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Carboxysomes are anabolic bacterial microcompartments that play an essential role in carbon fixation in cyanobacteria. This self-assembling proteinaceous organelle encapsulates the key CO 2 -fixing enzymes, Rubisco and carbonic anhydrase, using a polyhedral shell constructed by hundreds of shell protein paralogs. Deciphering the precise arrangement and structural organization of Rubisco enzymes within carboxysomes is crucial for understanding the formation process and overall functionality of carboxysomes. Here, we employed cryo-electron tomography and subtomogram averaging to delineate the three-dimensional packaging of Rubiscos within β-carboxysomes in the freshwater cyanobacterium Synechococcus elongatus PCC7942 that were grown under low light. Our results revealed that Rubiscos are arranged in multiple concentric layers parallel to the shell within the β-carboxysome lumen. We also identified the binding of Rubisco with the scaffolding protein CcmM in β-carboxysomes, which is instrumental for Rubisco encapsulation and β-carboxysome assembly. Using QconCAT-based quantitative mass spectrometry, we further determined the absolute stoichiometric composition of the entire β-carboxysome. This study and recent findings on the β-carboxysome structure provide insights into the assembly principles and structural variation of β-carboxysomes, which will aid in the rational design and repurposing of carboxysome nanostructures for diverse bioengineering applications.

Background: The available data exhibit inconsistent findings regarding the association between obesity and sleep problems among older adults. The objective of this study was to assess the potential association between obesity and sleep disorders in the older population., Methods: The data utilised in this cross-sectional investigation was obtained from the National Health and Nutritional Examination Survey (NHANES) conducted between 2005 and 2018. The study employed a multivariate logistic regression model and conducted subgroup analysis to evaluate the association between obesity and sleep disturbance., Results: The investigation consisted of 2,570 older people who provided complete information, out of which 324 individuals satisfied the criteria for sleep disturbance. The findings from the multivariable adjusted logistic regression model indicate that individuals in the overweight and normal weight groups exhibited decreased odds of experiencing sleep disorder, as evidenced by the adjusted odds ratios (AOR) of 0.46 (95% confidence interval [CI] = 0.34-0.61) and 0.33 (95% CI = 0.22-0.47), respectively. These results were statistically significant ( p  < 0.001) when compared to individuals in the obese group. The investigation of age and gender subgroups demonstrated similar associations between various BMI categories and sleep disorders in the older population., Conclusion: In summary, there exists a correlation between obesity and sleep disorders in the senior population. A significant association was observed between BMI and the likelihood of experiencing sleep disorders, indicating a dose-response relationship. Individuals with a higher BMI demonstrated a heightened likelihood of experiencing sleep disorders compared to those with a lower BMI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chen, Zhang, Yuan, Sun, Yao, Lu and Zheng.)

Purpose: Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied., Methods: We conducted a retrospective analysis of microbiological results through both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with nosocomial CNS infections. The aim of this study was to assess the clinical diagnostic effect of nosocomial mNGS in this population., Results: The study included 26 cases of nosocomial CNS infections in total. A total of 69.2% (18/26) of the samples tested positive for mNGS, which is substantially greater than the 7.7% (2/26; p <0.05) detected through conventional techniques. Administration of antibiotics before culture is most likely the cause of the low CSF culture rate. Twenty-five pathogenic strains that were missed by standard testing. Three pathogens that were consistent with the mNGS results were positive by routine tests. Eight cases were negative by mNGS due to low pathogen CSF titres. Compared to traditional testing, mNGS demonstrated 100% sensitivity and 33.3% specificity in diagnosing CNS infections. The thirty-day mortality rate was 26.9% (7/26)., Conclusion: Routine microbiologic testing frequently falls short of detecting all neuroinvasive pathogens. Our research suggests that mNGS offers an alternative means of detecting nosocomial CNS infections. By applying mNGS to CSF samples from patients with meningitis or encephalitis, we were able to improve the ability to diagnose nosocomial neurologic infections., Competing Interests: The authors have no conflicts of interest to declare for this work., (© 2024 Zhan et al.)

Zymogen granule 16 (ZG16) is a secretory glycoprotein found in zymogen granules, which also plays an important role in colorectal inflammation and cancer. Herein, a ZG16 gene knock-out (ZG16 -/- ) mouse line was established and we found that ZG16 deletion damaged the intestinal mucosal barrier and gut microbiota, which resulted in low-level inflammation and further promoted the development of ulcerative colitis and inflammation-related colorectal cancer. Meanwhile, a metabolomics analysis on mouse feces showed that the metabolites significantly differed between ZG16 -/- and WT mice, which were important mediators of host-microbiota communication and may impact the pulmonary inflammation of mice. Indeed, ZG16 -/- mice showed more severe inflammation in a bronchial asthma model. Taken together, the results demonstrate that ZG16 plays a pivotal role in inhibiting inflammation and regulating immune responses in colorectum and lung of experimental animals, which may provide a better understanding of the underlying mechanism of human inflammatory diseases associated with ZG16., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Gong et al.)

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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest: The authors declare that they have no competing interests.

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 NaH 14 CO 3 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 CO 2 fixation growth conditions., Conclusions: This proof-of-concept study illustrates the value of recruiting environmental isolates as industrial hosts for chemicals biomanufacturing, where CO 2 utilisation could replace, or augment, the use of biogenic feedstocks in non-sterile, industrialised bioreactors., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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 CO 2 -fixing enzyme Rubisco, owing to its low carboxylation rate and poor ability to discriminate between CO 2 and O 2 . In cyanobacteria and proteobacteria, carboxysomes function as the central CO 2 -fixing organelles that elevate CO 2 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 CO 2 . Our study provides proof-of-concept for a route to engineering fully functional CO 2 -fixing modules and entire CO 2 -concentrating mechanisms into chloroplasts to improve crop photosynthesis and productivity., (© 2023. The Author(s).)

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., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Author(s).)

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., Competing Interests: We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022. The Author(s).)

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 β-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., (© 2022. The Author(s).)

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.

Carboxysomes are the specific CO 2 -fixing microcompartments in all cyanobacteria. Although it is known that the organization and subcellular localization of carboxysomes are dependent on external light conditions and are highly relevant to their functions, how carboxysome organization and function are actively orchestrated in natural diurnal cycles has remained elusive. Here, we explore the dynamic regulation of carboxysome positioning and carbon fixation in the model cyanobacterium Synechococcus elongatus PCC 7942 in response to diurnal light-dark cycles, using live-cell confocal imaging and Rubisco assays. We found that carboxysomes are prone to locate close to the central line along the short axis of the cell and exhibit a greater preference of polar distribution in the dark phase, coupled with a reduction in carbon fixation. Moreover, we show that deleting the gene encoding the circadian clock protein KaiA could lead to an increase in carboxysome numbers per cell and reduced portions of pole-located carboxysomes. Our study provides insight into the diurnal regulation of carbon fixation in cyanobacteria and the general cellular strategies of cyanobacteria living in natural habitat for environmental acclimation.

Rubisco is the essential enzyme mediating the fixation of atmospheric CO 2 during photosynthesis. In cyanobacteria, Rubisco enzymes are densely packed and encapsulated in a specialized organelle known as the carboxysome. Well-defined Rubisco assembly and carboxysome formation are pivotal for efficient CO 2 fixation. Numerous chaperone proteins, including RbcX, are essential for proper protein folding and Rubisco assembly. In this study, we investigated the in vivo function of RbcX in the cyanobacterium Synechococcus elongatus PCC 7942 (Syn7942) using molecular, biochemical, and live-cell fluorescence imaging approaches. Our results show that genetic deletion of the rbcX gene affects Rubisco abundance, as well as carboxysome formation and spatial distribution. Moreover, RbcX appears as one component of the carboxysome and shows a dynamic interaction with Rubisco enzymes. These in vivo observations provide insight into the role of RbcX from Syn7942 in mediating carboxysome assembly. Understanding the molecular mechanism underlying Rubisco assembly and carboxysome biogenesis will provide essential information required for engineering functional CO 2 -fixing complexes in heterogeneous organisms, especially plants, with the aim of boosting photosynthesis and agricultural productivity., (© 2019 The author(s). All Rights Reserved.)

Copy number variation (CNV), referring to a genome structure variation, has attracted researchers' great interests. Thirty-two CNV regions (CNV region, CNVR) have been detected on chromosome 13 in our previous work. In order to detect the genes located in these CNVRs, we first obtained the annotated information from Ensembl database, and searched gene functional enrichments using DAVID online tools. In the 32 CNVRs, a total of 236 genes were identified, in which 169 genes were annotated. Gene Ontology (GO) analysis revealed that these genes mainly participate in proteolysis, cell adhesion, and macromolecular catabolic process. To study the genetic law of these CNVs, we chose the RCAN1 (regulators of calcineurin 1) gene as the candidate. We quantified the copy number of RCAN1 gene in 38 Laiwu pigs by using QPCR method, and analyzed the genetic laws in three Laiwu families including 15 pigs. QPCR results showed that both duplication and deletion occurred in RCAN1 gene among Laiwu pigs and the heredity mode corresponds with Mendelian genetic law.