Search for Cosmic-Ray Boosted Sub-MeV Dark-Matter-Electron Scattering in PandaX-4T.

We report the first search for the elastic scatterings between cosmic-ray boosted sub-MeV dark matter (DM) and electrons in the PandaX-4T liquid xenon experiment. Sub-MeV DM particles can be accelerated by scattering with electrons in the cosmic rays and produce detectable electron recoil signals in the detector. Using the commissioning data from PandaX-4T of 0.63 tonne·year exposure, we set new constraints on DM-electron scattering cross sections for DM masses ranging from 10 eV/c^{2} to 3 keV/c^{2}.

Shield-armed probiotic delivery system based on co-deposition of poly-dopamine and poly-l-lysine helps Lactiplantibacillus plantarum relieve hyperuricemia.

Hyperuricemia (HUA) is a disease characterized by an abnormal metabolism of purine. Lactic acid bacteria (LAB) have attracted much attention for their safe and effective treatment of HUA by inhibiting xanthine oxidase (XOD) and regulating gut microbiota. However, the effectiveness of probiotics can be compromised by the harsh environment of the gastrointestinal tract. In preliminary experiments, Lactiplantibacillus plantarum DY1, which is generally regarded as safe (GRAS), can lower uric acid. We have devised a straightforward and efficient technique for encapsulating DY1 using a coating comprising polydopamine (PDA) co-deposited with poly-l-lysine (PLL) to obtain DY1@PDLL. TEM, SEM, FT-IR and DLS tests showed that DY1 was successfully coated. Incubate at SGF or SIF for 3 h, the number of viable bacteria of free probiotics and DY1@PDLL decreased by 0.92 and 0.46 log cfu/mL, 1.66 and 0.66 log cfu/mL, respectively. The fluorescence intensity of the intestines of the DY1@PDLL treated mice was 3.96 times that of free probiotic. Notably, DY1@PDLL can reduce the uric acid levels of HUA mice by 31.63 % and free probiotics by 18.72 % (≈1.69 times). DY1@PDLL could also regulate gut microbiota and serum metabolic profile. These findings unequivocally highlight the remarkable potential of DY1@PDLL as an exceptional oral probiotic delivery system.

Advances and mechanisms of fungal symbionts in improving the salt tolerance of crops.

Soil salinization leads to reduced crop yields and waste of land resources, thereby impacting global food security. To meet the increasing demand for food and simultaneously alleviate pressure on soil resources, the development of sustainable agriculture is imperative. In contrast to physical and chemical methods, bioremediation represents an efficient and environmentally friendly approach. Fungal symbionts have been found to be associated with most plants in natural ecosystems, colonizing and residing within the internal tissues of host plants. Moreover, the potential of fungal symbionts in improving saline-alkaline soil has been widely recognized and confirmed. Numerous reports have documented the effectiveness of arbuscular mycorrhizal fungi in alleviating salt stress in plants. Meanwhile, research on other endophytic fungi for mitigating plant salt stress has emerged in recent years, which contributes to refining mechanisms for enhancing plant salt tolerance. In this review, we summarized various mechanisms by which endophytic fungi enhance plant salt tolerance. We also provided an overview of the challenges and development directions in the field of fungal symbiosis, with the aim of offering a viable strategy for the bioremediation of saline-alkali soils.

Characterization of Ucp1-iCre Knockin Mice Reveals the Recombination Activity in Male Germ Cells.

Ucp1 promoter-driven Cre transgenic mice are useful in the manipulation of gene expression specifically in thermogenic adipose tissues. However, the wildly used Ucp1-Cre line was generated by random insertion into the genome and showed ectopic activity in some tissues beyond adipose tissues. Here we characterized a knockin mouse line Ucp1-iCre generated by targeting IRES-Cre cassette immediately downstream the stop codon of the Ucp1 gene. The Cre insertion had little to no effect on UCP1 protein levels in brown adipose tissue. Ucp1-iCre mice of both genders exhibited normal thermogenesis and cold tolerance. When crossed with Rosa-tdTomato reporter mice, Ucp1-iCre mice showed robust Cre activity in thermogenic adipose tissues. Additionally, limited Cre activity was sparsely present in the hypothalamus (VMH), choroid plexus, kidney, adrenal glands, ovary, and testis in Ucp1-iCre mice, albeit to a much lesser extent and with reduced intensity compared to the conventional Ucp1-Cre line. Single-cell transcriptome analysis revealed UCP1 mRNA expression in male spermatocytes. Moreover, male Ucp1-iCre mice displayed a high frequency of Cre-mediated recombination in the germline, whereas no such effect was observed in female Ucp1-iCre mice. These findings suggest that Ucp1-iCre mice offer promising utility in the context of conditional gene manipulation in thermogenic adipose tissues, while also highlighting the need for caution in mouse mating and genotyping procedures.

Establishment of tumor marker reference intervals for different age and gender groups in the healthy population of South China.

To establish age- and sex-specific reference intervals (RIs) for serum tumor markers (AFP, CEA, CA125, CA199, CA153, HE4, CA724, CYFRA21-1, PSA, and NSE) among a cohort of healthy individuals in South China, a retrospective analysis was conducted on 51,353 samples collected from 2015 to 2020, during health assessments at Guangdong Provincial People's Hospital. The influence of age and gender on serum tumor markers was investigated. New RIs were determined using non-parametric rank-based methods per CLSI EP28-A3C guidelines. Significant differences were detected across age groups for AFP, CEA, CA125, CA199, HE4, CYFRA21-1, PSA, and NSE (p < 0.05). The upper reference limits (URLs) for CA153 and HE4 are significantly lower compared to our current laboratory standards. The URL for CA125 exceeds these limits in individuals under 50 but decreases in those aged 50 and above. For CA199, CEA, and PSA, the URLs are below current standards in individuals younger than 60 but exceed them in those aged 60 and older. Noteworthy elevations were observed in CA724, CYFRA21-1, and NSE levels. Our study establishes age- and sex-specific RIs for ten serum tumor markers among healthy individuals from South China, providing a fundamental resource for the prevention, early detection, and management of tumor-related disorders.

Changes in hemicellulose metabolism in banana peel during fruit development and ripening.

Hemicellulose is key in determining the fate of plant cell wall in almost all growth and developmental stages. Nevertheless, there is limited knowledge regarding its involvement in the development and ripening of banana fruit. This study investigated changes in the temporal-spatial distribution of various hemicellulose components, hemicellulose content, activities of the main hydrolysis enzymes, and transcription level of the main hemicellulose-related gene families in banana peels. Both hemicellulose and xylan contents were positively correlated to the fruit firmness observed in our previous study. On the contrary, the xylanase activity was negatively correlated to xylan content and the fruit firmness. The vascular bundle cells, phloem, and cortex of bananas are abundant in xyloglucan, xylan, and mannan contents. Interestingly, the changes in the signal intensity of the CCRC-M104 antibody recognizing non-XXXG type xyloglucan are positively correlated to hemicellulose content. According to RNA-Seq analysis, xyloglucan and xylan-related genes were highly active in the early stages of growth, and the expression of MaMANs and MaXYNs increased as the fruit ripened. The abundance of plant hormonal and growth-responsive cis-acting elements was detected in the 2 kb upstream region of hemicellulose-related gene families. Interaction between hemicellulose and cell wall-specific proteins and MaKCBP1/2, MaCKG1, and MaHKL1 was found. The findings shed light on cell wall hemicellulose's role in banana fruit development and ripening, which could improve nutrition, flavor, and reduce postharvest fruit losses.

Advanced electrochemical membrane technologies for near-complete resource recovery and zero-discharge of urine: Performance optimization and evaluation.

The depletion of nutrient sources in fertilizers demands a paradigm shift in the treatment of nutrient-rich wastewater, such as urine, to enable efficient resource recovery and high-value conversion. This study presented an integrated bipolar membrane electrodialysis (BMED) and hollow fiber membrane (HFM) system for near-complete resource recovery and zero-discharge from urine treatment. Computational simulations and experimental validations demonstrated that a higher voltage (20 V) significantly enhanced energy utilization, while an optimal flow rate of 0.4 L/min effectively mitigated the negative effects of concentration polarization and electro-osmosis on system performance. Within 40 min, the process separated 90.13% of the salts in urine, with an energy consumption of only 8.45 kWh/kgbase. Utilizing a multi-chamber structure for selective separation, the system achieved recovery efficiencies of 89% for nitrogen, 96% for phosphorus, and 95% for potassium from fresh urine, converting them into high-value products such as 85 mM acid, 69.5 mM base, and liquid fertilizer. According to techno-economic analysis, the cost of treating urine using this system at the lab-scale was $6.29/kg of products (including acid, base, and (NH4)2SO4), which was significantly lower than the $20.44/kg cost for the precipitation method to produce struvite. Excluding fixed costs, a net profit of $18.24/m3 was achieved through the recovery of valuable products from urine using this system. The pilot-scale assessment showed that the net benefit amounts to $19.90/m3 of urine, demonstrating significant economic feasibility. This study presents an effective approach for the near-complete resource recovery and zero-discharge treatment of urine, offering a practical solution for sustainable nutrient recycling and wastewater management.

Overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis: A case report.

RATIONALE: Anti-Myelin oligodendrocyte glycoprotein (MOG) and anti-metabotropic glutamate receptor 5 (mGluR5) double antibody positive encephalitis characterized by optic neuritis is extremely rare. We present a case of overlapping syndrome of MOG-IgG-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis. PATIENT CONCERNS: A 60-year-old Chinses woman presented to the hospital with progressive vision loss and headache for 1 week. The cerebrospinal fluid examination was within the normal range. Visual evoked potentials study disclosed prolonged latency of P100 bilaterally. Fundus examination revealed indistinct boundaries of both optic discs. Her brain magnetic resonance imaging showed patchy hyperintensity in the posterior horn of the left ventricle and the left optic nerve. Her serum was positive for anti-MOG and anti-mGluR5 antibodies. DIAGNOSIS: The patient was diagnosed with overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis mainly based on the clinical symptoms and further test of the antibody in serum. INTERVENTIONS AND OUTCOMES: She was subsequently subjected to empirical treatment with intravenous methylprednisolone. After discharge, she was given a tapering dose of oral prednisone, alongside mycophenolate mofetil. On outpatient follow-up, her symptoms showed no relapse after 1 month, and her condition remained stable. LESSONS: Early recognition of autoimmune encephalitis is crucial. The detection of cerebrospinal fluid and serum of autoimmune encephalitis and demyelinating diseases of the CNS, including MOG-IgG and mGluR5-IgG, should be strengthened in order to make a precise diagnosis and develop a comprehensive treatment plan in a timely manner.

Accuracy of ultrasound-guided iliopsoas tendon injection after total hip arthroplasty: a retrospective observational study.

PURPOSE: To describe and characterize the accuracy and benefit of a technique for performing ultrasound-guided needle placement for iliopsoas peritendon or bursa injections as an alternative method to fluoroscopic guidance. MATERIALS AND METHODS: Patients with a history of total hip arthroplasty who were referred by their orthopedic surgeon for iliopsoas peritendon or bursa corticosteroid injection for iliopsoas impingement syndrome between June 2017 and December 2019 were eligible for inclusion. Of these patients, 19 received a total of 26 ultrasound-guided needle placement followed by confirmatory fluoroscopic guidance prior to injection. Pre-injection and post-injection VAS scores were collected to monitor pain. Additionally, the patients were followed for 6 months via chart review after their injection to assess for complications, need for repeat injections, and progression to surgical intervention. The accuracy of a longitudinal in-plane distal to proximal approach to ultrasound guided needle placement was then evaluated. RESULTS: Ultrasound guided needle placement using a longitudinal in-plane distal to proximal approach demonstrated spread of contrast material in the intended anatomic location with fluoroscopic confirmation in patients who underwent iliopsoas peritendon or bursa injection post total hip arthroplasty. CONCLUSION: Ultrasound guided needle placement using a longitudinal in-plane distal to proximal approach can be an effective alternative technique for diagnostic or therapeutic iliopsoas peritendon injection in patients with total hip arthroplasty.

Combined First-Principles and Experimental Investigation into the Reactivity of Codeposited Chromium-Carbon under Pressure.

High-pressure synthesis in the diamond anvil cell suffers from the lack of a general approach for the control of precursor stoichiometry and homogeneity. Here, we present results from a new method we have developed that uses magnetron cosputtering to prepare stoichiometrically precise and atomically mixed amorphous films of Cr:C. Laser-heated diamond anvil cell experiments carried out on a flake of this sample at pressures between 13.5 and 24.3 GPa lead to the observation of Cr3C (Pnma) over the entire pressure range-in good agreement with our in-house theoretical predictions-but also reveal two other metastable phases that were not expected: a novel monoclinic chromium carbide phase and the NaCl-type CrC (Fm3̅m) phase. The unexpected stability of CrC is investigated by using first-principles methods, revealing a large stabilizing effect tied to substoichiometry at the carbon site. These results offer an important case study into the current limitations of crystal structure prediction methods with regard to phase complexity and bolster the growing need for advanced theoretical approaches that can more completely survey experimentally unexplored phase space.

Chromosome-level genome assembly and annotation of xerophyte secretohalophyte Reaumuria soongarica.

Reaumuria soongarica is a xerophytic shrub belonging to the Tamaricaceae family. The species is widely distributed in the deserts of Central Asia and is characterized by its remarkable adaptability to saline and barren desert environments. Using PacBio long-read sequencing and Hi-C technologies, we assembled a chromosome-level genome of R. soongarica. The genome assembly has a size of 1.28 Gb with a scaffold N50 of 116.15 Mb, and approximately 1.25 Gb sequences were anchored in 11 pseudo-chromosomes. A completeness assessment of the assembled genome revealed a BUSCO score of 97.5% and an LTR Assembly Index of 12.37. R. soongarica genome had approximately 60.07% repeat sequences. In total, 21,791 protein-coding genes were predicted, of which 95.64% were functionally annotated. This high-quality genome will serve as a foundation for studying the genomic evolution and adaptive mechanisms to arid-saline environments in R. soongarica, facilitating the exploration and utilization of its unique genetic resources.

Alternative molecular mechanisms for force transmission at adherens junctions via ß-catenin-vinculin interaction.

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, ß-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that ß-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and ß-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving ß-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin.

Short-term outcome of intracorporeal ileocolonic anastomosis in patients with visceral obesity.

The primary objective of this study was to compare short-term outcomes between Intracorporeal ileocolic anastomosis (IIA) and extracorporeal ileocolic anastomosis (EIA) after laparoscopic right hemicolectomy in patients with visceral obesity. The secondary objective was to identify risk factors associated with prolonged postoperative ileus (PPOI) after laparoscopic right hemicolectomy. This single-center retrospective study analyzed visceral obesity patients who underwent laparoscopic right hemicolectomy for primary bowel cancer between January 2020 and June 2023. Patients were categorized into IIA and EIA groups based on the type of anastomosis, and a 1:1 propensity score-matched analysis was performed. A total of 129 patients were initially included in this study, with 45 patients in each group following propensity score matching. The IIA group had significantly longer anastomosis times (p < 0.001), shorter incision length (p < 0.001), and shorter length of stay (p = 0.003) than the EIA group. Meanwhile, the IIA group showed a shorter time to first flatus (p = 0.044) and quicker tolerance of a solid diet (p = 0.030). On multivariate analysis, postoperative use of opioid analgesics is an independent risk factor for PPOI (OR: 3.590 95% CI 1.033-12.477, p = 0.044), while IIA is an independent protective factor (OR: 0.195 95% CI 0.045-0.843, p = 0.029). IIA remains a safe and feasible option for visceral obesity patients. It is also associated with a quicker recovery of bowel function and shorter length of stay when compared to EIA. Additionally, IIA is an independent protective factor for PPOI.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii.

OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.

Importance of computed tomography perfusion on assessing collateral circulation and prognosis of patients with acute anterior circulation large vessel occlusion after endovascular therapy.

This study probed the importance of computed tomography perfusion (CTP) on assessing collateral circulation and prognosis in patients with acute anterior circulation large vessel occlusion (AAC-LVO) after endovascular therapy (EVT). Retrospective analysis was performed on the case data of 124 AAC-LVO patients who achieved EVT in the First People's Hospital of Lianyungang. All patients received computed tomography (CT) examination. Based on the multi-phase computed tomography angiography (mCTA) score, patients were separated into poor collateral circulation group and good collateral circulation group. Based on modified Rankin scale (mRS) score, patients were separated into good prognosis group and poor prognosis group. The receiver operating characteristic (ROC) curve was used to measure the efficacy of CTP parameters in predicting good collateral circulation or good prognosis. Correlation between CTP parameters with mCTA collateral and 90-day mRS circulation score was analyzed using the Spearman correlation analysis. The age and admission national Institutes of Health stroke scale (NIHSS) scores of the good collateral circulation group were lower than the poor collateral circulation group, and low perfusion area volume with Tmax > 6 s (VTmax>6 s), infarct core area volume (VCBF<30 %)and hypoperfusion intensity ratio (HIR) were also lower. The mCTA collateral cycle score was negatively related to VTmax>6s, VCBF<30 % and HIR. The area under the curve (AUC) values of VTmax>6s and VCBF<30 % and HIR for predicting good collateral circulation were 0.763, 0.884 and 0.842, respectively, which suggested that perfusion parameters VTmax>6s, VCBF<30 % and HIR could effectively indicate the status of patients' collateral circulation. Relative to the poor prognosis group, patients in the good prognosis group possessed lower admission NIHSS score, younger age, smaller final infarct volume, lower HIR, VCBF<30 %, VTmax>6 s, Alberta Stroke Program Early CT(ASPECT) score, and higher mCTA score. Spearman correlation analysis unveiled that ASPECT score, mCTA score and 90-day mRS were negatively correlated. The final infarct volume, perfusion parameters HIR and VCBF<30 % were positively correlated with 90-day mRS. ROC analysis showed that all variates had good prognostic value for acute anterior circulation great vessel occlusion patients, while VCBF<30 % and HIR had high diagnostic value for prognosis. To sum up, CTP can provide a comprehensive imaging assessment of the collateral circulation of patients with AAC-LVO and has a higher predictive value for the prognosis assessment of patients with EVT in terms of VCBF<30 %, HIR score and mCTA collateral circulation score.

Population structure in Mixornis tit-babblers across Sunda Shelf matches interfluvia of paleo-rivers.

Rivers constitute an important biogeographic divide in vast areas of tropical rainforest, such as the Amazon and Congo Basins. Southeast Asia's rainforests are currently fragmented across islands divided by sea, which has long obscured their extensive history of terrestrial connectivity as part of a vast (but now submerged) subcontinent - Sundaland - during most of the Quaternary. The role of paleo-rivers in determining population structure in Sundaic rainforests at a time when these forests were connected remains little understood. We examined the coloration of museum skins and used the genomic DNA of museum samples and freshly-collected blood tissue of a pair of Sundaic songbird species, the pin-striped and bold-striped tit-babblers (Mixornis gularis and M. bornensis, respectively), to assess the genetic affinity of populations on small Sundaic islands that have largely been ignored by modern research. Our genomic and morphological results place the populations from the Anambas and Natuna Islands firmly within M. gularis from the Malay Peninsula in western Sundaland, even though some of these islands are geographically much closer to Borneo, where M. bornensis resides. Our results reveal genetic structure consistent with the course of Sundaic paleo-rivers and the location of the interfluvia they formed, and add to a small but growing body of evidence that rivers would have been of equal biogeographic importance in Sundaland's former connected forest landscape as they are in Amazonia and the Congo Basin today.

[The Regulatory Effect of RNA m6 A Methylation Modification on KDM4B Gene Expression in t (8;21) AML Cells by MeRIP-qPCR].

OBJECTIVE: To confirm the direct regulatory effect of WTAP-mediated RNA m6A modification on the KDM4B gene in t (8;21) acute myeloid leukemia (AML) cells through MeRIP combined with reverse transcription real-time quantitative PCR (RT-qPCR) technology. METHODS: The lentivirus-mediated shRNA target WTAP or KDM4B gene was used to transfect the t (8;21) AML cell lines: Kasumi-1 and SKNO-1, and cells transfected with randomly shuffled shRNA as the control. Using the Ultrapure RNA Extraction Kit (DNase I) to extract RNA. The Magna MeRIPTM m6A Kit was used to enrich methylated modified fragments, and detect the m6A methylated RNA regions by RT-qPCR, and the protein and mRNA expression levels of WTAP and KDM4B in cells were detected by Western blot and reverse transcription real-time quantitative PCR (RT-qPCR). Colony formation assays were used to detect the colony ability of cells in vitro. RESULTS: Silencing the expression of WTAP in Kasumi-1 cells, the enrichment of m6A methylation modification was significantly decreased in the 3'UTR of KDM4B mRNA(P < 0.01), and the protein(P < 0.001) and mRNA (Kasumi-1:P < 0.001; SKNO-1: P < 0.01) expression levels of KDM4B were also significantly inhibited in Kasumi-1 and SKNO-1 cells upon WTAP knockdown (all P < 0.01), accompanied by a significant decrease in the colony-forming ability of both cell lines (both P < 0.01). CONCLUSION: In t(8;21) AML cell lines, WTAP could regulate the expression of KDM4B by regulating the m6A modification of the 3'UTR of KDM4B mRNA, and silencing the expression of KDM4B could inhibit the cellular proliferation in vitro.

The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-ß1-induced fibrotic responses in renal fibroblasts and epithelial cells independently of Smad3 phosphorylation. Cellular uptake of Cf48 and its profibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3'UTR of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis that operates as an RNA-binding peptide to promote the production of extracellular matrix.

Taurocholic acid ameliorates hypertension through the activation of TGR5 in the hypothalamic paraventricular nucleus.

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.