Association between heart rate and mortality in patients with septic shock: an analysis revealed by time series data.

BACKGROUND: Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. METHODS: This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. RESULTS: A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P < 0.001, non-linear P < 0.001) when TWA-HR > 85 beats per minute (bpm). The log-rank test revealed in terms of the 28-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) was 1.92 (1.78-2.06, P < 0.001) for patients with high TWA-HR compared to normal TWA-HR group. Similarly, for the ICU mortality, the HR (95% CI) was 1.64 (1.52-1.78, P < 0.001), and for the in-hospital mortality, the HR (95% CI) was 1.61 (1.48-1.76, P < 0.001). Collectively, the sensitivity analysis consistently demonstrated higher 28-day mortality, ICU mortality, and in-hospital mortality in patients with TWA-HR > 85 bpm. CONCLUSION: Patients with septic shock whose heart rate was controlled no more than 85 bpm during ICU stay received survival benefit in terms of 28-day, ICU and in-hospital mortality. .

The triglyceride-glucose index dynamic trajectory reveals the association between the clinical subphenotype of insulin resistance and mortality in patients with sepsis.

BACKGROUND: The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis. METHODS: In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models. RESULTS: A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02-1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00-1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings. CONCLUSION: Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients.

Contribution of Radiation Sensitive Protein 51 Genotypes to Pterygium Risk in a Taiwanese Population.

BACKGROUND/AIM: In current literature, there is a notable lack of studies investigating the role of radiation-sensitive protein 51 (RAD-51) in pterygium diagnosis. Nevertheless, reports indicate elevated expression levels of RAD-51 among recurrent pterygium cases compared to those with primary pterygium. However, the genomic involvement of RAD-51 has yet to be explored in any population. This study aimed to assess the contribution of RAD-51 genotypes to pterygium risk in a representative Taiwanese population. MATERIALS AND METHODS: RAD-51 rs1801320 genotyping was successfully conducted in a Taiwanese cohort comprising 140 pterygium cases and 280 non-pterygium controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. RESULTS: The distribution of RAD-51 rs1801320 genotypes (GG, CG, and CC) in the pterygium group (70.0%, 25.7%, and 4.3%, respectively) did not significantly differ from that in the non-pterygium group (73.6%, 23.6%, and 2.8% for GG, CG, and CC genotypes, respectively; p for trend=0.6337). Carriers of the variant CG and CC RAD-51 rs1801320 genotypes exhibited 1.15- and 1.58-fold increased pterygium risk, respectively (95%CI=0.72-1.84 and 0.53-4.67, p=0.6552 and p=0.5914, respectively). In the dominant model, there appeared to be a slight association between variant genotypes CG and CC and pterygium risk (OR=1.19, 95%CI=0.76-1.87, p=0.0223). Allelic analysis revealed that the RAD-51 rs1801320 variant C allele was not significantly linked to pterygium risk (17.1% versus 14.6%, OR=1.20, 95%CI=0.82-1.78, p=0.3991). CONCLUSION: Variant genotypes at RAD-51 rs1801320 were firstly identified to associate with susceptibility to pterygium among Taiwanese individuals. Nonetheless, these findings warrant validation in larger and more diverse populations.

Involvement of M2 macrophages polarization in PM2.5-induced COPD by upregulating MMP12 via IL4/STAT6 pathway.

Biomass-related airborne fine particulate matter (PM2.5) is an important risk factor for chronic obstructive pulmonary disease (COPD). Macrophage polarization has been reported to be involved in PM2.5-induced COPD, but the dynamic characteristics and underlying mechanism of this process remain unclear. Our study established a PM2.5-induced COPD mouse model and revealed that M2 macrophages predominantly presented after 4 and 6 months of PM2.5 exposure, during which a notable increase in MMP12 was observed. Single cell analysis of lung tissues from COPD patients and mice further revealed that M2 macrophages were the dominant macrophage subpopulation in COPD, with MMP12 being involved as a hub gene. In vitro experiments further demonstrated that PM2.5 induced M2 polarization and increased MMP12 expression. Moreover, we found that PM2.5 increased IL-4 expression, STAT6 phosphorylation and nuclear translocation. Nuclear pSTAT6 then bound to the MMP12 promoter region. Furthermore, the inhibition of STAT6 phosphorylation effectively abrogated the PM2.5-induced increase in MMP12. Using a coculture system, we observed a significantly reduced level of E-cadherin in alveolar epithelial cells cocultured with PM2.5-exposed macrophages, while the decrease in E-cadherin was reversed by the addition of an MMP12 inhibitor to the co-culture system. Taken together, these findings indicated that PM2.5 induced M2 macrophage polarization and MMP12 upregulation via the IL-4/STAT6 pathway, which resulted in alveolar epithelial barrier dysfunction and excessive extracellular matrix (ECM) degradation, and ultimately led to COPD progression. These findings may help to elucidate the role of macrophages in COPD, and suggest promising directions for potential therapeutic strategies.

Catalytic Atroposelective Synthesis of N-N Axially Chiral Indolylamides.

The catalytic atroposelective synthesis of N-N axially chiral indolylamides was established via dynamic kinetic resolution, which makes use of chiral Lewis base-catalyzed asymmetric acylation of N-acylaminoindoles as a new type of platform molecule with anhydrides. By this strategy, a series of N-N axially chiral indolylamides were synthesized in overall good yields (up to 98%) with excellent enantioselectivities (up to 99% ee). Moreover, some of these N-N axially chiral indolylamides display some extent of anticancer activity, which demonstrates their potential application in medicinal chemistry. Therefore, this work has not only provided a new strategy for the synthesis of N-N axially chiral monoaryl indoles but also offered a new member of N-N axially chiral monoaryl indoles with configurational stability and promising application, thereby solving the challenges in atroposelective synthesis and application of N-N axially chiral monoaryl indoles.

Yeast surface display technology: Mechanisms, applications, and perspectives.

Microbial cell surface display technology, which relies on genetically fusing heterologous target proteins to the cell wall through fusion with cell wall anchor proteins, has emerged as a promising and powerful method with diverse applications in biotechnology and biomedicine. Compared to classical intracellular or extracellular expression (secretion) systems, the cell surface display strategy stands out by eliminating the necessity for enzyme purification, overcoming substrate transport limitations, and demonstrating enhanced activity, stability, and selectivity. Unlike phage or bacterial surface display, the yeast surface display (YSD) system offers distinct advantages, including its large cell size, ease of culture and genetic manipulation, the use of generally regarded as safe (GRAS) host cell, the ability to ensure correct folding of complex eukaryotic proteins, and the potential for post-translational modifications. To date, YSD systems have found widespread applications in protein engineering, waste biorefineries, bioremediation, and the production of biocatalysts and biosensors. This review focuses on detailing various strategies and mechanisms for constructing YSD systems, providing a comprehensive overview of both fundamental principles and practical applications. Finally, the review outlines future perspectives for developing novel forms of YSD systems and explores potential applications in diverse fields.

Association between early blood glucose dynamic trajectory and mortality for critically ill patients with heart failure: Insights from real-world data.

AIMS: This study endeavors to explore the ramifications of early dynamic blood glucose (BG) trajectories within the initial 48 h of intensive care unit (ICU) admission on mortality among critically ill heart failure (HF) patients. METHODS: The study employed a retrospective observational design, analyzing dynamic BG data of HF patients from the Medical Information Mart for Intensive Care IV database. The BG trajectory subphenotypes were identified using the hierarchical clustering based on the dynamic time-warping algorithm. The primary outcome of the study was 28-day mortality, with secondary outcomes including 180-day and 1-year mortality. RESULTS: We screened a total of 21,098 HF patients and finally 15,092 patients were included in the study. Our results identified three distinct BG trajectory subphenotypes: increasing (n = 3503), stabilizing (n = 6250), and decreasing (n = 5339). The increasing subphenotype was associated with the highest mortality risk at 28 days, 180 days, and 1 year. The stabilizing and decreasing subphenotypes showed significantly lower mortality risks across all time points, with hazard ratios ranging from 0.85 to 0.88 (P<0.05 for all). Sensitivity analyses confirmed the robustness of these findings after adjusting for various covariates. CONCLUSIONS: Increasing BG trajectory within 48 h of admission is significantly associated with higher mortality in patients with HF. It is necessary to devote greater attention to the early BG dynamic changes in HF patients to optimize clinical BG management and enhance patient prognosis.

An A2 ß-casein infant formula with high sn-2 palmitate and casein phosphopeptides supports adequate growth, improved stool consistency, and bone strength in healthy, term Chinese infants: a randomized, double-blind, controlled clinical trial.

The aim of this randomized, double-blind, controlled trial was to examine the effects of infant formula on the growth, stool consistency, and bone strength of infants (n = 120) over a period of 4 months. The investigational group was fed an A2 ß-casein cow's milk infant formula containing casein phosphopeptides (CPP) and high sn-2 palmitate (54% of total palmitate at sn-2). The control group was fed a standard cow's milk formula without CPP and with low sn-2 palmitate (29% of total palmitate at sn-2). The third group was fed human milk (HM) (n = 60). All three groups had similar baseline characteristics, and maintained similar BMI, sleep habits, and growth rates in body weight and length throughout the study. However, compared to the control group, infants in the investigational and human milk groups had significantly: (i) greater body length at 90, 120, and 150 days of age; (ii) greater growth rate in head circumference from 30 to 60 days of age, with larger head circumference at 60 days of age; (iii) larger daily stool frequency at 60, 90, and 120 days of age; (iv) softer stool at 60, 90, and 120 days of age; (v) higher bone quality index and bone speed of sound at 150 days of age; (vi) fewer hours of crying at 60 and 90 days of age; (vii) less abdominal distention, burp, and flatus at 60, 90, and 120 days of age; and (viii) less constipation at 90 days of age. At other time points, no significant differences were observed between the three groups. No serious adverse events (AEs) related to the study products were reported, and significantly fewer infants in the investigational and HM groups experienced at least one AE compared to the control group. The study suggests that the A2 ß-casein formula with high sn-2 palmitate and CPP supports adequate growth, is well tolerated, and may have beneficial effects on stool consistency, gastrointestinal comfort, crying duration, and bone density, comparable to HM. Clinical trial registration: https://clinicaltrials.gov/, NCT04749290.

Deciphering the triclosan degradation mechanism in Sphingomonas sp. strain YL-JM2C: Implications for wastewater treatment and marine resources.

Triclosan (TCS), an antimicrobial agent extensively incorporated into pharmaceuticals and personal care products, poses significant environmental risks because of its persistence and ecotoxicity. So far, a few microorganisms were suggested to degrade TCS, but the microbial degradation mechanism remains elusive. Here, a two-component angular dioxygenase (TcsAaAb) responsible for the initial TCS degradation was characterized in Sphingomonas sp. strain YL-JM2C. Whole-cell biotransformation and crude enzyme assays demonstrated that TcsAaAb catalyzed the conversion of TCS to 4-chlorocatechol and 3,5-dichlorocatechol rather than the commonly suggested product 2,4-dichlorophenol. Then two intermediates were catabolized by tcsCDEF cluster via an ortho-cleavage pathway. Critical residues (N262, F279, and F391) for substrate binding were identified via molecular docking and mutagenesis. Further, TcsAaAb showed activity toward methyl triclosan and nitrofen, suggesting its versatile potential for bioremediation. In addition, TCS-degrading genes were also present in diverse bacterial genomes in wastewater, ocean and soil, and a relatively high gene abundance was observed in marine metagenomes, revealing the transformation fate of TCS in environments and the microbial potential in pollutant removal. These findings extend the understanding of the microbe-mediated TCS degradation and contribute to the mining of TCS-degrading strains and enzymes, as well as their application in the bioremediation of contaminated environments.

PASTICCINO2 interacting with Golgi Anti-Apoptotic Proteins resists endoplasmic reticulum stress dependent on very long-chain fatty acids.

The endoplasmic reticulum (ER) is crucial for maintaining cell homeostasis because it is the primary site for synthesizing secreted and transmembrane proteins and lipids. The unfolded protein response (UPR) is activated to restore ER homeostasis under ER stress. However, the relationship between lipids and the ER stress response in plants is not well understood. Arabidopsis Golgi anti-apoptotic proteins (GAAPs) are involved in resisting ER stress. To elucidate the function of GAAPs, PASTICCINO2 (PAS2), involved in very long-chain fatty acid (VLCFA) synthesis, was found to interact with GAAPs and IRE1. Single pas2 and gaap1/gaap2pas2 double mutants exhibited increased seedling damage and impaired UPR response under chronic ER stress. Site mutation combined with genetic analysis revealed that the role of PAS2 in resisting ER stress depended on its VLCFA synthesis domain. VLCFA contents were upregulated under ER stress, which required GAAPs. Exogenous VLCFAs partially restored the defect in UPR upregulation caused by PAS2 or GAAP mutations under chronic ER stress. These findings demonstrate that the association of PAS2 with GAAPs confers plant resistance to ER stress by regulating VLCFA synthesis and the UPR. This provides a basis for further studies on the connection between lipids and cell fate decisions under stress.

Discovery of the 1-naphthylamine biodegradation pathway reveals a broad-substrate-spectrum enzyme catalyzing 1-naphthylamine glutamylation.

1-Naphthylamine (1NA), which is harmful to human and aquatic animals, has been used widely in the manufacturing of dyes, pesticides, and rubber antioxidants. Nevertheless, little is known about its environmental behavior and no bacteria have been reported to use it as the growth substrate. Herein, we describe a pathway for 1NA degradation in the isolate Pseudomonas sp. strain JS3066, determine the structure and mechanism of the enzyme NpaA1 that catalyzes the initial reaction, and reveal how the pathway evolved. From genetic and enzymatic analysis, a five gene-cluster encoding a dioxygenase system was determined to be responsible for the initial steps in 1NA degradation through glutamylation of 1NA. The γ-glutamylated 1NA was subsequently oxidized to 1,2-dihydroxynaphthalene which was further degraded by the well-established pathway of naphthalene degradation via catechol. A glutamine synthetase-like (GS-like) enzyme (NpaA1) initiates 1NA glutamylation, and this enzyme exhibits a broad substrate selectivity toward a variety of anilines and naphthylamine derivatives. Structural analysis revealed that the aromatic residues in the 1NA entry tunnel and the V201 site in the large substrate-binding pocket significantly influence NpaA1's substrate preferences. The findings enhance understanding of degrading polycyclic aromatic amines, and will also enable the application of bioremediation at naphthylamine contaminated sites.

Branched-chain amino acid transaminase 1 confers EGFR-TKI resistance through epigenetic glycolytic activation.

Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Cataract Development Among Pediatric Patients With Uveitis.

Importance: The long-term estimated risk of development of cataracts among pediatric patients with uveitis is not clear. Objective: To describe factors associated with the development of cataracts among pediatric patients with uveitis. Design, Setting, and Participants: This cohort study used the international TriNetX database to enroll pediatric patients with and without uveitis from January 1, 2002, to December 31, 2022. The nonuveitis cohort consisted of randomly selected control patients matched by age, sex, race and ethnicity, and specific comorbidities. Exposure: Diagnosis of uveitis, identified using diagnostic codes. Main Outcomes and Measures: The primary outcome was the risk of developing cataracts among the uveitis group compared with the nonuveitis comparison group, with hazard ratios (HRs) and 95% CIs reported. Results: A total of 22 687 pediatric patients with uveitis (mean [SD] age, 10.3 [5.6] years; 54.2% male) and 22 687 comparators without uveitis (mean [SD] age, 10.3 [5.6] years; 54.5% male) were enrolled in the study. The risk of cataracts was increased among pediatric patients with uveitis up to a follow-up duration of 20 years (HR, 17.17; 95%CI, 12.90-22.80) from the index date. Subgroup analyses revealed an elevated cataract risk across age groups: 0 to 6 years (HR, 19.09; 95% CI, 10.10-36.00), 7 to 12 years (HR, 27.16; 95% CI, 15.59-47.20), and 13 to 18 years (HR, 13.39; 95% CI, 8.84-20.30); both female sex (HR, 13.76; 95% CI, 9.60-19.71) and male sex (HR, 11.97; 95% CI, 8.47-16.91); and Asian (HR, 13.80; 95% CI, 3.28-58.07), Black or African American (HR, 10.41; 95% CI, 5.60-19.36), and White (HR, 15.82; 95% CI, 11.05-22.60) race. Furthermore, increased cataract risks were also observed among those with and without a history of immunosuppressive agents (with: HR, 26.52 [95% CI, 16.75-41.90]; without: HR, 17.69 [95% CI: 11.39-27.40]), a history of steroid eye drop use (with: HR, 29.51 [95% CI, 14.56-59.70]; without: HR, 16.49 [95% CI, 11.92-22.70]), and a history of intraocular procedures (with: HR, 11.07 [95%CI, 4.42-27.71]; without: HR, 14.49 [95% CI, 10.11-20.70]). Conclusions and Relevance: In this cohort study of pediatric patients with uveitis, an elevated risk of cataracts following a uveitis diagnosis was found compared with pediatric patients without uveitis. The findings suggest that pediatric patients with uveitis should be monitored for cataract development.

Fluorometric determination of mecA gene in MRSA with a graphene-oxide based bioassay using flap endonuclease 1-assisted target recycling and Klenow fragment-triggered signal amplification.

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium that causes a wide range of illnesses, necessitating the development of new technologies for its detection. Herein, we propose a graphene oxide (GO)-based sensing platform for the detection of mecA gene in MRSA using flap endonuclease 1 (FEN1)-assisted target recycling and Klenow fragment (KF)-triggered signal amplification. Without the target, all the DNA probes were adsorbed onto GO, resulting in fluorescence quenching of the dye. Upon the addition of the target, a triple complex was formed that triggered FEN1-assisted target recycling and initiated two polymerization reactions with the assistance of KF polymerase, generating numerous dsDNA that were repelled by GO. These dsDNAs triggered fluorescence enhancement when SYBR Green I was added. Therefore, the target DNA was quantified by measuring the fluorescence at excitation and emission wavelengths of 480/526 nm. This mecA gene assay showed a good linear range from 1 to 50 nM with a lower limit of detection of 0.26 nM, and displayed good applicability to the analysis of real samples. Thus, a new method for monitoring MRSA has been developed that has great potential for early clinical diagnosis and treatment.

Discovery of a Ni2+-dependent heterohexameric metformin hydrolase.

The biguanide drug metformin is a first-line blood glucose-lowering medication for type 2 diabetes, leading to its presence in the global environment. However, little is known about the fate of metformin by microbial catabolism. Here, we characterize a Ni2+-dependent heterohexameric enzyme (MetCaCb) from the ureohydrolase superfamily, catalyzing the hydrolysis of metformin into guanylurea and dimethylamine. Either subunit alone is catalytically inactive, but together they work as an active enzyme highly specific for metformin. The crystal structure of the MetCaCb complex shows the coordination of the binuclear metal cluster only in MetCa, with MetCb as a protein binder of its active cognate. An in-silico search and functional assay discover a group of MetCaCb-like protein pairs exhibiting metformin hydrolase activity in the environment. Our findings not only establish the genetic and biochemical foundation for metformin catabolism but also provide additional insights into the adaption of the ancient enzymes toward newly occurred substrate.

Current strategies for monitoring and controlling bacterial biofilm formation on medical surfaces.

Biofilms, intricate microbial communities that attach to surfaces, especially medical devices, form an exopolysaccharide matrix, which enables bacteria to resist environmental pressures and conventional antimicrobial agents, leading to the emergence of multi-drug resistance. Biofilm-related infections associated with medical devices are a significant public health threat, compromising device performance. Therefore, developing effective methods for supervising and managing biofilm growth is imperative. This in-depth review presents a systematic overview of strategies for monitoring and controlling bacterial biofilms. We first outline the biofilm creation process and its regulatory mechanisms. The discussion then progresses to advancements in biosensors for biofilm detection and diverse treatment strategies. Lastly, this review examines the obstacles and new perspectives associated with this domain to facilitate the advancement of innovative monitoring and control solutions. These advancements are vital in combating the spread of multi drug-resistant bacteria and mitigating public health risks associated with infections from biofilm formation on medical instruments.

Widespread and active piezotolerant microorganisms mediate phenolic compound degradation under high hydrostatic pressure in hadal trenches.

Phenolic compounds, as well as other aromatic compounds, have been reported to be abundant in hadal trenches. Although high-throughput sequencing studies have hinted at the potential of hadal microbes to degrade these compounds, direct microbiological, genetic and biochemical evidence under in situ pressures remain absent. Here, a microbial consortium and a pure culture of Pseudomonas, newly isolated from Mariana Trench sediments, efficiently degraded phenol under pressures up to 70 and 60 MPa, respectively, with concomitant increase in biomass. By analyzing a high-pressure (70 MPa) culture metatranscriptome, not only was the entire range of metabolic processes under high pressure generated, but also genes encoding complete phenol degradation via ortho- and meta-cleavage pathways were revealed. The isolate of Pseudomonas also contained genes encoding the complete degradation pathway. Six transcribed genes (dmpKLMNOPsed) were functionally identified to encode a multicomponent hydroxylase catalyzing the hydroxylation of phenol and its methylated derivatives by heterogeneous expression. In addition, key catabolic genes identified in the metatranscriptome of the high-pressure cultures and genomes of bacterial isolates were found to be all widely distributed in 22 published hadal microbial metagenomes. At microbiological, genetic, bioinformatics, and biochemical levels, this study found that microorganisms widely found in hadal trenches were able to effectively drive phenolic compound degradation under high hydrostatic pressures. This information will bridge a knowledge gap concerning the microbial aromatics degradation within hadal trenches. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00224-2.

Biologic and Clinical Characteristics of Isochromosome der(17)(q10)t(15;17) in Acute Promyelocytic Leukemia.

INTRODUCTION: Acute promyelocytic leukemia (APL) is genetically characterized by the fusion of promyelocytic leukemia (PML) gene with retinoic acid receptor alpha (RARα) resulting from a t(15;17)(q24;q21) chromosomal translocation. An infrequent but recurrent finding in APL is the formation of an isochromosome of the derivative chromosome 17; ider(17)(q10)t(15;17) or ider(17q). This rearrangement in APL results in an additional copy of the PML-RARα fusion gene as well as loss of 17p/TP53. Due to the infrequent occurrence of the ider(17q), the prognostic impact of this genetic finding is not well known. Case Presentation(s): Here, we describe the clinical characteristics and outcomes of our case series of 5 patients with ider(17q) APL treated at the University of Maryland and Johns Hopkins University. CONCLUSION: In our series, patients with APL with ider(17q) did not have a worse prognosis.