Engineering artificial cross-species promoters with different transcriptional strengths.

As a fundamental tool in synthetic biology, promoters are pivotal in regulating gene expression, enabling precise genetic control and spurring innovation across diverse biotechnological applications. However, most advances in engineered genetic systems rely on host-specific regulation of the genetic portion. With the burgeoning diversity of synthetic biology chassis cells, there emerges a pressing necessity to broaden the universal promoter toolkit spectrum, ensuring adaptability across various microbial chassis cells for enhanced applicability and customization in the evolving landscape of synthetic biology. In this study, we analyzed and validated the primary structures of natural endogenous promoters from Escherichia coli, Bacillus subtilis, Corynebacterium glutamicum, Saccharomyces cerevisiae, and Pichia pastoris, and through strategic integration and rational modification of promoter motifs, we developed a series of cross-species promoters (Psh) with transcriptional activity in five strains (prokaryotic and eukaryotic). This series of cross species promoters can significantly expand the synthetic biology promoter toolkit while providing a foundation and inspiration for standardized development of universal components The combinatorial use of key elements from prokaryotic and eukaryotic promoters presented in this study represents a novel strategy that may offer new insights and methods for future advancements in promoter engineering.

Nanoswimmers statistical mechanics: Unlocking whole-blood viscosity sensing for tumor microenvironment.

BACKGROUND AND OBJECTIVE: The ability to sense the biological microenvironment surrounding early-stage tumor tissues is critical for tumorigenesis tracing and tumor detection and treatment. An efficient tumor microenvironment (TME) sensing strategy remains a significant challenge. We propose a novel "seeing is sensing" approach that has the potential to discern the whole-blood viscosity (WBV) information of the TME by using a swarm of nanoswimmers (NS). METHODS: In this study, we employ statistical mechanics methods to derive the relationship between the aggregation of NS in the microscale and their macroscopic concentration distribution. We utilize the finite difference method to develop a discrete numerical model of the NS diffusion in the blood. We further develop a novel model for TME sensing that can dynamically detect the WBV by analyzing the kinematic motion of the NS swarm, which enables real-time detection of WBV by observing the Full Width at Half Maximum (FWHM) of the NS swarm motion. RESULTS: The viscosity value obtained with our sensing method is benchmarked against the gold standard results obtained from the Brookfield viscometer. The measurements obtained from both methods exhibit an excellent correlation, with a coefficient of determination (R2) of 0.9617. Furthermore, the constructed Bland-Altman plot reveals that the majority of observed data points lie within the limits of agreement of the 95% clinical confidence interval (lower limit of agreement = -0.0660, upper limit of agreement = 0.1130), thus validating the feasibility of our sensing strategy. CONCLUSIONS: We present a new sensing strategy that utilizes the diffusion dynamics of the NS swarm within the vascular network to infer variations in WBV. Comparative analysis with gold standard data substantiates the accuracy and applicability of this method in assessing WBV parameters in the vicinity of tumor tissues. Our work demonstrates relevant prospects for visualizing, comprehending, and evaluating the pathological progression of blood-related disorders in real-time.

A giant parathyroid carcinoma cause deformation of thorax: Case report.

We present a rare case of a large parathyroid carcinoma (PC) characterized by severe hyperparathyroidism, hypercalcemia, and osteoporosis. Long-standing calcium loss resulted in thoracic and facial deformities, initially misdiagnosed as oral malignancy.

Fetal hypoxia exposure induced Hif1a activation and autophagy in adult ovary granulosa cells.

Environmental hypoxia adversely impacts the reproduction of humans and animals. Previously, we showed that fetal hypoxia exposure led to granulosa cell (GC) autophagic cell death via the Foxo1/Pi3k/Akt pathway. However, the upstream regulatory mechanisms underlying GC dysfunction remain largely unexplored. Here, we tested the hypothesis that fetal hypoxia exposure altered gene expression programs in adult GCs and impaired ovarian function. We established a fetal hypoxia model in which pregnant mice were maintained in a high-plateau hypoxic environment from gestation day (E) 0--16.5 to study the impact of hypoxia exposure on the ovarian development and subsequent fertility of offspring. Compared with the unexposed control, fetal hypoxia impaired fertility by disordering ovarian function. Specifically, fetal hypoxia caused mitochondrial dysfunction, oxidant stress and autophagy in GCs in the adult ovary. RNA-seq analysis revealed that 437 genes were differentially expressed in the adult GCs of exposed animals. Western blotting results also revealed that fetal exposure induced high levels of hypoxia-inducible factor 1-alpha (Hif1a) expression in adult GCs. We then treated GCs isolated from exposed mice with PX-478, a specific pharmacological inhibitor of Hif-1a, and found that autophagy and apoptosis were effectively alleviated. Finally, by using a human ovarian granulosa-like tumor cell line (KGN) to simulate hypoxia in vitro, we showed that Hif1a regulated autophagic cell death in GCs through the Pi3k/Akt pathway. Together, these findings suggest that fetal hypoxia exposure induced persistent Hif1a expression, which impaired mitochondrial function and led to autophagic cell death in the GCs of the adult ovary.

Improving the production of natamycin in Streptomyces natalensis HW-2 by L-valine feeding.

L-valine (L-Val) was previously confirmed to promote natamycin biosynthesis in S. natalensis HW-2. In this study, natamycin yield was 1.9-fold increase with 0.5 g/L L-Val feeding. The level of free amino acids in the broth was significantly affected. Transcriptome analysis showed that 646 and 189 genes were significantly differential expression at 48 h and 60 h, respectively. 7 differential expression genes in branched-chain amino acids (BCAAs) degradation were up-regulated. To further investigate the role of BCAAs degradation on natamycin biosynthesis, the gene ilvE, which encoded branched-chain amino acid aminotransferase (BCAT), was homologously overexpressed. The optimal mutant, S. natalensis LY08, was obtained, and its natamycin production was increased by 179%. With the optimized L-Val supplementation concentration, natamycin yield was increased to 2.02 g/L by strain LY08. This finding indicated the roles of BCAAs degradation on natamycin biosynthesis, and provided an efficient strategy to improve natamycin production in S. natalensis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01570-8.

Integrated ultrasensitive metabolomics and single-cell transcriptomics identify crucial regulators of sheep oocyte maturation and early embryo development in vitro.

INTRODUCTION: Developmental competence of oocytes matured in vitro is limited due to a lack of complete understanding of metabolism and metabolic gene expression during oocyte maturation and embryo development. Conventional metabolic analysis requires a large number of samples and is not efficiently applicable in oocytes and early embryos, thereby posing challenges in identifying key metabolites and regulating their in vitro culture system. OBJECTIVES: To enhance the developmental competence of sheep oocytes, this study aimed to identify and supplement essential metabolites that were deficient in the culture systems. METHODS: The metabolic characteristics of oocytes and embryos were determined using ultrasensitive metabolomics analysis on trace samples and single-cell RNA-seq. By conducting integrated analyses of metabolites in cells (oocytes and embryos) and their developmental microenvironment (follicular fluid, oviductal fluid, and in vitro culture systems), we identified key missing metabolites in the in vitro culture systems. In order to assess the impact of these key missing metabolites on oocyte development competence, we performed in vitro culture experiments. Furthermore, omics analyses were employed to elucidate the underlying mechanisms. RESULTS: Our findings demonstrated that betaine, carnitine and creatine were the key missing metabolites in vitro culture systems and supplementation of betaine and L-carnitine significantly improved the blastocyst formation rate (67.48% and 48.61%). Through in vitro culture experiments and omics analyses, we have discovered that L-carnitine had the potential to promote fatty acid oxidation, reduce lipid content and lipid peroxidation level, and regulate spindle morphological grade through fatty acid degradation pathway. Additionally, betaine may participate in methylation modification and osmotic pressure regulation, thereby potentially improving oocyte maturation and early embryo development in sheep. CONCLUSION: Together, these analyses identified key metabolites that promote ovine oocyte maturation and early embryo development, while also providing a new viewpoint to improve clinical applications such as oocyte maturation or embryo culture.

Negative effects on the adaptive strategies of the lizards (Eremias argus) under starvation after exposure to Glufosinate-ammonium.

Herbicide exposure poses a higher risk to reptiles due to their frequent contact with soil. Besides, food restriction is also a common environmental pressure that can seriously affect the survival of reptiles. The adaptive strategies of reptiles in the face of emerging herbicide pollution and food shortage challenges are not yet known. Therefore, Eremias Argus (a kind of small reptile) was selected as the model to simulate the real scenario of food shortage in lizards, aiming to explore the comprehensive impact of glufosinate-ammonium (GLA: an emerging herbicide) and food restriction on lizards. The results revealed that lizards often regulate their physiological and biochemical activities through body thermal selection and tend to choose lower body temperature, reduce digestibility, and actively participate in fat energy mobilization to avoid oxidative damage in the state of hunger, finally in order to achieve homeostasis. However, herbicide GLA disrupted the lizards' efforts to resist the stress of food shortage and interfered with the normal thermoregulation and energy mobilization strategies of lizards facing starvation. The results of this study would improve our understanding of the impacts of Lizards under extreme stresses, help supplement reptile toxicology data and provide scientific basis for the risk assessment of herbicide GLA.

Prophylactic application of dexmedetomidine reduces the incidence of Emergence delirium in children: A systematic review and Meta-analysis.

BACKGROUND: Emergence delirium (ED) is a common postoperative cognitive dysfunction in children. ED may cause distress to patients and their families in the early post-anesthesia period and have long-term adverse effects on children. THE PRIMARY PURPOSE: was to verify whether dexmedetomidine can reduce the occurrence of ED in children. RESEARCH TYPE: Systematic review and meta-analysis of RCTs. DATA ACQUISITION: A search was conducted on Web of Science, WHO Trials, Cochrane Library, Clinical Trials.gov, and PubMed for all published studies from inception to 23 Oct.2022. ELIGIBILITY CRITERIA: Randomized clinical trials that met the following criteria: patients aged 1-18 years, study site in the PACU (Post-anesthesia care unit), incidence of ED as the primary outcome, and prophylactic use of dexmedetomidine defined as injected before admission to the PACU. RESULTS: A total of 7 randomized trials were included (6 studies during eye and neck surgery, 1 during hernia surgery), involving 512 patients (257 (50.1%) with dexmedetomidine, and 250 (49.9%) with control. ED was observed in 17.51% of the patients treated with dexmedetomidine and in 43.14% of those receiving control (risk ratio (RR) = 0.40, 95 % confidence interval [CI] [0.30 - 0.55], P < 0.00001). Additionally, the prophylactic application of dexmedetomidine also reduced the occurrence of Post-Operating Nausea and Vomiting (RR = 0.24, 95%CI [0.12 - 0.49], P = 0.0001) and PACU stay time after extubation (mean difference (MD) = -1.57, 95%CI [-3.07 to -0.07], P = 0.04). However, sensitivity analysis of RCTs showed that our effect estimates were not stable (MD = -1.78, 95%CI [-4.18 - 0.62], P = 0.15). CONCLUSION: The prophylactic use of dexmedetomidine was associated with a reduction of ED. However, our findings only apply to eye and neck surgery. TRIAL REGISTRATION: PROSPERO: CRD42022371840.

Study on quality characteristics, shelf-life prediction and frying mass transfer of breaded tilapia nuggets.

Deep-fried breaded tilapia nuggets (DFBTNs) have good market prospects as a tilapia deep-processed product. In this study, we used pre-optimized DFBTNs to simulate the mass change from storage to consumption and investigated the changes in storage shelf-life and frying mass transfer kinetics of DFBTNs. Microbial growth trend and shelf-life prediction models at different storage temperatures were developed using a modified Gompertz equation. The R2 of the fitted equations were all greater than 0.98, and the predicted shelf-life of the products was close to the actual measurement time. The ability of the electronic nose and tongue to differentiate between odor and taste can be used as a secondary indicator to determine whether a product is spoiled or not. During the reheating process of deep-frying, the batter shell moisture decreased (18.69 %→6.89 %), and the oil content increased (2.76 %→27.35 %). The mass transfer coefficient k fitted by Fick's second law for moisture evaporation was 0.0086, and the mass transfer coefficient k fitted by the first-order kinetic equation for oil absorption was 0.1137. This study is informative for storing and consuming DFBTNs, which can provide a basis for the deep processing and high-value utilization of tilapia.

Directional growth and reconstruction of ultrafine uranium oxide nanorods within single-walled carbon nanotubes.

Understanding the atomic structures and dynamic evolution of uranium oxides is crucial for the reliable operation of fission reactors. Among them, U4O9-as an important intermediate in the oxidation of UO2 to UO2+x -plays an important role in the nucleation and conversion of uranium oxides. Herein, we realize the confined assembly of uranyl within SWCNTs in liquid phase and reveal the directional growth and reconstruction of U4O9 nanorods in nanochannels, enabled by in situ scanning transmission electron microscopy (STEM) e-beam stimulation. The nucleation and crystallization of U4O9 nanorods in nanochannels obey the "non-classical nucleation" mechanism and exhibit remarkably higher growth rate compared to those grown outside. The rapid growth process is found to be accompanied by the formation and elimination of U atom vacancies and strain, aiming to achieve the minimum interfacial energy. Eventually, the segments of U4O9 nanorods in SWCNTs merge into single-crystal U4O9 nanorods via structural reconstruction at the interfaces, and 79% of them exhibit anisotropic growth along the specific 〈11̄0〉 direction. These findings pave the way for tailoring the atomic structures and interfaces of uranium oxides during the synthesis process to help improve the mechanical properties and stability of fission reactors.

Design, synthesis and antitumor activity of novel 4-oxobutanamide derivatives.

To find highly effective and low-toxicity antitumor drugs to overcome the challenge of cancer, we designed and synthesized a series of novel 4-oxobutanamide derivatives using the principle of molecular hybridization and tested the antiproliferative ability of the title compounds against human cervical carcinoma cells (HeLa), human breast carcinoma cells (MDA-MB-231) and human kidney carcinoma cells (A498). Among them, N1-(4-methoxybenzyl)-N4-(4-methoxyphenyl)-N1-(3,4,5-trimethoxyphenyl) succinimide DN4 (IC50 = 1.94 µM) showed the best proliferation activity on A498, superior to the positive control paclitaxel (IC50 = 8.81 µM) and colchicine (IC50 = 7.17 µM). Compound DN4 not only inhibited the proliferation, adhesion and invasion of A498, but also inhibited angiogenesis and tumor growth in a dose-dependent manner in the xenograft model of A498 cells. In addition, we also predicted the physicochemical properties and toxicity (ADMET) of these derivatives, and the results suggested that these derivatives may have the absorption, distribution, metabolism, excretion, and toxicity properties of drug candidates. Thus, compound DN4 may be a promising drug candidate for the treatment of cancer.

The Proteomic Landscape of Monocytes in Response to Colorectal Cancer Cells.

Colorectal cancer (CRC) involves a complex interaction between tumor cells and immune cells, notably monocytes, leading to immunosuppression. This study explored these interactions using in vitro coculture systems of THP-1 cells and CRC cell lines, employing quantitative proteomics to analyze protein changes in monocytes. Multiple analytical methods were utilized to delineate the altered proteomic landscape, identify key proteins, and their associated functional pathways for comprehensive data analysis. Differentially expressed proteins (DEPs) were selected and validated by cross-referencing them with publicly available TCGA and GEO data sets to explore their potential clinical significance. Our analysis identified 161 up-regulated and 130 down-regulated DEPs. The enrichment results revealed impairments in adhesion and innate immune functions in monocytes, potentially facilitating cancer progression. The down-regulation of FN1, THSB1, and JUN may contribute to these impairments. Furthermore, the overexpression of ADAMTSL4, PRAM1, GPNMB, and NPC2 on monocytes was associated with unfavorable prognostic outcomes in CRC patients, suggesting potential biomarkers or therapeutic targets. This study illustrated the proteomic landscape of monocytes in response to CRC cells, providing clues for future investigations of the crosstalk between cancer cells and monocytes within the tumor microenvironment.

Synergistic reduction of air pollutants and carbon dioxide emissions in Shanxi Province, China from 2013 to 2020.

Synergistic reduction of air pollutants and carbon dioxide (CO2) emissions is currently a key environmental policy in China, yet provincial-level studies remain scarce. To fill the gap, this study developed a coupled emission inventory from 2013 to 2020 in Shanxi, a coal-dependent province critical to China's energy security. This facilitated the investigation of emission trends, primary sources, synergistic effects, and spatial distribution. The results show that, while air pollutant emissions decreased significantly during the study period, CO2 emissions increased slightly. The main emitters of SO2, NOx, and CO2 were identified as power, heating, industrial boilers, and residential coal combustion. The iron and steel industry contributed significantly to PM2.5 emissions, coke production to VOCs, and vehicles to NOx and VOCs. NH3 emissions were mainly attributed to fertilizer use and livestock. Synergistic reductions were evident in coal-related sources, especially industrial boilers and residential coal combustion, underlining the importance of optimizing the energy structure. Anthropogenic emissions were concentrated in basins with poor dispersion conditions. Taiyuan, Yuncheng, and Linfen emerged as key areas for synergistic reduction efforts. This study provides important insights for environmental policy development in Shanxi and other coal-dependent regions.

Histone modification in psoriasis: Molecular mechanisms and potential therapeutic targets.

Psoriasis is an immune-mediated, inflammatory disease. Genetic and environmental elements are involved in the nosogenesis of this illness. Epigenetic inheritance serves as the connection between genetic and environmental factors. Histone modification, an epigenetic regulatory mechanism, is implicated in the development of numerous diseases. The basic function of histone modification is to regulate cellular functions by modifying gene expression. Modulation of histone modification, such as regulation of enzymes pertinent to histone modification, can be an alternative approach for treating some diseases, including psoriasis. Herein, we reviewed the regulatory mechanisms and biological effects of histone modifications and their roles in the pathogenesis of psoriasis.

Epithelial Piezo1 deletion ameliorates intestinal barrier damage by regulating ferroptosis in ulcerative colitis.

Ferroptosis, a recently discovered form of regulated cell death, has been implicated in the development of ulcerative colitis (UC). While Piezo1's role in inducing ferroptosis in chondrocytes and pulmonary endothelial cells is documented, its regulatory function in ferroptosis and intestinal epithelial cells in UC remains unclear. To address this, colonic tissue samples from patients with UC were examined, and specific intestinal epithelial Piezo1-deficient (Piezo1ΔIEC) mice were created to investigate Piezo1's role in UC pathogenesis. Elevated epithelial Piezo1 levels were observed in patients with UC, correlating with increased ferroptosis and tight junction (TJ) disruption. In dextran sulfate sodium (DSS)-induced colitis, Piezo1ΔIEC mice exhibited significantly reduced intestinal inflammation and improved gut barrier function compared to wild-type (WT) mice. Moreover, Piezo1 deficiency in colitis mice and lipopolysaccharide (LPS)-stimulated Caco-2 cells led to higher TJ protein levels, reduced lipid peroxidation, enhanced mitochondrial function, and altered expression of ferroptosis-associated proteins. Additionally, erastin, a ferroptosis activator, reversed the protective effect of Piezo1 silencing against LPS-induced ferroptosis in Caco-2 cells. Mechanistically, Piezo1 was found to regulate ferroptosis via the AMPK/mTOR signaling pathway. These findings highlight a novel role for Piezo1 deletion in mitigating ferroptosis in intestinal epithelial cells, suggesting Piezo1 as a potential therapeutic target for UC treatment.

High-intensity focused ultrasound ablation in the treatment of fumarate hydratase-deficient uterine leiomyoma.

OBJECTIVE: This study aimed to explore the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation for treating fumarate hydratase (FH)-deficient uterine leiomyomas. METHOD: Ten patients with FH-deficient uterine leiomyomas treated with HIFU ablation at the Third Xiangya Hospital from July 2017 to January 2023 were enrolled in this study. The effectiveness and adverse effects of HIFU were analyzed. RESULTS: The median age of the patients who received HIFU was 32.0 years (range: 28-41 years). Only 2 patients had solitary uterine leiomyomas, whereas the remaining 8 patients had multiple uterine leiomyomas. The median diameter of the largest myoma was 56 mm (range: 41-99 mm). Magnetic resonance imaging showed that the FH-deficient uterine leiomyomas of 8 patients presented as mixed intensity on T2WI, that of one patient was hypointense, and that of another patient was hyperintense on T2WI. All patients successfully underwent HIFU ablation in one session without severe adverse effects. The median nonperfusion volume ratio (NPVR) was 40% (30.0%-78.0%) after HIFU treatment. Four patients had NPVR ≥70%. At 3-month follow-up after HIFU ablation, the clinical symptoms of 5 of the 8 patients with symptoms before treatment were relieved. Six months after treatment, 4 of the 8 patients with symptoms were still in remission. All patients received reintervention by March 2024. The reintervention rates were 20%, 70%, and 90% at 12, 24, and 36 months, respectively, after HIFU ablation. CONCLUSION: HIFU is a safe and feasible treatment for FH-deficient uterine leiomyomas, and most patients show effective results in the short term after treatment. However, the reintervention rates are high, and the long-term effects are limited.

Myxoinflammatory fibroblastic sarcoma of the liver: Case report and literature review.

RATIONALE: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade malignant soft tissue sarcoma that primarily affects the distal extremities in adults, with the highest incidence in patients in their 40s and 50s. It has a high local recurrence rate and a low metastasis rate. Although MIFSs have been documented in other sites, an MIFS in the liver is highly unusual. Herein, we present a case of a patient with hepatic MIFS. PATIENT CONCERNS: The patient was a 58-year-old Chinese man with abdominal pain as the primary symptom. Abdominal computed tomography and magnetic resonance imaging revealed a mass in the right posterior lobe of the liver. The patient underwent surgical excision, and the excised specimen was identified as MIFS. Three years later, the patient returned to our hospital for abdominal pain. Computed tomography and magnetic resonance imaging revealed a mass in liver segments 2/3/4. DIAGNOSIS: Postoperative pathological examination of the tumor revealed the recurrence of MIFS. INTERVENTIONS: The patient underwent surgical resection of the MIFS. OUTCOMES: The patient received multiple pirarubicin-based chemotherapy treatments and an ALK inhibitor (anlotinib) within 6 months after surgery, but the tumor recurred. LESSONS: MIFS can not only occur in the proximal limbs, trunk, head, and neck but can also affect the abdominal organs. Surgical resection remains the primary treatment option for MIFS in the absence of any contraindications. Because the recurrence rate of MIFS is high, meticulous long-term monitoring is required.

Genomics-based identification of a cold adapted clade in Deinococcus.

BACKGROUND: Microbes in the cold polar and alpine environments play a critical role in feedbacks that amplify the effects of climate change. Defining the cold adapted ecotype is one of the prerequisites for understanding the response of polar and alpine microbes to climate change. RESULTS: Here, we analysed 85 high-quality, de-duplicated genomes of Deinococcus, which can survive in a variety of harsh environments. By leveraging genomic and phenotypic traits with reverse ecology, we defined a cold adapted clade from eight Deinococcus strains isolated from Arctic, Antarctic and high alpine environments. Genome-wide optimization in amino acid composition and regulation and signalling enable the cold adapted clade to produce CO2 from organic matter and boost the bioavailability of mineral nitrogen. CONCLUSIONS: Based primarily on in silico genomic analysis, we defined a potential cold adapted clade in Deinococcus and provided an updated view of the genomic traits and metabolic potential of Deinococcus. Our study would facilitate the understanding of microbial processes in the cold polar and alpine environments.

Pulmonary interstitial lesions in pemphigus mouse model: Verifying pemphigus may not be only limited to skin and mucosa.

Interstitial lung disease (ILD) has been identified as a prevalent complication and significant contributor to mortality in individuals with pemphigus. In this study, a murine model of pemphigus was developed through the subcutaneous administration of serum IgG obtained from pemphigus patients, allowing for an investigation into the association between pemphigus and ILD. Pulmonary interstitial lesions were identified in the lungs of a pemphigus mouse model through histopathology, RT-qPCR and Sircol assay analyses. The severity of these lesions was found to be positively associated with the concentration of IgG in the injected serum. Additionally, DIF staining revealed the deposition of serum IgG in the lung tissue of pemphigus mice, indicating that the subcutaneous administration of human IgG directly impacted the lung tissue of the mice, resulting in damage. This study confirms the presence of pulmonary interstitial lesions in the pemphigus mouse model and establishes a link between pemphigus and ILD.