A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles.

N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.

Electrospun polylactic acid nanofibers membrane with copper ion-loaded clay nanotubes for fresh-keeping packaging.

The plastics derived from fossil fuels for food packaging results in serious environmental problems. Developing environment-friendly materials for food packaging is urgent and essential. In this study, polylactic acid (PLA) composite nanofibers membranes were prepared with good biocompatibility and antibacterial property. Cu2+ loaded in the natural halloysite nanotubes (HNTs) was used for the antibacterial agent. Cu2+ was loaded in the HNTs and was confirmed by the X-ray photoelectron spectroscopy (XPS). PLA nanofibers with different HNTs-Cu content were continuous nanofibers with the nanoscale range. HNTs-Cu entered into the nanofiber successfully. Thermal analysis results showed composite nanofibers had good thermal stability. Composite nanofiber membranes had the good hydrophobic property. HNTs-Cu improved the mechanical property of composite nanofibers than pure PLA nanofibers. Tensile strength and elasticity modulus of composite nanofibers with 4 % HNTs-Cu content were the most outstanding. L929 cells were cultured on the nanofiber membranes for biocompatibility evaluation. Cell viability of nanofiber membranes was above the 90 %. Cell live/dead staining results showed L929 cells was seldom dead on the nanofiber membranes. PLA/HNTs-Cu nanofiber membranes exhibited excellent antibacterial effects on S. aureus and E. coli. The inhibitory rates against S. aureus and E. coli were 98.31 % and 97.80 % respectively. The fresh-keeping effects of nanofiber membranes were evaluated by the strawberry preservation. Strawberries covered by nanofiber membranes exhibited better appearance, lower weight loss and higher firmness than control, PLA and PLA/HNTs groups. It promised that PLA/HNTs-Cu composite nanofiber membranes have the significant potential application for active food packaging.

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.

XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis.

Endometrial carcinoma's (EC) etiology is complex and involves DNA repair gene polymorphisms like XRCC1-Arg399Gln and hOGG1-Ser326Cys, but their association with the disease is unclear. Following PRISMA, we conducted a systematic review and meta-analysis, collecting data from four databases. The studies needed to be population-based case-control studies examining the association between the named polymorphisms and EC. Quality was assessed with the Newcastle-Ottawa Scale. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated, and subgroup analyses were conducted based on ethnicity. Seven studies were included. Both polymorphisms were found to significantly increase EC risk, particularly in Caucasians. XRCC1-Arg399Gln showed a dominant model OR of 1.14 (95% CI: 1.01-1.29) and a homozygous model OR of 1.59 (95% CI: 1.12-2.25). The heterozygote model OR for hOGG1-Ser326Cys was 1.29 (95% CI: 1.02-1.63), and the allele OR was 1.31 (95% CI: 1.07-1.60). XRCC1-Arg399Gln and hOGG1-Ser326Cys may increase EC risk, primarily in Caucasian women, emphasizing the role of DNA repair in disease susceptibility. More extensive studies are needed to validate these findings in diverse ethnicities and investigate other DNA repair gene polymorphisms.

Dual Factor-Loaded Artificial Periosteum Accelerates Bone Regeneration.

In the clinic, inactivation of osteosarcoma using microwave ablation would damage the periosteum, resulting in frequent postoperative complications. Therefore, the development of an artificial periosteum is crucial for postoperative healing. In this study, we prepared an artificial periosteum using silk fibroin (SF) loaded with stromal cell-derived factor-1α (SDF-1α) and calcitonin gene-related peptide (CGRP) to accelerate bone remodeling after the microwave ablation of osteosarcoma. The prepared artificial periosteum showed a sustained release of SDF-1α and CGRP after 14 days of immersion. In vitro culture of rat periosteal stem cells (rPDSCs) demonstrated that the artificial periosteum is favorable for cell recruitment, the activity of alkaline phosphatase, and bone-related gene expression. Furthermore, the artificial periosteum improved the tube formation and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs). In an animal study, the periosteum in the femur of a rabbit was inactivated through microwave ablation and then removed. The damaged periosteum was replaced with the as-prepared artificial periosteum and favored bone regeneration. In all, the designed dual-factor-loaded artificial periosteum is a promising strategy to replace the damaged periosteum in the therapy of osteosarcoma for a better bone-rebuilding process.

Quercetin Alleviates Perimenopausal Depression Induced by Ovariectomy Combined with Chronic Unpredictable Mild Stress Through Regulating Serum Elements and Inhibiting Ferroptosis in Prefrontal Cortex of Rats.

This study investigated the effects of quercetin on the alterations of serum elements in perimenopausal depression rat model induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS) and possible mechanisms. According to the results of the sucrose preference test, the rats were randomly assigned to four groups: sham, OVX-CUMS, OVX-CUMS + 17ß-estradiol (17ß-estradiol: 0.27 mg/kg.bw), and OVX-CUMS + Quercetin (Quercetin: 50 mg/kg.bw). At the end of experiment, serum and prefrontal cortex of rats were collected. The inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that levels of calcium (Ca), magnesium (Mg), selenium (Se), cobalt (Co) and zinc (Zn) decreased, and levels of iron (Fe) and copper (Cu) increased in serum and prefrontal cortex of OVX-CUMS rats compared with sham group (p < 0.01). Meanwhile, the levels of the above elements in prefrontal cortex had correlation with behavioral characteristics in OVX-CUMS rats (p < 0.05 or p < 0.01). The abnormal elements in serum may cross blood-brain-barrier into the brain and induce oxidative stress, leading to ferroptosis. Furtherly, the expressions of ferroptosis-related protein including GPX4 and SLC7A11 were decreased in prefrontal cortex of OVX-CUMS rats (p < 0.01), which confirmed the above results. Quercetin treatment restored the above abnormal indicators (p < 0.05 or p < 0.01) induced by OVX-CUMS in rats. Our study suggested that quercetin regulated variation of elements in serum and prefrontal cortex, further inhibiting ferroptosis in prefrontal cortex through alleviating oxidative stress in OVX-CUMS rats.

Cang-ai volatile oil ameliorates imiquimod-induced psoriatic skin lesions by suppressing the ILC3s.

ETHNOPHARMACOLOGICAL RELEVANCE: Cang-ai volatile oil (CAVO) is an aromatic Chinese medicine with potent antibacterial and immune regulatory properties. While CAVO has been used to treat upper respiratory tract infections, depression, otomycosis, and bacterial infections in the skin, its effect on psoriasis is unknown. AIM OF THE STUDY: This study explores the effect and mechanism of CAVO in psoriasis intervention. MATERIAL AND METHODS: The effect of CAVO on the expression of IL-6 and IL-1ß was assessed in TNF-α-induced HaCaT cells using enzyme-linked immunosorbent assay (ELISA). Mice were given imiquimod (IMQ) and administered orally with different CAVO doses (0.03 and 0.06 g/kg) for 5 days. The levels of inflammatory cytokines related to group-3 innate lymphoid cells (ILC3s) in the skin were assessed using hematoxylin and eosin (H&E) staining, ELISA, and western blotting (WB). The frequency of ILC3s in mice splenocytes and skin cells was evaluated using flow cytometry. RESULTS: The results demonstrated that CAVO decreased the expression of IL-6 and IL-1ß in TNF-α- induced HaCaT cells. CAVO significantly reduced the severity of psoriatic symptoms in IMQ-induced mice. The expression of inflammatory cytokines in the skin, such as IL-1ß, IL-6, IL-8, IL-22, IL-23, and IL-17 A were decreased, whereas IL-10 levels were increased. The mRNA expressions of TNF-α, IL-23 A, IL-23 R, IL-22, IL-17 A, and RORγt were down-regulated in skin tissues. CAVO also decreased the levels of NF-κB, STAT3, and JAK2 proteins. CONCLUSIONS: CAVO potentially inhibits ILC3s activation to relieve IMQ-induced psoriasis in mice. These effects might be attributed to inhibiting the activation of NF-κB, STAT3, and JAK2 signaling pathways.

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.

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.

The cyclization/rearrangement of α-hydroxy ketones with trifluoromethyl N-acylhydrazones to synthesize multi-substituted trifluoromethyloxazolines.

A highly efficient and metal-free [3+2] cyclization/rearrangement reaction toward the synthesis of multisubstituted trifluoromethyloxazolines from α-hydroxyketones and trifluoromethyl N-acylhydrazones has been developed. The unprecedented rearrangement of the amide fragment under acidic conditions after cleavage of the N-N bond of acylhydrazones has opened up new avenues for the development of reactions involving trifluoromethyl N-acylhydrazones. DFT calculations show that the mechanism involves multiple proton transfer processes.

The alleviating effect of Scutellaria amoena extract on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NLRP3/ASC/caspase-1 axis.

Background: Scutellaria amoena (SA) is the root of S. amoena C.H. Wright of Labiatae, also known as Scutellaria southwestern. This is mainly distributed in Sichuan, Yunnan, and Guizhou in China. In southwest China, SA is used as an alternative method to genuine medicine for the treatment of allergy, diarrhea, inflammation, hepatitis, and bronchitis. Thus far, studies on the effects of SA on non-alcoholic steatohepatitis (NASH) are lacking. This paper investigated the effect of SA on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NOD-like receptor 3 (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis. Methods: A NASH rat model was induced by a high-fat diet (HFD) for 12 weeks, and rats were orally given different doses of SA extracts (150 and 300 mg/kg/d) for 6 weeks. Changes in histological parameters, body weight, organ indexes, cytokines, and biochemical parameters related to NLRP3 in NASH rats were checked. 16S rRNA gene sequencing and UPLC-MS/MS technology were used to analyze the changes in the gut microbiota composition and its metabolites in NASH rats. Results: SA significantly inhibited the HFD-induced increase in body weight, lipid levels, and inflammatory infiltration. SA notably inhibited the HFD-induced increase in the upper and lower factors of NLRP3, such as transforming growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, pro-IL-18, IL-1ß, pro-IL-1ß, NLRP3, ASC, and caspase-1. Additionally, mRNA expressions of caspase-1, NLRP3, and ASC were significantly downregulated after SA treatment. The results of the intestinal flora showed that SA could increase the diversity of flora and change its structure and composition in NASH rats by reducing Firmicutes/Bacteroidetes (F/B) ratio, Blautia (genus), Lachospiraceae (family), and Christensenellaceae R-7 group (genus), and increasing Muribaculaceae (family) and Bacteroides (genus). The metabolomics revealed that 24 metabolites were possibly the key metabolites for SA to regulate the metabolic balance of NASH rats, including chenodeoxycholic acid, xanthine, and 9-OxoODE. Nine metabolic pathways were identified, including primary bile acid biosynthesis, bile secretion, purine metabolism, and secondary bile acid biosynthesis. Conclusion: SA can regulate the intestinal microbial balance and metabolic disorder by inhibiting the NLRP3/ASC/caspase-1 axis to relieve NASH.

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.

Extracts from Seseli mairei Wolff attenuate imiquimod-induced psoriasis-like inflammation by inhibiting Th17 cells.

Objective: Seseli mairei Wolff extracts (SMWE) are widely used to treat psoriasis as a Chinese medicine, but their effect and mechanism are unclear. This study verified the effect of SMWE on psoriasis by regulating Th17 cells. Methods: HaCaT cells were treated with IL-17A in vitro to evaluate the effect of SMWE on psoriasis. In vivo, the mice psoriasis model was established using imiquimod (IMQ, 62.5 mg/d), and intragastrically treated with the different drugs for six days. The severity of skin inflammation was evaluated with Psoriasis Area and Severity Index (PASI) scores and pathology. The levels of inflammation cytokines were assessed with immunofluorescence, immunochemistry, ELISA, and real-time PCR. The number of Th17 cells was determined with flows. Results: SMWE inhibited the proliferation of HaCaT cells and reduced the IL-17A-induced IL-6 production in vitro. In vivo, SMWE deduced the levels of IL-1ß, IL-6, IL-8, IL-17A, IL-17F, IL-22, IL-23, and TNF-α, while increasing the level of IL-10 compared to the model group. SMWE also inhibited the levels of NF-κB, JAK2, and STAT3 proteins, while declining the expressions of Gr-1, and MPO. Interestingly, SMWE significantly decreased the number of Th17 cells. Conclusion: SMWE inhibited the proliferation of HaCaT cells and attenuated the development of psoriasis lesions by inhibiting Th17 cells to regulate the levels of inflammation cytokines.

Assessment of Ocular Deformation in Pathologic Myopia Using 3-Dimensional Magnetic Resonance Imaging.

IMPORTANCE: Ocular deformation in pathologic myopia can affect the entire globe. However, few studies have investigated the equatorial pattern of ocular shape. In addition, the correlation between equatorial and posterior morphology needs to be further explored. OBJECTIVE: To assess global ocular deformation in pathologic myopia. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based, cross-sectional study included 180 pathologic myopic eyes with atrophic maculopathy grading C2 (diffuse chorioretinal atrophy) or more from 180 participants who underwent comprehensive ophthalmic examination, including high-resolution 3-dimensional magnetic resonance imaging. In addition, 10 nonpathologic myopic eyes of 10 participants were set as the control group. Main Outcomes and Measures: According to the cross-sectional view of equator, equatorial shape was classified as round, rectangular, pyriform (noncircular and more protruded in 1 direction), vertical-elliptical, or horizontal-elliptical; according to the nasal and inferior views, the posterior shape was categorized as spheroidal, conical, bulb-shaped, ellipsoidal, multidistorted, and barrel-shaped. Equatorial circularity and ocular sphericity were used to quantitatively assess the morphological variability of the equatorial and posterior regions, respectively. The association between ocular morphology and ocular parameters and myopic maculopathy was also investigated. Results: The mean (SD) age of 180 participants with pathologic myopia was 55.14 (10.74) years, 127 were female (70.6%), and the mean (SD) axial length of studied eyes was 30.22 (2.25) mm. The predominant equatorial shape was pyriform (66 eyes [36.7%]), followed by round (45 eyes [25.0%]). The predominant posterior shape was bulb-shaped (97 eyes [52.2%]), followed by multidistorted (46 eyes [24.7%]). Equatorial circularity and equatorial shapes were correlated (r = -0.469; 95% CI, -0.584 to -0.346; P < .001) and ocular sphericity was correlated with posterior shapes (r = -0.533; 95% CI, -0.627 to -0.427; P < .001). In eyes with a vertical-elliptical equator, equatorial circularity and ocular sphericity were positively linearly correlated (R2 = 0.246; 95% CI, 0.050-0.496; P = .002) and the prevalence of inferior staphyloma was higher (27.8%; P = .04). Eyes with a horizontal-elliptical equator have the most horizontally oriented axis of corneal flat keratometry (median, 43.55 [interquartile range, 43.84] degrees; P = .01) and tended to present with multidistorted posterior shape (21.7%; P = .04). Conclusions and Relevance: These findings suggest ocular deformation is common in pathologic myopia and can affect the entire eye, including the equatorial and posterior regions. The morphological classification may enhance the understanding of the diverse patterns of ocular shape in pathologic myopia.

Synthesis of a Sm3+-doped YGa1.5Al1.5(BO3)4 phosphor via a mechanical activation-assisted solid-state reaction.

A Sm3+-doped YGa1.5Al1.5(BO3)4 (abbreviated as YGAB) phosphor was synthesized via a solid-state reaction with mechanical activation assistance in a high-energy density stirred bead mill. The samples were characterized by laser particle size analysis, specific surface area analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and fluorescence spectroscopy. In addition, the photoluminescence characteristics, luminescence decay, thermal stability, and LED application of the phosphors were also investigated. The results show that the mechanical activation of mixed raw materials before calcination can reduce the particle size and the activation energy of crystallization, resulting in the formation of the YGAB crystal phase at a lower calcination temperature. The mechanical activation in grinding can accelerate the subsequent solid-phase reaction, make Sm3+ ions more easily diffuse into the YGAB lattice, and improve the crystal structure of the synthesized phosphor, thus enhancing the optical properties of the phosphor. According to the photoluminescence emission (PL) and excitation (PLE) spectra, Sm3+ doped in the YGAB lattice can provide an efficient emission under 405 nm excitation. The optimum doping concentration of Sm3+ ions is 0.03 mol%. The optimum photoluminescence intensity, quantum yield, and fluorescence lifetime of the phosphor synthesized from mixed raw materials ground for 45 min can be obtained. The temperature-dependent PL spectra show that the emission intensity of the YGAB:0.03Sm3+ phosphor at 425 K is 84.7% of its initial intensity at room temperature. It is indicated that the YGAB:0.03Sm3+ phosphor synthesized could be used as one of the promising LED lighting materials.

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.

Untargeted metabolomics reveals the preventive effect of quercetin on nephrotoxicity induced by four organophosphorus pesticide mixtures.

This research aimed to explore the protective effect of quercetin against nephrotoxicity induced by four organophosphate pesticide mixtures (PM) using untargeted metabolomics technology in rat kidneys. Sixty male Wistar rats were randomly divided into six groups: control, low-dose quercetin treated (10 mg/kg bw), high-dose quercetin treated (50 mg/kg bw), PM-treated, and two dosages of quercetin + PM-treated. Metabolomics results showed that 17 differential metabolites were identified in the PM-treated group, and pathway analysis revealed that renal metabolic disorders include purine metabolism, glycerophospholipid metabolism, and vitamin B6 metabolism. When high-dose quercetin and PM-treated were administered to rats concurrently, the intensities of differential metabolites were substantially restored (p < 0.01), suggesting that quercetin can improve renal metabolic disorders caused by organophosphate pesticides (OPs). Mechanistically, quercetin could regulate the purine metabolism disorder and endoplasmic reticulum stress (ERS)-mediated autophagy induced by OPs by inhibiting XOD activity. Moreover, quercetin inhibits PLA2 activity to regulate glycerophospholipid metabolism and it could also exert antioxidant and anti-inflammatory effects to correct vitamin B6 metabolism in rat kidneys. Taken together, the high dose of quercetin (50 mg/kg. bw) has a certain protective effect on OPs-induced nephrotoxicity in rats, which provides a theoretical basis for quercetin against nephrotoxicity caused by OPs.