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Rural residential structures account for a substantial share of carbon emissions within the construction industry. Enhancing building envelopes can diminish structural carbon emissions, thereby facilitating the attainment of “dual carbon” objectives. Current algorithm-driven research on the low-carbon retrofitting of residential building envelopes generally neglects temperate regions in low-latitude plateaus, often misses embodied carbon, and utilizes rather limited methodologies for issue identification. This study focuses on rural dwellings in Lijiang, utilizing a cross-validation method that incorporates sensitivity analysis, infrared thermal imaging, and energy efficiency criteria to systematically identify vulnerable regions in the building envelope. Consequently, critical issues are converted into optimization variables for the NSGA-II method, aiming to minimize both embodied carbon and operational energy usage. BAPV is concurrently implemented to partially mitigate renovation expenses. A weighted summation approach delineates stakeholder preferences, resulting in three optimum options. The findings reveal that all three methods correspond to their unique preferences, illustrating distinct trade-offs among energy efficiency, carbon reduction, and economic feasibility. The government-oriented approach attained an energy saving rate (ESR) of 45.11%, a life cycle carbon reduction (LCCR) of 1215.76 kgCO2/m2, and a dynamic payback period (DPP) of 3.65 years. The architect-oriented approach realized the highest energy savings and carbon reduction (45.41%, 1218.96 kgCO2/m2), with a payback period of 3.99 years. The villager-oriented approach emphasized economic viability, achieving an energy savings rate of 41.55%, a carbon reduction of 1149.46 kgCO2/m2, and the shortest payback period of 2.87 years. This study provides an optimization process and reference parameters for building envelopes in a low-carbon design for residential buildings in temperate regions of low-latitude plateaus.

Renal tubular epithelial cells are one of the high energy-consuming cell types, which mainly depend on mitochondrial energy supply. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that is involved in alcohol metabolism and mitochondrial oxidative ATP production; however, its function in mitochondrial homoeostasis in acute kidney injury (AKI) is unclear. Here, we found that ALDH2 expression was predominantly decreased in cisplatin or maleic acid (MA) models both in vivo and in vitro. ALDH2 knockout (KO) mice exhibited exacerbated kidney impairment and apoptosis of tubular epithelial cells after cisplatin injection. In contrast, ALDH2 activation alleviated AKI and tubular cell apoptosis in both cisplatin- and MA-induced models. RNA sequencing revealed that the oxidative phosphorylation pathway was positively enriched in the renal tissues after Alda-1 pre-treatment in MA-induced mice. ALDH2 activation restored mitochondrial structure, mitochondrial membrane potential, and respiration rate, but downregulated glycolysis in MA-induced mice and human renal proximal tubular epithelial (HK-2) cells. Mechanistically, co-immunoprecipitation assays revealed that ALDH2 interacts with peroxisomal proliferator-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, and advanced its nuclear translocation. Subsequently, PGC-1α knockdown almost abolished the improvement of ALDH2 activation on MA-induced tubular epithelial cells damage. Thus, our study revealed that ALDH2 activation alleviated mitochondrial dysfunction in AKI by enhancing PGC-1α-mediated mitochondrial biogenesis. Hence, ALDH2 may act as a potential therapeutic target to prevent AKI progression.

Mitochondrial dysfunction is a crucial event in acute kidney injury (AKI), leading to a metabolic shift toward glycolysis and increased lactate production. Lactylation, a posttranslational modification derived from lactate, plays a significant role in various cellular processes, yet its implications in AKI remain underexplored. Here, a marked increase in lactate levels and pan‐Kla levels are observed in kidney tissue from AKI patients and mice, with pronounced lactylation activity in injured proximal tubular cells identified by single‐cell RNA sequencing. The lactylation of aldehyde dehydrogenase 2 (ALDH2) is identified at lysine 52 (K52la), revealing that ALDH2 lactylation exacerbates tubular injury and mitochondrial dysfunction. Conversely, the ALDH2 K52R mutation alleviates these injuries in HK‐2 cells and adeno‐associated virus‐infected kidney tissues in mice. Furthermore, ALDH2 lactylation can be modulated by upregulating SIRT3 in vivo and in vitro, which reduces ALDH2 lactylation, mitigating tubular injury and mitochondrial dysfunction. Mechanistically, immunoprecipitation‐mass spectrometry analysis demonstrates an interaction between ALDH2 and prohibitin 2 (PHB2), a crucial mitophagy receptor. ALDH2 lactylation promotes the ubiquitination‐proteasomal degradation of PHB2 to inhibit mitophagy and worsen mitochondrial dysfunction. These findings highlight the critical role of endogenous lactate in AKI and propose ALDH2 lactylation as a potential therapeutic target. Lactylation of aldehyde dehydrogenase 2 (ALDH2) at lysine 52 (K52la) exacerbates tubular injury and mitochondrial dysfunction in acute kidney injury (AKI), which can be modulated by upregulating SIRT3. Mechanistically, ALDH2 lactylation promotes the ubiquitination‐proteasomal degradation of prohibitin 2 (PHB2), a crucial mitophagy receptor, thereby impairing mitophagy and aggravating mitochondrial dysfunction. These findings highlight the pathological role of endogenous lactate in AKI and propose ALDH2 lactylation as a promising therapeutic target.

Background China has made tremendous progresses in serving the needs of its people living with rare diseases in the past decade, especially over the last 5 years. The Chinese government’s systematic approach included a series of coordinated initiatives, amongst these are: forming the Rare Disease Expert Committee (2016), funding the “Rare Diseases Cohort Study” (2016–2020), and publishing its first “Rare Disease Catalog” (2018). Herein, we present the National Rare Diseases Registry System (NRDRS)—China’s first national rare diseases registry, and the analysis of cases registered in the first 5 years ending Dec 31, 2020. Results The total 62,590 cases covered 166 disease/disease types, forming 183 disease cohorts. The data from nearly 22% of them (13,947 cases) is also linked to valuable biological samples. The average age of definitive diagnosis was 30.88 years; 36.07% of cases were under 18 years of age. Regional distribution analysis showed 60% of cases were from the more developed, wealthier East and North China, suggesting the local availability of quality care and patients’ financial status were key access factors. Finally, 82.04% of cases were registered from the five clinical departments: Neurology, Endocrine, Hematology, Cardiovascular, and Nephrology, suggesting that either these are most affected by rare diseases, or that there were disease non-specific ascertainment factors. Conclusions The preliminary analysis of the first 5-year’s data provides unique and valuable insight on rare disease distribution in China, and higlights the directions for enhancing equity, scale and utility.

Light and heavy chain deposition disease (LHCDD) is a clonal plasma cell or monoclonal B-cell dyscrasia characterized by deposition of monoclonal immunoglobulin light and heavy chains. LHCDD mainly belongs to monoclonal gammopathy of renal significance (MGRS), including a spectrum of kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. It may also occur as a renal complication of overt multiple myeloma. We report a 27-year-old man who presented clinically with chronic nephritic syndrome and was diagnosed with LHCDD confirmed by renal biopsy, accompanied by hypocomplementemia and bronchiolitis obliterans (BO). Notably, he initially developed acquired cutis laxa (CL) four years before renal dysfunction. Progressive dermatologic manifestations prompted repeat skin biopsies, revealing deposition of γ1 heavy chains, restrictive lambda light chains and complement components (C3, C4 and C1q) along dermal elastic fibers, establishing monoclonal gammopathy of dermatologic significance (MGODS) before systemic involvement. This case illustrates a rare constellation of MGRS, MGODS, and BO in a young adult and provides unique histologic and serologic evidence of classical complement pathway activation. Our findings support a potential immune-mediated mechanism underlying tissue injury in both renal and extrarenal manifestations of monoclonal gammopathy, highlighting the diagnostic value of early tissue biopsy and the importance of complement assessment in such cases.

Renal involvement of primary biliary cholangitis (PBC) usually presents as distal renal tubular acidosis. Proximal tubular (PT) dysfunctions in PBC were rarely reported with unclear clinicopathological characteristics and renal prognosis. We identified 11 cases of PBC with PT dysfunctions (PBC-PT). Their medical document, kidney pathology, and follow-up data were retrospectively reviewed and analyzed. The 11 PBC-PT patients were mainly middle-aged (57.8 ± 5.2 years) females (81.8%). Most of them were asymptomatic PBC (7, 63.6%) with a high prevalence of elevated serum immunoglobulin M (IgM, 81.8%) and G (IgG, 54.5%) levels. In the kidney, they had a mean estimated glomerular filtration rate (eGFR) level of 46.54 ± 23.03 ml/min/1.73m , and 81.8% of them had eGFR below 60 ml/min/1.73m . They showed different degrees of PT dysfunctions, including hyperuricosuria, hypouricemia, normoglycemic glycosuria, generalized aminoaciduria, hyperphosphaturia, and hypophosphatemia. Their kidney pathology showed tubulointerstitial nephritis with lymphoplasmacytic infiltrates, brush border defects, and proximal tubulitis. After glucocorticoids treatment, the PT dysfunctions manifesting as hypophosphatemia, hypouricemia, and renal glycosuria all recovered, and the eGFR levels were improved from 43.24 ± 19.60 ml/min/1.73m to 55.02 ± 21.14 ml/min/1.73m (  = 0.028), accompanied by significant improvements of serum IgM levels (from 5.97 ± 4.55 g/L to 2.09 ± 1.48 g/L,  = 0.019). The PT dysfunctions were rare in PBC patients, and glucocorticoids treatment could benefit the improvements of eGFR and tubular functions.

Sepsis-associated acute kidney injury (SA-AKI) is a severe and life-threatening condition with high morbidity and mortality among emergency patients, and it poses a significant risk of chronic renal failure. Clinical treatments for SA-AKI remain reactive and non-specific, lacking effective diagnostic biomarkers or treatment targets. In this study, we established an SA-AKI mouse model using lipopolysaccharide (LPS) and performed proteomics and metabolomics analyses. A variety of bioinformatic analyses, including gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), protein and protein interactions (PPI), and MetaboAnalyst analysis, were conducted to investigate the key molecules of SA-AKI. Integrated proteomics and metabolomics analysis revealed that sepsis led to impaired renal mitochondrial function and metabolic disorders. Immune-related pathways were found to be activated in kidneys upon septic infection. The catabolic products of polyamines accumulated in septic kidneys. Overall, our integrated analysis provides a multidimensional understanding of SA-AKI and identifies potential pathways for this condition.

Background Urinary uromodulin (uUMOD) is one of the novel biomarkers for predicting AKI. However, currently available publications showed inconsistent results. We designed this meta-analysis to evaluate the potential association between uUMOD and AKI. Methods We searched research articles with no language restriction in Medline, Web of Science, Cochrane Library, Embase, and 3 Chinese datasets from inception to February 2021. We used random-effects models to estimate the standardized mean difference (SMD) between patients with AKI or not, while the leave-one-out method and random-effects meta-regression to evaluate the sensitivity and the impact of potential confounders such as age and surgery. Results The meta-analysis comprising 3148 subjects from 11 studies showed that the uUMOD of the AKI group is significantly lower than the non-AKI group (SMD: − 0.71; 95% confidence interval (CI), − 1.00, − 0.42, P  < 0. 001, I 2 = 78.8%). Subgroup analysis revealed the difference is also significant in a different age, surgery condition, and assay time but not acute rejection (AR) group, especially in children (SMD: − 1.21, 95% CI: − 1.80, − 0.61; P  < 0.001) and patients undergoing surgery (SMD: − 1.03, 95% CI: − 1.75, − 0.30; P  < 0.001). Lower uromodulin is associated with higher odds for AKI incidence (odds ratio = 2.47, 95% CI: 1.12, 5.47; P  < 0.001, I 2 = 89%). Meta-reggression found that age was associated with the SMD of uUMOD. The study outcome was reliably confirmed by the sensitivity analysis. Conclusion The present study suggested a negative association between uUMOD and AKI especially in children and surgical patients.

Introduction Long-term exposure to ambient air pollution is related to major cardiovascular risk factors including diabetes, hypertension, hyperlipidemia and overweight, but with few studies in high-concentration nations like China so far. We aimed to investigate the association between long-term exposure to ambient fine particulate matter (particles with an aerodynamic diameter ≤ 2.5 μm, PM 2.5 ) and major cardiovascular risk factors in China. Methods Adult participants with selected biochemical tests were recruited from the Chinese Physiological Constant and Health Condition (CPCHC) survey conducted from 2007 to 2011. Gridded PM 2.5 data used were derived from satellite-observed data with adjustment of ground-observed data. District-level PM 2.5 data were generated to estimate the association using multivariate logistic regression model and generalized additive model. Results A total of 19,236 participants from the CPCHC survey were included with an average age of 42.8 ± 16.1 years, of which nearly half were male (47.0%). The annual average PM 2.5 exposure before the CPCHC survey was 33.4 (14.8–53.4) μg/m 3 , ranging from 8.0 μg/m 3 (Xiwuqi) to 94.7 μg/m 3 (Chengdu). Elevated PM 2.5 was associated with increased prevalence of hypertension (odds ratio (OR) =1.022, 95% confidence interval (95%CI): 1.001, 1.043) and decreased prevalence of overweight (OR = 0.926, 95%CI: 0.910, 0.942). Education significantly interacted with PM 2.5 in association with all the interesting risk factors. Each 10 μg/m 3 increment of PM 2.5 was associated with increased prevalence of diabetes (OR = 1.118, 95%CI: 1.037, 1.206), hypertension (OR = 1.101, 95%CI: 1.056, 1.147), overweight (OR = 1.071, 95%CI: 1.030, 1.114) in participants with poor education, but not in well-educated population. PM 2.5 exposure was negatively associated with hyperlipidemia in all participants (OR = 0.939, 95%CI: 0.921, 0.957). The results were robust in all the sensitivity analyses. Conclusion Association between long-term PM 2.5 exposure and cardiovascular risk factors might be modified by education. PM 2.5 was associated with a higher prevalence of diabetes, hypertension, and overweight in a less-educated population with time-expose dependency. Long-term exposure to PM 2.5 might be associated with a lower prevalence of hyperlipidemia.

Cerebral microbleeds (CMBs) in dialysis patients have recently attracted much attention, and the different locations of CMBs indicate different pathological processes. Previous studies on the relationship between CMBs and cognitive impairment (CI) in the general population and in dialysis patients have reported controversial results. A total of 180 chronic dialysis patients were enrolled in our study. Based on brain magnetic resonance imaging (MRI) analysis of CMBs, the patients were divided into 4 groups (without-CMBs group, strictly lobar group, strictly deep group, and mixed group). A wide range of cognitive tests was administered to evaluate cognitive function. The risk factors for CMBs were explored, and the correlation between CMB distribution and CI was investigated by regression analysis. The prevalence of CMBs was 32.8% in the total study population, 36.1% in the haemodialysis (HD) subgroup and 26.2% in the peritoneal dialysis (PD) PD subgroup. Sixteen subjects (8.9%) were classified as the lobar group, 12 subjects (6.7%) as the mixed group, and 31 subjects (17.2%) as the deep group. A significant association was shown between deep CMBs and impaired cognitive function, involving overall cognitive function, memory, language ability and executive function. Deep CMBs were significantly associated with dialysis vintage, mean arterial pressure (MAP) and lacunar infarcts number, while deep CMBs showed no correlation with dialysis modality and current heparin medication. Deep CMBs are closely associated with global and specific CI in dialysis patients. Blood pressure control may prevent deep CMBs and their associated CI.