Acquired Fanconi syndrome in mixed cryoglobulinemia patients: a single-center case series.

PURPOSE: Cryoglobulinemia is a pathological condition characterized by the presence of cryoglobulins in the blood, with cryoglobulinemic glomerulonephritis being the most frequent form of renal involvement. Fanconi syndrome presents as a generalized dysfunction of the proximal tubule, characterized by the presence of polyuria, phosphaturia, glycosuria, proteinuria, proximal renal tubular acidosis, and osteomalacia. We aimed to present five cases co-occurring with Fanconi syndrome and cryoglobulinemia. METHODS: We retrospectively summarized the cases of five patients with Fanconi syndrome and cryoglobulinemia at Peking Union Medical College Hospital from January 2012 to June 2022. The clinical features, diagnosis, treatment, and prognosis were systematically analyzed. RESULTS: All five patients exhibited typical features of Fanconi syndrome, and cryoglobulinemia was concurrently detected in all cases. These patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, and IgM constitutes the predominant monoclonal component in cryoglobulins. In addition to supplemental treatment, timely immunosuppressive therapy may potentially benefit the long-term renal prognosis of patients with this condition. CONCLUSION: Our findings highlight the rare co-occurrence of Fanconi syndrome and cryoglobulinemia in clinical practice. Despite the lack of causal evidence, the coexistence of Fanconi syndrome and tubulointerstitial injury is also noteworthy in patients with cryoglobulinemia, underscoring the importance of thorough evaluation and tailored management in patients presenting with overlapping renal manifestations. Key Points • Patients with mixed cryoglobulinemia can clinically present with tubulointerstitial injury, specifically manifesting as Fanconi syndrome. • In addition to typical symptoms of Fanconi syndrome, these patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, while IgM constitutes the monoclonal component in cryoglobulins. • Timely immunosuppressive therapy may improve long-term renal prognosis in these patients.

The value of G-CSF in women experienced at least one implantation failure: a systematic review and meta-analysis.

Objective: Despite the developments of in vitro fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium, and immune system interactions. Effective treatments are urgently required to improve successful implantation. Recently, many researchers have focused on granulocyte colony-stimulating factor (G-CSF) to regulate immune response and embryo-endometrium cross-talk. However, previous studies have reported inconsistent findings on the efficacy of G-CSF therapy on implantation failure. The objective of this review was to further explore the effects of G-CSF according to administration dosage and timing among women who experienced at least one implantation failure. Methods: We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials of G-CSF on implantation failure up to July 21, 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the heterogeneity of the studies with the I2 index was analyzed. Results: We identified a total of 2031 studies and finally included 10 studies in the systematic review and meta-analysis. G-CSF administration improved the clinical pregnancy rate (CPR), implantation rate (IR), biochemical pregnancy rate (BPR), and live birth rate (LBR) in women with at least one implantation failure. Subgroup analyses showed that G-CSF treatment could exert good advantages in improving CPR [OR=2.49, 95%CI (1.56, 3.98), I2 = 0%], IR [OR=2.82, 95%CI (1.29, 6.15)], BPR [OR=3.30, 95%CI (1.42, 7.67)] and LBR [OR=3.16, 95%CI (1.61, 6.22), I2 = 0%] compared with the blank control group. However, compared with placebo controls, G-CSF showed beneficial effects on CPR [OR=1.71, 95%CI (1.04, 2.84), I2 = 38%] and IR [OR=2.01, 95%CI (1.29, 3.15), I2 = 24%], but not on LBR. In addition, >150µg of G-CSF treatment increased CPR [OR=2.22, 95%CI (1.47, 3.35), I2 = 0%], IR [OR=2.67, 95%CI (1.47, 4.82), I2 = 0%] and BPR [OR=2.02, 95%CI (1.17, 3.47), I2 = 22%], while ≤150µg of G-CSF treatment improved miscarriage rate (MR) [OR=0.14, 95%CI (0.05, 0.38), I2 = 0%] and LBR [OR=2.65, 95%CI (1.56, 4.51), I2 = 0%]. Moreover, G-CSF administration on the day of embryo transfer (ET) could increase CPR [OR=2.81, 95%CI (1.37, 5.75), I2 = 0%], but not on the day of ovum pick-up (OPU) or human chorionic gonadotropin (HCG) injection. Conclusion: G-CSF has a beneficial effect on pregnancy outcomes to some extent among women who experienced at least one implantation failure, and the administration dosage and timing influence the effect size.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447046.

Effect of nutrition impact symptoms on oral nutritional supplements energy intake and use days in patients with head and neck cancer: A cross-sectional study.

BACKGROUND: This study aims to explore the effect of nutritional impact symptoms (NIS) on oral nutritional supplements (ONS) energy intake and use days among head and neck cancer (HNC) patients. METHODS: A cross-sectional study was conducted among HNC patients in a hospital in western China between January 2019 and June 2020. The NIS was from the Patient-Generated Subjective Global Assessment (PG-SGA) scale. Mann-Whitney test was used to examine the differences between different kinds of NIS and ONS use days. Binary logistic regression was used to determine the effect of NIS on ONS energy intake. RESULTS: The most prevalent four NIS were no appetite (35.3%), dysphagia (29.4%), vomiting (13.2%) and oral pain (12.5%), respectively. All patients in the study were malnutrition. Patients with xerostomia or oral pain had less ONS use days than those without these symptoms. Patients with vomiting (OR 0.09, 95% CI 0.02-0.50) or pain (OR 0.15, 95% CI 0.02-0.89) were less likely to have ONS energy intake ≥400 kcal/day than those without these symptoms after adjusting the confounding factors. In addition, one-point increase in total NIS score was associated with a lower proportion of ONS energy intake ≥400 kcal/day (OR 0.77, 95% CI 0.59-0.99). CONCLUSION: Xerostomia, oral pain, vomiting and pain should be strengthened and intervened to improve ONS use and nutritional status among HNC patients with malnutrition.

Process of mercury accumulation in urban strip river artificial wetland ecosystems: a case study of Changchun, a typical industrial city in Northeast China.

Mercury (Hg), as a global pollutant, is persistent, migratory, insidious, highly biotoxic and highly enriched, and is widely distributed in the atmosphere, hydrosphere, biosphere and lithosphere. Wetland ecosystems, as active mercury reservoirs, have become the most important sources and sinks of heavy metal mercury. Distinguished from natural wetlands, artificial wetlands located in urban sections of rivers face problems such as diverse urban pollution sources and complex spatial and temporal changes. Therefore, in this study, five intermittently distributed artificial wetlands were selected from the upstream to the downstream of the Changchun section of the Yitong River, a tributary of the Songhua River basin in the old industrial base of Northeast China. The mercury levels in the water bodies, sediments and plants of the artificial wetlands were collected and tested in four quarters from April 2023 to analyse the spatial and temporal distribution characteristics of total mercury. The results showed that the mercury levels in the water bodies, sediments and plants of the five wetlands showed a fluctuating trend with the river flow direction and had certain spatial and temporal distribution characteristics. This phenomenon was attributed to the sinking of external mercury pollution sources. In general, the wetland ecosystems showed a decreasing trend in the total Hg output of the downstream watershed. This may be due to the retention of particulate matter by aquatic plants in artificial wetlands to regular salvage of dead aquatic plants. At the same time urbanization and industrialization affect mercury levels in aquatic environments, so the risk of residential exposure needs to be looked at.

Association between severity of nonalcoholic fatty liver disease and major adverse cardiovascular events in patients assessed by coronary computed tomography angiography.

BACKGROUND: The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. METHODS: A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan-Meier analysis were used to assess poor prognosis. RESULTS: During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54-5.66]; p = 0.001) and CAD-RADS categories 3-5 (HR = 16.31[6.34-41.92]; p < 0.001) were independent risk factors for MACEs. The Kaplan-Meier analysis showed that moderate to severe NAFLD patients had a worsen prognosis than mild NAFLD patients (log-rank p < 0.001). Moreover, the combined receiver operating characteristic curve of the severity of NAFLD and CAD-RADS category showed a good predicting performance for the risk of MACEs, with an area under the curve of 0.849 (95% CI = 0.786-0.911). CONCLUSION: The severity of NAFLD was independent risk factor for MACEs in patients with obstructive CAD, having CAD-RADS 3-5 categories on CCTA.

Exploration and future trends on spatial correlation of green innovation efficiency in strategic emerging industries under the digital economy: A social network analysis.

With digital technological change and the increasing frequency of interregional innovation links, the spatial correlation and diversity of strategic emerging industries' green innovation efficiency (SEI-GIE) need to be explored in depth. This paper innovatively constructs the SEI-GIE input-output index system under digital economy. The proposed grey model FINGBM(1,1) with ω-order accumulation and weighted initial value optimization realizes effective prediction of 7 input-output indicators of 30 provinces in China from 2021 to 2025. Super-SBM-DEA, gravity model, and social network analysis are applied to explore spatial network structure's dynamic process of SEI-GIE from 12th to 14th Five-Year-Plan period (2011-2025). Empirical results show that (1) Under the effect of digital economy, the SEI-GIE in China generally shows a U-shaped fluctuation trend, in which the growth trend in the central region is obvious, and the western region shows significant fluctuations. (2) The spatial correlation network of SEI-GIE presents a complex and stable center-periphery circle. Particularly, the overall increase in network efficiency highlights the strong small-world characteristics. (3) Beijing, Shanghai, Zhejiang and Jiangsu have always been in the leading core position, with strong influence and control; And Tianjin's core position in the network will decline. Additionally, Guangxi and Chongqing have great potential, but Guangdong needs to strengthen its radiation effect. (4) Block model shows that plate-I (Beijing, Tianjin) receive spatial spillovers from others, while plates-III,IV have significant spillover effects. This study provides theoretical reference for policymakers from a network perspective to promote development of China's SEI-GIE.

Efficacy and safety of therapies related to acupuncture for acute herpes zoster: A PRISMA systematic review and network meta-analysis.

BACKGROUND: Herpes zoster (HZ) is mainly characterized by intense pain and severe skin lesions, particularly during the acute phase, which seriously affects the patient's quality of life. Acupuncture is a widely used and effective treatment for HZ. However, there are many types of acupuncture, which have different curative efficacy. This study employed a network meta-analysis (NMA) to assess and rank the clinical efficacy of different acupuncture therapies. METHODS: The database of Cochrane Library, Web of Science, PubMed, MEDLINE, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Database, VIP Database, and Wanfang Database were searched from inception to December 31, 2022 to identify eligible randomized controlled trials (RCTs) of acupuncture related therapies in the treatment of acute HZ. The outcome indicators measured were visual analogue scale (VAS), date of cessation of herpes increase (DCHI), effective rate (ER), postherpetic neuralgia (PHN), and adverse events (AEs). Bayesian network meta-analyses were performed using the GeMTC package (version 1.0-1) and R software (version 4.2.3). RESULTS: A total of 59 RCTs with 3930 patients were included. The results of this NMA were as follows: compared with pharmacotherapy, electroacupuncture (EA) + pricking and cupping (PC) shown the best efficacy to improve VAS score and reduce DCHI. In terms of ER, EA + fire needle (FN) had the highest results of probability ranking. PC was more effective in reducing the incidence of PHN. Furthermore, this study shown that the incidence of AEs associated with acupuncture-related therapies was acceptable. CONCLUSIONS: This study indicated that therapies related to acupuncture were both effective and safe in treating acute HZ, and could significantly reduce patients' symptoms such as pain and skin lesions with fewer adverse events. Clinically, the selection of the appropriate therapy should be based on practical considerations. However, due to the limitations of this study, more high-quality trials are required to evaluate the efficacy and safety of acupuncture-related therapy for the treatment of acute HZ.

Lipidomics random forest algorithm of seminal plasma is a promising method for enhancing the diagnosis of necrozoospermia.

BACKGROUND: Despite the clear clinical diagnostic criteria for necrozoospermia in andrology, the fundamental mechanisms underlying it remain elusive. This study aims to profile the lipid composition in seminal plasma systematically and to ascertain the potential of lipid biomarkers in the accurate diagnosis of necrozoospermia. It also evaluates the efficacy of a lipidomics-based random forest algorithm model in identifying necrozoospermia. METHODS: Seminal plasma samples were collected from patients diagnosed with necrozoospermia (n = 28) and normozoospermia (n = 28). Liquid chromatography-mass spectrometry (LC-MS) was used to perform lipidomic analysis and identify the underlying biomarkers. A lipid functional enrichment analysis was conducted using the LION lipid ontology database. The top 100 differentially significant lipids were subjected to lipid biomarker examination through random forest machine learning model. RESULTS: Lipidomic analysis identified 46 lipid classes comprising 1267 lipid metabolites in seminal plasma. The top five enriched lipid functions as follows: fatty acid (FA) with ≤ 18 carbons, FA with 16-18 carbons, monounsaturated FA, FA with 18 carbons, and FA with 16 carbons. The top 100 differentially significant lipids were subjected to machine learning analysis and identified 20 feature lipids. The random forest model identified lipids with an area under the curve > 0.8, including LPE(20:4) and TG(4:0_14:1_16:0). CONCLUSIONS: LPE(20:4) and TG(4:0_14:1_16:0), were identified as differential lipids for necrozoospermia. Seminal plasma lipidomic analysis could provide valuable biochemical information for the diagnosis of necrozoospermia, and its combination with conventional sperm analysis may improve the accuracy and reliability of the diagnosis.

N-glycosylation of SCAP exacerbates hepatocellular inflammation and lipid accumulation via ACSS2-mediated histone H3K27 acetylation.

Sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) is a widely expressed membrane glycoprotein that acts as an important modulator of lipid metabolism and inflammatory stress. N-glycosylation of SCAP has been suggested to modulate cancer development, but its role in NASH is poorly understood. In this study, the N-glycosylation of SCAP was analyzed by using sequential trypsin proteolysis and glycosidase treatment. The liver cell lines expressing wild-type and N-glycosylation sites mutated SCAP were constructed to investigate the N-glycosylation role of SCAP in regulating inflammation and lipid accumulation as well as the underlying mechanisms. The hepatic SCAP protein levels were significantly increased in C57BL/6J mice fed with western diet and sweet water (WD+SW) and diabetic db/db mice, which exhibited typical liver steatosis and inflammation. In vitro, the enhanced N-glycosylation increased the protein stability of SCAP and hence increased its total protein levels, while the ablation of N-glycosylation significantly decreased SCAP protein stability and alleviated lipid accumulation and inflammation in hepatic cell lines. Mechanistically, the presence of SCAP N-glycosylation increased not only the SREBP1-mediated acetyl-CoA synthetase 2 (ACSS2) transcription but also the AMPK-mediated S659 phosphorylation of ACCS2 protein, causing the enhanced ACSS2 levels in nucleus and hence increasing the histone H3K27 acetylation (H3K27ac), which is a key epigenetic modification associated with NASH. Modulating ACSS2 expression or its location in cytoplasm abolished the effects of SCAP N-glycosylation on H3K27ac and lipid accumulation and inflammation. In conclusion, SCAP N-glycosylation aggravates inflammation and lipid accumulation through enhancing ACSS2-mediated H3K27ac in hepatocytes.

Dysregulations of amino acid metabolism and lipid metabolism in urine of children and adolescents with major depressive disorder: a case-control study.

RATIONALE: The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied. OBJECTIVES: We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures. METHODS: Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel. RESULTS: In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD. CONCLUSIONS: Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD.

Two Mixed-Ligand Co(II) Complexes as Luminescent Materials and Loaded with Temozolomide-gel Particles in Nursing Against Glioma.

By employing a mixed-ligand strategy, we synthesized two new coordination polymers (CPs) featuring Co(II): {Co(H2L)(bib)]·2H2O}n (1) and {Co(L)(bib)2]·2H2O}n (2), where H4L represents 5-(3,5-dicarboxybenzyloxy) isophthalic acid, and bib denotes 1,4-bis(1-imidazolyl)benzene. These CPs were obtained through the reaction of H4L, a flexible carboxylic acid ligand, with Co(NO3)2·6H2O in various solvent mixtures, along with the N-donor co-ligand bib. Complexes 1 and 2 are formed through distinct coordination modes, resulting in their distinct structural features and excellent fluorescent properties. Based on ligand-centered fluorescence emission and the blue shift (CP 1) along with red shift (CP 2) characteristics, both complexes show promise for applications in fields such as blue fluorescence sensing materials and luminescent materials. After successfully synthesizing two CPs, CP 1 was chosen as the carrier for loading temozolomide (TMZ). Subsequently, leveraging the unique advantages of hydrogels, we developed a novel metal gel formulation loaded with TMZ. The inhibitory effect of this formulation on the growth of glioblastoma was evaluated. Our results demonstrate a significant suppression of glioblastoma cell proliferation by this system, providing an effective avenue for glioblastoma treatment.

Association Between CYP24A1 Polymorphisms and Bladder Cancer Risk in the Chinese Han Population.

In this cohort of 217 bladder cancer patients and 484 healthy controls, we explored the association between CYP24A1 variants (rs2762934, rs1570669, rs6068816, rs2296241) and bladder cancer risk in the Chinese Han population. Utilizing the Agena MassARRAY system, we genotyped four selected CYP24A1 polymorphisms. Logistic regression revealed a significant association of rs2762934 and rs1570669 with elevated bladder cancer risk, while rs6068816 exhibited a protective effect. Bioinformatics analysis of CYP24A1 expression in normal and cancerous bladder tissues indicated higher expression in normal tissue. In conclusion, our findings highlight the potential role of CYP24A1 variants in bladder cancer susceptibility.

Inactivation of ERK1/2 in cancer-associated hepatic stellate cells suppresses cancer-stromal interaction by regulating extracellular matrix in fibrosis.

The ERK1/2 pathway is involved in epithelial-mesenchymal transformation and cell cycle of tumor cells in hepatocellular carcinoma (HCC). In the present study, we investigated the involvement of ERK1/2 activation on hepatic stellate cells (HSCs). We identified ERK1/2 phosphorylation in activated HSCs of HCC samples. We found that tumor cells promoted the migration and invasion capacity of HSCs by activating ERK1/2 phosphorylation. Using high throughput transcriptome sequencing analysis, we found that ERK1/2 inhibition altered genes significantly correlated to signaling pathways involved in extracellular matrix remodeling. We screened genes and demonstrated that the ERK1/2 inhibition-related gene set significantly correlated to cancer-associated fibroblast infiltration in TCGA HCC tumor samples. Moreover, inhibition of ERK1/2 suppressed tumor cell-induced enhancement of HSC migration and invasion by regulating expression of fibrosis markers FAP, FN1 and COL1A1. In a tumor cell and HSC splenic co-transplanted xenograft mouse model, inhibition of ERK1/2 suppressed liver tumor formation by downregulating fibrosis, indicating ERK1/2 inhibition suppresses tumor-stromal interactions in vivo. Taken together, our data indicate that inhibition of ERK1/2 in tumor-associated HSCs suppresses tumor-stromal interactions and progression. Furthermore, inhibition of ERK1/2 may be a potential target for HCC treatment.

Comparison of bio-beads combined with Pseudomonas edaphica and three phosphate materials for lead immobilization: Performance, mechanism and plant growth.

Phosphate materials (PMs) combine with phosphate solubilizing bacteria play an essential roles in lead (Pb) immobilization, but their resulting ability to reduce Pb bioavailability may vary depending on PMs used. In this study, Pseudomonas edaphica GAU-665 and three PMs: tricalcium phosphate, calcium phytate and nano-hydroxyapatite were respectively encapsulated into bio-beads by sodium alginate, which immobilization efficiency of Pb2+ were 99.11%, 97.76% and 99.02% at initial Pb2+ concentration of 200 mg L-1, respectively. The Pb2+ immobilization performance of bio-beads under different conditions and their organic acids secreted were examined. Most Pb2+ was immobilized by bio-beads through combined functions of adsorption, precipitation, ion exchange and biomineralization, accompanied by the formation of more stable compounds such as Pb3(PO4)2, Pb5(PO4)3OH and Pb5(PO4)3Cl. Meanwhile, pot experimental results indicated that the inoculation of CPhy (calcium phytate) bio-beads with PSB have highest biomass and root growth of oat (Avena sativa L.) in Pb-stressed compared with CK, which increased the content of chlorophyll b (167.51%) in shoot. In addition, the CPhy bio-beads enhance the peroxidase, catalase activities and reduce the malondialdehyde content to alleviating lead physiological toxicity in oat, which reductions the Pb accumulation in shoot (52.06%) and root (81.04%), and increased the residual fraction of Pb by 165.80% in soil. These findings suggest the bio-beads combined with P. edaphica GAU-665 and calcium phytate is an efficient Pb immobilization material and provided feasible way to improve safety agricultural production and Pb-contaminated soil remediation.

[Characteristics of Epiphytic Bacterial Community on Submerged Macrophytes in Water Environment Supplemented with Reclaimed Water].

Biofilms attached to submerged macrophytes play an important role in improving the water quality of the water environment supplemented with reclaimed water. In order to explore the effects of reclaimed water quality and submerged macrophyte species on the characteristics of an epiphytic bacterial community, different types of submerged macrophytes were selected as research objects in this study. 16S rRNA high-throughput sequencing technology was used on the epiphytic bacteria and the surrounding environmental samples to analyze the bacterial community structure and functional genes. The results showed that approximately 20%-35% of the nitrogen and phosphorus nutrients were absorbed and utilized in the water environment supplemented with reclaimed water. However, the COD, turbidity, and chroma of the downstream water were significantly increased. The bacterial community of the biofilms attached to submerged macrophytes was significantly different from that in the surrounding environment (soil, sediment, and water body) and in the activated sludge that was treated by reclaimed water. In terms of bacterial community diversity, the richness and diversity were significantly lower than those of soil and sediment but higher than those of plankton bacteria in water. In terms of bacterial community composition, dominant genera and corresponding abundances were also different from those of other samples. The main dominant bacterial genera were Sphingomonas, Aeromonas, Pseudomonas, and Acinetobacter, accounting for 7%-40%, respectively. Both macrophyte species and the quality of reclaimed water (BOD5, TN, NH4+-N, and TP) could affect the bacterial community. However, the effect of water quality of the bacterial community was greater than that of macrophytes species. Additionally, the quality of reclaimed water also affected the abundance of functional genes in the bacterial community, and the relative abundance of nitrogen and phosphorus cycling functional genes was higher in areas with higher nitrogen and phosphorus concentrations.

Changes in serum sodium concentration during hemodialysis is a predictor of mortality and cardio-cerebrovascular event.

BACKGROUND: Previous study consistently showed that lower serum sodium (SNa) was associated with a greater risk of mortality in hemodialysis (HD) patients. However, few studies have focused on the change in SNa (ΔSNa = post-HD SNa - pre-HD SNa) during an HD session. METHODS: In a retrospective cohort of maintenance HD adults, all-cause mortality and cardio-cerebrovascular event (CCVE) were followed up for a medium of 82 months. Baseline pre-HD SNa and ΔSNa were collected; time-averaged pre-HD SNa and ΔSNa were computed as the mean values within 1-year, 2-year and 3-year intervals after enrollment. Cox proportional hazards models were used to evaluate the relationships of pre-HD and ΔSNa with outcomes. RESULTS: Time-averaged pre-HD SNa were associated with all-cause mortality (2-year pre-HD SNa: HR [95% CI] 0.86 [0.74-0.99], p = 0.042) and CCVE (3-year pre-HD SNa: HR [95% CI] 0.83 [0.72-0.96], p = 0.012) with full adjustment. Time-averaged ΔSNa also demonstrated an association with all-cause mortality (3-year ΔSNa: HR [95% CI] 1.26 [1.03-1.55], p = 0.026) as well as with CCVE (3-year ΔSNa: HR [95% CI] 1.51 [1.21-1.88], p = <0.001) when fully adjusted. Baseline pre-HD SNa and ΔSNa didn't exhibit association with both outcomes. CONCLUSIONS: Lower time-averaged pre-HD SNa and higher time-averaged ΔSNa were associated with a greater risk of all-cause mortality and CCVE in HD patients.

Selective Hydrogenation of Diethyl Malonate to 1,3-Propanediol Over Ga-Promoted Cu/SiO2 Catalysts With Enhanced Activity and Stability.

Cu catalysts with different compositions and different Cu and promoter contents were prepared by precipitation-gel method and studied for the selective hydrogenation of syngas or biomass-based diethyl malonate (DEM) to valuable 1,3-propanediol (1,3-PDO). The Ga-promoted 70Cu6Ga/SiO2 catalyst was found to exhibit the highest catalytic performance, achieving 100 % DEM conversion and 76.6 % 1,3-PDO selectivity under reaction conditions of 160 °C and 8 MPa H2. The 70Cu6Ga/SiO2 bimetallic catalyst also presented obviously better stability than that of the monometallic 70Cu/SiO2 catalyst in a continuous flow reactor over 180 h time-on stream. Characterization results showed that the incorporation of Ga increased the interaction between Cu and Ga species, hindered the full reduction of Cu2+ species, and thus increased the proportion of Cu+ and the number of Lewis acidic sites on the catalyst surface. The synergistic effect between Cu0 and Cu+ enhanced the adsorption and activation of ester carbonyl groups and their subsequent hydrogenation, eventually contributed to the outstanding performances of the CuGa/SiO2 bimetallic catalysts.

Complement Proteins in Serum Astrocyte-Derived Exosomes Are Associated with Poststroke Cognitive Impairment in Type 2 Diabetes Mellitus Patients.

Background: The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer's disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods: This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results: Mediation analyses showed that C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions: Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients.REGISTRATION: URL: http://www.chictr.org.cn/,ChiCTR1900021544.

Chemo-Enzymatic Strategy for the Efficient Synthesis of Steroidal Drugs with 10α-Methyl Group and a Side Chain at C17-Position from Biorenewable Phytosterols.

Steroidal pharmaceuticals with a 10α-methyl group or without the methyl group at C10-position are important medicines, but their synthesis is quite challenging, due to that the natural steroidal starting materials usually have a 10ß-methyl group which is difficult to be inverted to 10α-methyl group. In this study, 3-((1R,3aS,4S,7aR)-1-((S)-1-hydroxypropan-2-yl)-7a-methyl-5-oxooctahydro-1H-inden-4-yl) propanoic acid (HIP-IPA, 2e) was demonstrated as a valuable intermediate for the synthesis of this kind of active pharmaceutical ingredients (APIs) with a side chain at C17-position. Knockout of a ß-hydroxyacyl-CoA dehydrogenase gene and introduction of a sterol aldolase gene into the genetically modified strains of Mycobacterium fortuitum (ATCC 6841) resulted in strains N13Δhsd4AΩthl and N33Δhsd4AΩthl, respectively. Both strains transformed phytosterols into 2e. Compound 2e was produced in 62% isolated yield (25 g) using strain N13Δhsd4AΩthl, and further converted to (3S,3aS,9aS,9bS)-3-acetyl-3a,6-dimethyl-1,2,3,3a,4,5,8,9,9a,9b-decahydro-7H-cyclopenta[a]naphthalen-7-one, which is the key intermediate for the synthesis of dydrogesterone. This study not only overcomes a challenging synthetic problem by enabling an efficient synthesis of dydrogesterone-like steroidal APIs from phytosterols, the well-recognized cheap and readily available biobased raw materials, but also provides insights for redesigning the metabolic pathway of phytosterols to produce other new compounds of relevance to the steroidal pharmaceutical industry.

A data-adaptive methods in detecting exogenous methyltransferase accessible chromatin in human genome using nanopore sequencing.

MOTIVATION: Identifying chromatin accessibility is one of the key steps in studying the regulation of eukaryotic genomes. The combination of exogenous methyltransferase and nanopore sequencing provides an strategy to identify open chromatin over long genomic ranges at the single-molecule scale. However, endogenous methylation, non-open-chromatin-specific exogenous methylation and base-calling errors limit the accuracy and hinders its application to complex genomes. RESULTS: We systematically evaluated the impact of these three influence factors, and developed a model-based computational method, methyltransferase accessible genome region finder (MAGNIFIER), to address the issues. By incorporating control data, MAGNIFIER attenuates the three influence factors with data-adaptive comparison strategy. We demonstrate that MAGNIFIER is not only sensitive to identify the open chromatin with much improved accuracy, but also able to detect the chromatin accessibility of repetitive regions that are missed by NGS-based methods. By incorporating long-read RNA-seq data, we revealed the association between the accessible Alu elements and non-classic gene isoforms. AVAILABILITY AND IMPLEMENTATION: Freely available on web at https://github.com/Goatofmountain/MAGNIFIER.