Astrocyte-derived exosomal lncRNA 4933431K23Rik modulates microglial phenotype and improves post-traumatic recovery via SMAD7 regulation.

Astrocyte-microglial interaction plays a crucial role in brain injury-associated neuroinflammation. Our previous data illustrated that astrocytes secrete microRNA, leading to anti-inflammatory effects on microglia. Long non-coding RNAs participate in neuroinflammation regulation after traumatic brain injury. However, the effect of astrocytes on microglial phenotype via long non-coding RNAs and the underlying molecular mechanisms remain elusive. We used long non-coding RNA sequencing on murine astrocytes and found that exosomal long non-coding RNA 4933431K23Rik attenuated traumatic brain injury-induced microglial activation in vitro and in vivo and ameliorated cognitive function deficiency. Furthermore, microRNA and messenger RNA sequencing together with binding prediction illustrated that exosomal long non-coding RNA 4933431K23Rik up-regulates E2F7 and TFAP2C expression by sponging miR-10a-5p. Additionally, E2F7 and TFAP2C, as transcription factors, regulated microglial Smad7 expression. Using Cx3cr1-Smad7 overexpression of adeno-associated virus, microglia specifically overexpressed Smad7 in the attenuation of neuroinflammation, resulting in less cognitive deficiency after traumatic brain injury. Mechanically, overexpressed Smad7 physically binds to IκBα and inhibits its ubiquitination, preventing NF-κB signaling activation. The Smad7 activator asiaticoside alleviates neuroinflammation and protects neuronal function in traumatic brain injury mice. This study revealed that an exosomal long non-coding RNA from astrocytes attenuates microglial activation after traumatic brain injury by up-regulating Smad7, providing a potential therapeutic target.

An analysis of the potential association between obstructive sleep apnea and osteoporosis from the perspective of transcriptomics and NHANES.

BACKGROUND: Obstructive sleep apnea (OSA) and osteoporosis (OP) are prevalent diseases in the elderly. This study aims to reveal the clinical association between OSA and OP and explore potential crosstalk gene targets. METHODS: Participants diagnosed with OSA in the National Health and Nutrition Examination Survey (NHANES) database (2015-2020) were included, and OP was diagnosed based on bone mineral density (BMD). We explored the association between OSA and OP, and utilized multivariate logistic regression analysis and machine learning algorithms to explore the risk factors for OP in OSA patients. Overlapping genes of comorbidity were explored using differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Random Forest (RF) methods. RESULTS: In the OSA population, the weighted prevalence of OP was 7.0%. The OP group had more females, lower body mass index (BMI), and more low/middle-income individuals compared to the non-OP group. Female gender and lower BMI were identified as independent risk factors for OP in OSA patients. Gene expression profiling revealed 8 overlapping differentially expressed genes in OP and OSA patients. KCNJ1, NPR3 and WT1-AS were identified as shared diagnostic biomarkers or OSA and OP, all of which are associated with immune cell infiltration. CONCLUSION: This study pinpointed female gender and lower BMI as OP risk factors in OSA patients, and uncovered three pivotal genes linked to OSA and OP comorbidity, offering fresh perspectives and research targets.

Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization.

BACKGROUND: Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein. RESULTS: A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells (HRMECs). We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. Additionally, the expression of six lncRNAs and eleven differentially expressed angiogenic genes were validated by qPCR in HRMECs with or without siLGALS1. Several hub genes, such as NRIR, ZFPM2-AS1, LINC0121, apelin, claudin-5, and C-X-C motif chemokine ligand 10, were found to potentially interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response. CONCLUSIONS: The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.

Long Non-Coding RNAs in Retinal Ganglion Cell Apoptosis.

Traumatic optic neuropathy or other neurodegenerative diseases, including optic nerve transection, glaucoma, and diabetic retinopathy, can lead to progressive and irreversible visual damage. Long non-coding RNAs (lncRNAs), which belong to the family of non-protein-coding transcripts, have been linked to the pathogenesis, progression, and prognosis of these lesions. Retinal ganglion cells (RGCs) are critical for the transmission of visual information to the brain, damage to which results in visual loss. Apoptosis has been identified as one of the most essential modes of RGC death. Emerging evidence suggests that lncRNAs can regulate RGC degeneration by directly or indirectly modulating apoptosis-associated signaling pathways. This review presents a comprehensive overview of the role of lncRNAs in RGC apoptosis at transcriptional, post-transcriptional, translational, and post-translational levels, emphasizing on the potential mechanisms of action. The current limitations and future perspectives of exploring the connection between lncRNAs and RGC apoptosis have been summarized. Understanding the intricate molecular interaction network of lncRNAs and RGC apoptosis will open new avenues for the identification of novel diagnostic biomarkers, therapeutic targets, and molecules for prognostic evaluation of diseases related to RGC injury.

Long non-coding RNAs in retinal neovascularization: current research and future directions.

PURPOSE: Retinal neovascularization (RNV) is an intractable pathological hallmark of numerous ocular blinding diseases, including diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. However, current therapeutic methods have potential side effects and limited efficacy. Thus, further studies on the pathogenesis of RNV-related disorders and novel therapeutic targets are critically required. Long non-coding RNAs (lncRNAs) have various functions and participate in almost all biological processes in living cells, such as translation, transcription, signal transduction, and cell cycle control. In addition, recent research has demonstrated critical modulatory roles of various lncRNAs in RNV. In this review, we summarize current knowledge about the expression and regulatory functions of lncRNAs related to the progression of pathological RNV. METHODS: We searched databases such as PubMed and Web of Science to gather and review information from the published literature. CONCLUSIONS: In general, lncRNA MEG3 attenuates RNV, thus protecting the retina from excessive and dysregulated angiogenesis under high glucose stress. In contrast, lncRNAs MALAT1, MIAT, ANRIL, HOTAIR, HOTTIP, and SNHG16, have been identified as causative molecules in the pathological progression of RNV. Comprehensive and in-depth studies of the roles of lncRNAs in RNV indicate that targeting lncRNAs may be an alternative therapeutic approach in the near future, enabling new options for attenuating RNV progression and treating RNV-related retinal diseases.

Alleviating eutrophication by reducing the abundance of Cyanophyta due to dissolved inorganic carbon fertilization: Insights from Erhai Lake, China.

The eutrophication of lakes is a global environmental problem. Regulating nitrogen (N) and phosphorus (P) on phytoplankton is considered to be the most important basis of lake eutrophication management. Therefore, the effects of dissolved inorganic carbon (DIC) on phytoplankton and its role in mitigating lake eutrophication have often been overlooked. In this study, the relationships between phytoplankton and DIC concentrations, carbon isotopic composition, nutrients (N and P), and hydrochemistry in the Erhai Lake (a karst lake) were investigated. The results showed that when the dissolved carbon dioxide (CO2(aq)) concentrations in the water were higher than 15 µmol/L, the productivity of phytoplankton was controlled by the concentrations of TP and TN, especially by that of TP. When the N and P were sufficient and the CO2(aq) concentrations were lower than 15 µmol/L, the phytoplankton productivity was controlled by the concentrations of TP and DIC, especially by that of DIC. Additionally, DIC significantly affected the composition of the phytoplankton community in the lake (p<0.05). When the CO2(aq) concentrations were higher than 15 µmol/L, the relative abundance of Bacillariophyta and Chlorophyta was much higher than those of harmful Cyanophyta. Thus, high concentrations of CO2(aq) can inhibit harmful Cyanophyta blooms. During lake eutrophication, when controlling N and P, an appropriate increase in CO2(aq) concentrations by land-use changes or pumping of industrial CO2 into water may reduce the proportion of harmful Cyanophyta and promote the growth of Chlorophyta and Bacillariophyta, which may provide effectively assist in mitigating water quality deterioration in surface waters.

Comparison of different approaches of percutaneous vertebroplasty in the treatment of osteoporotic spinal compression fractures and analysis of influencing factors of re-fracture.

Objective: To compare the functional and radiological outcome of different approaches of percutaneous vertebroplasty (PVP) in the treatment of osteoporotic vertebral compression fractures (OVCF), and to analyze the factors affecting postoperative re-fracture in patients with OVCF. Methods: Medical data of 76 patients with OVCF who underwent PVP in our hospital from January 2021 to December 2021 were analyzed retrospectively. Based on the different intraoperative approaches, patients were divided into Unilateral-group (n=36) and Bilateral-group (n=40). The perioperative indexes, clinical efficacy, and spinal nerve function of the two groups were compared. Logistic regression analysis was used to determine the risk factors of postoperative re-fracture in patients with OVCF. The functional outcome was assessed with Oswestry disability index (ODI), American Spinal Injury Association (ASIA) nerve function classification and pain with Visual analogue scale (VAS). The radiological outcome was assessed by noting change of anterior vertebral height and change of kyphosis Cobb angle. Results: The amount of intraoperative bleeding, the number of X-ray irradiation and the volume of injected bone cement in the Unilateral-group were lower, and the operation time was shorter than Bilateral-group (all P<0.05). One week after the operation, the anterior height of the vertebral body was higher, the Cobb angle of kyphosis was lower, the VAS score was higher, and the ASIA grade was lower in the Unilateral-group compared to the Bilateral-group (P<0.05). Logistic regression analysis showed that the age, bone mineral density, volume of bone cement injection and PD were risk factors of postoperative re-fracture in patients with OVCF. Conclusion: Unilateral PVP treatment of OVCF has the advantages of less intraoperative bleeding, less X-ray irradiation and shorter operation time. At the same time, bilateral PVP is associated with improved bone cement dispersion, and the effect of improving patients' pain is better than that in the Unilateral PVP. Postoperative risk of re-fracture in OVCF patients correlated with age, bone mineral density, amount of bone cement injection and pedicle diameter.

Construction and analysis of mRNA, lncRNA, and transcription factor regulatory networks after retinal ganglion cell injury.

Retinal ganglion cell (RGC) injury is a critical pathological feature of several optic neurodegenerative diseases. The regulatory mechanisms underlying RGC injury remain poorly understood. Recent evidence has highlighted the important roles of long noncoding RNAs (lncRNAs) in degenerative neuropathy but few studies have focused on lncRNAs associated with RGC injury. In this study, we analyzed dysregulated lncRNAs associated with RGC injury, their potential regulatory functions, and the molecular mechanisms underlying the regulation of lncRNAs and transcription factors (TFs). We analyzed lncRNA and mRNA profiles in the GSE142881 dataset associated with RGC injury and identified 1049 differentially expressed genes (DEGs), with 18 differentially expressed (DE) TFs among 883 DE mRNAs and 312 DE lncRNAs. The predicted DE lncRNAs and DE mRNAs were used to construct a lncRNA-mRNA co-expression network. Functional enrichment analysis was performed to explore the functions of the lncRNAs and mRNAs. The co-expression network between DE lncRNAs and DE mRNAs was highly enriched in inflammatory and immune-related pathways, indicating that they play role in the process of RGC injury. Among the DE mRNAs, we screened 18 DE TFs, including activating transcription factor 3 (ATF3), associated with RGC injury. Co-expression analysis predicted that 13 lncRNAs were potential binding targets of ATF3. The screening of the potential targets of these 13 lncRNAs showed that they were also significantly enriched in functional pathways associated with inflammation and apoptosis. After analysis, we constructed the mRNA-ATF3-lncRNA regulatory network after RGCs injury. In summary, we identified the gene module associated with immune and inflammatory responses after optic nerve injury and constructed a regulatory network of lncRNA-TF-mRNA. The results indicate that lncRNAs, by binding to TFs, can regulate downstream genes and function during RGC injury. The results provide a foundation for further studies of the mechanism of RGC injury and provide insight into the clinical diagnosis and investigation direction of neurodegenerative diseases such as traumatic optic neuropathy and glaucoma.

Inhibition of p66Shc attenuates retinal ischemia-reperfusion injury-induced damage by activating the akt pathway.

Retinal ganglion cell (RGC) death is the direct cause of several optic neuropathies. Several studies have reported that the loss of p66Shc ameliorates neuronal injury and vascular abnormalities in ischemia-reperfusion (I/R) injury. However, whether p66Shc is involved in the loss of RGC remains unclear. Therefore, this study aimed to investigate the function of p66Shc due to retinal ischemia in mice. The retinal I/R model was constructed after an intravitreal injection of recombinant adeno-associated viruses (rAAV-EGFP or rAAV-p66Shc-EGFP) for 4 weeks. The expression of p66Shc was detected by western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. The survival of RGCs was determined using immunofluorescence staining. Retinal function was analyzed based on electroretinogram (ERG) findings. Retinal cell apoptosis was detected by TdT-mediated dUTP nick-end labeling staining. The protein expressions of Akt, phospho-Akt, Bax, and PARP were analyzed by western blotting. After rAAVs were successfully transfected, enhanced green fluorescent protein was expressed in all retinal cell layers, and the level of p66Shc after I/R injury was successfully reduced. We found that inhibition of p66Shc expression remarkably decreased the death of RGCs and prevented the loss of ERG a- and b-wave amplitudes caused by retinal ischemia. Mechanistically, downregulation of p66Shc resulted in reduced Bax, whereas increased phospho-Akt and PARP. Taken together, our study revealed that p66Shc acts through the Akt pathway to protect RGCs from retinal I/R injury-induced apoptosis and retinal dysfunction, making p66Shc a possible therapeutic target for glaucoma treatment.

Differential susceptibility of retinal ganglion cell subtypes against neurodegenerative diseases.

Retinal ganglion cells (RGCs) are essential to propagate external visual information from the retina to the brain. Death of RGCs is speculated to be closely correlated with blinding retinal diseases, such as glaucoma and traumatic optic neuropathy (TON). Emerging innovative technologies have helped refine and standardize the classification of RGCs; at present, they are classified into more than 40 subpopulations in mammals. These RGC subtypes are identified by a combination of anatomical morphologies, electrophysiological functions, and genetic profiles. Increasing evidence suggests that neurodegenerative diseases do not collectively affect the RGCs. In fact, which RGC subtype exhibits the strongest or weakest susceptibility is hotly debated. Although a consensus has not yet been reached, it is certain that assorted RGCs display differential susceptibility against irreversible degeneration. Interestingly, a single RGC subtype can exhibit various vulnerabilities to optic nerve damage in diverse injury models. Thus, elucidating how susceptible RGC subtypes are to various injuries can protect vulnerable RGCs from damage and improve the possibility of preventing and treating visual impairment caused by neurodegenerative diseases. In this review, we summarize in detail the progress and status quo of research on the type-specific susceptibility of RGCs and point out current limitations and the possible directions for future research in this field.

Using methanol to preserve retinas for immunostaining.

BACKGROUND: Experimental studies on retinal vasculature and retinal ganglion cells (RGCs) investigating the developmental and pathological conditions of the retina mainly rely on whole-mount retinal immunostaining. Methanol, an auxiliary fixed medium for retinal whole-mount preparations, has been used in some studies; however, its application in short- and long-term storage of retinas for further study has not been well described. We aimed to evaluate methanol use as a preservation treatment for further immunostaining of the retina. METHODS: We generated oxygen-induced retinopathy (OIR) and optic nerve crush (ONC) mouse models and used their retinas for analysis. We pipetted cold methanol (-20°C) on the surface of the retina to help fix the tissues while promoting permeability, after which the retinas were stored in cold methanol (-20°C) for 1, 6, or 12 months before being evaluated using various optical techniques. Thereafter, retinal whole-mount immunostaining was performed to analyse retinal neovascularisation and retinal hypoxia in OIR model, and retinal ganglion cell survival rate in ONC model. RESULTS: Quantitative analysis revealed no significant differences in the fixed retinas after long-term storage in terms of retinal vasculature or retinal hypoxia in the OIR model. Similarly, no significant difference was found in RGC survival rate after long-term storage in methanol. These results suggest that methanol can be used as a storage medium when preserving retinal whole-mount samples. CONCLUSIONS: Cold (-20°C) methanol can serve as an effective medium for long-term storage of fixed retinas, which is useful for further research.

Establishment and validation of an SIL-IS LC-MS/MS method for the determination of ibuprofen in human plasma and its pharmacokinetic study.

In this work, we developed and validated a highly sensitive, rapid and stable LC-MS/MS method for the determination of ibuprofen in human plasma with ibuprofen-d3 as a stable isotopically labeled internal standard (SIL-IS). Human plasma samples were prepared by one-step protein precipitation. The chromatographic separation was achieved on a Poroshell 120 EC-C18 (2.1 × 50 mm, 2.7 µm). Aqueous solution (containing 0.05% acetic acid and 5 mm NH4 Ac) and methanol were selected as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in negative ion mode. Multiple reaction monitoring mode was used for quantification using target fragment ions m/z 205.0 → 161.1 for ibuprofen and m/z 208.0 → 164.0 for SIL-IS, respectively. This method exhibited a linear range of 0.05-36 µg/ml for ibuprofen with correlation coefficient >0.99. Mean recoveries of ibuprofen in human plasma ranged from 78.4 to 80.9%. The RSD of intra- and inter-day precision were both < 5%. The accuracy was between 88.2 and 103.67%. The matrix effect was negligible in human plasma, including lipidemia and hemolytic plasma. A simple, efficient and accurate LC-MS/MS method was successfully established and applied to a pharmacokinetic study in healthy Chinese volunteers after a single oral administration of ibuprofen granules.

The clinical characteristics and prognosis of COVID-19 patients with cerebral stroke: A retrospective study of 113 cases from one single-centre.

To explore the clinical characteristics and prognosis of COVID-19 patients with cerebral stroke. A total of 2,474 COVID-19 patients from February 10th to March 24th, 2020 were admitted and treated in two branches (Optic Valley and Sino-French New City branch) of the Tongji Hospital. Data on the clinical characteristics, laboratory parameters and prognosis of COVID-19 patients with or without cerebral stroke were collected and comparatively analysed. Of the 2,474 COVID-19 patients, 113 (4.7%) patients had cerebral stroke and 25 (1.0%) patients had new-onset stroke. Eighty-eight (77.9%) patients in the previous-stroke group had cerebral ischaemia, while 25 (22.1%) patients in the new-onset stroke group had cerebral ischaemia. Most COVID-19 patients with stroke were elderly with more comorbidities such as hypertension, diabetes and heart diseases than patients without stroke. Laboratory examinations showed hypercoagulation and elevated serum parameters such as IL-6, cTnI, NT pro-BNP and BUN. Consciousness disorders, a long disease course and poor prognosis were also more commonly observed in stroke patients. The mortality rate of stroke patients was almost double (12.4% vs. 6.9%) that of patients without stroke. In addition, age, male sex and hypertension were independent predictors for new cerebral stroke in COVID-19 patients. In conclusion, the high risk of new-onset stroke must be taken into consideration when treating COVID-19 patients with an elderly age combined with a history of hypertension. These patients are more vulnerable to multiorgan dysfunction and an overactivated inflammatory response, in turn leading to an unfavourable outcome and higher mortality rate.

Vasculogenic mimicry, a negative indicator for progression free survival of lung adenocarcinoma irrespective of first line treatment and epithelial growth factor receptor mutation status.

BACKGROUND: Vascular mimicry (VM) was associated with the prognosis of cancers. The aim of the study was to explore the association between VM and anticancer therapy response in patients with lung adenocarcinoma. METHODS: This was a single-center retrospective study of patients with lung adenocarcinoma between March 1st, 2013, to April 1st, 2019, at the Second People's Hospital of Taizhou City. All included patients were divided into the VM and no-VM groups according to whether VM was observed or not in the specimen. Vessels with positive PAS and negative CD34 staining were confirmed as VM. The main outcome was progression-free survival (PFS). RESULTS: Sixty-six (50.4%) patients were male. Eighty-one patients received chemotherapy as the first-line treatment, and 50 patients received TKIs. Forty-five (34.4%) patients were confirmed with VM. There was no difference regarding the first-line treatment between the VM and no-VM groups (P = 0.285). The 86 patients without VM had a median PFS of 279 (range, 90-1095) days, and 45 patients with VM had a median PFS of 167 (range, 90-369) days (P < 0.001). T stage (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.10-1.71), N stage (HR = 1.43, 95%CI: 1.09-1.86), M stage (HR = 2.85, 95%CI: 1.76-4.61), differentiation (HR = 1.85, 95%CI: 1.29-2.65), therapy (HR = 0.32, 95%CI: 0.21-0.49), VM (HR = 2.12, 95%CI: 1.33-3.37), and ECOG (HR = 1.41, 95%CI: 1.09-1.84) were independently associated with PFS. CONCLUSION: The benefits of first-line TKIs for NSCLC with EGFR mutation are possibly better than those of platinum-based regimens in patients without VM, but there is no difference in the benefit of chemotherapy or target therapy for VM-positive NSCLC harboring EGFR mutations.

Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury.

BACKGROUND: The interaction between astrocytes and microglia plays a vital role in the damage and repair of brain lesions due to traumatic brain injury (TBI). Recent studies have shown that exosomes act as potent mediators involved in intercellular communication. METHODS: In the current study, the expression of inflammatory factors and miR-873a-5p in the lesion area and oedema area was evaluated in 15 patients with traumatic brain injury. Exosomes secreted by astrocytes were detected by immunofluorescence, Western blot and electron microscopy. A mouse model of TBI and an in vitro model of LPS-induced primary microglia were established to study the protective mechanism of exosomes from miR-873a-5p overexpressing in TBI-induced nerve injury. RESULTS: We discovered that exosomes derived from activated astrocytes promote microglial M2 phenotype transformation following TBI. More than 100 miRNAs were detected in these astrocyte-derived exosomes. miR-873a-5p is a major component that was highly expressed in human traumatic brain tissue. Moreover, miR-873a-5p significantly inhibited LPS-induced microglial M1 phenotype transformation and the subsequent inflammation through decreased phosphorylation of ERK and NF-κB p65. This effect also greatly improved the modified neurological severity score (mNSS) and attenuated brain injury in a strictly controlled cortical impact mouse model. CONCLUSIONS: Taken together, our research indicates that miRNAs in the exosomes derived from activated astrocytes play a key role in the astrocyte-microglia interaction. miR-873a-5p, as one of the main components of these astrocyte-derived exosomes, attenuated microglia-mediated neuroinflammation and improved neurological deficits following TBI by inhibiting the NF-κB signalling pathway. These findings suggest a potential role for miR-873a-5p in treating traumatic brain injury.

Biochemical characterization of an organic solvent-tolerant glycosyltransferase from Bacillus licheniformis PI15 with potential application for raspberry ketone glycoside production.

Raspberry ketone is a primary aroma component of the red raspberry. The glycosylation of this compound is a potential approach used to improve its pharmaceutical properties. In this work, raspberry ketone glycosides are produced in bacteria for the first time. Bacillus licheniformis PI15, an organic solvent-tolerant glycosyltransferase-producing strain, was isolated from chemically polluted soil. The cloning and heterologous expression of a glycosyltransferase, which was designated PI-GT1, in Escherichia coli BL21 resulted in the expression of an active and soluble protein that accounted for 15% of the total cell protein content. Purified PI-GT1 was highly active and stable over a broad pH range (6.0-10.0) and showed excellent pH stability. PI-GT1 maintained almost 60% of its maximal activity after 3 H of incubation at 20-40 °C and demonstrated optimal activity at 30 °C. Additionally, PI-GT1 displayed high stability and activity in the presence of hydrophilic solvents with log P ≤ -0.2 and retained more than 80% of its activity after 3 H of treatment. Supplementation with 10% DMSO markedly improved the glycosylation of raspberry ketone, resulting in a value 26 times higher than that in aqueous solution. The organic solvent-tolerant PI-GT1 may have potential uses in industrial chemical and pharmaceutical synthesis applications.

Associations between nephrolithiasis and diabetes mellitus, hypertension and gallstones: A meta-analysis of cohort studies.

AIM: To review and clarify the strengths and directions of associations between nephrolithiasis and hypertension (HTN), diabetes mellitus (DM) and gallstones (GS) given the inconsistent results reported in cohort studies. METHODS: Relevant literature was searched in PubMed and EMBASE from inception to July 2019, for cohort studies that examined the relationships between kidney stones and these three diseases among adults. Pooled relative risks (RRs) were calculated by maximally adjusted risk estimates using a random effect model. Subgroup analysis, meta-regression and sensitivity analysis were conducted whenever appropriate. RESULTS: Of 3537 papers, 21 articles with each including 1 to 3 cohorts were identified. In this meta-analysis, nephrolithiasis was reciprocally linked to HTN, DM and GS. Kidney stones were significantly associated with 31%, 33% and 46% higher risks of incident HTN, DM and GS whereas GS was associated with a significantly higher risk of nephrolithiasis (RR: 1.49; 95% CI, 1.28-1.73), followed by HTN (RR: 1.30; 95% CI, 1.11-1.52) and DM (RR: 1.18; 95% CI, 1.07-1.29). Also, females with DM (RR: 1.29; 95% CI, 1.08-1.55) were more likely to develop kidney stones than diabetic male patients (RR: 0.91; 95% CI, 0.75-1.10). CONCLUSION: Although additional studies are needed to confirm these findings and elucidate the mechanisms, this study revealed possible bidirectional associations between nephrolithiasis and HTN, diabetes and GS, which reinforced the notion of nephrolithiasis as a systemic disease that requires comprehensive investigations.

Dietary and lifestyle factors for primary prevention of nephrolithiasis: a systematic review and meta-analysis.

BACKGROUND: Dietary and lifestyle factors may play an important role in the increasing prevalence of nephrolithiasis. We aimed to review and quantify the associations between lifestyle factors and incident nephrolithiasis and suggest lifestyle changes for the primary prevention of nephrolithiasis. METHODS: PubMed, EMBASE, and Cochrane Library were searched up to May 2019, for observational studies and randomized controlled trials (RCTs) that assessed modifiable lifestyle factors and risk of nephrolithiasis in adults. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were computed using a random effects model. The I2 statistic was employed to evaluate heterogeneity. Subgroup analysis, sensitivity analysis and meta-regression were also conducted whenever possible. RESULTS: Fifty relevant articles with 1,322,133 participants and 21,030 cases in total were identified. Prominent risk factors for incident stones were body mass index (1.39,1.27-1.52), dietary sodium (1.38, 1.21-1.56), fructose, meat, animal protein, and soda. In contrast, protective factors included fluid intake (0.55, 0.51-0.60), a Dietary Approaches to Stop Hypertension (DASH) style diet (0.69, 0.64-0.75), alcohol (0.69, 0.56-0.85), water, coffee, tea, vegetables, fruits, dietary fiber, dietary calcium (0.83, 0.76-0.90), and potassium. Vitamin D (1.22, 1.01-1.49) and calcium (1.16, 1.00-1.35) supplementation alone increased the risk of stones in meta-analyses of observational studies, but not in RCTs, where the cosupplementation conferred significant risk. CONCLUSIONS: Several modifiable factors, notably fluid intake, dietary patterns, and obesity, were significantly associated with nephrolithiasis. Long-term RCTs are required to investigate the cost-effectiveness of dietary patterns for stone prevention. The independent and combined effects of vitamin D and calcium supplementation on nephrolithiasis need further elucidation.

Applicability of multifunctional preprocessing device for simultaneous estimation of spreading of green tea, withering of black tea and shaking of oolong tea.

BACKGROUND: Preprocessing technologies of fresh tea leaves have a great influence on tea quality. A multifunctional preprocessing device for tea raw materials has been designed and utilized as a novel item of equipment to synchronously meet the process needs of spreading of green tea, withering of black tea and shaking of oolong tea. RESULTS: The preprocessing parameters of fresh tea leaves for spreading of green tea, withering of black tea and shaking of oolong tea were optimized by orthogonal experiments. Sensory assessment combined with statistical tools was employed as an analytical method to evaluate the pretreatment effect of processing different sorts of tea. The range analysis and variance analysis of tea sensory evaluation combined with chemical components (total polyphenols, free amino acids and soluble sugar) showed that A3 B2 C3 (70%, 25 °C, 8 h), A1 B3 C1 (60%, 28 °C, 18 h) and A1 B1 C3 (5 min, 20 °C, discontinuous leaf turning c) were considered to be the optimum schemes for the best pretreatment conditions of the above three major processing types of tea, respectively. The verification experiment of the proposed schemes was performed with satisfactory performance. CONCLUSION: This study demonstrated that a multifunctional preprocessing device for fresh tea leaves can be successfully applied to simultaneously estimate spreading of green tea, withering of black tea and shaking of oolong tea. © 2019 Society of Chemical Industry.

Analysis of related risk factors of hidden blood loss after anterior cervical fusion.

BACKGROUND: This study was carried out to analyze the risk factors of perioperative blood loss during anterior cervical fusion (ACF) and to provide guidance in perioperative blood management for patients undergoing ACF. MATERIAL AND METHODS: A retrospective study was conducted on a consecutive series of 219 patients who had undergone anterior cervical corpectomy fusion (ACCF) and anterior cervical discectomy fusion (ACDF) between January 2016 and July 2017. Patients were categorized into a low hidden blood loss (HBL) group or high HBL group. These two groups were compared for demographic distribution and clinical data to investigate the related risk factors of HBL after ACF. RESULTS: The results of the comparison between the high and the low HBL groups indicated that age, gender, concurrent medical diseases, prothrombin time (PT), surgical segmentation, operative time, intraoperative bleeding, total drainage, time for extraction of drainage tube, loss of red blood cell volume, preoperative blood volume, perioperative HBL and total perioperative blood loss were statistically significant between the two groups (P < 0.05). Furthermore, logistic multivariate regression analysis of 13 factors with statistical significance in univariate analysis showed that intraoperative hemorrhage (OR = 0.985, P = 0.000) and total drainage (OR = 0.970, P = 0.000) were risk factors for high HBL. CONCLUSION: The risk factors for HBL after ACF are varied. Multivariate logistic regression analysis showed that intraoperative blood loss and total drainage were risk factors for high HBL. The authors believe that a reasonable surgical strategy, improved surgical techniques, rational use of hemostatics during surgery, decreased intraoperative blood loss and total drainage can help to reduce HBL.