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In chronobiology, shifting light/dark cycles is a common method to disrupt circadian rhythms. While the direction and magnitude of a phase shift (e.g., +6 denoting a 6‐h advanced shift) dictate the temporal change before and after the shift, little attention has been paid to the duration and relative proportion of daytime and nighttime during the shift, leading to a critical, unexamined variable in circadian research. In this study, we introduce the concepts of "L‐shift" (longer light phase on the shift day) and "D‐shift" (longer dark phase), and investigate how these variations impact the adaptability of mice to jet lag. By examining multiple phase shifts (12L vs. 12D, +6L vs. +6D, −6L vs. −6D), we demonstrate that L‐shifts not only facilitate faster adaptation but also significantly reduce the severity of sepsis in a jet lag‐sensitive lipopolysaccharide‐induced sepsis model. Further investigations with additional phase shifts at 1‐h intervals (+8 to +11) reinforced the enhanced fitness of mice under L‐shifts. Mechanistically, L‐shifts were found to increase sleep duration, thereby improving circadian entrainment, with sleep deprivation nullifying the adaptability differences between lighting protocols. These findings underscore a previously unrecognized factor in circadian biology and suggest that optimizing lighting protocols could profoundly improve adaptability to circadian disruptions. This research opens new avenues for enhancing therapeutic strategies and refining experimental designs in the field of chronobiology. [ABSTRACT FROM AUTHOR]

The regulation of the mammalian circadian clock is largely dependent on heredity. In model animals for circadian rhythm studies, C57BL/6 and BALB/c mice exhibit considerable differences in their adaptation to circadian disruption, yet deeper comparisons remain unexplored. Here, we have established embryonic fibroblast cells derived from C57BL/6 mice (MEF) and BALB/c (BALB/3T3) mice, which have been transfected with the Bmal1 promoter-driven luciferase (Bmal1-Luc) reporter gene. Next, dexamethasone was applied for various cyclic stimulations, which revealed that Bmal1 bioluminescence of MEF cells was entrained to 24 to 26 h cycles, whereas BALB/3T3 cells have a wider range (22 to 28 h) with lower amplitudes. Behaviorally, BALB/c mice swiftly adapted to a 6-h advance light/dark cycle, unlike C57BL/6 mice. Furthermore, we found the expression of the circadian rhythm gene Npas2 in BALB/c mice is significantly lower than that in C57BL/6 mice. This observation is consistent with the differentially expressed genes (DEGs) in the intestine and lung tissues of C57BL/6 and BALB/c mice, based on the RNA-seq datasets downloaded from the Gene Expression Omnibus (GEO). In summary, our study uncovers that BALB/c mice possess greater resilience in circadian rhythm than C57BL/6 mice, both cellular and behaviorally, identifying potential genes underlying this difference. [ABSTRACT FROM AUTHOR]

One of the fundamental techniques in genetic engineering is the creation of Escherichia coli competent cells using the CaCl2 method. However, little is known about the mechanism of E. coli competence formation. We have previously found that the cspA gene may play an indispensable role in the preparation of E. coli DH5α competent cells through multiomics analysis. In the present study, the cellular localization, physicochemical properties, and function of the protein expressed by the cspA gene were analyzed. To investigate the role of the cspA gene in E. coli transformation, cspA‐deficient mutant was constructed by red homologous recombination. The growth, transformation efficiency, and cell morphology of the cspA‐deficient strain and E. coli were compared. It was found that there were no noticeable differences in growth and morphology between E. coli and the cspA‐deficient strain cultured at 37°C, but the mutant exhibited increased transformation efficiencies compared to E. coli DH5α for plasmids pUC19, pET‐32a, and p1304, with enhancements of 2.23, 2.24, and 3.46 times, respectively. It was proved that cspA gene is an important negative regulatory gene in the CaCl2 preparation of competent cells. [ABSTRACT FROM AUTHOR]

Improving the explosion resistance of the building wall has been a hot topic in the current protection engineering research, in this process, corrugated steel and polyisocyanate oxazolidine (POZD) were widely used, but there are few studies on the anti-explosion performance of the composite structure of the two. In this paper, the effects of POZD and corrugated steel on the explosion resistance of POZD-coated corrugated steel plate reinforced concrete slab (PSRC) under contact explosion were studied by test and numerical simulation. The finite element (FE) model of the PSRC slab was established by using Arbitrary Lagrangian–Eulerian (ALE) method. The principle of POZD coating reinforced structure was revealed by analyzing the attenuation process of stress wave propagation in the structure. Subsequently, a series of numerical calculations were conducted to investigate the effect of POZD thickness and corrugated steel angle on the performance of the PSRC slab under explosive load. The relationship between structural damage characteristics and the POZD coating was established, the empirical formula of the normalized maximum mid-span displacement considering POZD thickness and TNT mass was obtained. The effect of corrugated steel with different angles on its anti-explosion performance was analyzed, the empirical formula of the maximum deflection considering corrugated steel angle and TNT mass was obtained. Studies have shown that the peak stress of the stress wave generated by the explosion is only 2.79% of the incident wave after the POZD coating is coated on the back of the structure, the anti-explosion performance of the structure is greatly improved. Increasing the thickness of POZD can significantly increase the anti-explosion performance of PSRC slab, the maximum deflection of PSRC slab decreases exponentially with increasing POZD thickness. The explosion resistance of PSRC slab was enhanced with increasing corrugated steel angles. The corrugated steel angles is 50 , the improvement effect of PSRC is the best. [ABSTRACT FROM AUTHOR]

Circadian disruption such as shift work, jet lag, has gradually become a global health issue and is closely associated with various metabolic disorders. The influence and mechanism of circadian disruption on renal injury in chronic kidney disease (CKD) remains inadequately understood. Here, we evaluated the impact of environmental light disruption on the progression of chronic renal injury in CKD mice. By using two abnormal light exposure models to induce circadian disruption, we found that circadian disruption induced by weekly light/dark cycle reversal (LDDL) significantly exacerbated renal dysfunction, accelerated renal injury, and promoted renal fibrosis in mice with 5/6 nephrectomy and unilateral ureteral obstruction (UUO). Mechanistically, RNA‐seq analysis revealed significant immune and metabolic disorder in the LDDL‐conditioned CKD kidneys. Consistently, renal content of ATP was decreased and ROS production was increased in the kidney tissues of the LDDL‐challenged CKD mice. Untargeted metabolomics revealed a significant buildup of lipids in the kidney affected by LDDL. Notably, the level of β‐NMN, a crucial intermediate in the NAD+ pathway, was found to be particularly reduced. Moreover, we demonstrated that both β‐NMN and melatonin administration could significantly rescue the light‐disruption associated kidney dysfunction. In conclusion, environmental circadian disruption may exacerbate chronic kidney injury by facilitating inflammatory responses and disturbing metabolic homeostasis. β‐NMN and melatonin treatments may hold potential as promising approaches for preventing and treating light‐disruption associated CKD. [ABSTRACT FROM AUTHOR]

One of the commonly employed methods in molecular biology is to utilize calcium chloride to treat Escherichia coli for the preparation of competent cells to facilitate foreign gene expression. However, the molecular mechanisms underlying Ca2+ mediation of competent cell formation and identification of the key genes involved in the process remain unclear. In previous studies, the combined analysis of transcriptomics and proteomics revealed bhsA as one of the crucial genes. The gene ontology functional annotation of bhsA identified it as a member of the YhcN family encoding an outer membrane protein that confers resistance to various stresses. The IPR0108542 domain found within the protein plays a significant role in stress response and biofilm formation in E. coli. Analysis of the STRING database showed that the proteins interacting with bhsA are primarily involved in biofilm formation and stress resistance. Using the RED homologous recombination method, a bhsA deletion strain was constructed to verify its role in E. coli genetic transformation. Although the mutant strain showed no significant differences in morphology or growth trend when compared to the wild‐type strain, its transformation efficiency decreased by 1.14‐ and 1.64‐fold with plasmids pUC19 and pET‐32a. Furthermore, the 1‐N‐phenylnaphthylamine assay indicated a 1.71‐fold reduction in cell membrane permeability in the mutant strain. [ABSTRACT FROM AUTHOR]

CO 2 emissions from headwater streams are a crucial component of greenhouse gas flux in inland waters. However, the influence of groundwater, a major contributor to streams in the Asian Water Tower (Qinghai-Tibet Plateau, QTP), on CO 2 levels remains unclear. This study employed stable isotope analysis and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to demonstrate that groundwater-derived dissolved inorganic carbon (DIC) significantly enhanced CO 2 supersaturation in the Shuiluo stream on the QTP. Specifically, the partial pressure of CO 2 (pCO 2 ), indicative of CO 2 emission potential, increased more than threefold to 1,615 ± 495 μatm in groundwater-rich sites, nearly one time higher than the mean value (843 μatm) across the QTP. Groundwater-derived carbonate weathering had a significant impact of 76.6 % on the increased pCO 2 , whereas the degradation of highly unsaturated polyphenolics with high O/C contributed to 15.8 %. The estimated inflow of groundwater-derived DIC could reach 9.59 ± 0.34 Tg C/y in total runoff across the QTP, highlighting significant CO 2 sources. This study presents new findings on the effects of groundwater-derived DIC on stream CO 2 emissions in weathered regions and expands our knowledge of fluvial CO 2 emissions on the QTP., 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 Ltd. All rights reserved.)

Objective: To investigate the associations between data-driven dietary patterns, immune function, and incident type 2 diabetes (T2D) and the mediating effects of immune function., Methods: This study included 375,665 participants without diabetes at baseline in the UK Biobank study. Dietary patterns were derived through principal component analysis of food frequency questionnaire data. Immune function was assessed using 14 individual inflammatory markers and an integrated low-grade inflammation score (INFLA-score). Cox proportional hazard models were used to estimate the associations of dietary patterns or immune function with incident T2D. Linear regressions were used to estimate the associations of dietary patterns with immune function. Mediating effects of immune function were quantified., Results: During a median 14.6-year follow-up, 13,932 participants developed T2D. Four dietary patterns were identified: prudent diet (high in whole grains, vegetables, fruits, fish), wheat/dairy/eggs restrictive diet (limiting these foods), meat-based diet (high in red/processed meat, salt), and full-cream dairy diet (preference for full cream milk or dairy products). The prudent diet was negatively (HR Q4 vs Q1 , 0.69 [95% CI, 0.65-0.72]), while the wheat/dairy/eggs restrictive diet (HR Q4 vs Q1 , 1.08 [95% CI, 1.03-1.13]), meat-based diet (HR Q4 vs Q1 , 1.12 [95% CI, 1.06-1.17]), and full-cream dairy diet (HR Q4 vs Q1 , 1.08 [95% CI, 1.03-1.12]) were positively associated with incident T2D (all p for trend ≤0.04). The prudent diet was negatively and the full-cream dairy diet was positively associated with most inflammatory markers. Most inflammatory markers, especially INFLA-score (HR, 1.18 [95% CI, 1.16-1.20]), were positively associated with incident T2D. INFLA-score mediated 13% of the association with incident T2D for the prudent diet and 34% for the full-cream dairy diet., Conclusions: This study identified four distinct dietary patterns and a range of inflammatory markers associated with incident T2D. A notable proportion of the associations between dietary patterns and T2D was mediated by immune function.

Abnormal transcription initiation from alternative first exon has been reported to promote tumorigenesis. However, the prevalence and impact of gene expression regulation mediated by alternative tandem transcription initiation were mostly unknown in cancer. Here, we developed a robust computational method to analyze alternative tandem transcription start site (TSS) usage from standard RNA sequencing data. Applying this method to pan-cancer RNA sequencing datasets, we observed widespread dysregulation of tandem TSS usage in tumors, many of which were independent of changes in overall expression level or alternative first exon usage. We showed that the dynamics of tandem TSS usage was associated with epigenomic modulation. We found that significant 5' untranslated region shortening of gene TIMM13 contributed to increased protein production, and up-regulation of TIMM13 by CRISPR-mediated transcriptional activation promoted proliferation and migration of lung cancer cells. Our findings suggest that dysregulated tandem TSS usage represents an addtional layer of cancer-associated transcriptome alterations.

One of the commonly employed methods in molecular biology is to utilize calcium chloride to treat Escherichia coli for the preparation of competent cells to facilitate foreign gene expression. However, the molecular mechanisms underlying Ca 2+ mediation of competent cell formation and identification of the key genes involved in the process remain unclear. In previous studies, the combined analysis of transcriptomics and proteomics revealed bhsA as one of the crucial genes. The gene ontology functional annotation of bhsA identified it as a member of the YhcN family encoding an outer membrane protein that confers resistance to various stresses. The IPR0108542 domain found within the protein plays a significant role in stress response and biofilm formation in E. coli. Analysis of the STRING database showed that the proteins interacting with bhsA are primarily involved in biofilm formation and stress resistance. Using the RED homologous recombination method, a bhsA deletion strain was constructed to verify its role in E. coli genetic transformation. Although the mutant strain showed no significant differences in morphology or growth trend when compared to the wild-type strain, its transformation efficiency decreased by 1.14- and 1.64-fold with plasmids pUC19 and pET-32a. Furthermore, the 1-N-phenylnaphthylamine assay indicated a 1.71-fold reduction in cell membrane permeability in the mutant strain., (© 2023 Wiley-VCH GmbH.)