A case report of autosomal recessive polycystic kidney disease with noncompaction of ventricular myocardium: coincidence or different manifestations of ciliopathy?

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited cystic disease characterized by bilateral renal cyst formation and congenital liver fibrosis. Cardiovascular disorders such as noncompaction of ventricular myocardium (NVM) have not been reported with ARPKD. CASE PRESENTATION: A 5-month-old girl was examined after presenting with a fever and turbid urine for one day and was diagnosed as urinary tract infection. Urinary ultrasound showed multiple round, small cysts varying in size in both kidneys. Genetic testing revealed two heterozygous mutations and one exon deletion in the polycystic kidney and hepatic disease 1 gene, indicating a diagnosis of ARPKD. During hospitalization, she was found to have chronic heart failure after respiratory tract infection, with an ejection fraction of 29% and fraction shortening of 13%. When the patient was 15 months old, it was found that she had prominent trabeculations and deep intertrabecular recesses with the appearance of blood flow from the ventricular cavity into the intertrabecular recesses by echocardiography. The noncompaction myocardium was 0.716 cm and compaction myocardium was 0.221 cm (N/C = 3.27), indicating a diagnosis of NVM. Liver and kidney function remained normal during four-year follow-up. CONCLUSIONS: This is the first report of NVM in a patient with ARPKD. It is unsure if the coexistence of NVM and ARPKD is a coincidence or they are different manifestations of ciliary dysfunction in the heart and kidneys.

Wanting-liking dissociation and altered dopaminergic functioning: Similarities between internet gaming disorder and tobacco use disorder.

Background: Although internet gaming disorder (IGD) has been included in the DSM-5 for approximately 10 years, debate remains regarding its existence and classification. Methods: The current research incorporated three approaches. First, implicit association tests were used to examine for potential dissociation between wanting and liking in IGD. Second, brain features in wanting and liking circuits were tested and compared with tobacco use disorder (TUD) when performing a cue-craving task to explore the neural features of wanting and liking. Third, dopaminergic systems were investigated in IGD and TUD using neuromelanin-sensitive MRI. Results: The implicit association test results supported a wanting-liking dissociation in IGD participants. Functional MRI data suggested neural correlates underlying wanting-liking dissociation in IGD and TUD participants, with positive correlations suggesting greater dissociation with increasing addiction severity. Neuromelanin results suggest dopaminergic differences in IGD and TUD relative to healthy control participants. Conclusions: A wanting-liking dissociation in IGD participants suggests gaming motivations in IGD relating to incentive sensitization rather than hedonic responses. The neuromelanin-sensitive MRI results suggest dopaminergic involvement in IGD and TUD. The findings suggest similar brain-behaviour mechanisms for IGD and TUD based on an incentive-sensitization model for addiction, having implications for potential therapeutic strategies and policy-based interventions.

Rural recreation tourism in the Panxi region of China in the context of ecological welfare.

Urbanisation has improved living, health and welfare standards but degraded the ecological environment. Tourism models are constantly innovating, and the rural health model is attracting attention to rural recreation, and research on eco-welfare performance and tourism efficiency in ethnic minority rural areas is an important foundation for the construction of ecological civilisation and sustainable development in ethnic minority rural areas. The Panxi region of China has abundant sunshine, mild winters and a good ecological environment, and the rich tourism resources are stimulating rural health tourism. Herein, we used the Super-SBM model to measure eco-welfare performance and rural recreation and tourism efficiency in this region, then used the coupling coordination model to assess coupled co-scheduling of eco-welfare performance and rural health tourism efficiency, the Tobit model was constructed to test the influencing factors of the coupling coordination degree of eco-welfare performance and rural health tourism efficiency in Panxi region. The results show that the growth rate of social fixed asset investment, industrial structure and social development level have a positive effect on the coupling and coordination of eco-welfare performance and rural recreation and tourism efficiency in Panxi, while population density and ecological civilization degree have a negative effect on them. Therefore, the development of rural recreation tourism in Panxi can be promoted by playing a guiding role of the government, promoting the transformation of industrial structure, establishing citizens' awareness of green environmental protection and improving the efficiency of natural resources utilization.

Study of the collaborative prevention and control mechanisms of ecological and environmental risks in China's Yangtze River Economic Belt.

The Yangtze River Economic Belt, as a globally important economic growth pole and population concentration area, has always received attention to its ecological and environmental issues. Currently, there is little research on the synergy among the ecological environment risk prevention and control mechanisms in this region. Strengthening research in this area has important scientific value for improving the effectiveness of ecological risk prevention and control and the sustainable development of the Yangtze River Economic Belt. Based on the data from 11 provinces and cities in the Yangtze River Economic Belt from 2017 to 2021, this study establishes an indicator system with benefit incentive mechanisms, risk regulatory mechanisms, and risk governance mechanisms as frameworks. By employing a composite system synergy model, this study utilizes the entropy weight method to assign weights to each indicator and calculates the orderliness and synergy of the three mechanisms separately. The results show that: (1) There are differences in the orderliness of mechanisms among the regions. The downstream area has the highest orderliness of the three mechanisms, with the middle stream area higher than the upstream area in terms of incentive mechanisms and risk governance mechanisms. (2) The orderliness of each mechanism has slight fluctuations but shows an overall upward trend, with the orderliness of regulatory mechanisms significantly higher than that of incentive mechanisms and governance mechanisms. (3) In terms of synergy, the three major mechanisms show a stable upward trend in synergy but with a relatively low degree of synergy. Based on these findings, future efforts should focus on optimizing mechanism construction and information sharing, improving incentive mechanisms, strengthening risk regulatory mechanisms, and consolidating the effectiveness of risk governance mechanisms.

Generation of an induced pluripotent stem cell line (SDASi001-A) from a Schimke immune-osseous dysplasia patient with SMARCAL1 mutations.

A human induced pluripotent stem cell (iPSC) line (SDASi001-A) was generated from patient with Schimke immune-osseous dysplasia (SIOD), carrying heterozygous mutations in SMARCAL1 gene. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating delivery of OCT4, SOX2, KFL4, BCL-XL and c-MYC. The iPSC line expresses pluripotency markers, displays a normal karyotype, and has the ability to differentiate into cells of three germ layers in vitro. This iPSC line represents a valuable cell model for SIOD in humans.

Brain responses to decision-making in easy and hard choices in internet gaming disorder: Implications for irrepressible gaming behaviours.

BACKGROUND: Impaired decision-making was observed in internet gaming disorder (IGD), however, these studies did not differentiate 'hard' to 'easy' decisions, and only the 'hard' decision-making could reveal the mechanism underlying this issue. METHODS: We recruited forty-eight individuals with IGD and forty-six recreational internet game users (RGUs) as a control group in this study. fMRI data were collected when they were finishing a value-matching delayed discount task (DDT), which included easy and hard decisions judging based on the indifference points of every participant. The correlations between brain responses during DDT and IGD severity and the effective connectivity between brain regions were calculated. RESULTS: Compared to RGUs, IGD subjects showed enhanced activation in the orbitofrontal cortex (OFC) when facing hard choices, and this feature was associated with IGD severity. In addition, individuals with IGD showed increased effective connectivity from the OFC to the dorsolateral prefrontal cortex and the OFC to the occipital lobe and decreased effective connectivity from the occipital lobe to the OFC. CONCLUSION: The current study showed that the abnormal activation in the OFC was associated with IGD severity and higher OFC-DLPFC/OFC-occipital lobe effective connectivity and lower occipital lobe-OFC effective connectivity when individuals with IGD faced different choices in the DDT. These findings suggest the neural mechanisms of impulsive decision-making in individuals with IGD due to dysfunction with subjective evaluation and dysfunction of the connection with the executive control system.

Juvenile dermatomyositis and nephrotic syndrome: A case report and a mini literature review.

Background: Renal involvement is rarely reported in juvenile dermatomyositis and may be caused by the toxic effects of myoglobinuria or an autoimmune reaction. We report a case of dermatomyositis and nephrotic syndrome in a child to explore the association between juvenile dermatomyositis and renal involvement. Case presentation: An 8-year-old girl with skin rash, edema, proximal muscle weakness predominantly involving the lower extremities, low-grade fever, and foamy urine was admitted to our hospital. Her laboratory tests met the criteria of nephrotic syndrome. She had elevated creatine kinase and lactate dehydrogenase and was diagnosed with juvenile dermatomyositis after electromyography and muscle MRI. Anti-NXP2 antibodies were positive. Her proteinuria was relieved soon after treatment with prednisone and methotrexate, but her muscle strength progressively decreased. The disease was relieved after pulse methylprednisolone treatment and mycophenolate mofetil, but recurred after drug reduction with mild proteinuria. Adalimumab was used for treatment and helped reduce the doses of glucocorticoid and mycophenolate mofetil. Conclusion: Juvenile dermatomyositis may be one of the rare causes of nephrotic syndrome. The mechanism involved in JDM combined with renal injury may be multifactorial. Autoantibodies may play important roles in both muscle and renal damage.

Edge-centric functional network analyses reveal disrupted network configuration in autism spectrum disorder.

BACKGROUND: Neuroscientific evidence suggests that the pathological symptoms associated with autism spectrum disorders (ASD) are not confined to a single brain region but involve networks of the brain on a larger spatial scale. Analyzing diagrams of edge-edge interactions could provide important perspectives on the organization and function of complex systems. METHODS: Resting-state fMRI data from 238 ASD patients and 311 healthy controls (HCs) were included in the current study. We used the thalamus as the mediating node to calculate the edge functional connectivity (eFC) of the brain network and compared the ASD subjects and HCs. RESULTS: Compared with the HCs, the ASD subjects exhibited abnormalities in the central node thalamus and four brain regions (amygdala, nucleus accumbens, pallidum and hippocampus), as well as in the eFC formed by the inferior frontal gyrus (IFG) (or middle temporal gyrus (MTG)). In addition, ASD subjects showed variable characteristics of the eFC between nodes in different networks. CONCLUSIONS: The changes in these brain regions may be due to the disturbance in the reward system, which leads to coherence in the instantaneous comovement of the functional connections formed by these brain regions in ASD. This notion also reveals a functional network feature between the cortical and subcortical regions in ASD.

Downregulation of KLF10 contributes to the regeneration of survived renal tubular cells in cisplatin-induced acute kidney injury via ZBTB7A-KLF10-PTEN axis.

Acute kidney injury (AKI) is a common clinical dysfunction with complicated pathophysiology and limited therapeutic methods. Renal tubular injury and the following regeneration process play a vital role in the course of AKI, but the underlining molecular mechanism remains unclear. In this study, network-based analysis of online transcriptional data of human kidney found that KLF10 was closely related to renal function, tubular injury and regeneration in various renal diseases. Three classical mouse models confirmed the downregulation of KLF10 in AKI and its correlation with tubular regeneration and AKI outcome. The 3D renal tubular model in vitro and fluorescent visualization system of cellular proliferation were constructed to show that KLF10 declined in survived cells but increased during tubular formation or conquering proliferative impediment. Furthermore, overexpression of KLF10 significantly inhibited, whereas knockdown of KLF10 extremely promoted the capacity of proliferation, injury repairing and lumen-formation of renal tubular cells. In mechanism, PTEN/AKT pathway were validated as the downstream of KLF10 and participated in its regulation of tubular regeneration. By adopting proteomic mass spectrum and dual-luciferase reporter assay, ZBTB7A were found to be the upstream transcription factor of KLF10. Our findings suggest that downregulation of KLF10 positively contributed to tubular regeneration in cisplatin induced acute kidney injury via ZBTB7A-KLF10-PTEN axis, which gives insight into the novel therapeutic and diagnostical target of AKI.

Disrupted network integration and segregation involving the default mode network in autism spectrum disorder.

Changes in the brain's default mode network (DMN) in the resting state are closely related to autism spectrum disorder (ASD). Module segmentation can effectively elucidate the neural mechanism of ASD and explore intra- and inter-network connections by means of the participation coefficient (PC). We used that resting-state fMRI data from 269 ASD patients and 340 healthy controls (HCs) in the current study. From the results, ASD subjects showed a significantly higher PC of the DMN than HC subjects. This difference was related to lower intra-module connections within the DMN and higher inter-network connections between the DMN and other networks. When the subjects were split into age groups, the results were verified in the 7-12- and 12-18-year-old age groups but not in the young adult group (18-25 years). When the subjects were divided according to different subtypes of ASD, the results were also observed in the classic autism and pervasive developmental disorder groups, but not in the Asperger disorder group. In conclusions, less developed network segregation in the DMN could be a valid biomarker for ASD. This provides network scientists with new insights into the intermodular connectivity configurations of complex networks from different dimensions in a systematic and comprehensive manner.

Association between glomerular C4d deposition, proteinuria, and disease severity in children with IgA nephropathy.

BACKGROUND: C4d may be used as a marker to evaluate the condition and prognosis of adults with IgA nephropathy, but there have been few studies of children with IgA nephropathy. METHODS: C4d immunohistochemical staining was performed on samples from children with IgA nephropathy with C1q-negative immunofluorescence. The clinical and pathological treatment and prognostic characteristics of children in the C4d-positive and -negative groups were compared. RESULTS: A total of sixty-five children with IgA nephropathy were included in the study and were followed up for an average of 37 months. C4d was mainly deposited along the capillary loops. The urinary protein-to-creatinine ratio (UPCR) in the C4d-positive group was significantly higher than that in the C4d-negative group (3.97 vs. 0.81, P < 0.001), and the average integrated optical density value of each child was positively correlated with the UPCR (r = 0.441, P < 0.001). There was a significant difference in the proportions of children with mesangial hypercellularity (M1) (68.97% vs. 44.44%, P = 0.048) and segmental glomerulosclerosis (S1) (65.52% vs. 33.33%, P = 0.010) between the C4d-positive group and the C4d-negative group. The proportion of children who received immunosuppressants in the C4d-positive group was higher than that in the C4d-negative group (86.21% vs. 36.11%, P < 0.001). There was no significant difference in the proportion of children developing kidney failure between the two groups. CONCLUSION: C4d was found to be associated with proteinuria, segmental lesions, and immunosuppressant treatment. Activation of the lectin pathway may reflect the severity of clinical and pathological manifestations of IgA nephropathy in children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Disrupted dynamic network reconfiguration of the executive and reward networks in internet gaming disorder.

BACKGROUND: Studies have shown that people with internet gaming disorder (IGD) exhibit impaired executive control of gaming cravings; however, the neural mechanisms underlying this process remain unknown. In addition, these conclusions were based on the hypothesis that brain networks are temporally static, neglecting dynamic changes in cognitive processes. METHODS: Resting-state fMRI data were collected from 402 subjects [162 subjects with IGD and 240 recreational game users (RGUs)]. The community structure (recruitment and integration) of the executive control network (ECN) and the basal ganglia network (BGN), which represents the reward network, of patients with IGD and RGUs were compared. Mediation effects among the different networks were analyzed. RESULTS: Compared to RGUs, subjects with IGD had a lower recruitment coefficient within the right ECN. Further analysis showed that only male subjects had a lower recruitment coefficient. Mediation analysis showed that the integration coefficient of the right ECN mediated the relationship between the recruitment coefficients of both the right ECN and the BGN in RGUs. CONCLUSIONS: Male subjects with IGD had a lower recruitment coefficient than RGUs, which impairing their impulse control. The mediation results suggest that top-down executive control of the ECN is absent in subjects with IGD. Together, these findings could explain why subjects with IGD exhibit impaired executive control of gaming cravings; these results have important therapeutic implications for developing effective interventions for IGD.

Identification of resident progenitors labeled with Top2a responsible for proximal tubular regeneration in ischemia reperfusion-induced acute kidney injury.

BACKGROUND: Acute kidney injury is a common fatal disease with complex etiology and limited treatment methods. Proximal tubules (PTs) are the most vulnerable segment. Not only in injured kidneys but also in normal kidneys, shedding of PTs often happens. However, the source cells and mechanism of their regeneration remain unclear. METHODS: ScRNA and snRNA sequencing data of acute injured or normal kidney were downloaded from GEO database to identify the candidate biomarker of progenitor of proximal tubules. SLICE algorithm and CytoTRACE analyses were employed to evaluate the stemness of progenitors. Then the repairing trajectory was constructed through pseudotime analyses. SCENIC algorithm was used to detect cell-type-specific regulon. With spatial transcriptome data, the location of progenitors was simulated. Neonatal/ adult/ aged mice and preconditioning AKI mice model and deconvolution of 2 RNA-seq data were employed for validation. RESULTS: Through cluster identification, PT cluster expressed Top2a specifically was identified to increase significantly during AKI. With relatively strong stemness, the Top2a-labeled PT cluster tended to be the origin of the repairing trajectory. Moreover, the cluster was regulated by Pbx3-based regulon and possessed great segmental heterogeneity. Changes of Top2a between neonatal and aged mice and among AKI models validated the progenitor role of Top2a-labeled cluster. CONCLUSIONS: Our study provided transcriptomic evidence that resident proximal tubular progenitors labeled with Top2a participated in regeneration. Considering the segmental heterogeneity, we find that there is a group of reserve progenitor cells in each tubular segment. When AKI occurs, the reserve progenitors of each tubular segment proliferate and replenish first, and PT-progenitors, a cluster with no obvious PT markers replenish each subpopulation of the reserve cells.

Connectome-based prediction of the severity of autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is characterized by social and behavioural deficits. Current diagnosis relies on behavioural criteria, but machine learning, particularly connectome-based predictive modelling (CPM), offers the potential to uncover neural biomarkers for ASD. Objective: This study aims to predict the severity of ASD traits using CPM and explores differences among ASD subtypes, seeking to enhance diagnosis and understanding of ASD. Methods: Resting-state functional magnetic resonance imaging data from 151 ASD patients were used in the model. CPM with leave-one-out cross-validation was conducted to identify intrinsic neural networks that predict Autism Diagnostic Observation Schedule (ADOS) scores. After the model was constructed, it was applied to independent samples to test its replicability (172 ASD patients) and specificity (36 healthy control participants). Furthermore, we examined the predictive model across different aspects of ASD and in subtypes of ASD to understand the potential mechanisms underlying the results. Results: The CPM successfully identified negative networks that significantly predicted ADOS total scores [r (df = 150) = 0.19, P = 0.008 in all patients; r (df = 104) = 0.20, P = 0.040 in classic autism] and communication scores [r (df = 150) = 0.22, P = 0.010 in all patients; r (df = 104) = 0.21, P = 0.020 in classic autism]. These results were reproducible across independent databases. The networks were characterized by enhanced inter- and intranetwork connectivity associated with the occipital network (OCC), and the sensorimotor network (SMN) also played important roles. Conclusions: A CPM based on whole-brain resting-state functional connectivity can predicted the severity of ASD. Large-scale networks, including the OCC and SMN, played important roles in the predictive model. These findings may provide new directions for the diagnosis and intervention of ASD, and maybe could be the targets in novel interventions.

Gender difference in network relationship between inter-temporal decisions and prefrontal activation levels in internet gaming disorder.

Background: Impulsivity and decision-making are key factors in addiction. However, little is known about how gender and time sensitivity affect impulsivity in internet gaming disorder (IGD). Objective: To investigate the gender difference of impulsive decision-making and relevant brain responses in IGD. Methods: We conducted a functional magnetic resonance imaging (fMRI) study with 123 participants, including 59 IGD individuals (26 females) and 64 matched recreational game users (RGUs, 23 females). Participants performed a delay-discounting task during fMRI scanning. We examined gender-by-group effects on behavioral and neural measures to explore the preference for immediate over delayed rewards and the associated brain activity. We also investigated the network correlations between addiction severity and behavioral and neural measures, and analyzed the mediating role of brain activity in the link between delay discounting parameters and IGD severity. Results: We found significant gender-by-group interactions. The imaging results revealed gender-by-group interactions in the dorsolateral prefrontal cortex, medial frontal gyrus, and inferior frontal gyrus (IFG). Post hoc analysis indicated that, for females, RGUs showed higher activity than IGD individuals in these brain regions, while for males IGD individuals exhibited higher activity than RGUs. The activation in the left IFG mediated the relation between Internet Addiction Test score and discount rate in females. In males, the activation in the right dlPFC mediated the relation between IAT score and time sensitivity. Discussion: Our findings imply that male IGD participants demonstrate impaired intertemporal decisions associated with neural dysfunction. Influencing factors for impulsive decision-making in IGD diverge between males (time sensitivity) and females (discount rate). These findings augment our comprehension of the neural underpinnings of gender differences in IGD and bear significant implications for devising effective intervention strategies for treating people with IGD.

Trend dynamics of gout prevalence among the Chinese population, 1990-2019: A joinpoint and age-period-cohort analysis.

Background: The burden of gout is increasing worldwide, which places a heavy burden on society and healthcare systems. This study investigates the independent effects of age, period, and cohort on the gout prevalence from 1990 to 2019 in China, compares these effects by gender and then predicts the future burden of gout over the next decade. Methods: The data were obtained from the Global Burden of Disease (GBD) study in 2019. Joinpoint regression model was employed to calculate the annual percentage change (APC) in gout prevalence, and the age-period-cohort analysis was utilized to estimate the independent effects of age, period, and cohort. ARIMA model was extended to predict the gout epidemic in 2020-2029. Results: In 2019, there were 16.2 million cases of gout in China, with an age-standardized prevalence rate (ASPR) of 12.3‰ and 3.9‰ in men and women, respectively. During 1990-2019, the ASPR of gout was increasing significantly, with an average APC of 0.9%. The periods of 2014-2017 and 2001-2005 were "joinpoint" for men and women (APC: 6.3 and 5.6%). The age-period-cohort analyses revealed that the relative risk (RR) of developing gout increased with age, peaking at 70-74 years in men (RRage(70-74) = 162.9) and 75-79 years in women (RRage(75-79)=142.3). The period effect trended upward, with a more rapid increase in women (RRperiod(2019) = 2.31) than men (RRperiod(2019) = 2.23). The cohort effect generally peaked in the earlier cohort born in 1905-1909 for both sexes. Gout prevalence showed a strong positive correlation with the consumption of meat and aquatic products (rmeat = 0.966, raquaticproducts = 0.953). Within 2029, the ASPR of gout was projected to be 11.7‰ and 4.0‰ in men and women, respectively. Conclusion: The prevalence of gout is increasing at an alarming rate in China; thus, it is necessary to provide targeted health education, regular screening, and accessible urate-lowering therapy healthcare to prevent and protect against gout in China, particularly in older women.

Connectome-based predictive modelling of smoking severity in smokers.

The functional connectivity within and between networks could provide a framework to characterize the neurobiological mechanism of nicotine addiction. This study examined the brain regions that were functionally connected in response to smoking cues and established the brain-behaviour relationships in smokers. Sixty-seven male smokers were enrolled and scanned while performing the cue-reactivity and Stroop task. A whole-brain analysis approach, connectome-based predictive modelling (CPM), was conducted on the data from the cue-reactivity task to identify the networks that could predict the smoking severity with the Shen atlas as templates. Then, the brain-behaviour relationships were verified in a different brain state (Stroop task). CPM identified the smoking severity-related network, as indicated by a significant correlation between predicted and actual smoking severity scores (r = 0.31, p = 0.02). Identified networks mainly involved the canonical networks implicated in the reward process (motor/sensory network and salience network) and executive control (frontoparietal network). Network strength in the Stroop task marginally significantly predicted smoking severity scores (r = 0.23, p = 0.06), partially replicating the brain-behaviour relationship. The CPM results identified the whole-brain neural network related to smoking severity, which was cross-validated by the AAL and Shen atlas. These findings contribute to more profound insights into neural substrates underlying the smoking severity.

Effect Modification of Hyperuricemia, Cardiovascular Risk, and Age on Chronic Kidney Disease in China: A Cross-Sectional Study Based on the China Health and Nutrition Survey Cohort.

Introduction: The question of whether the increased burden of chronic kidney disease (CKD) is caused by the interaction of hyperuricemia and cardiovascular disease (CVD) risk factors or is accelerated by aging remains unresolved. The purpose of this study is to better understand the effect modification of hyperuricemia, cardiovascular risk, and age on CKD among the Chinese population. Methods: This cross-sectional study of 8243 participants was derived from the China Health and Nutrition Survey (CHNS) in 2009. Inclusion criteria included age ≥18 years, non-pregnancy, and no history of high-protein diet prior to blood test. Demographics, comorbidities, health-related behaviors, and serum biomarkers were collected. Interaction association of hyperuricemia, CVD risk and age with CKD were analyzed using Logistic regression. Results: CKD was detected in 359 (27.2%, 95% CI 24.8∼29.7%) of 1321 participants with hyperuricemia and 680 (9.8%, 95% CI 9.1∼10.5%) of 6,922 participants without hyperuricemia, and these patterns remained significant after controlling for age, gender, and Framingham risk score (adjusted odds ratio [aOR] 3.82, 95% CI 3.20∼4.57). We found a negative multiplicative interaction between hyperuricemia and CVD risk on CKD. The aOR in low-CVD risk groups was 5.51 (95% CI 4.03∼7.52), followed by medium-CVD risk groups (aOR: 3.64, 95% CI 2.61∼5.09) and high-CVD risk groups (aOR: 2.89, 95% CI 2.12∼3.96). CVD risk was less associated with CKD in hyperuricemia group (aOR: 0.92, 95% CI 0.68∼1.22) than in non-hyperuricemia group (aOR: 1.43, 95% CI 1.21∼1.70). Furthermore, hyperuricemia and age had a significant additive effect on CKD, with a synergy index of 2.26 (95% CI 1.45∼3.52). Coexisting with older age and hyperuricemia, the likelihood of developing CKD was higher than the sum of the two alone. Conclusion: The link between hyperuricemia and CKD begins at a young age and becomes stronger in the low CVD risk group. For young adults, early detection of hyperuricemia, routine CVD risk assessment, and timely intervention of modifiable factors are warranted.

Nuclear farnesoid X receptor attenuates acute kidney injury through fatty acid oxidation.

Acute kidney injury (AKI) is a life-threatening condition that is one of most common side effects of cisplatin therapy. Fatty acid oxidation (FAO) is the main source of energy production in kidney proximal tubular epithelial cells (PTECs) but it is inhibited in AKI. Recent work demonstrated that activation of the farnesoid X receptor (FXR) protects against AKI, but the underlying mechanism remains elusive. Using a model of cisplatin-induced AKI, we found that FXR and FAO-related genes were remarkably downregulated while kidney lipid accumulated. Proximal tubule-specific or whole body FXR knockout worsened, while pharmacological activation attenuated these effects. Conversely, FXR knockout in non-proximal tubules did not. RNA-sequencing of PTECs demonstrated increased transcripts involved in metabolic pathways in cells overexpressing FXR versus control after cisplatin treatment, specifically transcripts associated with FAO and peroxisome proliferator-activated receptor-γ (PPARγ) signaling. Furthermore, FXR overexpression or activation improved FAO and inhibited intracellular lipid accumulation in cisplatin-treated cells. In vivo studies have shown that pharmacological activation of PPARγ can prevent cisplatin-induced lipid accumulation, kidney tubule injury and kidney function decline. However, inhibition of PPARγ eliminated the protective effects of FXR compared to control mice during the cisplatin treatment phase and after ischemia-reperfusion injury. Consistent with findings in vivo, FXR/PPARγ reduced lipid accumulation by improving FAO in cisplatin-treated cells. Furthermore, the inhibition of carnitine palmitoyltransferase 1α abolished the protective effect of FXR in cisplatin-treated mice. Thus, FXR improves FAO and reduced lipid accumulation via PPARγ in PTECs of the kidney. Hence, reconstruction of the FXR/PPARγ/FAO axis may be a novel therapeutic strategy for preventing or treating AKI.

Facet-dependent electrooxidation of propylene into propylene oxide over Ag3PO4 crystals.

The electrooxidation of propylene into propylene oxide under ambient conditions represents an attractive approach toward propylene oxide. However, this process suffers from a low yield rate over reported electrocatalysts. In this work, we develop an efficient electrocatalyst of Ag3PO4 for the electrooxidation of propylene into propylene oxide. The Ag3PO4 cubes with (100) facets exhibit the highest yield rate of 5.3 gPO m-2 h-1 at 2.4 V versus reversible hydrogen electrode, which is 1.6 and 2.5 times higher than those over Ag3PO4 rhombic dodecahedra with (110) facets and tetrahedra with (111) facets, respectively. The theoretical calculations reveal that the largest polarization of propylene on Ag3PO4 (100) facets is beneficial to break the symmetric π bonding and facilitate the formation of C-O bond. Meanwhile, Ag3PO4(100) facets exhibit the lowest adsorption energies of *C3H6 and *OH, inducing the lowest energy barrier of the rate-determining step and thus accounting for the highest catalytic performance.