CMTM3 regulates neutrophil activation and aggravates sepsis through TLR4 signaling.

Regulation of neutrophil activation plays a significant role in managing sepsis. CKLF-like MARVEL transmembrane domain containing (CMTM)3 is a membrane protein involved in immune response. Here, we find that CMTM3 expression is elevated in sepsis and plays a crucial role in mediating the imbalance of neutrophil migration. Cmtm3 knockout improves the survival rate of septic mice, mitigate inflammatory responses, and ameliorate organ damage. Mechanistically, the deletion of Cmtm3 reduced the expression of Toll-like receptor 4 (TLR4) on neutrophils, leading to a decrease in the expression of C-X-C motif chemokine receptor 2 (CXCR2) on the cell membrane. This resulted in a reduced migration of neutrophils from the bone marrow to the bloodstream, thereby attenuating their recruitment to vital organs. Our findings suggest that targeting CMTM3 holds promise as a therapeutic approach to ameliorate the dysregulation of neutrophil migration and multi-organ damage associated with sepsis.

Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function.

T regulatory (Treg) cells are essential for self-tolerance whereas they are detrimental for dampening the host anti-tumor immunity. How Treg cells adapt to environmental signals to orchestrate their homeostasis and functions remains poorly understood. Here, we identified that transcription factor EB (TFEB) is induced by host nutrition deprivation or interleukin (IL)-2 in CD4+ T cells. The loss of TFEB in Treg cells leads to reduced Treg accumulation and impaired Treg function in mouse models of cancer and autoimmune disease. TFEB intrinsically regulates genes involved in Treg cell differentiation and mitochondria function while it suppresses expression of proinflammatory cytokines independently of its established roles in autophagy. This coordinated action is required for mitochondria integrity and appropriate lipid metabolism in Treg cells. These findings identify TFEB as a critical regulator for orchestrating Treg generation and function, which may contribute to the adaptive responses of T cells to local environmental cues.

Expanding the tolerance of segmented Influenza A Virus genome using a balance compensation strategy.

Reporter viruses provide powerful tools for both basic and applied virology studies, however, the creation and exploitation of reporter influenza A viruses (IAVs) have been hindered by the limited tolerance of the segmented genome to exogenous modifications. Interestingly, our previous study has demonstrated the underlying mechanism that foreign insertions reduce the replication/transcription capacity of the modified segment, impairing the delicate balance among the multiple segments during IAV infection. In the present study, we developed a "balance compensation" strategy by incorporating additional compensatory mutations during initial construction of recombinant IAVs to expand the tolerance of IAV genome. As a proof of concept, promoter-enhancing mutations were introduced within the modified segment to rectify the segments imbalance of a reporter influenza PR8-NS-Gluc virus, while directed optimization of the recombinant IAV was successfully achieved. Further, we generated recombinant IAVs expressing a much larger firefly luciferase (Fluc) by coupling with a much stronger compensatory enhancement, and established robust Fluc-based live-imaging mouse models of IAV infection. Our strategy feasibly expands the tolerance for foreign gene insertions in the segmented IAV genome, which opens up better opportunities to develop more versatile reporter IAVs as well as live attenuated influenza virus-based vaccines for other important human pathogens.

The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection.

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

MiR-18a affects hypoxia induced glucose metabolism transition in HT22 hippocampal neuronal cell line through the Hif1a gene.

Hypoxia can cause a variety of diseases, including ischemic stroke and neurodegenerative diseases. Within a certain range of partial pressure of oxygen, cells can respond to changes in oxygen. Changes in oxygen concentration beyond a threshold will cause damage or even necrosis of tissues and organs, especially for the central nervous system. Therefore, it is very important to find appropriate measures to alleviate damage. MiRNAs can participate in the regulation of hypoxic responses in various types of cells. MiRNAs are involved in regulating hypoxic responses in many types of tissues by activating the hypoxia-inducible factor (HIF) to affect angiogenesis, glycolysis and other biological processes. By analyzing differentially expressed miRNAs in hypoxia and hypoxia-related studies, as well as the HT22 neuronal cell line under hypoxic stress, we found that the expression of miR-18a was changed in these models. MiR-18a could regulate glucose metabolism in HT22 cells under hypoxic stress by directly regulating the 3'UTR of the Hif1a gene. As a small molecule, miRNAs are easy to be designed into small nucleic acid drugs, so this study can provide a theoretical basis for the research and treatment of nervous system diseases caused by hypoxia.

Discovery of novel chrysin derivatives as potential Anti-Psoriasis agents.

Psoriasis is a chronic inflammatory disease and is difficult to cure. In this work, a series of novel chrysin derivatives have been designed and prepared while evaluating anti-inflammatory activities in vitro and in vivo. In vitro, RAW264.7 cells were used to detect the inflammatory activities at first, and compounds 4h, 4k, and 4o significantly decreased the levels of NO, TNF-α, and IL-6. In particular, compound 4o showed superior anti-inflammatory activities than other compounds. Moreover, compound 4o decreased the level of IL-17A in LPS-induced HaCaT cells in vitro. The effect and mechanism of anti-inflammatory activities on psoriasis were determined by imiquimod (IMQ)-induced psoriasis-like mice in vivo. Compound 4o deduced the level of IL-6, IL-17A, IL-22, IL-23, and TNF-α, and showed potent anti-psoriasis activity. Further mechanism study suggested that compound 4o could improve the skin inflammation of psoriasis by inhibiting the NF-κB and STAT3 signaling pathways.

PSMD3 gene mutations cause pathological myopia.

PURPOSE: Genetic factors play a prominent role in the pathogenesis of pathological myopia (PM). However, the exact genetic mechanism of PM remains unclear. This study aimed to determine the candidate mutation of PM in a Chinese family and explore the potential mechanism. METHODS: We performed exome sequencing and Sanger sequencing in a Chinese family and 179 sporadic PM cases. The gene expression in human tissue was investigated by RT-quantitative real-time PCR (RT-qPCR) and immunofluorescence. Cell apoptotic rates were tested by annexin V-APC/7AAD and flow cytometry. Psmd3 knock-in mice with point mutation were generated for measuring myopia-related parameters. RESULTS: We screened a novel PSMD3 variant (c.689T>C; p.F230S) in a Chinese family with PM, and another rare mutation (c.1015C>A; p.L339M) was identified in 179 unrelated cases with PM. RT-qPCR and immunofluorescence confirmed the expression of PSMD3 in human eye tissue. Mutation of PSMD3 decreased the mRNA and protein expression, causing apoptosis of human retinal pigment epithelial cells. In in vivo experiments, the axial length (AL) of mutant mice increased significantly compared with that of wild-type mice (p<0.001). CONCLUSIONS: A new potential pathogenic gene, PSMD3, in a PM family was identified, and it may be involved in the elongation of AL and the development of PM.

Trajectories of peripheral white blood cells count around the menopause: a prospective cohort study.

BACKGROUND: Menopause significantly impacts the immune system. Postmenopausal women are more susceptible to infection. Nonetheless, the pattern of change in peripheral white blood cell counts around the menopause remains poorly understood. METHODS: We conducted a prospective longitudinal cohort study with repeated measurements using Kailuan cohort study of 3632 Chinese women who participated in the first checkup (2006-2007) and reached their final menstrual period (FMP) by the end of the seventh checkup (2018-2020). Peripheral WBC count indicators included total white blood cells (TWBC), neutrophils (NEUT), lymphocytes (LYM), and monocytes (MON). Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of WBC count indicators as a function of time before or after the final menstrual period (FMP). Interaction and subgroup analysis were used to explore the effects of age and body mass index (BMI) on changes in WBC indicators around FMP. RESULTS: WBC count indicators decreased before the FMP, and the reduction in TWBC, NEUT, and MON continued for 2 years following the FMP. LYM and NEUT declined during < -1 years and - 4 ∼ + 2 years relative to FMP, respectively. A reduction in MON was observed pre-FMP, extending continuously through the two-year period post-FMP. TWBC declined from - 3 to + 2 years relative to FMP, but both MON and TWBC increased during > + 2 years. The baseline age had an interaction effect on changes in WBC indicators during specific menopausal stages, except for TWBC. Individuals in different age subgroups showed distinct trajectories for NEUT, LYM and MON around the FMP. High baseline BMI had a synergistic effect on changes in specific menopause segments for TWBC, LYM, and MON. The impact of menopause on TWBC and LYM was postponed or counterbalanced in high BMI individuals. Individuals in three BMI subgroups experienced similar MON changes around FMP, and there were slight variations during < -4 years. CONCLUSIONS: Menopause was associated with count changes of peripheral WBC. The trajectories of various WBC types differ around menopause. Age and BMI affected WBC trajectory around menopause. The menopause period may represent a window of opportunity to promote immune health in middle-aged women.

VISION AND METAMORPHOPSIA OUTCOMES OF MACULAR BUCKLING FOR FOVEOSCHISIS-ASSOCIATED MACULAR DETACHMENT IN HIGHLY MYOPIC EYES.

PURPOSE: To assess the functional outcomes in visual acuity, metamorphopsia, and vision-related quality of life (VR-QOL) and to evaluate prognostic factors after macular buckling (MB) surgery in eyes with high myopia and foveoschisis (FS)-associated macular detachment (MD). METHODS: Thirty-nine eyes of 39 patients with FS-associated MD who underwent MB surgery were enrolled. Measured outcomes comprised best-corrected visual acuity (BCVA), metamorphopsia, VR-QOL, axial length (AL), macular reattachment, and resolution of foveoschisis. In addition, factors affecting final BCVA and metamorphopsia were analyzed. RESULTS: At 12 months postoperatively, 36 eyes (92.31%) achieved macular reattachment, 37 eyes (94.87%) achieved complete resolution of foveoschisis, and metamorphopsia diminished in 31 eyes (79.49%). LogMAR BCVAs at baseline and months 1, 3, 6, and 12 postoperatively were 0.62 ± 0.35 (20/83), 0.65 ± 0.3 (20/89), 0.59 ± 0.31 (20/77), 0.54 ± 0.31 (20/69), and 0.46 ± 0.27 (20/57) (P < 0.001), respectively. Metamorphopsia scores by M-CHARTS were 1.36° ± 0.51°, 1.04° ± 0.51°, 0.74° ± 0.47°, 0.59° ± 0.47°, and 0.13° ± 0.29° (P < 0.001). All Visual Function Questionnaire-25 subscales demonstrated significant improvement postoperatively, with the exception of "general health" (P = 0.08) and "driving" (P = 0.111). Preoperative BCVA was an independent risk factor for postoperative BCVA at month 12 (r = 0.638, P < 0.001), and the preoperative M-score was an independent risk factor for postoperative M-score at month 12 (r = 0.187, P = 0.045). CONCLUSION: MB surgery significantly improved BCVA, metamorphopsia, and VR-QOL in patients with FS-associated MD. Preoperative BCVA and metamorphopsia score were prognostic factors for postoperative BCVA and metamorphopsia score at month 12.

Dietary Inflammatory Index and diabetic retinopathy risk in US adults: findings from NHANES (2005-2008).

BACKGROUND: Inflammation is associated with the pathophysiology of diabetic retinopathy (DR). Within the framework of complete dietary patterns, the Dietary Inflammatory Index (DII) was formulated to evaluate the inflammatory properties inherent in a diet. The main purpose of the current study was to assess the relationship between DII and DR using National Health and Nutrition Examination Survey (NHANES). METHODS: The original sample size included 1,148 diabetes patients out of 2005-2008 NHANES surveys. Twenty-four-hour dietary consumptions were used to calculate the DII scores. Demographic characteristics and retina examinations were collected for the comparison between DR and non-DR groups in diabetes patients. The relationship between DII and DR was analyzed by a logistic regression model. RESULTS: 227 subjects (110 non-DR and 117 DR) were selected in the analyses by using undersampling method to balance the sample size. Compared with non-DR group, DR group had higher DII values (1.14 ± 0.29 vs. 1.49 ± 0.21, p = 0.32), higher levels of HbA1c (6.8 ± 1.1% vs. 7.7 ± 2.6%, p < 0.001), longer duration of diabetes (6.52 ± 12 years vs. 14 ± 11 years, p < 0.001). The odds rate (OR) of DII for DR from the logistic regression was 1.38 (95%CI 1.06-1.81, p < 0.001). HbA1c, diabetes duration and obesity were important influencing factors, and their ORs were 1.81 (95% CI:1.31-2.50), 1.12 (95%CI:1.04-1.20), 4.01 (95%CI:1.12-14.32), respectively. In addition, the most important dietary indices for DR were different across males and females. CONCLUSIONS: The current study demonstrates that a higher DII is associated with an increased risk of DR in US adults. Considering diet as a modifiable factor, limiting pro-inflammatory diets or encouraging an anti-inflammatory diet may be a promising and cost-effective method in the management of DR.

Incidence, risk factors, and outcomes of the transition of HIPEC-induced acute kidney injury to acute kidney disease: a retrospective study.

BACKGROUND: Acute kidney injury (AKI) is recognized as a common complication following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Characterized by prolonged renal function impairment, acute kidney disease (AKD) is associated with a higher risk of chronic kidney disease (CKD) and mortality. METHODS: From January 2018 to December 2021, 158 patients undergoing CRS-HIPEC were retrospectively reviewed. Patients were separated into non-AKI, AKI, and AKD cohorts. Laboratory parameters and perioperative features were gathered to evaluate risk factors for both HIPEC-induced AKI and AKD, with the 90-day prognosis of AKD patients. RESULTS: AKI developed in 21.5% of patients undergoing CRS-HIPEC, while 13.3% progressed to AKD. The multivariate analysis identified that ascites, GRAN%, estimated glomerular filtration rate (eGFR), and intraoperative (IO) hypotension duration were associated with the development of HIPEC-induced AKI. Higher uric acid, lessened eGFR, and prolonged IO hypotension duration were more predominant in patients proceeding with AKD. The AKD cohort presented a higher risk of 30 days of in-hospital mortality (14.3%) and CKD progression (42.8%). CONCLUSIONS: Our study reveals a high incidence of AKI and AKI-to-AKD transition. Early identification of risk factors for HIPEC-induced AKD would assist clinicians in taking measures to mitigate the incidence.

[Risk factors for acute respiratory distress syndrome in patients with traumatic hemorrhagic shock].

OBJECTIVE: To investigate the risk factors of acute respiratory distress syndrome (ARDS) after traumatic hemorrhagic shock. METHODS: This was a retrospective cohort study of 314 patients with traumatic hemorrhagic shock at Trauma Medicine Center, Peking University People's Hospital from December 2012 to August 2021, including 152 male patients and 162 female patients, with a median age of 63.00 (49.75-82.00) years. The demographic data, past medical history, injury assessment, vital signs, laboratory examination and other indicators of these patients during hospitalization were recorded. These patients were divided into two groups, ARDS group (n=89) and non-ARDS group (n=225) according to whether there was ARDS within 7 d of admission. Risk factors for ARDS were identified using Logistic regression. The C-statistic expressed as a percentage [area under curve (AUC) of the receiver operating characteristic (ROC) curve] was used to assess the discrimination of the model. RESULTS: The incidence of ARDS after traumatic hemorrhagic shock was 28.34%. Finally, Logistic regression model showed that the independent risk factors of ARDS after traumatic hemorrhagic shock included male, history of coronary heart disease, high acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, road traffic accident and elevated troponin Ⅰ. The OR and 95% confidence intervals (CI) were 4.01 (95%CI: 1.75-9.20), 5.22 (95%CI: 1.29-21.08), 1.07 (95%CI: 1.02-1.57), 2.53 (95%CI: 1.21-5.28), and 1.26 (95%CI: 1.02-1.57), respectively; the P values were 0.001, 0.020, 0.009, 0.014, and 0.034, respectively. The ROC curve was used to analyze the value of each risk factor in predicting ARDS. It was found that the AUC for predicting ARDS after traumatic hemorrhagic shock was 0.59 (95%CI: 0.51-0.68) for male, 0.55 (95%CI: 0.46-0.64) for history of coronary heart disease, 0.65 (95%CI: 0.57-0.73) for APACHE Ⅱ score, 0.58 (95%CI: 0.50-0.67) for road traffic accident, and 0.73 (95%CI: 0.66-0.80) for elevated troponin Ⅰ, with an overall predictive value of 0.81 (95%CI: 0.74-0.88). CONCLUSION: The incidence of ARDS in patients with traumatic hemorrhagic shock is high, and male, history of coronary heart disease, high APACHE Ⅱ score, road traffic accident and elevated troponin Ⅰ are independent risk factors for ARDS after traumatic hemorrhagic shock. Timely monitoring these indicators is conducive to early detection and treatment of ARDS after traumatic hemorrhagic shock.

A comprehensive analysis of immune features and construction of an immune gene diagnostic model for sepsis.

Sepsis is a life-threatening syndrome resulting from immune system dysfunction that is caused by infection. It is of great importance to analyze the immune characteristics of sepsis, identify the key immune system related genes, and construct diagnostic models for sepsis. In this study, the sepsis transcriptome and expression profiling data were merged into an integrated dataset containing 277 sepsis samples and 117 non-sepsis control samples. Single-sample gene set enrichment analysis (ssGSEA) was used to assess the immune cell infiltration. Two sepsis immune subtypes were identified based on the 22 differential immune cells between the sepsis and the healthy control groups. Weighted gene co-expression network analysis (WCGNA) was used to identify the key module genes. Then, 36 differentially expressed immune-related genes were identified, based on which a robust diagnostic model was constructed with 11 diagnostic genes. The expression of 11 diagnostic genes was finally assessed in the training and validation datasets respectively. In this study, we provide comprehensive insight into the immune features of sepsis and establish a robust diagnostic model for sepsis. These findings may provide new strategies for the early diagnosis of sepsis in the future.

Transcriptional control of carbohydrate catabolism by the CcpA protein in the ruminal bacterium Streptococcus bovis.

As a potent, pleiotropic regulatory protein in Gram-positive bacteria, catabolite control protein A (CcpA) mediates the transcriptional control of carbohydrate metabolism in Streptococcus bovis, a lactate-producing bacterium that plays an essential role in rumen acidosis in dairy cows. Although the rumen uptake of carbohydrates is multi-substrate, the focus of S. bovis research thus far has been on the glucose. With the aid of gene deletion, whole-genome sequencing, and transcriptomics, we have unraveled the role of CcpA in carbohydrate metabolism, on the one hand, and acidosis, on the other, and we show that the S. bovis strain S1 encodes "Carbohydrate-Active Enzymes" and that ccpA deletion slows the organism's growth rate and modulates the organic acid fermentation pathways toward lower lactate, higher formate, and acetate in the maltose and cellobiose. Furthermore, this study revealed the different regulatory functions of the CcpA protein in rumen metabolism and acidosis.IMPORTANCEThis study is important as it illustrates the varying regulatory role of the Streptococcus bovis catabolite control protein A protein in carbohydrate metabolism and the onset of acidosis in dairy cattle.

Development of an HiBiT-tagged reporter H3N2 influenza A virus and its utility as an antiviral screening platform.

The balance of the segmented genome derived from naturally occurring influenza A viruses (IAVs) is delicate and vulnerable to foreign insertions, thus most reporter IAVs up to date are generated using the backbone of the laboratory-adapted strains. In this study, we constructed a reporter influenza A/H3N2 virus (A/NY-HiBiT) which was derived from a clinical isolate, by placing a minimized HiBiT tag to the N-terminus of the viral nuclear-export protein (NEP). Here, we show that this 11-amino acid HiBiT tag did not adversely impact the viral genome balance, and the recombinant A/NY-HiBiT virus maintains its relative stability. Moreover, the replication profile of the HiBiT-tagged virus can be measured by a simple Nano-Glo assay, providing a robust high-throughput screening (THS) platform. We used this platform to evaluate a collection of the pre-purified fractions which were derived from rare Chinese medicinal materials, and we identified three fractions, including wild Trametes robiniophila (50% methanol fraction), Ganoderma (water fraction), and wild Phellinus igniarius (ethyl acetate fraction), as potent anti-IAV actives. Our results demonstrate that this IAV reporter can be used as a powerful HTS platform for antiviral development.

Flavonoids for depression and anxiety: a systematic review and meta-analysis.

Natural flavonoids are the most plentiful form of polyphenols. Given the anti-inflammatory and antioxidant properties of flavonoids, researchers discovered that it might be effective in treating depression and anxiety. The effect of flavonoids on depression and anxiety was investigated by a meta-analysis and systematic review. We searched PubMed, Embase, and Medline databases up to October 15, 2021. We selected 11 studies, among them, 10 studies were chosen to evaluate the depression effects of flavonoids and 7 studies were used to assess anxiety disorder. The meta-analysis showed that flavonoids have an overall significant effect on depression (p = 0.004, Hedge's g = -0.487, 95% CI -0.814 to -0.160) and anxiety (p = 0.006, Hedge's g = -0.741, 95% CI -1.266 to -0.217). Subgroup analysis indicated that the symptoms of depression were significantly improved in the studies when the dose of flavonoids was 50-100mg/day or the treatment duration was ≥8weeks. Anxiety symptoms were improved in the studies with the dose of flavonoids was ≥50mg/day. There was no evidence of publication bias. Our findings suggest that flavonoids might improve symptoms of depression and anxiety. However, a small number of participants and studies were included in this meta-analysis. Therefore, the results should be interpreted with caution.

Transport Pathways of Nitrate Formed from Nocturnal N2O5 Hydrolysis Aloft to the Ground Level in Winter North China Plain.

Particulate nitrate (NO3-) has currently become the major component of fine particles in the North China Plain (NCP) during winter haze episodes. However, the contributions of formation pathways to ground NO3- in the NCP are not fully understood. Herein, the NO3- formation pathways were comprehensively investigated based on model simulations combined with two-month field measurements at a rural site in the winter NCP. The results indicated that the nocturnal chemistry of N2O5 hydrolysis aloft could contribute evidently to ground NO3- at the rural site during the pollution episodes with high aerosol water contents, achieving the contribution percentages of 25.2-30.4% of the total. In addition to the commonly proposed vertical mixing of breaking nocturnal boundary layer in the early morning, two additional transport pathways (frontal downdrafts and downslope mountain breezes) in the nighttime were found to make higher contributions to ground NO3-. Considering the dominant role (69.6-74.8%) of diurnal chemistry in NO3- formation, reduction of NOx emissions in the daytime may be an effective control measure for reducing regional NO3- in the NCP.

Characteristics and risk factors for renal recovery after acute kidney injury in critically ill patients in cohorts of elderly and non-elderly: a multicenter retrospective cohort study.

BACKGROUND: The purpose of this study was to explore the risk factors for renal nonrecovery among elderly and nonelderly patients with acute kidney injury (AKI) in critically ill patients. METHODS: A multicenter retrospective cohort of 583 critically ill patients with AKI was examined. We found the best cutoff value for predicting renal recovery by age was 63 years old through logistic regression. All patients were divided into two cohorts, age <63 and age ≥63-years old; on the basis of renal recovery at 30 days after AKI, the two patient cohorts were further divided into a renal recovery group and a renal nonrecovery group. Multivariate logistic regression was used to analyze the risk factors affecting renal recovery in the two cohorts. RESULTS: The 30-day renal recovery rate of patients aged <63 years was 70.0% (198/283), multivariate analysis showed that the independent risk factors affecting renal nonrecovery in age <63 years old included AKI stage, blood lactate level and hemoglobin level. The 30-day renal recovery rate of patients aged ≥63 years was 28.7% (86/300), multivariate analysis showed that the independent risk factors for renal nonrecovery in age ≥63-years old included diabetes mellitus, surgery with general anesthesia, AKI stage, APACHE II score, eGFR, and hemoglobin level. CONCLUSIONS: The renal nonrecovery after AKI in critically ill patients in patients aged ≥63 years was more strongly affected by multiple risk factors, such as diabetes mellitus, surgery with general anesthesia, eGFR, and APACHE II score, in addition to hemoglobin and AKI stage.

Metabolic characterization of human intraocular fluid in patients with pathological myopia.

Pathological myopia (PM) and its associated complications can lead to permanent vision loss. However, the cellular mechanisms underlying PM development remain unclear. To identify the metabolic alterations that may contribute to the pathophysiology of PM, we performed non-targeted metabolomics analysis using ultra-high-performance liquid chromatography with tandem mass spectrometry in age- and sex-matched patients with PM (n = 30) and individuals without myopia as controls (n = 30). Targeted metabolomics and insulin microarray were used to validate the results. We identified 508 metabolites in the aqueous humour (AH) and 601 in the vitreous humour (VH). Statistical evaluation revealed that 104 metabolites in AH and 114 metabolites in VH were significantly different between the two groups (variable important for the projection >1, fold change >1.5, or < 0.667, and P < 0.05). The four metabolic pathways enriched in both AH and VH identified to be associated with PM were: bile secretion, insulin secretion, thyroid hormone synthesis, and cGMP-PKG signaling pathway. The concentration of 10 amino acids was significantly higher in the PM than in the controls. Insulin microarray analysis showed that insulin, insulin-like growth factor 2 (IGF-2), IGF-2R, insulin-like growth factor binding protein 1 (IGFBP-1), IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-6 levels were significantly higher in PM patients compared to that in the controls. Thus, this study identified potential metabolite biomarkers for PM and provided novel insights into the mechanisms underlying this disorder.

Is Urban Greening an Effective Solution to Enhance Environmental Comfort and Improve Air Quality?

Urban greening has often been proposed as a cost-effective solution to improve environmental comfort, but may also deteriorate air quality. Quantifying these two opposing effects of urban greening is necessary to develop successful environmental policies for specific mega-city clusters. In this study, a high-resolution regional climate and air quality model (WRF-Chem, v4.0.3) was employed to test three scenarios aimed at quantifying the impact of land-use change and biogenic emissions from urban greening on regional climate and air quality. It was found that urban greening could effectively decrease the near-surface temperature by up to 0.45 °C, but the increased biogenic volatile organic compound (BVOC) emissions offset some of this cooling effect (by up to 65%). Land-use change due to urban greening dominated the improvement in human comfort but worsened diffusion conditions to result in the convergence of fine particulate matter in specific areas. The selection of low-emission tree species may be imperative, although increased emissions from urban greening will not change the sensitivity of ozone to precursors under the current scenario of anthropogenic emissions. This is because BVOC emissions due to urban greening will become a more important source of pollution with the development of clean energy and the popularity of low-carbon lifestyles.