Effects of Acute Sleep Deprivation on Sporting Performance in Athletes: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Using meta-analysis to comprehensively and quantitatively evaluate the impact of acute sleep deprivation on different sports performance of athletes, this study aims to provide scientific guidance for coaches in optimizing and adjusting training and competition arrangements. Methods: Establishing literature inclusion and exclusion criteria, we conducted searches in both Chinese and English databases. Using stata 14.0, we analyzed 75 indicators from 27 included literature, focusing on three aspects: the impact of acute sleep deprivation on overall athletic performance, the impact on sporting performance across various athletic abilities, and the disparities in athletic performance between morning and afternoon following acute sleep deprivation. Results: The effect size of acute sleep deprivation on overall athletic performance was -0.56 (P<0.05). Sub-analyses revealed effect sizes of -0.23 (P<0.05) for whole night sleep deprivation, -1.17 (P<0.05) for partial sleep deprivation at the end of the night, and -0.25 (P>0.05) for partial sleep deprivation in the beginning of the night. The effect sizes of acute sleep deprivation on high intensity intermittent exercise, skill control, speed, aerobic endurance, and explosive power indicators were -1.57, -1.06, -0.67, -0.54, and -0.39 respectively (P<0.05). The effect sizes of acute sleep deprivation on the overall athletic performance in the morning and afternoon were -0.30, and -1.11, respectively (P<0.05). Conclusion: Acute sleep deprivation significantly impairs the overall athletic performance of athletes, with a more pronounced negative impact observed with partial sleep deprivation at the end of the night. Various types of exercise performance are adversely affected by acute sleep deprivation, with magnitude of impact ranking high intensity intermittent, skill control, speed, aerobic endurance, and explosive power. Following acute sleep deprivation, athletes' overall sporting performance in the afternoon is inferior to that in the morning.

Conjugated Polymer/Recombinant Escherichia coli Biohybrid Systems for Photobiocatalytic Hydrogen Production.

Biohybrid photocatalysts are composite materials that combine the efficient light-absorbing properties of synthetic materials with the highly evolved metabolic pathways and self-repair mechanisms of biological systems. Here, we show the potential of conjugated polymers as photosensitizers in biohybrid systems by combining a series of polymer nanoparticles with engineered Escherichia coli cells. Under simulated solar light irradiation, the biohybrid system consisting of fluorene/dibenzo [b,d]thiophene sulfone copolymer (LP41) and recombinant E. coli (i.e., a LP41/HydA BL21 biohybrid) shows a sacrificial hydrogen evolution rate of 3.442 mmol g-1 h-1 (normalized to polymer amount). It is over 30 times higher than the polymer photocatalyst alone (0.105 mmol g-1 h-1), while no detectable hydrogen was generated from the E. coli cells alone, demonstrating the strong synergy between the polymer nanoparticles and bacterial cells. The differences in the physical interactions between synthetic materials and microorganisms, as well as redox energy level alignment, elucidate the trends in photochemical activity. Our results suggest that organic semiconductors may offer advantages, such as solution processability, low toxicity, and more tunable surface interactions with the biological components over inorganic materials.

Protective effect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a common pathogen that causes bacterial pneumonia. However, with increasing bacterial resistance, there is an urgent need to develop new drugs to treat S. pneumoniae infections. Nanodefensin with a 14-carbon saturated fatty acid (ND-C14) is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of human α-defensin 5 (HD5) via an amide bond. However, it is unclear whether ND-C14 is effective against lung infections caused by S. pneumoniae. METHODS: In vitro, three groups were established, including the control group, and the HD5 and ND-C14 treatment groups. A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S. pneumoniae. The morphological changes of S. pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy. In vivo, mice were divided into sham, vehicle, and ND-C14 treatment groups. Mice in the sham group were treated with 25 µL of phosphate-buffered saline (PBS). Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25 µL of bacterial suspension with 2×108 CFU/mL (total bacterial count: 5×106 CFU), and then the mice were given 25 µL PBS or intratracheally injected with 25 µL of ND-C14 (including 20 µg or 50 µg), respectively. Survival rates were evaluated in the vehicle and ND-C14 treatment groups. Bacterial burden in the blood and bronchoalveolar lavage fluid were counted. The lung histology of the mice was assessed. A propidium iodide uptake assay was used to clarify the destructive effect of ND-C14 against S. pneumoniae. RESULTS: Compared with HD5, ND-C14 had a better bactericidal effect against S. pneumoniae because of its stronger ability to destroy the membrane structure of S. pneumoniae in vitro. In vivo, ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S. pneumoniae. ND-C14 reduced bacterial burden and lung tissue injury. Moreover, ND-C14 had a membrane permeation effect on S. pneumoniae, and its destructive ability increased with increasing ND-C14 concentration. CONCLUSION: The ND-C14 may improve bactericidal effects on S. pneumoniae both in vitro and in vivo.

Bleomycin promotes rAAV2 transduction via DNA-PKcs/Artemis-mediated DNA break repair pathways.

Because it is safe and has a simple genome, recombinant adeno-associated virus (rAAV) is an extremely appealing vector for delivery in in vivo gene therapy. However, its low transduction efficiency for some cells, limits its further application in the field of gene therapy. Bleomycin is a chemotherapeutic agent approved by the FDA whose effect on rAAV transduction has not been studied. In this study, we systematically investigated the effect of Bleomycin on the second-strand synthesis and used CRISPR/CAS9 and RNAi methods to understand the effects of Bleomycin on rAAV vector transduction, particularly the effect of DNA repair enzymes. The results showed that Bleomycin could promote rAAV2 transduction both in vivo and in vitro. Increased transduction was discovered to be a direct result of decreased cytoplasmic rAAV particle degradation and increased second-strand synthesis. TDP1, PNKP, and SETMAR are required to repair the DNA damage gap caused by Bleomycin, TDP1, PNKP, and SETMAR promote rAAV second-strand synthesis. Bleomycin induced DNA-PKcs phosphorylation and phosphorylated DNA-PKcs and Artemis promoted second-strand synthesis. The current study identifies an effective method for increasing the capability and scope of in-vivo and in-vitro rAAV applications, which can amplify cell transduction at Bleomycin concentrations. It also supplies information on combining tumor gene therapy with chemotherapy.

Turning cationic antimicrobial peptide KR-12 into self-assembled nanobiotics with potent bacterial killing and LPS neutralizing activities.

Gram-negative sepsis has become a substantial and escalating global healthcare challenge due to the growing antibiotic resistance crisis and the sluggish development of new antibiotics. LL-37, a unique Cathelicidin species found in humans, exhibits a wide range of bioactive properties, including direct bactericidal effects, inflammation regulation, and LPS neutralization. KR-12, the smallest yet potent peptide fragment of LL-37, has been modified to create more effective antimicrobials. In this study, we designed two myristoylated derivatives of KR-12, referred to as Myr-KR-12N and Myr-KR-12C. These derivatives displayed remarkable ability to spontaneously assemble into nanoparticles when mixed with deionized water. Myristoylated KR-12 derivatives exhibited broad-spectrum and intensified bactericidal activity by disrupting bacterial cell membranes. In particular, Myr-KR-12N showed superior capability to rescue mice from lethal E. coli-induced sepsis in comparison with the conventional antibiotic meropenem. We also confirmed that the myristoylated KR-12 nanobiotic possesses significant LPS binding capacity and effectively reduces inflammation in vitro. In an in vivo context, Myr-KR-12N outperformed polymyxin B in rescuing mice from LPS-induced sepsis. Crucially, toxicological assessments revealed that neither Myr-KR-12N nor Myr-KR-12C nanobiotics induced meaningful hemolysis or caused damage to the liver and kidneys. Collectively, our study has yielded an innovative nanobiotic with dual capabilities of bactericidal action and LPS-neutralization, offering substantial promise for advancing the clinical translation of antimicrobial peptides and the development of novel antibiotics. This addresses the critical need for effective solutions to combat Gram-negative sepsis, a pressing global medical challenge.

Development of an Inosine Hyperproducer from Bacillus licheniformis by Systems Metabolic Engineering.

Inosine is widely used in food, chemical, and medicine. This study developed Bacillus licheniformis into an inosine hyperproducer through systems metabolic engineering. First, purine metabolism was activated by deleting inhibitors PurR and YabJ and overexpressing the pur operon. Then, the 5-phosphoribosyl-1-pyrophosphate (PRPP) supply was increased by optimizing the glucose transport system and pentose phosphate pathway, increasing the inosine titer by 97% and decreasing the titers of byproducts by 36%. Next, to prevent the degradation of inosine, genes deoD and pupG coding purine nucleoside phosphorylase were deleted, accumulating 0.91 g/L inosine in the culture medium. Additionally, the downregulation of adenosine 5'-monophosphate (AMP) synthesis pathway increased the inosine titer by 409%. Importantly, enhancing the glycine and aspartate supply increased the inosine titer by 298%. Finally, the guanosine synthesis pathway was blocked, leading to strain IR-8-2 producing 27.41 g/L inosine with a 0.46 g inosine/g glucose yield and a 0.38 g/(L·h) productivity in a shake flask.

Chemoautotrophic production of gaseous hydrocarbons, bioplastics and osmolytes by a novel Halomonas species.

BACKGROUND: Production of relatively low value, bulk commodity chemicals and fuels by microbial species requires a step-change in approach to decrease the capital and operational costs associated with scaled fermentation. The utilisation of the robust and halophilic industrial host organisms of the genus Halomonas could dramatically decrease biomanufacturing costs owing to their ability to grow in seawater, using waste biogenic feedstocks, under non-sterile conditions. RESULTS: We describe the isolation of Halomonas rowanensis, a novel facultative chemoautotrophic species of Halomonas from a natural brine spring. We investigated the ability of this species to produce ectoine, a compound of considerable industrial interest, under heterotrophic conditions. Fixation of radiolabelled NaH14CO3 by H. rowanensis was confirmed in mineral medium supplied with thiosulfate as an energy source. Genome sequencing suggested carbon fixation proceeds via a reductive tricarboxylic acid cycle, and not the Calvin-Bensen-Bassham cycle. The mechanism of energy generation to support chemoautotrophy is unknown owing to the absence of an annotated SOX-based thiosulfate-mediated energy conversion system. We investigated further the biotechnological potential of the isolated H. rowanensis by demonstrating production of the gaseous hydrocarbon (bio-propane), bioplastics (poly-3-hydroxybutyrate) and osmolytes (ectoine) under heterotrophic and autotrophic CO2 fixation growth conditions. CONCLUSIONS: This proof-of-concept study illustrates the value of recruiting environmental isolates as industrial hosts for chemicals biomanufacturing, where CO2 utilisation could replace, or augment, the use of biogenic feedstocks in non-sterile, industrialised bioreactors.

Engineering α-carboxysomes into plant chloroplasts to support autotrophic photosynthesis.

The growth in world population, climate change, and resource scarcity necessitate a sustainable increase in crop productivity. Photosynthesis in major crops is limited by the inefficiency of the key CO2-fixing enzyme Rubisco, owing to its low carboxylation rate and poor ability to discriminate between CO2 and O2. In cyanobacteria and proteobacteria, carboxysomes function as the central CO2-fixing organelles that elevate CO2 levels around encapsulated Rubisco to enhance carboxylation. There is growing interest in engineering carboxysomes into crop chloroplasts as a potential route for improving photosynthesis and crop yields. Here, we generate morphologically correct carboxysomes in tobacco chloroplasts by transforming nine carboxysome genetic components derived from a proteobacterium. The chloroplast-expressed carboxysomes display a structural and functional integrity comparable to native carboxysomes and support autotrophic growth and photosynthesis of the transplastomic plants at elevated CO2. Our study provides proof-of-concept for a route to engineering fully functional CO2-fixing modules and entire CO2-concentrating mechanisms into chloroplasts to improve crop photosynthesis and productivity.

Population pharmacokinetics of nalbuphine in patients undergoing general anesthesia surgery.

Purpose: The aim of this study was to build a population pharmacokinetics (PopPK) model of nalbuphine and to estimate the suitability of bodyweight or fixed dosage regimen. Method: Adult patients who were undergoing general anesthetic surgery using nalbuphine for induction of anesthesia were included. Plasma concentrations and covariates information were analyzed by non-linear mixed-effects modeling approach. Goodness-of-fit (GOF), non-parametric bootstrap, visual predictive check (VPC) and external evaluation were applied for the final PopPK model evaluation. Monte Carlo simulation was conducted to assess impact of covariates and dosage regimens on the plasma concentration to nalbuphine. Results: 47 patients aged 21-78 years with a body weight of 48-86 kg were included in the study. Among them, liver resection accounted for 14.8%, cholecystectomy for 12.8%, pancreatic resection for 36.2% and other surgeries for 36.2%. 353 samples from 27 patients were enrolled in model building group; 100 samples from 20 patients were enrolled in external validation group. The results of model evaluation showed that the pharmacokinetics of nalbuphine was adequately described by a two-compartment model. The hourly net fluid volume infused (HNF) was identified as a significant covariate about the intercompartmental clearance (Q) of nalbuphine with objective function value (OFV) decreasing by 9.643 (p < 0.005, df = 1). Simulation results demonstrated no need to adjust dosage based on HNF, and the biases of two dosage methods were less than 6%. The fixed dosage regimen had lower PK variability than the bodyweight regimen. Conclusion: A two-compartment PopPK model adequately described the concentration profile of nalbuphine intravenous injection for anesthesia induction. While HNF can affect the Q of nalbuphine, the magnitude of the effect was limited. Dosage adjustment based on HNF was not recommended. Furthermore, fixed dosage regimen might be better than body weight dosage regimen.

Single-particle cryo-EM analysis of the shell architecture and internal organization of an intact α-carboxysome.

Carboxysomes are proteinaceous bacterial microcompartments that sequester the key enzymes for carbon fixation in cyanobacteria and some proteobacteria. They consist of a virus-like icosahedral shell, encapsulating several enzymes, including ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), responsible for the first step of the Calvin-Benson-Bassham cycle. Despite their significance in carbon fixation and great bioengineering potentials, the structural understanding of native carboxysomes is currently limited to low-resolution studies. Here, we report the characterization of a native α-carboxysome from a marine cyanobacterium by single-particle cryoelectron microscopy (cryo-EM). We have determined the structure of its RuBisCO enzyme, and obtained low-resolution maps of its icosahedral shell, and of its concentric interior organization. Using integrative modeling approaches, we have proposed a complete atomic model of an intact carboxysome, providing insight into its organization and assembly. This is critical for a better understanding of the carbon fixation mechanism and toward repurposing carboxysomes in synthetic biology for biotechnological applications.

Targeted Lipidomics and Inflammation Response to Six Weeks of Sprint Interval Training in Male Adolescents.

Lipids play an important role in coordinating and regulating metabolic and inflammatory processes. Sprint interval training (SIT) is widely used to improve sports performance and health outcomes, but the current understanding of SIT-induced lipid metabolism and the corresponding systemic inflammatory status modification remains controversial and limited, especially in male adolescents. To answer these questions, twelve untrained male adolescents were recruited and underwent 6 weeks of SIT. The pre- and post-training testing included analyses of peak oxygen consumption (VO2peak), biometric data (weight and body composition), serum biochemical parameters (fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol, testosterone, and cortisol), inflammatory markers, and targeted lipidomics. After the 6-week SIT, the serum C-reactive protein (CRP), interleukin (IL)-1ß, IL-2, IL-4, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß significantly decreased (p < 0.05), whereas IL-6 and IL-10/TNF-α significantly increased (p < 0.05). In addition, the targeted lipidomics revealed changes in 296 lipids, of which 33 changed significantly (p < 0.05, fold change > 1.2 or <1/1.2). The correlation analysis revealed that the changes in the inflammatory markers were closely correlated with the changes in some of the lipids, such as LPC, HexCer, and FFA. In conclusion, the 6-week SIT induced significant changes in the inflammatory markers and circulating lipid composition, offering health benefits to the population.

A Validated UHPLC-MS/MS Method for Determination of Nalbuphine in Human Plasma and Application for Pharmacokinetic Study of Patients Undergoing General Anesthesia.

Nalbuphine was a semisynthetic opioid analgesic widely used in the treatment of both acute and chronic pain. We developed and validated a rapid, simple and sensitive method by ultra-performance liquid chromatography-tandem mass spectrometry (MS/MS) for the simultaneous quantitation of nalbuphine in human plasma, and we reported the pharmacokinetic features of patients during general anesthesia for abdominal surgery. Sample separation was achieved on a Kinetex Phenyl-Hexyl column (50 × 2.1 mm, 1.7 µm) after simple protein precipitation with acetonitrile. The mobile phase was composed of acetonitrile and 3 mM of ammonium acetate aqueous solution with 0.1% formic acid. Gradient elution was used in 4.5 min with a flow rate of 0.5 mL/min at 40°C. MS detection using AB Sciex QTRAP 5500 mass spectrometer was characterized by electrospray ionization for positive ions in multiple reaction monitoring mode. Quantitative ion pairs were m/z 358.4 â†’ 340.1 for nalbuphine and m/z 340.0 â†’ 268.3 for nalmefene, which were used as the internal standard (IS). The calibration curves showed good linearity (r2>0.99) over concentration range of 0.1-500 ng/mL. The intra-and inter-batch precisions were within 10.67%, and accuracy ranged from 94.07 to 105.34%. The IS-normalized matrix factors were 1.02-1.03 with RSD% (≤5.82%). The recoveries ranged from 101.09 to 106.30%. In conclusion, a rapid, simple, sensitive and economical analytical method was developed and validated to detect the concentration in plasma samples obtained from patients receiving nalbuphine intravenous injection and was successfully applicated to human pharmacokinetic studies of nalbuphine.

Producing fast and active Rubisco in tobacco to enhance photosynthesis.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) performs most of the carbon fixation on Earth. However, plant Rubisco is an intrinsically inefficient enzyme given its low carboxylation rate, representing a major limitation to photosynthesis. Replacing endogenous plant Rubisco with a faster Rubisco is anticipated to enhance crop photosynthesis and productivity. However, the requirement of chaperones for Rubisco expression and assembly has obstructed the efficient production of functional foreign Rubisco in chloroplasts. Here, we report the engineering of a Form 1A Rubisco from the proteobacterium Halothiobacillus neapolitanus in Escherichia coli and tobacco (Nicotiana tabacum) chloroplasts without any cognate chaperones. The native tobacco gene encoding Rubisco large subunit was genetically replaced with H. neapolitanus Rubisco (HnRubisco) large and small subunit genes. We show that HnRubisco subunits can form functional L8S8 hexadecamers in tobacco chloroplasts at high efficiency, accounting for ∼40% of the wild-type tobacco Rubisco content. The chloroplast-expressed HnRubisco displayed a ∼2-fold greater carboxylation rate and supported a similar autotrophic growth rate of transgenic plants to that of wild-type in air supplemented with 1% CO2. This study represents a step toward the engineering of a fast and highly active Rubisco in chloroplasts to improve crop photosynthesis and growth.

Macrophage ferroportin serves as a therapeutic target against bacteria-induced acute lung injury by promoting barrier restoration.

Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were characterized by increased expression of ferroportin (FPN). Specifically deleting FPN in myeloid cells conferred significant resistance to bacterial infection with improved survival by decreasing extracellular bacterial growth and preserving pulmonary barrier integrity in mice. Mechanistically, macrophage FPN deficiency not only limited the availability of iron to bacteria, but also promoted tissue restoration via growth factor amphiregulin, which is regulated by cellular iron-activated Yes-associated protein signaling. Furthermore, pharmacological treatment with C-Hep, the self-assembled N-terminally cholesterylated minihepcidin that functions in the degradation of macrophage FPN, protected against bacteria-induced lung injury. Therefore, therapeutic strategies targeting the hepcidin-FPN axis in macrophages may be promising for the clinical treatment of acute lung injury.

SQEIR: An epidemic virus spread analysis and prediction model.

In 2019, a new strain of coronavirus pneumonia spread quickly worldwide. Viral propagation may be simulated using the Susceptible Infectious Removed (SIR) model. However, the SIR model fails to consider that separation of patients in the COVID-19 incubation stage entails difficulty and that these patients have high transmission potential. The model also ignores the positive effect of quarantine measures on the spread of the epidemic. To address the two flaws in the SIR model, this study proposes a new infectious disease model referred to as the Susceptible Quarantined Exposed Infective Removed (SQEIR) model. The proposed model uses the weighted least squares for the optimal estimation of important parameters in the infectious disease model. Based on these parameters, new differential equations were developed to describe the spread of the epidemic. The experimental results show that this model exhibits an accuracy 6.7% higher than that of traditional infectious disease models.

Pharmacokinetic Study of Nalbuphine in Surgical Patients Undergoing General Anesthesia with Varying Degrees of Liver Dysfunction.

Purpose: This study aimed to characterize the pharmacokinetics of nalbuphine in patients undergoing general anesthesia with varying degrees of liver dysfunction. Patients and Methods: Twenty-four patients were enrolled and divided into three cohorts based on liver function: normal liver function (n = 13), mild liver dysfunction (n = 5), and moderate/severe liver dysfunction (n = 6). During the induction of anesthesia, they received 15 mg of nalbuphine intravenously. Venous blood samples were collected from each patient. The plasma concentration of nalbuphine was determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The pharmacokinetic parameters of nalbuphine were calculated by non-compartmental analysis (NCA) using Phoenix WinNonlin software. Results: Compared with the normal liver function group, the plasma elimination half-life (T1/2) of nalbuphine was increased by approximately 33% in the moderate/severe liver dysfunction group (2.66 h vs 3.54 h, P<0.05), and the volume of distribution (Vd) increased by approximately 85% (100.08 L vs 184.95 L, P<0.05). Multivariate analysis revealed that weight and platelet were associated with clearance (CL); total bilirubin as an independent factor was associated with T1/2, and weight associated with area under the curve (AUC(0→∞)) independently. Conclusion: The T1/2, mean residence time, and Vd of nalbuphine in patients with moderate/severe liver dysfunction were prolonged or increased significantly compared with those in the normal liver function group. These data suggest that it may need to be used with caution when nalbuphine is administered to patients with moderate or severe liver dysfunction.

Structure and assembly of cargo Rubisco in two native α-carboxysomes.

Carboxysomes are a family of bacterial microcompartments in cyanobacteria and chemoautotrophs. They encapsulate Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrase catalyzing carbon fixation inside a proteinaceous shell. How Rubisco complexes pack within the carboxysomes is unknown. Using cryo-electron tomography, we determine the distinct 3D organization of Rubisco inside two distant α-carboxysomes from a marine α-cyanobacterium Cyanobium sp. PCC 7001 where Rubiscos are organized in three concentric layers, and from a chemoautotrophic bacterium Halothiobacillus neapolitanus where they form intertwining spirals. We further resolve the structures of native Rubisco as well as its higher-order assembly at near-atomic resolutions by subtomogram averaging. The structures surprisingly reveal that the authentic intrinsically disordered linker protein CsoS2 interacts with Rubiscos in native carboxysomes but functions distinctively in the two α-carboxysomes. In contrast to the uniform Rubisco-CsoS2 association in the Cyanobium α-carboxysome, CsoS2 binds only to the Rubiscos close to the shell in the Halo α-carboxysome. Our findings provide critical knowledge of the assembly principles of α-carboxysomes, which may aid in the rational design and repurposing of carboxysome structures for new functions.

Biogenesis of a bacterial metabolosome for propanediol utilization.

Bacterial metabolosomes are a family of protein organelles in bacteria. Elucidating how thousands of proteins self-assemble to form functional metabolosomes is essential for understanding their significance in cellular metabolism and pathogenesis. Here we investigate the de novo biogenesis of propanediol-utilization (Pdu) metabolosomes and characterize the roles of the key constituents in generation and intracellular positioning of functional metabolosomes. Our results demonstrate that the Pdu metabolosome undertakes both "Shell first" and "Cargo first" assembly pathways, unlike the ß-carboxysome structural analog which only involves the "Cargo first" strategy. Shell and cargo assemblies occur independently at the cell poles. The internal cargo core is formed through the ordered assembly of multiple enzyme complexes, and exhibits liquid-like properties within the metabolosome architecture. Our findings provide mechanistic insight into the molecular principles driving bacterial metabolosome assembly and expand our understanding of liquid-like organelle biogenesis.

Human defensin-inspired discovery of peptidomimetic antibiotics.

SignificanceWe report the development of peptidomimetic antibiotics derived from a natural antimicrobial peptide, human α-defensin 5. By engaging multiple bacterial targets, the lead compound is efficacious in vitro and in vivo against bacteria with highly inducible antibiotic resistance, promising a useful therapeutic agent for the treatment of infections caused by antibiotic-resistant bacteria.