in elderly patients undergoing diagnostic flexible bronchoscopy (DFB), and compare with midazolam, a commonly used sedative. METHODS: A total of 100 elderly patients (age range 65-80 yr; American Society of Anesthesiologists Physical Status I-III) undergoing DFB were randomly allocated into 2 groups according to the sedatives used for induction: the remimazolam group and the midazolam group. Sedation induction was initiated by an intravenous bolus of remimazolam (0.135 mg/kg) or midazolam (0.045 mg/kg), respectively, both groups were combined with a high-dose of alfentanil (18 µg/kg), and supplemented with high-flow nasal cannula (HFNC) oxygen supply at a flow rate of 45 L/min. If the target depth of sedation was not achieved, propofol would be titrated as a rescue. The primary outcome was the success rate of sedation at a single induced dose to achieve target depth (Ramsay sedation score [RSS] = 4) during induction, intraoperative changes in vital signs, postoperative follow-up situation and incidence of post-bronchoscopy adverse events were evaluated as secondary outcomes. RESULTS: The success rate of sedation in the remimazolam group was significantly higher than that in the midazolam group (65.2% vs 39.6%, P = .013), while the incidence of extra sleep within 6 hours after procedure was lower in the remimazolam group as compared to the midazolam group (10.9% vs 31.3%, P = .016). No statistically significant differences were observed between the 2 groups regarding hemodynamic fluctuations, incidence of hypoxemia, and cough response during the procedure, as well as postoperative recall, willingness to undergo reexamination, and other post-bronchoscopy adverse events. CONCLUSIONS: Bolus administration of remimazolam offers advantages over midazolam for deep sedation in elderly patients undergoing DFB, in terms of a higher success rate of sedation and a lower incidence of extra sleep within 6 hours after procedure, though the safety profiles of both groups were favorable.

Presurgical computed tomography-guided localization of lung ground glass nodules: comparing hook-wire and indocyanine green.

BACKGROUND: Presurgical computed tomography (CT)-guided localization is frequently employed to reduce the thoracotomy conversion rate, while increasing the rate of successful sublobar resection of ground glass nodules (GGNs) via video-assisted thoracoscopic surgery (VATS). In this study, we compared the clinical efficacies of presurgical CT-guided hook-wire and indocyanine green (IG)-based localization of GGNs. METHODS: Between January 2018 and December 2021, we recruited 86 patients who underwent CT-guided hook-wire or IG-based GGN localization before VATS resection in our hospital, and compared the clinical efficiency and safety of both techniques. RESULTS: A total of 38 patients with 39 GGNs were included in the hook-wire group, whereas 48 patients with 50 GGNs were included in the IG group. There were no significant disparities in the baseline data between the two groups of patients. According to our investigation, the technical success rates of CT-based hook-wire- and IG-based localization procedures were 97.4% and 100%, respectively (P = 1.000). Moreover, the significantly longer localization duration (15.3 ± 6.3 min vs. 11.2 ± 5.3 min, P = 0.002) and higher visual analog scale (4.5 ± 0.6 vs. 3.0 ± 0.5, P = 0.001) were observed in the hook-wire patients, than in the IG patients. Occurrence of pneumothorax was significantly higher in hook-wire patients (27.3% vs. 6.3%, P = 0.048). Lung hemorrhage seemed higher in hook-wire patients (28.9% vs. 12.5%, P = 0.057) but did not reach statistical significance. Lastly, the technical success rates of VATS sublobar resection were 97.4% and 100% in hook-wire and IG patients, respectively (P = 1.000). CONCLUSIONS: Both hook-wire- and IG-based localization methods can effectively identified GGNs before VATS resection. Furthermore, IG-based localization resulted in fewer complications, lower pain scores, and a shorter duration of localization.

Integrative omics analysis elucidates the genetic basis underlying seed weight and oil content in soybean.

Synergistic optimization of key agronomic traits by traditional breeding has dramatically enhanced crop productivity in the past decades. However, the genetic basis underlying coordinated regulation of yield- and quality-related traits remains poorly understood. Here, we dissected the genetic architectures of seed weight and oil content by combining genome-wide association studies (GWAS) and transcriptome-wide association studies (TWAS) using 421 soybean (Glycine max) accessions. We identified 26 and 33 genetic loci significantly associated with seed weight and oil content by GWAS, respectively, and detected 5,276 expression quantitative trait loci (eQTLs) regulating expression of 3,347 genes based on population transcriptomes. Interestingly, a gene module (IC79), regulated by two eQTL hotspots, exhibited significant correlation with both seed weigh and oil content. Twenty-two candidate causal genes for seed traits were further prioritized by TWAS, including Regulator of Weight and Oil of Seed 1 (GmRWOS1), which encodes a sodium pump protein. GmRWOS1 was verified to pleiotropically regulate seed weight and oil content by gene knockout and overexpression. Notably, allelic variations of GmRWOS1 were strongly selected during domestication of soybean. This study uncovers the genetic basis and network underlying regulation of seed weight and oil content in soybean and provides a valuable resource for improving soybean yield and quality by molecular breeding.

Design, synthesis and bioactivity of a new class of antifungal amino acid-directed phthalide compounds.

BACKGROUND: Peanut southern blight disease, caused by Sclerotium rolfsii, is a destructive soil-borne fungal disease. The current control measures, which mainly employ succinate dehydrogenase inhibitors, are prone to resistance and toxicity to non-target organisms. As a result, it is necessary to explore the potential of eco-friendly fungicides for this disease. RESULTS: Fourteen novel phthalide compounds incorporating amino acid moieties were designed and synthesized. The in vitro activity of analog A1 [half maximal effective concentration (EC50 ) = 332.21 mg L-1 ] was slightly lower than that of polyoxin (EC50 = 284.32 mg L-1 ). It was observed that on the seventh day, the curative activity of A1 at a concentration of 600.00 mg L-1 was 57.75%, while the curative activity of polyoxin at a concentration of 300.00 mg L-1 was 42.55%. These results suggested that our compound exhibited in vivo activity. Peanut plants treated with A1 showed significant agronomic improvements compared to the untreated control. Several compounds in this series exhibited superior root absorption and conduction in comparison to the endothermic fungicide thifluzamide. The growth promotion and absorption-conduction experiments demonstrated the reason for the superior in vivo activity of the target compound. Cytotoxic assays have demonstrated that this series of targeted compounds exhibit low toxicity levels toward human lo2 liver cells. CONCLUSION: Our results provide a new strategy for the design and synthesis of novel green compounds. Furthermore, the target compound A1 can serve as a lead for further development of green fungicides. © 2024 Society of Chemical Industry.

How redox gradient potentially influences nitrate reduction coupled with sulfur cycling: A new insight into nitrogen cycling in the hyporheic zone of effluent-dominated rivers.

The coupled N and S cycling in variable redox gradients in the hyporheic zone (HZ) of the rivers receiving effluents from wastewater treatment plants is unclear. Using two representative effluent-dominated rivers as model systems, a metagenome approach was employed to explore the spatiotemporal redox zonation of the HZ and the N/S cycling processes within the system. The results manifested that nitrate reduction represented the fundamental nitrogen pathway in the HZ. Interestingly, DNRA coupled with sulfur reduction, and denitrification coupled with sulfur oxidation were respectively abundant in the oxic and anoxic zone. Lower nitrate concentration (0-2.72 mg-N/L) and more abundant genes involved in denitrification (napB, NarGHI) and sulfur oxidation (sseA, glpE) were detected in the anoxic zone. Contrarily, the nitrate concentration (0.07-4.87 mg-N/L) and the abundance of genes involved in sulfur reduction (ttrB, sudA) and DNRA (nirBD) were observed more abundant in the oxic zone. Therefore, the results verified the oxygen-limited condition did not suppress but rather facilitated the denitrification process in the presence of active S cycling. The high relative abundances of nosZ gene encoding sequence (3-5 % relative to all nitrogen-cycling processes) in both the effluent-discharging area and downstream area highly confirmed that HZ was capable of alleviating the N2O emission in the region. The functional keystone taxa were revealed through co-occurrence network analysis. The structural equation model shows that the genes of N/S cycling were positively impacted by functional keystone taxa, especially the N cycling genes. Functional keystone taxa were proven driven by the redox gradient, demonstrating their positive roles in mediating N/S cycling processes. The promoting effect on nitrate reduction coupled with sulfur cycling was clarified when redox conditions oscillated, providing a new perspective on mitigating nitrogen pollution and greenhouse gas emissions in effluent-receiving rivers.

Transition of organic matter from allochthonous to autochthonous alters benthic nutrient dynamics via microbial food webs.

The impoundment of rivers by dams has significantly modified sedimentation patterns and trophic structures. As a result, the algal-derived organic matter (OM), as opposed to terrestrial-derived OM, plays an increasingly important role along the river-reservoir gradient. This study utilized water-sediment microcosms to explore the impacts of allochthonous and autochthonous OM deposition on benthic nutrient dynamics mediated by microbial food webs. Our results revealed that OM addition led to increased fluxes of NH4+ and CO2, with the highest flux induced by cyanobacteria OM, followed by diatom and allochthonous OM. N2 release flux was promoted by allochthonous and diatom OM deposition but inhibited by cyanobacteria OM deposition. The amendment of autochthonous OM increased the activity of dehydrogenase and urease, while allochthonous OM with a higher C/N ratio enhanced the catalytic abilities of polyphenol oxidase and ß-glucosidase. Furthermore, OM deposition significantly reduced microbial community richness and diversity, except for eukaryotic richness, and induced pronounced changes in bacterial and eukaryotic community structures. Allochthonous OM deposition stimulated the utilization of bacteria and protozoan on native OM, resulting in a positive priming effect of 26.78 %. In contrast, diatom and cyanobacteria OM additions exerted negative priming effects of -44.53 % and -29.76 %, respectively. Bayesian stable isotope mixing models showed that diatom OM was primarily absorbed by protozoan and metazoan, while cyanobacteria OM was more easily decomposed by bacteria and transferred to higher trophic levels through microbial food webs. In addition, bacterial ammonification accounted for 74.5 % of NH4+ release in the allochthonous OM deposition treatment, whereas eukaryotic excretion contributed separately 83.3 % and 83.1 % to NH4+ release in the diatom and cyanobacteria OM addition treatments. These findings highlight the significance of accounting for the regulatory capacity of OM deposition when studying benthic metabolism within river-reservoir systems.

Deciphering solute transport, microbiota assembly patterns and metabolic functions in the hyporheic zone of an effluent-dominated river.

We lack a clear understanding of how anthropogenic pressures, exemplified by effluent discharge from wastewater treatment plants, destabilize microbial communities in the hyporheic zone (HZ) of receiving rivers. In this study, the spatiotemporal characteristics of hydrological parameters, and the physicochemical properties of surface and subsurface water in a representative effluent-dominated river were monitored. Sequencing of 16S rRNA amplicons and metagenomes revealed the microbial community structure in the HZ of both effluent discharge area and downstream region. The keystone taxa (taxa vital in determining the composition of each microbial cluster) and the keystone functions they controlled were subsequently identified. Effluent discharge amplified the depth of the oxic/suboxic zone and the hyporheic exchange fluxes in the effluent discharge area, which was 50-120% and 40-300% higher than in the downstream region, respectively. Microbial community structure pattern analysis demonstrated an enhancement in the rate of dispersal, an increase in microbial diversity, and an improved community network complexity in the effluent discharge area. By contrast, the number of keystone taxa in the effluent discharge area was 50-70% lower than that of the downstream region, resulting in reduced community network stability and functionality. The keystone taxa controlling metabolic functions in the networks categorized to effluent discharge area were comprised of more genera related to nitrogen and sulfur cycling, e.g., Dechloromonas, Desulfobacter, Flavobacterium, Nitrosomonas, etc., highlighting a research need in monitoring species associated with nutrient element cycling in the HZ of receiving waterbodies. The results showed that the keystone taxa could contribute positively to network stability, which was negatively correlated to hyporheic exchange fluxes and redox gradients. This study provides valuable insights that will improve our understanding of how river ecosystems respond to changes in anthropogenic pressures.

Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest.

Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.

FFAR4 activation inhibits lung adenocarcinoma via blocking respiratory chain complex assembly associated mitochondrial metabolism.

Despite notable advancements in the investigation and management of lung adenocarcinoma (LUAD), the mortality rate for individuals afflicted with LUAD remains elevated, and attaining an accurate prognosis is challenging. LUAD exhibits intricate genetic and environmental components, and it is plausible that free fatty acid receptors (FFARs) may bridge the genetic and dietary aspects. The objective of this study is to ascertain whether a correlation exists between FFAR4, which functions as the primary receptor for dietary fatty acids, and various characteristics of LUAD, while also delving into the potential underlying mechanism. The findings of this study indicate a decrease in FFAR4 expression in LUAD, with a positive correlation (P < 0.01) between FFAR4 levels and overall patient survival (OS). Receiver operating characteristic (ROC) curve analysis demonstrated a significant diagnostic value [area under the curve (AUC) of 0.933] associated with FFAR4 expression. Functional investigations revealed that the FFAR4-specific agonist (TUG891) effectively suppressed cell proliferation and induced cell cycle arrest. Furthermore, FFAR4 activation resulted in significant metabolic shifts, including a decrease in oxygen consumption rate (OCR) and an increase in extracellular acidification rate (ECAR) in A549 cells. In detail, the activation of FFAR4 has been observed to impact the assembly process of the mitochondrial respiratory chain complex and the malate-aspartate shuttle process, resulting in a decrease in the transition of NAD+ to NADH and the inhibition of LUAD. These discoveries reveal a previously unrecognized function of FFAR4 in the negative regulation of mitochondrial metabolism and the inhibition of LUAD, indicating its potential as a promising therapeutic target for the treatment and diagnosis of LUAD.

The nuclease-associated short prokaryotic Argonaute system nonspecifically degrades DNA upon activation by target recognition.

Prokaryotic Argonautes (pAgos) play a vital role in host defense by utilizing short nucleic acid guides to recognize and target complementary nucleic acids. Despite being the majority of pAgos, short pAgos have only recently received attention. Short pAgos are often associated with proteins containing an APAZ domain and a nuclease domain including DUF4365, SMEK, or HNH domain. In contrast to long pAgos that specifically cleave the target DNA, our study demonstrates that the short pAgo from Thermocrispum municipal, along with its associated DUF4365-APAZ protein, forms a heterodimeric complex. Upon RNA-guided target DNA recognition, this complex is activated to nonspecifically cleave DNA. Additionally, we found that the TmuRE-Ago complex shows a preference for 5'-OH guide RNA, specifically requires a uridine nucleotide at the 5' end of the guide RNA, and is sensitive to single-nucleotide mismatches between the guide RNA and target DNA. Based on its catalytic properties, our study has established a novel nucleic acid detection method and demonstrated its feasibility. This study not only expands our understanding of the defense mechanism employed by short pAgo systems but also suggests their potential applications in nucleic acid detection.

In Situ Interfacial Engineering of CeO2 /Bi2 WO6 Heterojunction with Improved Photodegradation of Tetracycline and Organic Dyes: Mechanism Insight and Toxicity Assessment.

The construction of heterojunction photocatalysts is an auspicious approach for enhancing the photocatalytic performance of wastewater treatment. Here, a novel CeO2 /Bi2 WO6 heterojunction is synthesized using an in situ liquid-phase method. The optimal 15% CeO2 /Bi2 WO6 (CBW-15) is found to have the highest photocatalytic activity, achieving a degradation efficiency of 99.21% for tetracycline (TC), 98.43% for Rhodamine B (RhB), and 94.03% for methylene blue (MB). The TC removal rate remained at 95.38% even after five cycles. Through active species capture experiments, •O2 - , h+ , and •OH are the main active substances for TC, RhB, and MB, respectively. The possible degradation pathways for TC are analyzed using liquid chromatography-mass spectrometry (LC-MS). The photoinduced charge transfer and possible degradation mechanisms are proposed through experimentation and density functional theory (DFT) calculations. Toxicity assessment experiments show a significant reduction in toxicity during the TC degradation process. This study uncovers the mechanism of photocatalytic degradation in CeO2 /Bi2 WO6 and provides new insights into toxicity assessment.

The Heimlich maneuver and chest compression relieve mask ventilation difficulties caused by asymptomatic laryngeal mass: A case report and review of literature.

RATIONALE: Some laryngeal masses are typically asymptomatic and easily ignored. However, they can be rare causes of unanticipated difficult airway, leading to critical situations such as "cannot ventilate" or "cannot ventilate and cannot intubate" during anesthesia induction. Inappropriate airway management in such scenarios can have catastrophic consequences for an anesthetized patient. Here we report a case of sudden, unanticipated difficult mask ventilation caused by an asymptomatic supraglottic mass during sedative induction, which was quickly and effectively relieved by the Heimlich maneuver and chest compression. PATIENT CONCERNS: We report a rare case of airway crisis occurred during sedative induction in a 63-year-old patient scheduled for a routine flexible bronchoscopy, and no evidence of respiratory difficulty or signs of obstruction was found in preoperative evaluation. DIAGNOSES: A detailed examination of laryngopharyngeal structure under bronchoscopy revealed a supraglottic soft-tissue mass with a size of 1.6 × 0.8 cm covering the membranous part of the glottic area, which was the true cause of difficult mask ventilation in this patient during sedative induction. INTERVENTIONS: As the unanticipated difficult mask ventilation occurred, 2-handed mask ventilation was initiated immediately for 9 attempts but failed. Fortunately, the airway crisis was successfully relieved with 2 Heimlich attempts and 3 chest compressions, and no need for a laryngeal mask airway. OUTCOMES: Once the airway crisis was relieved and the supraglottic mass was confirmed, the patient underwent a second sedative anesthesia and a successful laryngeal mask airway-assisted bronchoscopy, with no post-bronchoscopy adverse events. LESSONS: Asymptomatic supraglottic masses can cause valve-like upper airway obstruction and lead to unanticipated difficult mask ventilation. The Heimlich maneuver and chest compression may be effective in such critical situations and can serve as an emergency intervention.

Bisphenol B induces developmental toxicity in zebrafish via oxidative stress.

Bisphenol A (BPA) is a typical endocrine disruptor, and the use of bisphenol B (BPB) as a substitute is gradually increasing. Some studies have shown that BPB also has endocrine disrupting effects, but its effects on the early stages of fish growth and development have not been reported. In this paper, zebrafish embryos were exposed to different concentrations of BPB until the 6th day post fertilization (dpf), and the toxic effects of BPB on the early development of zebrafish and the possible molecular mechanisms were investigated. The results showed that BPB exposure at 10, 100, and 1000 µg/L induced developmental toxic effects such as early neurotoxicity and cardiovascular toxicity in zebrafish, and the toxic effects were positively correlated with the degree of oxidative damage. These adverse results were ameliorated by the classical antioxidant N-acetyl-L-cysteine (NAC), suggesting the involvement of oxidative stress in BPB-induced early developmental toxicity. The above data suggest that BPB exposure increases oxidative damage and suppresses the expression of genes critical for early neurological and cardiovascular development, ultimately leading to early developmental toxicity in juvenile zebrafish. This study contributes to broadening our understanding of the toxic effects of BPB and provides a basic theoretical basis for the next management support of bisphenol analogs.