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Exposure to the toxic metal cadmium (Cd) is a well-established risk factor for hepatic inflammation, but it remains unclear how metabolic components, such as different fatty acids (FAs), interact with Cd to influence this process. Understanding these interactions is essential for identifying potential preventative and therapeutic targets for this disorder. To address this question, we conducted in vitro and in vivo studies to investigate the combinatorial effect of Cd and saturated FAs on hepatic inflammation. Specifically, we assessed the cytotoxicity of Cd on macrophages and their polarization and inflammatory activation upon co-exposure to Cd and saturated FAs. Our results showed that while saturated FAs had minimal impact on the cytotoxicity of Cd on macrophages, they significantly collaborated with Cd in predisposing macrophages towards a pro-inflammatory M1 polarization, thereby promoting inflammatory activation. This joint effect of Cd and saturated FAs resulted in persistent inflammation and hepatic steatohepatitis in vivo. In summary, our study identified macrophage polarization as a novel mechanism by which co-exposure to Cd and saturated lipids induces hepatic inflammation. Our findings suggest that intervening in macrophage polarization may be a potential approach for mitigating the adverse hepatic effects of Cd.

Abstract Control of the directional bounce of droplets impacting solid surfaces is crucial for many agricultural and industrial applications. However, for the universal impact process of raindrops on plant leaves, little is known about how the highly coupled and complicated fluid–structure interaction controls the postimpact motion of droplets and endows the leaves with tenacious vitality. Here, we report a leaf‐like superhydrophobic cantilever to flexibly bounce droplets with well‐defined directionality and controllability. Through theoretical modeling and three‐dimensional fluid–solid coupling simulations, we find that the flexible cantilever significantly relieves the impacting forces of raindrops to reduce droplet fragmentation and enhance water repellency. The results further uncover the scaling relations of the droplet bouncing direction with respect to Weber number and cantilever stiffness. By this technique, the seemed disorganized postimpact movements of droplets are programmable and predictable, achieving the goal of where to point and where to hit automatically. This work advances the understanding of natural droplet impact phenomena, opens a new avenue for delicately controlling liquid motion in space with soft materials, and inspires a plethora of applications like soft robots to transport materials and energies, monitor plant growth as well as predict pathogen transmission in plants.

Abstract Introduction Renal impairment is a common complication in coronavirus disease 2019 (COVID‐19), although its prognostic significance remains unknown. Objectives This study determines the impact of early renal impairment on the clinical outcome of COVID‐19. Methods Patients diagnosed with COVID‐19 and hospitalized in Xiaogan Central Hospital from 20 January to 29 February 2020 were retrospectively included and grouped into two cohorts (cohort with normal renal function and cohort with renal insufficiency) based on the renal function detected on admission. Records of clinical manifestation, laboratory findings and clinical outcome were collected and compared between these two cohorts. Results A total 543 COVID‐19 patients were included. Among these patients, 70 patients developed early renal impairment, with an incidence of 12.89%. A significantly higher white blood cell (WBC) count, C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatine (Cr), blood urine nitrogen (BUN) and brain natriuretic peptide (BNP) and a significantly lower blood platelet (PLT), lymphocyte count, prealbumin and albumin (ALB) were detected in the cohort with renal insufficiency (P 65 years old, complication of diabetes, renal impairment on admission (Cr > 73 μmol/L and eGFR 9.5 × 109/L and ALB

Mammalian epididymal epithelial cells are crucial for sperm maturation. Historically, vacuole-like ultrastructures in epididymal epithelial cells were observed via transmission electron microscopy but were undefined. Here, we utilize volume electron microscopy (vEM) to generate 3D reconstructions of epididymal epithelial cells and identify these vacuoles as intercellular organelle reservoirs (IORs) in the lateral intercellular space (LIS), which contains protein aggregates, autophagosomes, lysosome-related organelles and mitochondrial residues. Immunolabelling of organelle markers such as P62, LC3, LAMP1 and TOMM20 confirm these findings. The IOR size or number varies across four epididymal regions and decreases with age. Rab27a mutant mice exhibit reduced IORs in the caput epididymis and a subfertility phenotype, suggesting the involvement of Rab27a in the formation of IORs. Furthermore, we observe the presence of IORs between intestinal epithelial cells besides epididymis. Amino acid transporters at IOR edges suggest dynamic protein recycling. Our findings reveal that the IOR is an important structure critical for organelle turnover and recycling outside epithelial cells with limited self-degradation capabilities. Undefined vacuole-like ultrastructures between epididymal cells have been observed. Here, the authors reveal that these structures contain organelle residues and protein aggregates that suggest a reservoir for protein recycling. [ABSTRACT FROM AUTHOR]

Phlomoides rotata, a traditional medicinal plant, is commonly found on the Tibetan Plateau at altitudes of 3100–5200 m. Its primary active medicinal compounds, flavonoids and phenylethanol glycosides (PhGs), exhibit various pharmacological effects, including hemostatic, anti-inflammatory, antitumor, immunomodulatory, and antioxidant activities. This study analyzed flavonoid and PhG metabolites in the roots of P. rotata collected from Henan County (HN), Guoluo County (GL), Yushu County (YS), and Chengduo County (CD) in Qinghai Province. A total of differentially abundant metabolites (DAMs) including 38 flavonoids and 21 PhGs were identified. Six genes (UFGT1, CHS1, COMT2, C4H3, C4H8, and C4H5) and four enzymes (4CL, C4H, PPO, and ALDH) were found to play key roles in regulating flavonoid and PhG biosynthesis in P. rotata roots. With increasing altitude, the relative content of 15 metabolites, the expression of seven genes, and the activity of four enzymes associated with flavonoid and PhG metabolism increased. These findings enhance our understanding of the regulatory mechanisms of flavonoid and PhG metabolism in P. rotata and provide insights into the potential pharmaceutical applications of its bioactive compounds. [ABSTRACT FROM AUTHOR]

To analyze the role of disulfidptosis in ulcerative colitis (UC), large-scale datasets combined with weighted gene co-expression network analysis (WGCNA) and machine learning were utilized and analyzed. When the hub genes that are associated with UC disease phenotypes and have predictive performance were identified, immune cell infiltration and the CeRNA network were constructed, the role of hub genes in UC pathogenies and biotherapy were investigated, and molecular docking studies and mice-verified tests were carried out to further explore the potential core genes and potential target. Finally, we found 21 DRGs involved in UC pathogenesis, including SLC3A2, FLNA, CAPZB, TLN1, RPN1, etc. Moreover, SLC3A2, TLN1, and RPN1 show a notable correlation with UC inflammatory state, and the expression of DRGs is closely related to the response to UC biotherapy. Our study suggests that disulfidptosis plays a crucial role in the pathogenesis and disease progression of UC. Higher expression of DRGs is commonly observed in moderate to severe UC patients, which may also affect their response to biologic therapies. Among the identified genes, SLC3A2 stands out, providing new insights into the underlying mechanisms of UC and potentially serving as a novel therapeutic target for the treatment of UC. [ABSTRACT FROM AUTHOR]

Human brain experiences vibration of certain magnitude and frequency during various physical activities such as vehicle transportation and machine operation, which may cause traumatic brain injury or other brain diseases. However, the mechanisms of brain pathogenesis due to vibration are not fully elucidated due to the lack of techniques to study brain functions while applying vibration to the brain at a specific magnitude and frequency. Here, this study reported a custom-built head-worn electromagnetic actuator that applied vibration to the brain in vivo at an accurate frequency inside a magnetic resonance imaging scanner while cerebral blood flow (CBF) was acquired. Using this technique, CBF values from 45 healthy volunteers were quantitatively measured immediately following vibration at 20, 30, 40 Hz, respectively. Results showed increasingly reduced CBF with increasing frequency at multiple regions of the brain, while the size of the regions expanded. Importantly, the vibration-induced CBF reduction regions largely fell inside the brain's default mode network (DMN), with about 58 or 46% overlap at 30 or 40 Hz, respectively. These findings demonstrate that vibration as a mechanical stimulus can change strain conditions, which may induce CBF reduction in the brain with regional differences in a frequency-dependent manner. Furthermore, the overlap between vibration-induced CBF reduction regions and DMN suggested a potential relationship between external mechanical stimuli and cognitive functions.

The problem of population aging in China is becoming increasingly serious. Increasing outdoor space can increase the frequency of outdoor activities for the elderly and effectively improve their quality of life. In this study, we examined the thermal comfort of outdoor activity spaces for older adults in summer using a subjective questionnaire in Guangzhou City, calculated and analyzed the perception and comfort range of microclimatic factors for older adults in hot and humid areas, and explored gender differences. The specific results were as follows: (1) The neutral physiological equivalent temperature (PET) for the overall respondents was 30.4 °C, compared to an acceptable PET of 33.8 °C. The neutral wind speed and acceptable wind speed for the overall respondents were both 0.4 m/s. The neutral relative humidity for the overall respondents was 56.49%, whereas the acceptable relative humidity was 64.94%. (2) Gender differences were observed among older respondents regarding PET and relative humidity, while no significant gender differences were found among older respondents regarding wind speed. (3) Summer thermal sensation voting for older adults in hot and humid areas were mainly centered on “hot” (30.2%), and “not too hot nor cold” (38.7%). The wind sensation voting was centered on “not high or low” (44.6%). Humidity sensation voting was mainly concentrated on “not wet nor dry” (69.4%). This study provides guidance to urban planners and architects to help them create urban environments that are more comfortable and responsive to the needs of the aging population.

Alternative mRNA processing is a critical mechanism for proteome expansion and gene regulation in higher eukaryotes. The SR family proteins play important roles in splicing regulation. Intriguingly, mammalian genomes encode many poorly characterized SR-like proteins, including subunits of the mRNA 3'-processing factor CFIm, CFIm68 and CFIm59. Here we demonstrate that CFIm functions as an enhancer-dependent activator of mRNA 3' processing. CFIm regulates global alternative polyadenylation (APA) by specifically binding and activating enhancer-containing poly(A) sites (PASs). Importantly, the CFIm activator functions are mediated by the arginine-serine repeat (RS) domains of CFIm68/59, which bind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is inhibited by CFIm68/59 hyper-phosphorylation. The remarkable functional similarities between CFIm and SR proteins suggest that interactions between RS-like domains in regulatory and core factors may provide a common activation mechanism for mRNA 3' processing, splicing, and potentially other steps in RNA metabolism.

Telomere elongation through telomerase enables chromosome survival during cellular proliferation. The conserved multifunctional shelterin complex associates with telomeres to coordinate multiple telomere activities, including telomere elongation by telomerase. Similar to the human shelterin, fission yeast shelterin is composed of telomeric sequence-specific double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1, and Tpz1. Here, we report the crystal structure of the fission yeast Tpz1475-508-Poz1-Rap1467-496 complex that provides the structural basis for shelterin bridge assembly. Biochemical analyses reveal that shelterin bridge assembly is a hierarchical process in which Tpz1 binding to Poz1 elicits structural changes in Poz1, allosterically promoting Rap1 binding to Poz1. Perturbation of the cooperative Tpz1-Poz1-Rap1 assembly through mutation of the "conformational trigger" in Poz1 leads to unregulated telomere lengthening. Furthermore, we find that the human shelterin counterparts TPP1-TIN2-TRF2 also assemble hierarchically, indicating cooperativity as a conserved driving force for shelterin assembly.