Unconventional superconductivity in chiral molecule-TaS2 hybrid superlattices.

Chiral superconductors, a unique class of unconventional superconductors in which the complex superconducting order parameter winds clockwise or anticlockwise in the momentum space1, represent a topologically non-trivial system with intrinsic time-reversal symmetry breaking (TRSB) and direct implications for topological quantum computing2,3. Intrinsic chiral superconductors are extremely rare, with only a few arguable examples, including UTe2, UPt3 and Sr2RuO4 (refs. 4-7). It has been suggested that chiral superconductivity may exist in non-centrosymmetric superconductors8,9, although such non-centrosymmetry is uncommon in typical solid-state superconductors. Alternatively, chiral molecules with neither mirror nor inversion symmetry have been widely investigated. We suggest that an incorporation of chiral molecules into conventional superconductor lattices could introduce non-centrosymmetry and help realize chiral superconductivity10. Here we explore unconventional superconductivity in chiral molecule intercalated TaS2 hybrid superlattices. Our studies reveal an exceptionally large in-plane upper critical field Bc2,|| well beyond the Pauli paramagnetic limit, a robust π-phase shift in Little-Parks measurements and a field-free superconducting diode effect (SDE). These experimental signatures of unconventional superconductivity suggest that the intriguing interplay between crystalline atomic layers and the self-assembled chiral molecular layers may lead to exotic topological materials. Our study highlights that the hybrid superlattices could lay a versatile path to artificial quantum materials by combining a vast library of layered crystals of rich physical properties with the nearly infinite variations of molecules of designable structural motifs and functional groups11.

Chiral molecular intercalation superlattices.

The discovery of chiral-induced spin selectivity (CISS) opens up the possibility to manipulate spin orientation without external magnetic fields and enables new spintronic device designs1-4. Although many approaches have been explored for introducing CISS into solid-state materials and devices, the resulting systems so far are often plagued by high inhomogeneity, low spin selectivity or limited stability, and have difficulties in forming robust spintronic devices5-8. Here we report a new class of chiral molecular intercalation superlattices (CMIS) as a robust solid-state chiral material platform for exploring CISS. The CMIS were prepared by intercalating layered two-dimensional atomic crystals (2DACs) (such as TaS2 and TiS2) with selected chiral molecules (such as R-α-methylbenzylamine and S-α-methylbenzylamine). The X-ray diffraction and transmission electron microscopy studies demonstrate highly ordered superlattice structures with alternating crystalline atomic layers and self-assembled chiral molecular layers. Circular dichroism studies show clear chirality-dependent signals between right-handed (R-) and left-handed (S-) CMIS. Furthermore, by using the resulting CMIS as the spin-filtering layer, we create spin-selective tunnelling junctions with a distinct chirality-dependent tunnelling current, achieving a tunnelling magnetoresistance ratio of more than 300 per cent and a spin polarization ratio of more than 60 per cent. With a large family of 2DACs of widely tunable electronic properties and a vast selection of chiral molecules of designable structural motifs, the CMIS define a rich family of artificial chiral materials for investigating the CISS effect and capturing its potential for new spintronic devices.

WD repeat domain 82 (Wdr82) facilitates mouse iPSCs generation by interfering mitochondrial oxidative phosphorylation and glycolysis.

BACKGROUND: Abundantly expressed factors in the oocyte cytoplasm can remarkably reprogram terminally differentiated germ cells or somatic cells into totipotent state within a short time. However, the mechanism of the different factors underlying the reprogramming process remains uncertain. METHODS: On the basis of Yamanaka factors OSKM induction method, MEF cells were induced and reprogrammed into iPSCs under conditions of the oocyte-derived factor Wdr82 overexpression and/or knockdown, so as to assess the reprogramming efficiency. Meanwhile, the cellular metabolism was monitored and evaluated during the reprogramming process. The plurpotency of the generated iPSCs was confirmed via pluripotent gene expression detection, embryoid body differentiation and chimeric mouse experiment. RESULTS: Here, we show that the oocyte-derived factor Wdr82 promotes the efficiency of MEF reprogramming into iPSCs to a greater degree than the Yamanaka factors OSKM. The Wdr82-expressing iPSC line showed pluripotency to differentiate and transmit genetic material to chimeric offsprings. In contrast, the knocking down of Wdr82 can significantly reduce the efficiency of somatic cell reprogramming. We further demonstrate that the significant suppression of oxidative phosphorylation in mitochondria underlies the molecular mechanism by which Wdr82 promotes the efficiency of somatic cell reprogramming. Our study suggests a link between mitochondrial energy metabolism remodeling and cell fate transition or stem cell function maintenance, which might shed light on the embryonic development and stem cell biology.

Fabrication of a high-quality, small blaze angle grating for visible short-wave infrared hyperspectral cameras.

This study outlines the development of a low line density, small blaze angle grating, optimized for a visible to short-wave infrared hyperspectral camera. An analysis of grating specifications was conducted to meet the precise requirements of this application, particularly focusing on the stringent tolerance limits for the blaze angle. A specialized ruling tool adjustment device was designed to adhere to these exacting blaze angle tolerances. The grating groove shape was examined using atomic force microscopy (AFM), and the theoretical diffraction efficiency of the grating was calculated based on these observations. Additionally, laser-based methods were employed to measure the actual diffraction efficiency of the grating, while interferometry was used to assess the grating's diffraction wavefront. The test results demonstrate our capability to fabricate high-quality gratings with a low line density and small blaze angles that are suitable for advanced hyperspectral imaging applications.

Investigating a Method for a Horizontal Comprehensive Eco-Compensation Standard of Interregional Ecological Regulating Services.

Horizontal eco-compensation lacks effective solutions for implementing comprehensive multifactor compensation and determining the compensation standard. To meet those needs, a method named entropy flat surface was proposed and put into practice. However, some scientific problems were found. More specifically, the measurement method of the ecological value was controversial, and the value diffusion model did not reflect the change in the value gradient caused by spatial distance, while the value diffusion had an unclear scope. Therefore, this work optimized and studied the entropy curved-surface method in the case of E'zhou City. The main goal was to build a value-surface model of ecological regulating services based on maximum entropy production. As far as a tangible normal distribution surface is concerned, the model was more consistent with the ecosystem's energy flow characteristics. The external output of value could be precisely expressed by the dynamic and stable expansion state of the surface model. Therefore, the eco-compensation relations and results were clear. Theoretically, the E'Cheng and Huarong Districts should pay a total of 114 million CNY to the Liangzi Lake District. Our work provided a new perspective, in terms of finding a rule of the ecological regulating service values of the macro morphological structure, simulating the transmission and diffusion of multiple values in interregional areas, solving the calculation problem of the horizontal ecological comprehensive compensation standard, and clarifying the relations of compensation.

Hongqu Rice Wines Ameliorate High-Fat/High-Fructose Diet-Induced Metabolic Syndrome in Rats.

AIM: This study evaluated the possible protective impact of different vintages of Hongqu rice wines on metabolic syndrome (MetS) in rats induced by high-fat/high-fructose diet (HFFD). METHODS: Rats were randomly divided into six groups and treated with (a) basal diet (13.9 kJ/g); (b) HFFD (20.0% w/w lard and 18.0% fructose, 18.9 kJ/g) and (c-f) HFFD with 3-, 5-, 8- and 15-year-aged Hongqu rice wines (9.96 ml/kg body weight), respectively, at an oral route for 20 weeks. RESULTS: Hongqu rice wines could alleviate HFFD-induced augment of body weight gain and fat accumulation, and the release of pro-inflammatory cytokines. Glycolipid metabolic abnormalities caused by HFFD were ameliorated after Hongqu rice wines consumption by lowering levels of fasting insulin, GSP, HOMA-IR, AUC of OGTT and ITT, and lipid deposition (reduced contents of TG, TC, FFA and LDL-C, and elevated HDL-C level) in the serum and liver, probably via regulating expressions of genes involving in IRS1/PI3K/AKT pathway, LDL-C uptake, fatty acid ß-oxidation, and lipolysis, export and synthesis of TG. In addition, concentrations of MDA and blood pressure markers (ANG-II and ET-1) declined, and activities of antioxidant enzymes (SOD and CAT) were improved in conditions of Hongqu rice wines compared to those in the HFFD group. Eight-year-aged Hongqu rice wine produced a more effective effect on alleviating HFFD-caused MetS among different vintages of Hongqu rice wines. CONCLUSION: To sum up, Hongqu rice wines exhibited ameliorative effects on HFFD-induced MetS in rats based on antiobesity, antihyperlipidemic, antihyperglycemic, antioxidant, anti-inflammatory and potential antihypertensive properties.

Use of the systemic inflammation response index (SIRI) as a novel prognostic marker for patients on peritoneal dialysis.

BACKGROUND: The systemic inflammatory response index (SIRI), a novel inflammation maker, has proven to be associated with prognostic outcomes in various diseases. However, few studies have been conducted assessing how SIRI may influence outcomes of patients on peritoneal dialysis (PD). Herein, we assessed the predictive value of SIRI on mortality all-cause mortality, including cardiovascular disease (CVD) in PD patients. METHODS: A total of 646 PD patients were enrolled in this study. PD patients received regular PD treatments at the Zhujiang Hospital from 1 January 2011 to 31 December 2018. SIRI values could be computed as follows: neutrophil count × monocyte count/lymphocyte count. Patients were divided into two groups according to the median level of SIRI. Cox regression analysis and Kaplan-Meier methods were applied to analyze the relationship between SIRI and mortality outcomes in PD patients. RESULTS: During the median 31-month follow-up period, 97 (15.0%) PD patients died from all-causes, and 47 (49.0%) died of CVD. Kaplan-Meier analyses revealed that a high SIRI corresponded to the high mortality of all-cause deaths, including CVD (both p < 0.001) in patients on PD. After adjusting for potential confounders, the higher SIRI level was significantly associated with an increased all-cause mortality (HR: 2.007, 95% CI: 1.304-3.088, p = 0.002) and cardiovascular mortality (HR: 2.847, 95% CI: 1.445-5.608, p = 0.002). CONCLUSIONS: SIRI was a promising predictor of mortality in PD patients, with a higher SIRI corresponding to increased risk of mortality.

High-quality and large-area echelle grating ruled on 500-mm ruling engine for the fiber array solar optical telescope (FASOT).

A 300 mm×500 mm large-area echelle grating with groove density of 79 grooves/mm is fabricated for the spectrometer of the fiber array solar optical telescope (FASOT). This paper focusses on measurement methods of the grating performance. We present a method to evaluate the grating's stray light intensity, which is measured to a level of 10-4. The directly measured grating efficiency is approximately 90% of the designed value, and an indirect measurement method based on the grating groove profile is proposed. Based on the Rayleigh criterion and the grating diffraction wavefront, a physical optics method and a geometric grating method are proposed and are used to calculate the actual grating resolving power; the calculated results exceed 95% of the grating's theoretical resolving power. These results show that the CIOMP-6 ruling engine has sufficient precision to fabricate high-quality, large-area echelle gratings.

Depletion of multidrug-resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion.

Ebselen, an organo-selenium compound with well-characterized toxicology and pharmacology, recently exhibited potent antibacterial activity against glutathione (GSH)-negative bacteria by disrupting redox homeostasis. In this paper, we show that ebselen and silver ion in combination exert strong bactericidal activity against multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) BC1, a model MDR GSH-positive bacterium. The mechanisms were found to involve consumption of total intracellular GSH and inhibition of thioredoxin reductase activity, which was highly related to reactive oxygen species up-regulation. Furthermore, the therapeutic efficacy of ebselen and silver ion against UPEC-induced cystitis was assessed in a mouse model. Treatment with ebselen and silver ion significantly reduced bacterial loads, down-regulated the expression levels of tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on-site and decreased white/red blood cell counts in mild cystitis model mice, which demonstrated the anti-inflammatory property of these agents. In addition, ebselen and silver ion also exhibited significantly high protective ability (100%) against acute cystitis infections. These results together may lay the foundation for further analysis and development of ebselen and silver ion as antibacterial agents for treatment of MDR UPEC infections.

Fibrinogen/Albumin ratio: A more powerful prognostic index for patients with end-stage renal disease.

BACKGROUND: Microinflammation is linked to an increased risk of death due to cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). Although the fibrinogen/albumin ratio (FAR), a novel inflammatory marker, has been shown to predict mortality in various diseases, limited evidence is available for its role in ESRD. The purpose of this study is to explore the prognostic value of the FAR in ESRD patients on peritoneal dialysis (PD). METHODS: In this retrospective observational study, we enrolled patients with ESRD who underwent PD therapy in our hospital between 1 January 2011 and 31 December 2017. The Kaplan-Meier method and Cox proportional hazards models were used to determine the contact between the FAR level and mortality. RESULTS: A total of 562 patients were enrolled in our research. The median FAR was 0.12, and patients were divided into two groups (low FAR group: FAR < 0.12, n = 250, and high FAR group: FAR ≥ 0.12, n = 312) according to the median FAR. Kaplan-Meier curves showed that the cumulative incidences of both all-cause mortality and CVD mortality were significantly higher in patients with FAR ≥ 0.12 (both P < .001). In multivariable analysis, the high FAR group had an important increased risk of all-cause and CVD mortality (HR: 1.80; 95% CI: 1.03-3.14, P = .038 and HR: 2.31; 95% CI: 1.17-4.59, P = .016, respectively). CONCLUSIONS: Our results suggest that a high baseline FAR value is an independent prognostic factor in ESRD patients on PD.

Effect of the measuring mirror surface shape error on ruled groove straightness and the grating diffraction wavefront.

Measuring mirror requirements and their impact on groove errors are related to the error compensation strategy for a ruling engine. We analyze why the measuring mirror of the CIOMP-6 engine affects the groove straightness and the grating diffraction wavefront. We study a theoretical model of the relationship between the measuring mirror's surface shape error and the grating wavefront, propose a requirement for the measuring mirror surface shape error, and reprocess the measuring mirror. Comparative ruling experiments prove that the grating's wavefront quality at the diffraction order along the groove direction improved significantly after reprocessing of the measuring mirror.

Molecular Characteristics, Phylogeny and Expression Profile of the PTEN Gene in Goats.

Phosphatase and the tensin homologue deleted on chromosome ten (PTEN) has pleiotropic effects on cell growth, organ development, glucose metabolism and insulin resistance in mammals. In the present study, we investigated the molecular characteristics, phylogeny and expression profile of the PTEN gene in different tissues of Jianzhou Daer goats. In this study, eight different tissues from E90, E135 and D90 female goats were collected to quantify the expression pattern of the PTEN gene using quantitative real-time PCR (qPCR), western blotting and FISH. In addition, the dynamic expression of PTEN was also determined during the differentiation of goat precursor adipose cells. A 1212-bp fragment (accession number MG923848), encoding a 403-amino acid protein with a putative molecular weight of 47.14 kDa, was identified in Jianzhou Daer goats by reverse-transcription polymerase chain reaction (RT-PCR). The phylogenetic tree showed that caprine PTEN had a relatively close relationship with ovine PTEN and bovine PTEN. qPCR revealed that PTEN was highly expressed in the liver, lung and spleen, while the lowest expression levels were observed in muscle tissues (P < 0.05). Moreover, the expression of the PTEN gene showed a decreasing trend during the differentiation of goat precursor adipose cells. RNA in situ hybridization yielded a consistent result with the qPCR data. Indeed, low protein expression was found in psoas major muscle and longissimus dorsi muscle, as well as in kidney and liver. However, PTEN protein was expressed at the highest level in the brain. The expression levels of PTEN mRNA and protein were inconsistent with each other, possibly because of post-transcriptional regulation. The findings obtained in our study lay a foundation for further investigations examining the caprine PTEN gene in embryo and organ development.

Prevalence of Pain and Effects of a Brief Mindfulness-Based Intervention on Chinese Community-Dwelling Older Adults with Chronic Pain.

This study aimed to screen the prevalence of pain in Chinese community-dwelling older adults and to evaluate the effects of a brief mindfulness-based intervention on chronic pain. The prevalence of pain among Chinese older adults was 40.5%. The brief mindfulness intervention had significant effects on reducing pain intensity (P = 0.004), and increasing the mindfulness measures: observing, acting with awareness, non-judging and non-reactivity inner experience (all P values < 0.05). Pain prevalence among Chinese older adults was relatively high. This study showed that a brief mindfulness-based intervention reduced ratings of pain intensity and enhanced ratings of the perception of mindfulness.

Retinoids, anxiety and peripartum depressive symptoms among Chinese women: a prospective cohort study.

BACKGROUND: The current study aimed to investigate whether serum RBP levels can be a key predictor of peripartum depression (PPD). METHODS: This was a prospective cohort study, conducted at a general teaching hospital in South China. Research participants were evaluated at three time points: the third trimester of pregnancy (T1), after delivery at week one (T2), and after delivery week six (T3) using a set of self-reported questionnaires and blood sample assays. RESULTS: A total of 156 subjects were included for data analysis. The prevalence of anxiety symptoms ranged from 32.69% to 36.53%. The prevalence of PPD was also high and ranged from 27.56% to 35.89%. In the third trimester, significant predictors of depressive symptoms include serum retinol-binding protein (RBP) concentrations and estradiol levels (P = 0.008 and 0.033, respectively). At one week after delivery, serum concentrations of RBP at T2 were still significant predictors of depressive symptoms (P = 0.020, and serum estradiol concentrations at T1 were a significant predictor (P = 0.010). The most stable predictor of depressive symptoms at T3 was anxiety symptoms, especially at T3 time point (P < 0.001). Serum RBP concentrations at T1 and T2 were still significant predictors of depressive symptoms at T3. CONCLUSION: A high prevalence of anxiety and depressive symptoms tended to persist in Chinese women during the peripartum period. This study, which found the potential contribution of RBP to the occurrence of PPD, requires that large sample studies be conducted in future with a longer-term follow-up period, in order to confirm its results.

Delta-like 1 homolog in Capra hircus: molecular characteristics, expression pattern and phylogeny.

To research the molecular characteristics, expression pattern and phylogeny of the Delta-like 1 homolog gene (Dlk1) in goats. Dlk1 transcripts were identified in the Jianyang Da'er goats by reverse-transcription polymerase chain reaction (RT-PCR). Phylogenetic trees were constructed by Bayesian inference and neighbor-joining methods. Quantitative real-time PCR (qPCR), western blotting and in situ hybridization were performed to analyze the expression pattern of Dlk1. Five alternatively transcripts were identified in different tissues and designated as Dlk1-AS1, 2, 3, 4 and 5. Compared with the normal transcript Dlk1-AS1, Dlk1-AS4 and Dlk1-AS5 retained the identical open reading frame (ORF) and encoded proteins with truncated epidermal-growth-factor like repeats of 121 and 83 amino acids, respectively. Using the Bayesian inference method, the consensus phylogenetic tree indicated that caprine Dlk1 had a closer relationship with bovine Dlk1 than with Dlk1 from pigs, humans and mice. qPCR revealed high expression levels of Dlk1 in the kidney (P < 0.01). However, mRNA and protein levels presented an inconsistent correlation, possibly because of post-transcriptional regulation. RNA in situ hybridization indicated that Dlk1 mRNA was localized in the interlobular bile duct and alongside the hepatocyte nuclei, in the epithelial cells of proximal and distal convoluted tubules and in the connective region between the mesothelium and myocardium in the heart. The Dlk1 gene in goats produces alternatively spliced transcripts, with specific expression and cellular localization patterns. These findings would lay the foundation for further study.

Circadian Gating of Thyroid Hormone Action in Hepatocytes.

Thyroid hormones, thyroxin (T4) and the biologically active triiodothyronine (T3), play important roles in liver metabolic regulation, including fatty acid biosynthesis, beta-oxidation, and cholesterol homeostasis. These functions position TH signaling as a potential target for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated T3 levels in the circulation are associated with increased hepatic lipid turnover, which is also under the control of the circadian clock system. In this study, we developed a cell system to study the impact of hepatocyte circadian rhythms on the metabolic response to T3 treatment under control and steatotic conditions. Synchronized AML-12 circadian reporter hepatocytes were treated with T3 at different circadian phases and metabolic conditions. T3 treatment increased metabolic activity in a dose-independent fashion and had no significant effect on circadian rhythms in AML-12 cells. T3 had marked time-of-treatment-dependent effects on metabolic transcript expression. Steatosis induction altered metabolic transcript expression in AML-12 cells. In this condition, the circadian rhythm period was lengthened, and this effect was independent of T3. Under steatotic conditions, T3 had marked time-of-treatment dependent effects on metabolic transcript expression, which differed from those observed under control conditions. These findings reveal a time-of-day-dependent response of hepatocytes to T3, which is further modulated by the metabolic state. Our data suggest that time has a strong influence on liver TH action, which might be considered when treating MASLD.

Broadband nonlinear modulation of incoherent light using a transparent optoelectronic neuron array.

Nonlinear optical processing of ambient natural light is highly desired for computational imaging and sensing. Strong optical nonlinear response under weak broadband incoherent light is essential for this purpose. By merging 2D transparent phototransistors (TPTs) with liquid crystal (LC) modulators, we create an optoelectronic neuron array that allows self-amplitude modulation of spatially incoherent light, achieving a large nonlinear contrast over a broad spectrum at orders-of-magnitude lower intensity than achievable in most optical nonlinear materials. We fabricated a 10,000-pixel array of optoelectronic neurons, and experimentally demonstrated an intelligent imaging system that instantly attenuates intense glares while retaining the weaker-intensity objects captured by a cellphone camera. This intelligent glare-reduction is important for various imaging applications, including autonomous driving, machine vision, and security cameras. The rapid nonlinear processing of incoherent broadband light might also find applications in optical computing, where nonlinear activation functions for ambient light conditions are highly sought.

Combination of S1-N-Terminal and S1-C-Terminal Domain Antigens Targeting Double Receptor-Binding Domains Bolsters Protective Immunity of a Nanoparticle Vaccine against Porcine Epidemic Diarrhea Virus.

Variants of coronavirus porcine epidemic diarrhea virus (PEDV) frequently emerge, causing an incomplete match between the vaccine and variant strains, which affects vaccine efficacy. Designing vaccines with rapidly replaceable antigens and high efficacy is a promising strategy for the prevention of infection with PEDV variant strains. In our study, three different types of self-assembled nanoparticles (nps) targeting receptor-binding N-terminal domain (NTD) and C-terminal domain (CTD) of S1 protein, named NTDnps, CTDnps, and NTD/CTDnps, were constructed and evaluated as vaccine candidates against PEDV. NTDnps and CTDnps vaccines mediated significantly higher neutralizing antibody (NAb) titers than NTD and CTD recombinant proteins in mice. The NTD/CTDnps in varying ratios elicited significantly higher NAb titers when compared with NTDnps and CTDnps alone. The NTD/CTDnps (3:1) elicited NAb with titers up to 92.92% of those induced by the commercial vaccine. Piglets immunized with NTD/CTDnps (3:1) achieved a passive immune protection rate of 83.33% of that induced by the commercial vaccine. NTD/CTDnps (3:1) enhanced the capacity of mononuclear macrophages and dendritic cells to take up and present antigens by activating major histocompatibility complex I and II molecules to stimulate humoral and cellular immunity. These data reveal that a combination of S1-NTD and S1-CTD antigens targeting double receptor-binding domains strengthens the protective immunity of nanoparticle vaccines against PEDV. Our findings will provide a promising vaccine candidate against PEDV.

Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption.

Mechanical loading is required for bone homeostasis, but the underlying mechanism is still unclear. Our previous studies revealed that the mechanical protein polycystin-1 (PC1, encoded by Pkd1) is critical for bone formation. However, the role of PC1 in bone resorption is unknown. Here, we found that PC1 directly regulates osteoclastogenesis and bone resorption. The conditional deletion of Pkd1 in the osteoclast lineage resulted in a reduced number of osteoclasts, decreased bone resorption, and increased bone mass. A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney disease, which is mainly caused by loss-of-function mutation of the PKD1 gene, is associated with a lower risk of hip fracture than those with other chronic kidney diseases. Moreover, mice with osteoclast-specific knockout of Pkd1 showed complete resistance to unloading-induced bone loss. A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass. Pharmacological regulation of the PC1-TAZ axis alleviated unloading- and estrogen deficiency- induced bone loss. Thus, the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis.

Ferulic acid supplementation alleviates hyperuricemia in high-fructose/fat diet-fed rats via promoting uric acid excretion and mediating the gut microbiota.

The prevalence of hyperuricemia (HUA) has been rising, and it is typically accompanied by renal injury and intestinal flora disorder, leading to a non-negligible health crisis. Ferulic acid (FA), as a familiar polyphenol, has been proven to exert anti-hyperuricemic properties via inhibiting uric acid (UA) synthesis; however, the detailed underlying mechanisms remain unclear. The aim of this study was to explore the regulatory effect of FA on UA excretion as a potential strategy for reducing UA levels, and the comorbidities of HUA. FA treatment downregulated the expression of urate absorption transporter genes and repressed the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway in UA-stimulated HK-2 cells. To examine these effects in vivo, FA or allopurinol (positive control) was given to rats with HUA induced by a high-fructose/fat diet (HFFD) for 20 weeks. FA markedly decreased the serum UA, blood urea nitrogen, and creatinine levels. The expression of urate absorption transporters was downregulated, whereas the expression of secretion transporters was upregulated in the kidneys and intestines of FA-treated HUA rats. Additionally, FA mitigated renal oxidative stress, and suppressed the activation of the TLR4/NF-κB pathway and the downstream inflammatory response-related markers in the kidneys. Moreover, FA remodeled the composition of the gut microbiota, characterized by an increase in beneficial bacteria (e.g., Lactobacillus and Ruminococcus) and a decrease in pathogenic bacteria (e.g., Bacteroides). In conclusion, our study validated FA as an effective nutrient to ameliorate HFFD-induced HUA, suggesting its potential to mitigate the HUA-associated renal impairment and intestinal microbiota disturbance.