Crosstalk among proximal tubular cells, macrophages, and fibroblasts in acute kidney injury: single-cell profiling from the perspective of ferroptosis.

The link between ferroptosis, a form of cell death mediated by iron and acute kidney injury (AKI) is recently gaining widespread attention. However, the mechanism of the crosstalk between cells in the pathogenesis and progression of acute kidney injury remains unexplored. In our research, we performed a non-negative matrix decomposition (NMF) algorithm on acute kidney injury single-cell RNA sequencing data based specifically focusing in ferroptosis-associated genes. Through a combination with pseudo-time analysis, cell-cell interaction analysis and SCENIC analysis, we discovered that proximal tubular cells, macrophages, and fibroblasts all showed associations with ferroptosis in different pathways and at various time. This involvement influenced cellular functions, enhancing cellular communication and activating multiple transcription factors. In addition, analyzing bulk expression profiles and marker genes of newly defined ferroptosis subtypes of cells, we have identified crucial cell subtypes, including Egr1 + PTC-C1, Jun + PTC-C3, Cxcl2 + Mac-C1 and Egr1 + Fib-C1. All these subtypes which were found in AKI mice kidneys and played significantly distinct roles from those of normal mice. Moreover, we verified the differential expression of Egr1, Jun, and Cxcl2 in the IRI mouse model and acute kidney injury human samples. Finally, our research presented a novel analysis of the crosstalk of proximal tubular cells, macrophages and fibroblasts in acute kidney injury targeting ferroptosis, therefore, contributing to better understanding the acute kidney injury pathogenesis, self-repairment and acute kidney injury-chronic kidney disease (AKI-CKD) progression.

Photoacoustic detection of transient phase transformation of nanoparticles.

The controllable preparation of spherical micro/nano particles of various materials has been achieved via the technology of the laser synthesis and processing of colloids (LSPC) recently. However, there is limited in situ research on the evolution processes of nanoparticles in photothermal transient environments, such as solid-state crystal transformations and changes of state, which limits the understanding and application of LSPC. Photoacoustic (PA) signals are sensitive to the optical, thermal and elastic properties of the medium, and can be used to measure the thermal and spectroscopic properties of matter. In this paper, the PA signals generated by the interaction of the laser with the surrounding liquid medium (ethanol, water, glycerin, etc.) and nanoparticles (Ag, TiO2, CeO2, ZrO2, etc.) are studied when the tunable LSPC technique provides different photothermal conditions (such as thermal expansion, solid crystal transformation and evaporation). It is found that semiconductors with different bandgaps, as light absorbers, have the ability to selectively absorb laser beams of different wavelengths. By changing the wavelength, the PA intensity can be adjusted accordingly. In addition, based on the fast laser heating and tunable fluence characteristics of non-focused laser beams in LSPC technology, transient processes such as material phase transitions and changes of state can be excited separately by adjusting the laser fluence. Taking titanium dioxide as an example, the PA signals generated by laser selective excitation of A-R (anatase into rutile) phase transitions and rutile vaporization can be detected.

The complete chloroplast genome sequence of Pinus bhutanica (Pinaceae) and its phylogenetic implications.

Pinus bhutanica is a critically endangered conifer and occurs only in central Bhutan, northwestern Yunnan and southeastern Xizang in China. In this study, the complete chloroplast genome of Pinus bhutanica was first assembled based on next-generation sequencing. The genome sequence was 116,919 bp in length with an overall GC content of 38.75%. A total of 106 functional genes were detected in the genome, including 72 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. The phylogenetic tree reconstructed by 12 chloroplast genomes revealed that P. bhutanica is most closely related to Pinus wangii in subsection Strobus of Pinus.

Heart failure with preserved ejection fraction in haemodialysis patients: prevalence, diagnosis, risk factors, prognosis.

AIMS: Heart failure (HF) is a common complication and the leading cause of mortality in maintenance haemodialysis (MHD) patients. Few studies have investigated heart failure with preserved ejection fraction (HFpEF), which is known to affect a majority of patients. The objective of this study is to explore the prevalence, clinical profiles, diagnosis, risk factors and prognosis of MHD patients with HFpEF. METHODS AND RESULTS: Four hundred thirty-nine patients haemodialyzsed for over 3 months were enrolled in the study and evaluated for HF according to the European Society of Cardiology guidelines. Clinical and laboratory parameters were recorded at baseline. The median follow-up of the study was 22.5 months. A total of 111 (25.3%) MHD patients were diagnosed with HF, while 94 (84.7%) of the HF patients were classified into HFpEF. The cut-off value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 4922.5 pg/mL for predicting HFpEF (sensitivity 0.840, specificity 0.723, AUC 0.866) in MHD patients. Age, diabetes mellitus, coronary artery disease and serum phosphorus were independent risk factors for the incidence of HFpEF in MHD patients while normal urine volume, haemoglobin, serum iron and serum sodium were protective factors. MHD patients with HFpEF had a higher risk of all-cause mortality than those without HF (hazard ratio 2.47, 95% confidence interval 1.55-3.91, P < 0.0001). CONCLUSIONS: The majority of MHD patients with HF were categorized into HFpEF, with a poor long-term survival rate. NT-proBNP beyond 4922.5 pg/mL performed well in the prediction of HFpEF in MHD patients.

Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors.

Background: It remains not well known whether skeletal muscle mass (SMM) loss has any impact on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer. We aimed to evaluate the association between SMM and clinical outcome of patients with advanced lung cancer receiving ICIs as first line or second line. Materials and Methods: From March 1st, 2019 to March 31st, 2021 at our hospital, 34 patients with advanced lung cancer treated with first-line or second-line ICIs were enrolled retrospectively. The estimation of skeletal muscle index (SMI) for sarcopenia was assessed at the level of the third lumbar vertebra (L3) on computed tomography (CT) images obtained within 4 weeks before initiation of ICIs treatment. The impact of sarcopenia (low SMI) on progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. The effect of various variables on PFS was evaluated using Cox proportional hazards regression model with univariate and multivariate analysis. The impact on treatment response including objective response rate (ORR) and disease control rate (DCR) and immunotherapy related adverse events (irAEs) between patients with and without sarcopenia was compared by the chi-squared test. The comparison of SMI value between patients with objective response (OR), disease control (DC) and those without OR and DC was used student t-test or Mann-Whitney U test. Results: Both in univariate and multivariate analysis, sarcopenia and treatment lines were the predictive factors for PFS (p < 0.05). Patients with sarcopenia had significantly shorter PFS than that of non-sarcopenic ones [6.57 vs. 16.2 months, hazard ratios (HR) = 2.947 and 3.542, and 95% confidence interval (CI): 1.123-13.183 and 1.11-11.308, p = 0.022 and 0.033]. No significant difference in ORR and irAEs was found. Patients with sarcopenia had lower DCR than those without sarcopenia. The mean SMI value of DCR group and non-DCR group was 32.94 ± 5.49 and 44.77 ± 9.06 cm2/m2, respectively (p = 0.008). Conclusion: Sarcopenia before immunotherapy might be a significant predictor for poor prognosis including shorter PFS and lower DCR in patients with advanced lung cancer treated with ICIs as first line or second line.

Cystatin C-based estimated GFR performs best in identifying individuals with poorer survival in an unselected Chinese population: results from the China Health and Retirement Longitudinal Study (CHARLS).

Background: The decline in estimated glomerular filtration rate (eGFR) has been reported as a risk factor for mortality. However, it remains unclear which eGFR equation is most useful in predicting death in the general Chinese population. Methods: The association was examined between eGFR and all-cause mortality using data from the China Health and Retirement Longitudinal Study. Participants with complete data in 2011 and survival follow-up in 2013, 2015 and 2018 were included and analyzed in three separate cohorts, which included 8160, 8154 and 8020 participants, respectively. Logistic regression analyses, receiver operating characteristic curve, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were computed to compare the discriminative power of eGFR derived by abbreviated Modification of Diet in Renal Disease (MDRD), Chinese coefficient-modified MDRD (MDRD-CN), Japanese coefficient-modified MDRD (MDRD-JPN), CKD-EPIcr, Japanese coefficient-modified CKD-EPIcr (CKD-EPIcr-JPN), CKD-EPIcys, CKD-EPIcr-cys, CKD-EPIcr fit without race and CKD-EPIcr-cys fit without race. Results: A decreased eGFR (<60 ml/min/1.73 m2) was significantly associated with increased mortality at 2 years no matter which eGFR equation was used (odds ratio ranged between 2.02 and 4.94, all P < 0.001). The association remained significant after adjusting multiple covariates when MDRD-CN, CKD-EPIcys or CKD-EPIcr-cys fit without race was used. CKD-EPIcys showed the highest discriminative power for mortality (area under the curve 0.744 ± 0.40) and outperformed other equations (all P < 0.001) except for CKD-EPIcr-cys. The overall risk classification was also improved when the CKD-EPIcys equation was adopted as indicated by continuous NRI and IDI. Similar results were observed at 4 and 7 years. Conclusions: A decline in eGFR by all equations could predict poorer survival, among which the CKD-EPIcys equation showed the best discriminative power.

ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma.

5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a catalysing enzyme in the de novo purine biosynthetic pathway, has been previously reported to be upregulated and to participate in myeloma and hepatocellular carcinoma progression. In the present study, by using bioinformatics technology, a higher ATIC expression was identified in lung adenocarcinoma (LUAD) tissues than in normal tissues, and ATIC expression was found to be positively associated with Myc expression in LUAD tissues. In addition, the role of ATIC in modulating the growth and migration of LUAD cells was explored and the involvement of Myc was revealed. ATIC expression in 56 paired LUAD and tumour adjacent non-cancerous tissues was assessed using reverse transcription-quantitative PCR and western blot analysis. Pearson's correlation analysis was applied to evaluate the correlation between ATIC and Myc expression levels in LUAD tissues. A rescue experiment was performed to explore the role of ATIC/Myc in regulating the growth, migration and invasion of HCC827 and NCI-H1435 cells. It was demonstrated that ATIC was overexpressed in LUAD tissues, particularly in advanced-stage LUAD, and was predicted to be associated with an advanced TNM stage, a higher lymph node metastasis rate, poor tissue differentiation and a lower overall survival rate. ATIC overexpression promoted cell growth, migratory and invasive capacities, whereas this effect was abrogated by Myc knockdown in the HCC827 and NCI-H1435 cells. On the whole, the present study demonstrates that ATIC promotes LUAD cell growth and migration by increasing Myc expression.

Generation of non-iterative phase-only hologram based on a hybrid phase mask.

The random phase method and quadratic phase method are most widely used in the generation of non-iterative phase holograms. However, the former leads to the reconstruction being severely disturbed by speckle noise, with serious loss of detailed information, and the latter leads to the reconstruction being contaminated with ringing artifacts. To solve these problems, we present a novel, to the best of our knowledge, method capable of generating non-iterative phase holograms, hereafter referred to as hybrid-phase-only holograms (HPOHs). Our proposal is to use a weight factor to combine the random phase and quadratic phase to generate a hybrid phase mask. The hybrid phase mask is then superimposed on the target image to obtain a complex hologram by simple Fourier transform. Followed by retaining the phase of the complex hologram, we can generate the corresponding HPOH. The effects of different weight factors on the holographic reconstructions are discussed. Numerical simulations of reconstruction quality associated with the proposed method, random phase method, and quadratic phase method are presented for comparison purposes. Optical experiments based on liquid crystal on silicon also demonstrate the validity of the method.

The effect of triglycerides to high-density lipoprotein cholesterol ratio on the reduction of renal function: findings from China health and retirement longitudinal study (CHARLS).

BACKGROUND: Previous studies show that abnormal lipoprotein metabolism can increase the prevalence of chronic kidney disease (CKD). This study prospectively investigated the association of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and renal dysfunction in the Chinese population. METHODS: This longitudinal cohort research examined 7,316 participants (age range: 22-93) from the China Health and Retirement Longitudinal Study (CHARLS), including 6,560 individuals with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (normal renal function, NRF) group and 756 with eGFR < 60 mL/min/1.73 m2 (impaired renal function, IRF) group. In NRF group, reduction in renal function was defined as eGFR < 60 mL/min/1.73 m2 at exit visit and in IRF group, it was defined as decline in eGFR category, average eGFR decline > 5 mL/min/1.73 m2 per year or > 30 % decrease in eGFR from baseline. RESULTS: The study results showed that TG/HDL-C ratio was positively associated with the risk of renal function decline in the NRF group (OR 1.30, 95 %CI 1.03-1.65, P = 0.03) and the IRF group (OR 1.90, 95 %CI 1.21-3.23, P = 0.02) when adjusting for age, gender, obesity, diabetes, hypertension, waist circumference, drinking, smoking, history of heart disease and stroke, low-density lipoprotein cholesterol and eGFR category. Analysis of the IRF group indicated that relative to the group of TG/HDL-C < 1.60, the group of TG/HDL-C ≥ 2.97 had an increased risk for the decline of eGFR category (OR 1.89, 95 %CI 1.12-3.21, P = 0.02) and > 30 % decline in eGFR (OR 2.56, 95 %CI 1.05-6.38, P = 0.04). CONCLUSIONS: The high TG/HDL-C ratio was an independent risk factor for declining renal function in the Chinese population.

Short sleep duration increases the risk of hyperuricemia among Chinese adults: findings from the China Health and Nutrition Survey.

STUDY OBJECTIVES: Hyperuricemia is a growing public health problem with its increasing prevalence. Few studies have investigated the association between sleep duration and hyperuricemia. The objective of this study is to explore whether short sleep duration is an independent risk factor of hyperuricemia in Chinese adults. METHODS: The data we analyzed was extracted from the 2009 wave of the China Health and Nutrition Survey. The population we analyzed included 8289 participants aged 18 years or older with sleep of 5-10 h per 24 h. We categorized the population into three groups by sleep duration: 5-6 h (short sleeper),7-8 h (regular sleeper), and 9-10 h (long sleeper). Hyperuricemia was defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women. RESULTS: Among the three groups, 9.8% were short sleepers, 68.4% were regular sleepers and 21.8% were long sleepers. The prevalences of hyperuricemia were 19.5%,15.2% and 15.5% respectively. The risks of hyperuricemia in regular and long sleep groups were lower than short sleep group, and the association remained after adjusting for indexes including age, gender, chronic kidney disease, hypertension, diabetes mellitus, high low-density lipoprotein cholesterol (LDL-c), and obesity. In subgroup analysis, we found the association was still observed in participants without hypertension, diabetes mellitus or obesity. CONCLUSIONS: Our findings suggest that short sleep duration is associated with higher risk of hyperuricemia independently of cardiometabolic risk factors, especially in individuals without traditional hyperuricemia risk factors.

Association between urbanisation and the risk of hyperuricaemia among Chinese adults: a cross-sectional study from the China Health and Nutrition Survey (CHNS).

OBJECTIVE: To explore the association between urbanicity and hyperuricaemia (HUA) and whether urbanicity is an independent risk factor for HUA in Chinese adults. DESIGN: Data analysis from a cross-sectional survey. SETTING AND PARTICIPANTS: 8579 subjects aged 18 years or older were enrolled in the study from the 2009 wave of the China Health and Nutrition Survey to analyse the association between urbanicity and HUA. We divided them into three categories according to urbanisation index (low, medium and highly urbanised groups). MAIN OUTCOME MEASURES: HUA was defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women. RESULTS: The prevalence of HUA in low, medium and highly urbanised groups was 12.2%, 14.6% and 19.8%, respectively. The independent factors influencing serum uric acid included age, gender, hypertension, diabetes, chronic kidney disease, drinking, obesity and community-level urbanisation index (ß=0.016, p<0.001). The risk of HUA in the highly urbanised group was significantly higher than that of the low urbanised group (OR 1.771, 95% CI 1.545 to 2.029, p<0.001), even after adjusting for other covariates (OR 1.661, 95% CI 1.246 to 2.212, p=0.001). In a subgroup analysis, we found that age, gender, comorbidity (such as hypertension, diabetes, obesity and chronic kidney disease) and physical activity affected the association between urbanisation and the risk of HUA. CONCLUSIONS: Our findings suggest that living in highly urbanised areas is linked with higher risk of HUA independent of cardiometabolic and health-related behavioural risk factors, which have been shown to increase along with urbanisation.

Hydrogen sulfide attenuates renal fibrosis by inducing TET-dependent DNA demethylation on Klotho promoter.

Hypoxia is a key pathogenetic characteristic of chronic kidney disease (CKD). Klotho has renoprotective effect and its expression is commonly suppressed in CKD patients. We showed that chronic hypoxia in unilateral ureteral obstruction model mice is associated with renal Klotho promoter methylation and expression silencing. Administration of low-dose of sodium hydrosulfide (NaHS) effectively ameliorated renal tubulointerstitial fibrosis in the mouse model by demethylating Klotho promoter and restoring its expression. Mechanistically, hypoxia microenvironment in CKD reduced cellular oxygen availability and Fe2+ concentration, and led to impaired activity of ten-eleven translocation (TET), which is critical in maintaining Klotho promoter demethylation status. NaHS treatment greatly improved hypoxia condition, restored TET activity, reversed DNA methylation, and thus, increased Klotho expression. Our results strongly suggested that correcting hypoxia condition to restore TET activity could be a promising therapeutic strategy against CKD.

Association between exposure to the Chinese famine during early life and the risk of chronic kidney disease in adulthood.

BACKGROUND AND OBJECTIVES: Famine exposure in human early life is proven to be associated with urinary protein concentration and renal function but has not been studied with chronic kidney disease. We aimed to explore the association between exposure to the Chinese famine (from 1959 to 1962) in early life and the risk of chronic kidney disease in adulthood. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We selected 6267 participants from the baseline survey of China Health and Retirement Longitudinal Study (CHARLS) 2011-2012. Based on the birth year, they were divided into fetal exposed, preschool exposed, school-aged exposed, and non-exposed groups. The estimated glomerular filtration rate (eGFR) was calculated according to Japanese coefficient-modified Chronic Kidney Disease Epidemiology Collaboration equation. Chronic kidney disease (CKD) was defined as eGFR less than 60 mL/min per 1.73 m2. RESULTS: The prevalence of CKD in fetal exposed, preschool exposed, school-aged exposed and non-exposed groups was 4.27%, 5.41%, 9.65% and 2.42%, respectively. The risk of CKD in fetal exposed, preschool exposed and school-aged exposed groups was significantly higher than the non-exposed group. In addition, after stratification by gender and famine severity, we found that only fetal exposure to the severe famine was associated with the elevated risk of CKD among male adults (OR 4.44, 95%CI 1.10-17.92, P < 0.05), even after adjusting for age, marital status, household per capita income, history of kidney disease, hypertension, diabetes or abnormal glucose tolerance, smoking, drinking, rural/urban residence and highest educational attainment of parents. CONCLUSIONS: Severe famine exposure as a fetus might increase the risk of chronic kidney disease in male adults.

Assessing the difference of tolerance and phytoremediation potential in mercury contaminated soil of a non-food energy crop, Helianthus tuberosus L. (Jerusalem artichoke).

This study was conducted to evaluate the effects of mercury stress on growth, photosynthesis and mercury accumulation in different cultivars of a non-food energy crop, Jerusalem artichoke, and to screen appropriate cultivars for their efficacy in the phytoremediation of mercury (Hg2+) contaminated soil. Cultivars LZJ033 (high above-ground biomass and nutrient content, and strongly sexual reproduction) and LZJ119 (a long period of vegetative growth) exhibited more tolerance to mercury stress than LZJ047 (the highest tuber yield and total sugar content). The lines LZJ119 and LZJ047 showed delays in emergence time of about four weeks, and LZJ047 exhibited the highest mortality rate, 85.19%, under treatment with 10 mg kg-1 mercury. The MDA (malondialdehyde) content increased whereas and the Pn (net photosynthetic rate), Fv ∕Fm (the maximum quantum yield of PSII photochemistry) and chlorophyll content decreased in response to mercury stress. The stem diameter, stem biomass and photosynthetic rate of Jerusalem artichoke showed some modest increases in response to mercury stress and exhibited hormesis at least 1 mg kg-1 mercury treatment. Overall, LZJ119 produced more biomass under mercury stress, whereas LZJ033 exhibited a greater capacity for mercury bioaccumulation. Accordingly, LZJ119 may be a good candidate cultivar for use in cases of moderate-low mercury contamination, whereas LZJ033 may be a better candidate under conditions of high mercury contamination. When Jerusalem artichoke was cultivated in mercury contaminated soil, it not only removed the mercury from soil but also produced large amounts of tubers and shoots which could be used as feedstock for the production of bioethanol.