EXPRESS: Association of suPAR, ST2, and Galectin-3 with eGFR Decline and Mortality in Patients with Advanced Heart Failure with Reduced Ejection Fraction.

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of eGFR in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants mean age was 59 years, median eGFR 60 ml/min/1.73m2, 45 participants died, 33 received VAD, and 25 received OHT. Higher baseline serum standardized suPAR [ß coefficient =-0.36 √(ml/min/1.73m2), 95% CI (-0.48, -0.24), P<0.001], standardized galectin-3 [-0.14 √(ml/min/1.73m2) (-0.27, -0.02), P=0.02], and log NT-proBNP [-0.23 √(ml/min/1.73m2) (-0.31, -0.15), P<0.001], were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.

Specific Gravity Improves Identification of Clinically Significant Quantitative Proteinuria from the Dipstick Urinalysis.

BACKGROUND: CKD is often underdiagnosed during early stages when GFR is preserved due to underutilization of testing for quantitative urine albumin-to-creatinine ratio (UACR) or protein-to-creatinine ratio (UPCR). Semi-quantitative dipstick proteinuria (DSP) on urinalysis is widely obtained but not accurate for identifying clinically significant proteinuria. METHODS: We identified all patients with a urinalysis and UACR or UPCR obtained on the same day at a tertiary referral center. The accuracy of DSP alone or in combination with specific gravity against a gold-standard of UACR ≥30 mg/g or UPCR ≥0.15 g/g, characterizing clinically significant proteinuria, was evaluated using logistic regression. Models were internally validated using 10-fold cross validation. The specific gravity for each DSP above which significant proteinuria is unlikely was determined. RESULTS: Of 11,229 patients, clinically significant proteinuria was present in 4,073 (36%). The area under the receiver operating characteristic curve (95% confidence interval) was 0.77 (0.76, 0.77) using DSP alone and 0.82 (0.82, 0.83) in combination with specific gravity (P<0.001), yielding a specificity of 0.93 (standard error, SE=0.02) and positive likelihood ratio of 9.52 (SE=0.85). The optimal specific gravity cut-offs to identify significant proteinuria were ≤1.0012, 1.0238, and 1.0442, for DSP of trace, 30, and 100 mg/dL. At any specific gravity, a DSP ≥300 mg/dL was extremely likely to represent significant proteinuria. CONCLUSION: Adding specific gravity to DSP improves recognition of clinically significant proteinuria and can be easily used to identify patients with early-stage CKD who may not have otherwise received a quantified proteinuria measurement for both clinical and research purposes.

Acute hepatic and kidney injury after ingestion of Lepiota brunneoincarnata: Report of 2 cases.

Lepiota brunneoincarnata is a highly toxic mushroom species known to cause acute liver failure. However, there are limited reports investigating L. brunneoincarnata causing acute hepatic and renal damage. The present article reports 2 cases of L. brunneoincarnata poisoning in a mother and son from Chuxiong City, Yunnan Province, China. Both patients presented with gastrointestinal symptoms approximately 8-9 h after ingesting the suspect mushrooms and sought medical attention 27-28 h post-ingestion, both exhibiting acute hepatic and kidney injuries. Morphological and molecular biology studies confirmed the species of the mushrooms as L. brunneoincarnata. Liquid chromatography-tandem mass spectrometry analysis revealed mean fresh-weight concentrations of 123.5 µg/g α-amanitin and 45.7 µg/g ß-amanitin in the mushrooms. The patients underwent standard treatments, including multiple-dose activated charcoal, oral silibinin capsules, N-acetylcysteine, penicillin G, hemoperfusion, and plasma exchange. One patient recovered completely and was discharged after 16 days of hospitalization. The other patient exhibited gradual improvement in liver and renal function; however, renal function deteriorated 9 days after ingestion, and the patient declined renal replacement therapy and returned home 14 days post-ingestion. The patient was then re-hospitalized due to oliguria and edema in both lower extremities. Renal biopsy revealed acute tubular necrosis, inflammatory cell infiltration, minor glomerular capsular fibrosis, loss of microvilli in the renal tubular epithelial cells, and interstitial edema. The patient underwent 2 rounds of continuous renal replacement therapy, which eventually resulted in improvement, and was discharged 31 days after mushroom consumption. It is noteworthy that this patient had already progressed to chronic kidney insufficiency 11 months after intoxication.

The relationship between work-family conflict and job satisfaction for preschool teachers in rural China: a moderated mediation model.

Background: Job satisfaction for preschool teachers in rural areas has an important impact on their professional development, physical and mental health, and the development of preschool education. However, few studies have explored the factors that influence rural preschool teachers' job satisfaction. Purpose: This study aims to examine the influence of rural preschool teachers' work-family conflict on their job satisfaction, and the mediating effect of occupational identity, the moderating effect of social support. Method: Participants included 3,065 rural preschool teachers from Zhejiang Province in mainland China. Teachers completed questionnaires on work-family conflict, occupational identity, job satisfaction, and social support. The correlation and moderated mediation analyses were conducted using SPSS PROCESS. Results: (1) work-family conflict is associated with poorer job satisfaction in preschool teachers; (2) occupational identity mediates the relationship between work-family conflict and job satisfaction; and (3) a high level of social support alleviates the negative influence of work-family conflict on job satisfaction and promotes the positive effect of occupational identity on job satisfaction. Conclusion: The study revealed the negative impact of work-family conflict on preschool teachers' job satisfaction, and the protecting effect of social support, which has important implications for improving teachers' future job satisfaction.

Structural identification of an polysaccharide isolated from Epimedium brevicornum and its beneficial effect on promoting osteogenesis in osteoblasts induced by high glucose.

AIM: Diabetes osteoporosis (DOP) is a chronic bone metabolic disease induced by diabetes, whose morbidity continues to increase. Epimedium brevicornum Maxim (EB), a popular Chinese traditional medicine, has been used to treat bone diseases in China for thousands of years. But its material basis and specific mechanism of action are not clear. METHODS: Epimedium brevicornum crude polysaccharide (EPE) is the main component, in this research the characterized the structure of EBPC1 purified from EPE was detected and its effects on cell proliferation, differentiation, and cytoskeletal in osteoblasts induced by high glucose. RESULTS: The molecular weight of EBPC1 was 10.5 kDa. It was mainly comprised of glucose and galactose, and the backbone of EBPC1 was→4)-α-D-Galp-(1→4)-α-D-Galp-(1→6)-ß-D-Galp-(1→6)-ß-D-Galp-(1→4)-α-D-Glcp-(1→4)-α-D-Glcp-(1→. The results from in vitro experiments revealed that EBPC1 significantly increased alkaline phosphatase (ALP) activity and mineralized nodule formation in primary osteoblasts, also significantly up-regulated expression of Alp mRNA and Runx2 mRNA in the presence of EBPC1 pretreatment. Moreover, EBPC1 modulated apoptosis via the regulation of Bax/Bcl2. CONCLUSION: These results indicate that EBPC1 treatment can promote osteogenesis during DOP, which can ameliorate apoptosis by regulating Bax/Bcl2 and accelerating osteogenesis in osteoblasts.

Smarca4 deficiency induces Pttg1 oncogene upregulation and hyperproliferation of tubular and interstitial cells during kidney development.

Kidney formation and nephrogenesis are controlled by precise spatiotemporal gene expression programs, which are coordinately regulated by cell-cycle, cell type-specific transcription factors and epigenetic/chromatin regulators. However, the roles of epigenetic/chromatin regulators in kidney development and disease remain poorly understood. In this study, we investigated the impact of deleting the chromatin remodeling factor Smarca4 (Brg1), a human Wilms tumor-associated gene, in Wnt4-expressing cells. Smarca4 deficiency led to severe tubular defects and a shortened medulla. Through unbiased single-cell RNA sequencing analyses, we identified multiple types of Wnt4 Cre-labeled interstitial cells, along with nephron-related cells. Smarca4 deficiency increased interstitial cells but markedly reduced tubular cells, resulting in cells with mixed identity and elevated expression of cell-cycle regulators and genes associated with extracellular matrix and epithelial-to-mesenchymal transition/fibrosis. We found that Smarca4 loss induced a significant upregulation of the oncogene Pttg1 and hyperproliferation of Wnt4 Cre-labeled cells. These changes in the cellular state could hinder the cellular transition into characteristic tubular structures, eventually leading to fibrosis. In conclusion, our findings shed light on novel cell types and genes associated with Wnt4 Cre-labeled cells and highlight the critical role of Smarca4 in regulating tubular cell differentiation and the expression of the cancer-causing gene Pttg1 in the kidney. These findings may provide valuable insights into potential therapeutic strategies for renal cell carcinoma resulting from SMARCA4 deficiency.

Rapid and sensitive detection of aqueous ammonia harnessing nanocomposite functionalized tilted fiber Bragg grating.

A high sensitive aqueous ammonia sensor based on tilted fiber Bragg grating (TFBG) had been reported. The sensors were fabricated by a 10 ° TFBG coated by a membrane receptor named as Polyaniline/Graphene oxide on the surface of the fiber. The correlative concentrations of aqueous ammonia were demodulated by global monitoring of the envelope area of cladding modes in the transmitted spectrum of the TFBG. Tests have shown that the proposed sensor can provide a linear and rapid response of aqueous ammonia within 22 seconds, in a concentration range from 1-12 ppm. Moreover, the limit of detection can even reach 0.08 ppm, through the theoretical analysis of our experimental results. The proposed sensor has good performance, is easy to manufacture and of small size, making it a good choice for real-time, in-situ, label-free detection of aqueous ammonia in the future.

Observation of the effect of angiojet to treat acute lower extremity arterial embolization.

BACKGROUND: Through significant advances in the treatment of peripheral arterial occlusive disease, acute ischemia of the lower extremity is still associated with significant morbidity, limb threat and mortality. The two main causes of acute ischemia in lower extremities are arterial embolism and atherosclerotic arteries. Timely recognition and treatment of acute limb ischemia in emergency situations is essential in order to minimize the duration of ischemia. AIM: To investigate the application effect of angiojet thrombolysis in the treatment of acute lower extremity arterial embolization. METHODS: Sixty-two patients with acute lower extremity arterial embolization admitted to our hospital from May 2018 to May 2020 were selected. Among them, the observation group (twenty-eight cases) had received angiojet thrombolysis, and the control group (thirty-four cases) had received femoral artery incision and thrombectomy. After thrombus clearance, significant residual stenosis of the lumen was combined with balloon dilation and/or stent implantation. When the thrombus removal was not satisfactory, catheter-directed thrombolysis was performed. The incidence of postoperative complications, recurrence rate and recovery of the two groups were compared. RESULTS: There were no significant differences in postoperative recurrence (target vessel reconstruction rate), anklebrachial index and the incidence of postoperative complications between the two groups (P > 0.05); there were statistically significant differences in postoperative pain score and postoperative rehabilitation between the two groups (P < 0.05). CONCLUSION: The application of angiojet in the treatment of acute lower limb artery thromboembolism disease is safe and effective, minimally invasive, quicker recovery after operation, less postoperative complications, which is more suitable for the treatment of femoral popliteal arterial thromboembolism lesions. If the thrombus removal is not satisfactory, the combination of coronary artery aspiration catheter and catheterized directed thrombolysis can be used. Balloon dilation and stent implantation can be considered for obvious lumen stenosis.

The role of Eya1 and Eya2 in the taste system of mice from embryonic stage to adulthood.

Members of the Eya family, which are a class of transcription factors with phosphatase activity, are widely expressed in cranial sensory organs during development. However, it is unclear whether these genes are expressed in the taste system during development and whether they play any role in specifying taste cell fate. In this study, we report that Eya1 is not expressed during embryonic tongue development but that Eya1-expressing progenitors in somites or pharyngeal endoderm give rise to tongue musculature or taste organs, respectively. In the Eya1-deficient tongues, these progenitors do not proliferate properly, resulting in a smaller tongue at birth, impaired growth of taste papillae, and disrupted expression of Six1 in the papillary epithelium. On the other hand, Eya2 is specifically expressed in endoderm-derived circumvallate and foliate papillae located on the posterior tongue during development. In adult tongues, Eya1 is predominantly expressed in IP3R3-positive taste cells in the taste buds of the circumvallate and foliate papillae, while Eya2 is persistently expressed in these papillae at higher levels in some epithelial progenitors and at lower levels in some taste cells. We found that conditional knockout of Eya1 in the third week or Eya2 knockout reduced Pou2f3+, Six1+ and IP3R3+ taste cells. Our data define for the first time the expression patterns of Eya1 and Eya2 during the development and maintenance of the mouse taste system and suggest that Eya1 and Eya2 may act together to promote lineage commitment of taste cell subtypes.

Unsociability and social adjustment of Chinese preschool migrant children: The moderating role of resilience.

Objectives: The present study examined the moderating effect of children's resilience on the relations between unsociability and social adjustment (i.e., prosocial behaviors, peer exclusion, interpersonal skills, internalizing problems) in Chinese preschool migrant children. Methods: Participants were N = 148 children (82 boys, M age = 62.32 months, SD = 6.76) attending two public kindergartens in Shanghai, People's Republic of China. Mothers provided ratings of children's unsociability and resilience; teachers assessed children's social adjustment outcomes, and children reported their receptive vocabulary. Results: Unsociability was positively associated with peer exclusion and internalizing problems, and negatively associated with prosocial behaviors and interpersonal skills among Chinese preschool migrant children. Moreover, children's resilience significantly moderated the relationship between unsociability and social adjustment. Specifically, among children with lower levels of resilience, unsociability was significantly and positively associated with peer exclusion and internalizing problems, while among children with higher levels of resilience, unsociability was not associated with social adjustment difficulties. Conclusion: The current findings inform us of the importance of improving children's resilience to buffer the negative adjustment among Chinese migrant unsociable young children. The findings also highlight the importance of considering the meaning and implication of unsociability for preschool migrant children in Chinese culture.

Validation of a predictive model for hospital-acquired acute kidney injury with emergence of SARS-CoV-2 variants.

We previously developed and validated a model to predict acute kidney injury (AKI) in hospitalized coronavirus disease 2019 (COVID-19) patients and found that the variables with the highest importance included a history of chronic kidney disease and markers of inflammation. Here, we assessed model performance during periods when COVID-19 cases were attributable almost exclusively to individual variants. Electronic Health Record data were obtained from patients admitted to 19 hospitals. The outcome was hospital-acquired AKI. The model, previously built in an Inception Cohort, was evaluated in Delta and Omicron cohorts using model discrimination and calibration methods. A total of 9104 patients were included, with 5676 in the Inception Cohort, 2461 in the Delta cohort, and 967 in the Omicron cohort. The Delta Cohort was younger with fewer comorbidities, while Omicron patients had lower rates of intensive care compared with the other cohorts. AKI occurred in 13.7% of the Inception Cohort, compared with 13.8% of Delta and 14.4% of Omicron (Omnibus p = 0.84). Compared with the Inception Cohort (area under the curve (AUC): 0.78, 95% confidence interval (CI): 0.76-0.80), the model showed stable discrimination in the Delta (AUC: 0.78, 95% CI: 0.75-0.80, p = 0.89) and Omicron (AUC: 0.74, 95% CI: 0.70-0.79, p = 0.37) cohorts. Estimated calibration index values were 0.02 (95% CI: 0.01-0.07) for Inception, 0.08 (95% CI: 0.05-0.17) for Delta, and 0.12 (95% CI: 0.04-0.47) for Omicron cohorts, p = 0.10 for both Delta and Omicron vs Inception. Our model for predicting hospital-acquired AKI remained accurate in different COVID-19 variants, suggesting that risk factors for AKI have not substantially evolved across variants.

Hypochloremia as a novel adverse prognostic factor in acute liver failure.

BACKGROUND AND AIMS: Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America. METHODS: The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21-day all-cause mortality or requirement for liver transplantation (death/LT). RESULTS: Patients with hypochloremia (<98 mEq/L) had a significantly higher 21-day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant-free cumulative survival in the hypochloremic group than in the normo- or hyper-chloremic groups (log-rank, χ2 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21-day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969-0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13-0.25) but underestimated the probability of transplant-free survival in 34% of patients (NRI = -0.34, 95% CI: -0.39 to -0.28). CONCLUSIONS: Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG-Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT.

Cardiac myxoma shedding leads to lower extremity arterial embolism: A case report.

BACKGROUND: Left cardiac myxoma (CM) is the most common benign tumor of primary cardiac tumors, but because of its special position caused by pathological physiology change, caused by the complications of the heavier, the surface is often accompanied by blood clots, once fall out, it causes peripheral vascular embolization, such as acute lower limb artery embolization, harmfulness is large, high morbidity, and easy to occur repeatedly. CASE SUMMARY: A 67-year-old male patient suddenly appeared numbness and weakness of the left lower limb and could not walk without obvious incentive. The patient was finally diagnosed as left CM complicated with acute lower limb arterial embolism after completing cardiac ultrasound, computer tomography angiography, and histopathological analysis, such as hematoxylin-eosin stain staining, immunohistochemistry and special staining including alcian blue staining and periodic acid schiff staining. Arterial thrombosis was removed successfully by femoral artery thrombectomy, postoperative numbness and weakness of the patient's left lower limb disappeared, skin temperature became warm, and dorsal foot artery pulsation was accessible. The patient was readmitted to the hospital 8 mo after discharge for left atrial mass resection, and was diagnosed as CM by postoperative histopathological examination. CONCLUSION: Although CM is rare, it may be considered as the source of embolism in patients with acute limb ischemia. Repeated loss of thrombus on the tumor and its surface may lead to repeated embolism of peripheral vessels. Cardiac ultrasound is helpful for early diagnosis. Here, we use this case report to highlight left CM as an important cause of acute limb ischemia and to report our experience in the diagnosis and treatment of lower limb arterial embolism caused by CM detachment.

The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and REST-binding sequences to maintain nephron progenitor identity.

Eya1 is critical for establishing and maintaining nephron progenitor cells (NPCs). It belongs to a family of proteins called phosphatase-transcriptional activators but without intrinsic DNA-binding activity. However, the spectrum of the Eya1-centered networks is underexplored. Here, we combined transcriptomic, genomic and proteomic approaches to characterize gene regulation by Eya1 in the NPCs. We identified Eya1 target genes, associated cis-regulatory elements and partner proteins. Eya1 preferentially occupies promoter sequences and interacts with general transcription factors (TFs), RNA polymerases, different types of TFs, chromatin-remodeling factors with ATPase or helicase activity, and DNA replication/repair proteins. Intriguingly, we identified REST-binding motifs in 76% of Eya1-occupied sites without H3K27ac-deposition, which were present in many Eya1 target genes upregulated in Eya1-deficient NPCs. Eya1 copurified REST-interacting chromatin-remodeling factors, histone deacetylase/lysine demethylase, and corepressors. Coimmunoprecipitation validated physical interaction between Eya1 and Rest/Hdac1/Cdyl/Hltf in the kidneys. Collectively, our results suggest that through interactions with chromatin-remodeling factors and specialized DNA-binding proteins, Eya1 may modify chromatin structure to facilitate the assembly of regulatory complexes that regulate transcription positively or negatively. These findings provide a mechanistic basis for how Eya1 exerts its activity by forming unique multiprotein complexes in various biological processes to maintain the cellular state of NPCs.

A missense mutation in Kcnc3 causes hippocampal learning deficits in mice.

Although a wide variety of genetic tools has been developed to study learning and memory, the molecular basis of memory encoding remains incompletely understood. Here, we undertook an unbiased approach to identify novel genes critical for memory encoding. From a large-scale, in vivo mutagenesis screen using contextual fear conditioning, we isolated in mice a mutant, named Clueless, with spatial learning deficits. A causative missense mutation (G434V) was found in the voltage-gated potassium channel, subfamily C member 3 (Kcnc3) gene in a region that encodes a transmembrane voltage sensor. Generation of a Kcnc3G434V CRISPR mutant mouse confirmed this mutation as the cause of the learning defects. While G434V had no effect on transcription, translation, or trafficking of the channel, electrophysiological analysis of the G434V mutant channel revealed a complete loss of voltage-gated conductance, a broadening of the action potential, and decreased neuronal firing. Together, our findings have revealed a role for Kcnc3 in learning and memory.

Enantioselective Radical Trifluoromethylation of Benzylic C-H Bonds via Cooperative Photoredox and Copper Catalysis.

The first enantioselective radical trifluoromethylation of benzylic C-H bonds has been established by a cooperative photoredox and copper catalysis system, providing straightforward access to structurally diverse benzylic trifluoromethylation products in good yields with excellent enantioselectivities under mild conditions. Our method features a broad substrate scope and excellent functional group compatibility. Merging the cooperative photoredox catalysis with copper catalysis is essential for the reaction, where the photoredox catalysis is used for the generation of benzylic radicals from alkyl arenes through a hydrogen atom transfer process and the copper catalysis is used for the enantioselective trifluoromethylation of the benzylic radicals.

Evaluation of the mechanism of Rujiling capsules in the treatment of hyperplasia of mammary glands based on network pharmacology and molecular docking.

OBJECTIVE: The present study aimed to elucidate the molecular network mechanism of the Rujiling capsule in the treatment of hyperplasia of mammary glands through network pharmacology and molecular docking. MATERIALS AND METHODS: TCMSP and TCMID databases were screened for the active components and their action targets of the Rujiling capsule, whereas the disease targets of hyperplasia of mammary glands were searched in GeneCard and DisGeNET databases. Venny software was employed to identify the common targets of drugs and diseases. Cytoscape software was used to construct the network pharmacological diagram of "drug-active components-target" and the intersection targets were subjected to protein-protein interaction analysis by STRING platform and Cytoscape software. The DAVID database was exploited for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of the intersection target. After that, the key target genes with a degree value greater than the median were verified with the active components in molecular docking. RESULTS: A total of 691 drug targets, 251 disease targets, and 108 intersection targets were obtained after retrieval and screening. Among the 686 items enriched by GO included 522 biological processes, 110 molecular functions, and 54 cellular components. At the same time, 114 signal pathways were enriched by KEGG. The results of molecular docking revealed that the docking energies of main active components and some core targets were all <-5 kcal/mol. CONCLUSION: Henceforth, highlighted the role of the Rujiling capsule in the treatment of hyperplasia of mammary glands through multiple components, multiple targets, and multiple signal pathways.

Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice.

Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising the question of if it is calories, fasting, or time of day that is the cause of this increased life span. We show here that 30% CR was sufficient to extend the life span by 10%; however, a daily fasting interval and circadian alignment of feeding acted together to extend life span by 35% in male C57BL/6J mice. These effects were independent of body weight. Aging induced widespread increases in gene expression associated with inflammation and decreases in the expression of genes encoding components of metabolic pathways in liver from ad libitum-fed mice. CR at night ameliorated these aging-related changes. Our results show that circadian interventions promote longevity and provide a perspective to further explore mechanisms of aging.

Label-free detection of breast cancer cells using a functionalized tilted fiber grating.

The detection of circulating tumor cells (CTCs) still faces a huge challenge partially because of low abundance of CTCs (1-10 cells/mL). In this work, a plasmonic titled fiber Bragg grating biosensor is proposed for detection of breast cancer cells. The biosensor is made by an 18° TFBG with a 50 nm-thick gold nanofilm coating over the surface of the fiber, further immobilized with a specific antibody against GPR30, which is a membrane receptor expressed in many breast cancers, serving as bait. In vitro tests have confirmed that the proposed biosensor can detect breast cancer cells in concentration of 5 cells/mL within 20 minutes and has good linearity in the range of 5-1000 cells/mL, which has met the requirement of CTC detection in real conditions. Furthermore, theoretical analysis based on the experimental results shows that the limit of detection can even reach single-cell level. Our proposed biosensor has a simple structure, is easy to manufacture, is of small size, and has a good performance, making it a good choice for real-time, label-free, and milliliter-volume detection of cancer cells in future.

Risk Prediction for Acute Kidney Injury in Patients Hospitalized With COVID-19.

Rationale & Objective: Acute kidney injury (AKI) is common in patients hospitalized with COVID-19, but validated, predictive models for AKI are lacking. We aimed to develop the best predictive model for AKI in hospitalized patients with coronavirus disease 2019 and assess its performance over time with the emergence of vaccines and the Delta variant. Study Design: Longitudinal cohort study. Setting & Participants: Hospitalized patients with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction result between March 1, 2020, and August 20, 2021 at 19 hospitals in Texas. Exposures: Comorbid conditions, baseline laboratory data, inflammatory biomarkers. Outcomes: AKI defined by KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria. Analytical Approach: Three nested models for AKI were built in a development cohort and validated in 2 out-of-time cohorts. Model discrimination and calibration measures were compared among cohorts to assess performance over time. Results: Of 10,034 patients, 5,676, 2,917, and 1,441 were in the development, validation 1, and validation 2 cohorts, respectively, of whom 776 (13.7%), 368 (12.6%), and 179 (12.4%) developed AKI, respectively (P = 0.26). Patients in the validation cohort 2 had fewer comorbid conditions and were younger than those in the development cohort or validation cohort 1 (mean age, 54 ± 16.8 years vs 61.4 ± 17.5 and 61.7 ± 17.3 years, respectively, P < 0.001). The validation cohort 2 had higher median high-sensitivity C-reactive protein level (81.7 mg/L) versus the development cohort (74.5 mg/L; P < 0.01) and higher median ferritin level (696 ng/mL) versus both the development cohort (444 ng/mL) and validation cohort 1 (496 ng/mL; P < 0.001). The final model, which added high-sensitivity C-reactive protein, ferritin, and D-dimer levels, had an area under the curve of 0.781 (95% CI, 0.763-0.799). Compared with the development cohort, discrimination by area under the curve (validation 1: 0.785 [0.760-0.810], P = 0.79, and validation 2: 0.754 [0.716-0.795], P = 0.53) and calibration by estimated calibration index (validation 1: 0.116 [0.041-0.281], P = 0.11, and validation 2: 0.081 [0.045-0.295], P = 0.11) showed stable performance over time. Limitations: Potential billing and coding bias. Conclusions: We developed and externally validated a model to accurately predict AKI in patients with coronavirus disease 2019. The performance of the model withstood changes in practice patterns and virus variants.