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Abstract The trade-off between rapid growth and other important physiological traits (e.g., survival and adaptability) poses a fundamental challenge for microbes to achieve fitness maximization. Studies on Bacillus subtilis biology often use strains derived after a process of lab ‘domestication’ from an ancestral strain known as Marburg strain. The domestication process led to loss of a large plasmid (pBS32) encoding a phosphatase (RapP) that dephosphorylates the Spo0F protein and thus regulates biofilm formation and sporulation. Here, we show that plasmid pBS32, and more specifically rapP, enhance growth rates by preventing premature expression of the Spo0F-Spo0A-mediated adaptive response during exponential phase. This results in reallocation of proteome resources towards biosynthetic, growth-promoting pathways without compromising long-term fitness during stationary phase. Thus, RapP helps B. subtilis to constrain physiological trade-offs and economize cellular resources for fitness improvement.

Abstract Objective This study aimed to investigate the relationship between serum lactate levels at admission to the intensive care unit (ICU) and the clinical outcomes of children with sepsis. Methods We used the Pediatric Intensive Care (PIC) database to identify 288 pediatric patients with sepsis. We analyzed the relationship between lactate levels and hospital and ICU mortality in sepsis by establishing a segmented multivariable Cox regression model. We also conducted subgroup analysis as well as analyzed the restricted cubic spline curves. Results After adjusting for all potential confounding factors, an increase of 1 mmol/L in lactate levels was found to be associated with an 17% rise in the 28-day hospital mortality risk among sepsis patients (HR: 1.17, 95% CI: 1.08–1.27, P = 0.0002). When considering lactate as a categorical variable, the mortality risk of patients with lactate levels ≥ 2.2 mmol/L was significantly increased (HR: 3.61, 95% CI: 1.24–10.54, P = 0.0189). The restricted cubic spline curve analysis revealed a nonlinear correlation between lactate and 28-day mortality, with an inflection point at 2.2 mmol/L. Similar findings were also observed in the assessment of secondary outcomes. Conclusions Our study demonstrates a non-linear correlation between lactate levels and 28-day mortality in pediatric sepsis, with a critical threshold of 2.2mmol/l for lactate levels in septic patients. Early assessment of lactate levels is recommended for children with sepsis to facilitate prompt intervention and mitigate the risk of fatality.

Objective Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the mechanism by which SS regulates growth and development in goats is still unclear. Methods In this study, we randomly selected eight 7-month-old Dazu black goats (DBGs) of similar body weight and equally assigned four bucks as the immunised and negative control groups. The immunised group received the Salmonella typhi attenuated vaccine X9241 (ptCS/2SS-asd) orally, whilst the negative control group received the empty vector vaccine X9241 (pVAX-asd) orally. Results The SS concentration in the serum of goats in the immunised group was significantly lower than that in the negative control group, and the daily gain was significantly higher (p

Abstract Evolutionary dynamics of inversion and its impact on biochemical traits are a puzzling question. Here, we show abundance of inversions in three Curcuma species (turmeric, hidden ginger and Siam tulip). Genes within inversions display higher long terminal repeat content and lower expression level compared with genomic background, suggesting inversions in Curcuma experience relaxed genetic constraints. It is corroborated by depletion of selected SNPs and enrichment of deleterious mutations in inversions detected among 56 Siam tulip cultivars. Functional verification of tandem duplicated terpene synthase (TPS) genes reveals that genes within inversions become pseudogenes, while genes outside retain catalytic function. Our findings suggest that inversions act as a counteracting force against tandem duplication in balancing birth and death of TPS genes and modulating terpenoid contents in Curcuma. This study provides an empirical example that inversions are likely not adaptive but affect biochemical traits.

Abstract Achieving solid superlubricity in high-humidity environments is of great practical importance yet remains challenging nowadays, due to the complex physicochemical roles of water and concomitant oxidation on solid surfaces. Here we report a facile way to access humidity-insensitive solid superlubricity (coefficient of friction 0.0035) without detectable wear and running-in at a humidity range of 2–80%. Inspired by the concept of structural superlubricity, this is achieved between Au-capped microscale graphite flake and graphene nanoflake-covered hydrogen-free amorphous carbon (GNC a-C). Such GNC a-C exhibits reduced pinning effects of water molecules and weak oxidation, which demonstrates stable structural superlubricity even after air exposure of the surfaces for 365 days. The manufacturability of such design enables the macroscopic scale-up of structural superlubricity, achieving the leap from 4 μm × 4 μm contact to 3 mm ball-supported contact with a wide range of materials. Our results suggest a strategy for the macroscale application of structural superlubricity under ambient condition.

G protein-coupled receptors (GPCRs) are pivotal in mediating diverse physiological and pathological processes, rendering them promising targets for drug discovery. GPCRs account for about 40% of FDA-approved drugs, representing the most successful drug targets. However, only approximately 15% of the 800 human GPCRs are targeted by market drugs, leaving numerous opportunities for drug discovery among the remaining receptors. Cell expression systems play crucial roles in the GPCR drug discovery field, including novel target identification, structural and functional characterization, potential ligand screening, signal pathway elucidation, and drug safety evaluation. Here, we discuss the principles, applications, and limitations of widely used cell expression systems in GPCR-targeted drug discovery, GPCR function investigation, signal pathway characterization, and pharmacological property studies. We also propose three strategies for constructing genome-wide pan-GPCR cell libraries, which will provide a powerful platform for GPCR ligand screening, and facilitate the study of GPCR mechanisms and drug safety evaluation, ultimately accelerating the process of GPCR-targeted drug discovery.

Abstract The study investigates the global impact of land property rights on land use efficiency (LUE), as measured by the key indicator for United Nations Sustainable Development Goal 11.3.1, namely Land Consumption Rate to Population Growth Rate. By utilizing human-land change data from 165 countries spanning the period between 1990 and 2020, we have developed a fixed effects model and employed legal origins as an instrumental variable to examine the influence of land property rights security on LUE. Our findings demonstrate that the security of land property rights significantly influences LUE, with common law countries exhibiting higher levels of LUE compared to civil law countries while controlling for other variables. Stability in property rights encourages long-term investments in infrastructure and sustainable land management practices, thereby enhancing land productivity and mitigating urban sprawl. Furthermore, safeguarding property rights limits governments’ power to expropriate lands, facilitating rational and efficient land transactions that contribute towards achieving Sustainable Development Goals.

In order to investigate the non-Darcy seepage characteristics of crushed gangue filling in the goaf under the action of the overlying rock layer, the self-developed crushed rock seepage test system is utilized to carry out uniaxial lateral limit compression and seepage tests using the steady state permeability method on four kinds of pressurized crushed gangue with different initial grades, and to obtain the porosity, fractal dimensions, permeability, Euler’s number, and the energy dissipation law in the non-Darcy seepage process of the crushed gangue under different effective stress conditions. The study shows that: under high osmotic pressure and high porosity, the fluid flow rate is faster, resulting in the E value is much larger than 0.1, at this time, it shows the characteristics of high-speed non-Darcy seepage; the change process of porosity with the effective stress can be divided into two phases, when the n value tends to be 0.4, the particles of each size interval have a good mass ratio, and it is easy to be compacted; with the increase of fractal dimension, the degree of particle fragmentation is increased, and the permeability of the sample is linearly decreasing; it is deduced that there is an inverse relationship between the Euler number and the flow rate, and the momentum transfer of the fluid gradually decreases with the increase of flow rate.

Abstract PANoptosis induces programmed cell death (PCD) through extensive crosstalk and is associated with development of cancer. However, the functional mechanisms, clinical significance, and potential applications of PANoptosis-related genes (PRGs) in colorectal cancer (CRC) have not been fully elucidated. Functional enrichment of key PRGs was analyzed based on databases, and relationships between key PRGs and the immune microenvironment, immune cell infiltration, chemotherapy drug sensitivity, tumor progression genes, single-cell cellular subgroups, signal transduction pathways, transcription factor regulation, and miRNA regulatory networks were systematically explored. This study identified 5 key PRGs associated with CRC: BCL10, CDKN2A, DAPK1, PYGM and TIMP1. Then, RT-PCR was used to verify expression of these genes in CRC cells and tissues. Clinical significance and prognostic value of key genes were further verified by multiple datasets. Analyses of the immune microenvironment, immune cell infiltration, chemotherapy drug sensitivity, tumor progression genes, single-cell cellular subgroups, and signal transduction pathways suggest a close relationship between these key genes and development of CRC. In addition, a novel prognostic nomogram model for CRC was successfully constructed by combining important clinical indicators and the key genes. In conclusion, our findings offer new insights for understanding the pathogenesis of CRC, predicting CRC prognosis, and identifying multiple therapeutic targets for future CRC therapy.

Plant growth-promoting rhizobacteria (PGPR) such as Bacillus and Pseudomonas have drawn broad attention and interest due to their agricultural benefits. One of the major benefits of PGPR lies at their biocontrol capabilities against various plant pathogens. The biocontrol capability of PGPR is closely related to its capability of producing various kinds of antimicrobial substances. Major antimicrobial secondary metabolites secreted by PGPR include non-ribosomal lipopeptides (NRLPs), polyketides, ribosomal peptides, phenazines, pyrrolnitrins, etc. This review focuses on the major antimicrobial secondary metabolites produced by Bacillus and Pseudomonas including their classifications, structures, mechanisms of action and genetic regulations. We have also discussed their applications in plant biocontrol and provided insights into future development of improved biocontrol strains using synthetic biology approaches.