Dual Oxidation of Epoxides with a High-Valent Cu(III)-CF3 Compound and DMSO to Access 1,2-Diketones.

This study reports sequential dehydrogenation and transfer oxygenation of 1,2-diarylepoxides by high-valent phenCu(III)(CF3)3 and DMSO to produce 1,2-diketones. The Cu(III)-CF3 compound serves as a CF3 radical source to abstract the hydrogen atom of the epoxide ring. The resulting ether α-carbon radical undergoes ring-opening rearrangement to give a ketone α-carbon radical intermediate, which is oxygenated by DMSO with the release of Me2S. The combination of a Cu(III)-CF3 compound and DMSO may be exploited to develop other novel oxidation reactions.

Altruistic motivation or instrumental motivation: The spatial spillover effect of corporate social responsibility on corporate green innovation.

In recent years, the concept of corporate social responsibility has gained more attention from investors, and green innovation has become a key factor in China's economic growth. Despite this, regional disparities still remain, and the impact of corporate social responsibility on green innovation in local and surrounding areas is worth exploring. This article uses a Spatial Durbin Model to analyze the spatial spillover effect and mechanism of corporate social responsibility on green innovation of A-share listed companies in China from 2010 to 2020. The results show that corporate social responsibility behavior motivated by "tools" has a negative effect on local enterprises' green innovation, while also having a negative spillover effect on surrounding areas, thus affecting the spatial pattern of green innovation. Further research suggests that fulfilling corporate social responsibility can attract investors, alleviate financing constraints, and change corporate resource investment strategies, thus promoting cross-regional resource flow and enhancing green innovation. The results of this study remain consistent when the matrix and variables are changed. This article provides new insights into corporate social responsibility and green innovation, and offers policy recommendations to improve green innovation in enterprises.

KLF5/MDM2 Axis Modulates Oxidative Stress and Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells: The Role in Diabetic Cataract.

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then, KLF5 was knocked down in human lens epithelial cells (HLECs) to explore its functional roles and underlying mechanisms. Dual-luciferase reporter assay and chromatin immunoprecipitation analysis were used to detect whether KLF5 could bind the promoter of E3 ubiquitin ligase mouse double minute 2 (MDM2), a key regulator of EMT. Lastly, the regulation of KLF5 in the biological behaviors of HLECs via MDM2 was analyzed. We found a significant increase of KLF5 in the DC lens anterior capsular, diabetic rat lens, and high glucose (HG)-stimulated HLECs. Knockdown of KLF5 inhibited oxidative stress, inflammation, migration, and EMT of HG-stimulated HLECs. KLF5 silencing impeded MDM2 expression and restricted the activation of MARK1/FAK and NF-κB signaling pathways in HLECs under HG condition. Additionally, KLF5 was found to bind the MDM2 promoter and enhance the transcriptional activity of MDM2. The protective effects by silencing KLF5 on HG-cultured HLECs could be offset by MDM2 overexpression. We demonstrated that knockdown of KLF5 alleviated oxidative stress, migration, and EMT of HG-cultured HLECs by regulating MDM2, suggesting a potential therapeutic strategy for DC.

Real-world adherence to toxicity management guidelines for immune checkpoint inhibitor-induced diabetes mellitus.

Objective: Immune checkpoint inhibitors(ICIs) have improved survival and are increasingly used for cancer. However, ICIs use may be limited by immune-related adverse events (irAEs), such as ICI-induced diabetes mellitus(ICI-DM). The objective of the present study was to characterize ICI-DM patients and real-world adherence to guidelines. Research design and methods: The present study was a retrospective review of electronic records of ICI-DM patients at the First Affiliated Hospital of Nanjing Medical University between July 2018 and October 2022. Results: 34.8% (8/23)patients monitored blood glucose in every treatment cycle. The proportion of patients with severe diabetic ketoacidosis(DKA) was lower in the tight glycemic monitoring group than the non-tight glycemic monitoring group (16.7% vs. 55.6%, p = 0.049). 78.3%(18/23) patients with hyperglycemia visited a non-endocrinologist first, but 95.7% of patients were then referred to an endocrinologist. Twenty patients were tested for distinguishing the etiology of hyperglycemia and 20% patients with positive glutamic acid decarboxylase antibody(GADA), 55% with C-peptide <3.33pmol/L. High screening rates for other ICI-induced endocrinopathies were observed and half of the patients with ICI-DM developed other endocrine gland irAEs, with the most common being thyroiditis. Moreover, five patients developed non-endocrine serious adverse events(SAEs). Twelve (52.2%) patients were withdrawn from ICI due to ICI-DM. The time to progression of tumor in ICI-DM patients in the continue and interruption group was longer than in the withdrawal group (333.5 ± 82.5 days vs. 183.1 ± 62.4 days, p = 0.161). Only 17.4% of ICI-DM patients were completely managed according to guidelines. Thus, the present study proposed a screening, diagnosis, and management algorithm for ICI-DM in real-world practice. Conclusion: The present study reported the largest number of ICI-DM cases described in a single institute, providing insight into real-world ICI-DM management guideline adherence and highlighting the clinical challenges in ICI-DM management.

Growth differentiation factor-15/adiponectin ratio as a potential biomarker for metabolic syndrome in Han Chinese.

Aims: Growth differentiation factor-15 (GDF-15) and adiponectin are adipokines that regulate metabolism. This study aimed to evaluate the roles of GDF-15, adiponectin, and GDF-15/adiponectin ratio (G/A ratio) as biomarkers for detecting metabolic syndrome (MS). Materials and methods: This cross-sectional study included 676 participants aged 20-70 years in Jurong, China. The participants were divided into four groups based on sex and age (<40 and ≥40 years). MS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Receiver operating characteristic curves were used to evaluate the performance of GDF-15, adiponectin, and the G/A ratio in predicting MS. Results: The prevalence of MS was 22.0% (149/676). Logistic regression analysis indicated that the G/A ratio and adiponectin levels, but not GDF-15 levels, were correlated with MS [odds ratio; 95% CI 1.010 (1.006-1.013) and 0.798 (0.735-0.865), respectively] after adjusting for confounding factors. The G/A ratio displayed a significant relationship with MS in each subgroup and with each MS component in both men and women; however, adiponectin concentrations were significantly associated with MS and all its components only in men (all P <0.05). The area under the curve (AUC) of the G/A ratio and the adiponectin level for MS was 0.758 and 0.748, respectively. The highest AUC was 0.757 for the adiponectin level in men and 0.724 for the G/A ratio in women. Conclusions: This study suggests that the G/A ratio and adiponectin are potential biomarkers for detecting MS in women and men, respectively.

Comprehensive study of volatile compounds and transcriptome data providing genes for grape aroma.

BACKGROUND: Fruit aroma is an important quality with respect to consumer preference, but the most important aroma compounds and their genetic regulatory mechanisms remain elusive. RESULTS: In this study, we qualitatively analysed volatile compounds in the pulp and skin of five table grape cultivars with three aroma types (muscat, strawberry, and neutral) using solid-phase microextraction gas chromatography/mass spectrometry. We identified 215 aroma compounds, including 88 esters, 64 terpenes, and 29 alcohols, and found significant differences in the number of compounds between the pulp and skin, especially for terpenes. Skin transcriptome data for the five grape cultivars were generated and subjected to aroma compound-gene correlation analysis. The combined transcriptomic analysis and terpene profiling data revealed 20 candidate genes, which were assessed in terms of their involvement in aroma biosynthetic regulation, including 1 VvCYP (VIT_08s0007g07730), 2 VvCCR (VIT_13s0067g00620, VIT_13s0047g00940), 3 VvADH (VIT_00s0615g00010, VIT_00s0615g00030, VIT_ 00s0615g00020), and 1 VvSDR (VIT_08s0040g01200) in the phenylpropanoids synthesis pathway, and 1 VvDXS (VIT_05s0020g02130) and 6 VvTPS (VIT_13s0067g00370, Vitis_vinifera_newGene_3216, VIT_13s0067g00380, VIT_13s0084g00010, VIT_00s0271g00010, and VIT_13s0067g00050) in the methylerythritol phosphate pathway (involved in the production and accumulation of aromatic compounds). Additionally, 2 VvMYB (VIT_17s0000g07950, VIT_03s0063g02620) and 1 VvGATA (VIT_15s0024g00980) transcription factor played important regulatory roles in the accumulation of key biosynthetic precursors of these compounds in grapes. Our results indicated that downstream genes, specifically 1 VvBGLU (VIT_03s0063g02490) and 2 VvUGT (VIT_17s0000g07070, VIT_17s0000g07060) are involved in regulating the formation and volatilization of bound compounds in grapes. CONCLUSIONS: The results of this study shed light on the volatile compounds and "anchor points" of synthetic pathways in the pulp and skin of muscat and strawberry grapes, and provide new insight into the regulation of different aromas in grapes.

Improving the catalytic activity of ß-glucosidase from Coniophora puteana via semi-rational design for efficient biomass cellulose degradation.

In order to improve the degradation activity of ß-glucosidase (CpBgl) from Coniophora puteana, the structural modification was conducted. The enzyme activity of mutants CpBgl-Q20C and CpBgl-A240S was increased by 65.75% and 58.58%, respectively. These mutants exhibited maximum activity under the same conditions as wild-type CpBgl (65 â„ƒ and pH 5.0), slightly improved stabilities compared that of the wild-type, and remarkably enhanced activities in the presence of Mn2+ or Fe2+. The Vmax of CpBgl-Q20C and CpBgl-A240S was increased to 138.18 and 125.14 µmol/mg/min, respectively, from 81.34 µmol/mg/min of the wild-type, and the catalysis efficiency (kcat/Km) of CpBgl-Q20C (335.79 min-1/mM) and CpBgl-A240S (281.51 min-1/mM) was significantly improved compared with that of the wild-type (149.12 min-1/mM). When the mutant CpBgl-Q20C were used in the practical degradation of different biomasses, the glucose yields of filter paper, corncob residue, and fungi mycelia residue were increased by 17.68%, 25.10%, and 20.37%, respectively. The spatial locations of the mutation residues in the architecture of CpBgl and their unique roles in the enzyme-substrate binding and catalytic efficiency were probed in this work. These results laid a foundation for evolution of other glycoside hydrolases and the industrial bio-degradation of cellulosic biomass in nature.

Therapeutic potential of pupilloplasty combined with phacomulsification and intraocular lens implantation against uveitis-induced cataract.

AIM: To evaluate the therapeutic effect of pupilloplasty combined with phacomulsification and intraocular lens implantation (PPI) in uveitis-induced cataract. METHODS: Total 28 patients with uveitis-induced cataract were enrolled. Within 3mo before the PPI, 7 cases accompanied with glaucoma maintained carteolol hydrochloride for lowering intraocular pressure, and 1 case maintained glucocorticoid for anti-inflammation. The baseline characteristics, treatment processes, and outcomes of enrolled cases were retrospectively analyzed. Hematoxylin and eosin (HE) staining was performed to reveal the histopathological changes of iris tissues. RESULTS: Iris hemorrhage was the only intraoperative complication observed in 2 cases. After the surgery, normal intraocular pressure, right position of intraocular lens, and improved visual gain [best corrected visual acuity (BCVA)>0.5] were achieved. Postoperative keratic precipitates was observed in 2 cases, which was recovered within 1wk. During the follow-up of 5-10y, no recurrence of uveitis was found in 27 cases (96.43%). Uveitis only recurred in one case with the onset of ankylosing spondylitis. HE staining showed iris stroma (all samples), pigment cell hyperplasia in pigment epithelium (n=9) and stroma (n=19), inflammatory cell infiltration in iris (n=7), and neovascularization in iris surface (n=2). CONCLUSION: PPI improves the visual gain and prevents the long-term recurrence of uveitis in patients with uveitis-induced cataract, including those with preoperative intraocular pressure abnormality (glaucoma) and inflammation (active uveitis). Uveitis presents stroma atrophy, pigment cell hyperplasia, and inflammatory cell infiltration, even in a quiet state.

Risk factors and a predictive model for the development of epilepsy after Japanese encephalitis.

BACKGROUND: We aimed to study seizure characteristics during the acute phase of Japanese encephalitis (JE) in children, determine the risk factors of postencephalitic epilepsy (PEE), establish a risk prediction model for the disease, and construct a nomogram to visualize the model. METHODS: We retrospectively analyzed the clinical data and follow-up results of 328 children with JE who were hospitalized between January 2011 and December 2020. Risk factors were screened using univariable analysis, a predictive model was built using binary logistic analysis, lasso regression was used for variable screening, and a nomogram was developed. RESULTS: Of the 328 children with JE enrolled in the study, 216 (65.9%, 216/328) had seizures in the acute phase. The incidence of PEE was 14.7% (39/264), The cumulative percentages of PEE after discharge was 10.6% (28/264)at 6 months, which increased to 13.6%(36/264)at 3 years. 38.5% of patients with PEE had generalized onset seizures, and 17.9% had focal motor seizures. Univariable analysis revealed that 22 clinical indicators were related to the PPE; Multivariable analysis identified seizure number >5 (OR (95%CI) = 3.013 (1.046-8.676), P = 0.041), status epilepticus (OR (95%CI) = 3.918 (1.212-12.669), P = 0.023), and Coma (OR (95%CI) = 22.495 (8.686-58.285), P<0.001) as independent risk factors for PEE. The risk prediction model: ln(p/1p)= -3.533 + 1.103 × (seizures number > 5) +1.366 × (status epilepticus) + 3.113 × (Coma) was developed, and a nomogram was constructed. The area under the ROC curve (AUC), calibration plot, and Hosmer-Lemeshow test showed that the model had good discrimination and calibration. Ordinary bootstrapping was used for internal validation, and the predictive results of the original and test sets were consistent. CONCLUSIONS: Seizure is a common manifestation during acute encephalitis and sequelae in children with JE. The nomogram constructed in this study could be used for early prediction, and could facilitate early intervention.

A Nomogram to Predict Bacterial Meningitis-associated Hydrocephalus: A Single-Center Retrospective Study.

OBJECTIVE: We aimed to develop a predictive nomogram for the early detection of hydrocephalus in children with bacterial meningitis. METHODS: This retrospective study was based on data of children with bacterial meningitis admitted to our hospital between January 2016 and December 2020. Risk factors were evaluated using univariate analysis, and the predictive model/nomogram was built using binary logistic analysis. A nomogram calibration plot, Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve evaluated the predictive performance. Ordinary bootstrapping processed the internal validation. RESULTS: We enrolled 283 patients who matched the inclusion criteria, among whom 41 cases (14.49%) had confirmed bacterial meningitis-associated hydrocephalus (BMAH). The incidence of sequelae in the patients with BMAH was 88.9% (24/27), which was significantly higher than that in the patients without BMAH. Univariate regression analysis revealed that 14 clinical indicators were associated with BMAH. Multivariate analysis identified 4 variables as independent risk factors to establish the predictive model: repeated seizures, loss of consciousness, procalcitonin ≥7.5 ng/dL and mechanical ventilation. And a graphical nomogram was designed. The area under the ROC curve was 0.910. In the Hosmer-Lemeshow test the P value was 0.610. The mean absolute error in the calibration plot was 0.02. Internal validation showed the testing set was in good accordance with the original set when internal validation was performed. CONCLUSIONS: The predictive model/nomogram of BMAH could be used by clinicians to determine hydrocephalus risk.

Novel Likely Pathogenic Variants Identified by Panel-Based Exome Sequencing in Congenital Cataract Patients.

PURPOSE: To identify likely pathogenic variants in three families with congenital cataracts via panel-based exome sequencing. METHODS: A panel containing 153 genes associated with congenital cataracts was designed. Genes were selected through reference to databases including the Human Gene Mutation Database (HGMD), Online Mendelian Inheritance in Man (OMIM), Genetic Home Reference, and the latest peer-reviewed publications on the genetics of hereditary cataracts. Panel-based exome sequencing was performed with the Illumina HiSeq X-Ten platform, and then the identified variants were confirmed with Sanger sequencing and evaluated according to the American College of Medical Genetics and Genomics (ACMG) criteria. RESULTS: Three likely pathogenic variants were found. A novel CRYBB2: c.230G > T p.G77V variant was identified in family A, a novel CRYBB2: c.230G > A p.G77D variant was identified in family B, and a novel CRYGD: c.475delG p.A159Pfs∗9 variant was identified in family C. CONCLUSION: Panel-based exome sequencing revealed three likely pathogenic variants in three unrelated Chinese families with congenital cataracts. These data expand the genetic spectrum associated with congenital cataracts.

Whole-exome sequencing identification of a recurrent CRYBB2 variant in a four-generation Chinese family with congenital nuclear cataracts.

Congenital cataracts is the most common cause of visual impairment and blindness in children. Although there have been extensive studies into the pathogenesis of congenital cataracts, the pathogenic mechanism underlying the recurrent variant CRYBB2:c.62T>A(p.I21N) has not been previously reported. Thus, the present study aimed to use whole-exome sequencing (WES) to identify potential genetic variants and investigate how they may have induced the occurrence of cataracts in a four-generation Chinese family with congenital nuclear cataracts. The medical history of this family was recorded and WES was conducted for one proband. Sanger sequencing was used to verify the presence of the putative variant in all participants. PolyPhen-2, SIFT and ProtScale were used to analyze the effect of the identified variants on protein function and hydrophobicity, and Pymol was used to show the structure of the wild-type (Wt) and mutant ß-crystallin B2 (CRYBB2) protein. Full-length Wt-CRYBB2 or mutant-CRYBB2 (I21N-CRYBB2) were fused to green fluorescent protein (GFP), and the recombinant plasmids were transfected into HeLa cells. Reverse transcription-quantitative PCR and western blotting were used to detect the expression levels of CRYBB2 mRNA and protein. Immunofluorescence and flow cytometry analyses were used to detect protein localization and apoptosis, respectively. A recurrent variant CRYBB2:c.62T>A(p.I21N) was identified in a four-generation Chinese family with congenital nuclear cataracts. Multiple-sequence alignment of CRYBB2 demonstrated that codon 21 was highly conserved. Pymol revealed that the structure of the I21N-CRYBB2 protein was distinct from that of Wt-CRYBB2. PolyPhen-2 predicted that it had a variant provean score 1.0, suggesting it was 'probably damaging', and SIFT predicted it had a variant provean score of -5.113, indicating it was 'deleterious'. ProtScale indicated that the hydrophobicity of the mutation site was significantly reduced. The protein expression levels of the I21N-CRYBB2 were decreased compared with the Wt-CRYBB2. Immunofluorescence analysis revealed that the variant I21N-CRYBB2 protein tended to accumulate around the nucleus, and flow cytometry analysis indicated that it increased cell apoptosis. Furthermore, I21N-CRYBB2 induced the activation of the unfolded protein response (UPR). In conclusion, a pathogenic variant of CRYBB2:c.62T>A(p.I21N) was identified via WES in a four-generation Chinese family with congenital nuclear cataracts. Through biological analysis, it was found that the variant induced abnormal protein aggregation, activated the UPR and triggered excessive cell apoptosis, which may lead to the occurrence of congenital nuclear cataracts in this family.

Whole-exome sequencing identifies an RS1 variant in a Chinese family with X-linked retinoschisis.

A notable behavioural feature of X-linked retinoschisis (XLRS) is extensive structural schisis (splitting) of the outer plexiform and inner nuclear layers of the neurosensory retina, which is partly combined with complications related to vitreous hemorrhage, macular holes and retinal detachment. The present study aimed to identify the pathogenic gene mutation in a three-generation Chinese family with XLRS by whole-exome sequencing (WES). The clinical information of a three-generation Chinese family with cases of XLRS was collected. WES was performed for the proband. A comparison with the human reference genome sequence (hg38) and bioinformatic analysis were performed to reveal putative variants and Sanger sequencing was applied to verify mutations in this family and healthy control participants. Intraretinal cystic spaces were detected by optical coherence tomography imaging. Structures of the wild-type and mutant retinoschisin 1 (RS1) protein were modelled by PyMol. Almost all patients had a history of vision loss and abnormal blue-purple colour vision; however, the phenotypes of the 4 patients were distinctly different. There was no linear correlation between phenotypic severity and age. A recurrent RS1 (Xp22.2) mutation (NM_000330: c.559C>T) was detected, resulting in the p.Q187X variant. According to the protein model, this variant is likely pathogenic. The present study was the first to report that RS1:c.559C>T induces XLRS in a three-generation Chinese pedigree, with the mutation leading to premature termination of translation of the RS1 protein. WES was able to diagnose XLRS, which has the characteristics of clinical and genetic heterogeneity.

Clinical characteristics of Epstein-Barr virus infection in the pediatric nervous system.

BACKGROUND: To investigate the clinical characteristics of Epstein-Barr virus (EBV) infection in the pediatric nervous system (NS). METHODS: We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children's hospital of Chongqing Medical University from January 2008 to April 2019. RESULTS: EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0-4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain-Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV. CONCLUSION: There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.

A rice chloroplast-localized ABC transporter ARG1 modulates cobalt and nickel homeostasis and contributes to photosynthetic capacity.

Transport and homeostasis of transition metals in chloroplasts, which are accurately regulated to ensure supply and to prevent toxicity induced by these metals, are thus crucial for chloroplast function and photosynthetic performance. However, the mechanisms that maintain the balance of transition metals in chloroplasts remain largely unknown. We have characterized an albino-revertible green 1 (arg1) rice mutant. ARG1 encodes an evolutionarily conserved protein belonging to the ATP-binding cassette (ABC) transporter family. Protoplast transfection and immunogold-labelling assays showed that ARG1 is localized in the envelopes and thylakoid membranes of chloroplasts. Measurements of metal contents, metal transport, physiological and transcriptome changes revealed that ARG1 modulates cobalt (Co) and nickel (Ni) transport and homeostasis in chloroplasts to prevent excessive Co and Ni from competing with essential metal cofactors in chlorophyll and metal-binding proteins acting in photosynthesis. Natural allelic variation in ARG1 between indica and temperate japonica subspecies of rice is coupled with their different capabilities for Co transport and Co content within chloroplasts. This variation underpins the different photosynthetic capabilities in these subspecies. Our findings link the function of the ARG1 transporter to photosynthesis, and potentially facilitate breeding of rice cultivars with improved Co homeostasis and consequently improved photosynthetic performance.

The effect of early mobilization in critically ill patients: A meta-analysis.

BACKGROUND: The aim of this meta-analysis was to assess if early mobilization and rehabilitation in the intensive care unit (ICU) could reduce ICU-acquired weakness (ICU-AW), improve functional recovery, improve muscle strength, shorten the length of ICU and hospital stays, and reduce the mortality rate. METHODS: A comprehensive literature search in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and National Knowledge Infrastructure, China (CNKI) was performed. Results were expressed as a risk ratio (RR) with 95% confidence intervals (95% CIs) or weight mean difference (WMD) with 95% CIs. Pooled estimates were calculated using a fixed-effects or random-effects model according to the heterogeneity among studies. RESULTS: Fifteen randomized controlled trials involving a total of 1941 patients were included in this meta-analysis. Pooled estimates suggested that early mobilization significantly reduced the incidence of ICU-AW (RR = 0.49, 95% CI: 0.26, 0.91; P = .025), shortened the length of ICU (WMD = -1.82 days, 95% CI: -2.88, -0.76; P = .001) and hospital (WMD = -3.90 days, 95% CI: -5.94, -1.85; P < .001) stays, and improved the Medical Research Council score (WMD = 4.47, 95% CI: 1.43, 7.52; P = .004) and Barthel Index score at hospital discharge (WMD = 21.44, 95% CI: 10.97, 31.91; P < .001). Moreover, early mobilization also decreased complications such as deep vein thrombosis (RR = 0.16, 95% CI: 0.04, 0.59; P = .006), ventilator-associated pneumonia (RR = 0.26, 95% CI: 0.11, 0.63; P = .003), and pressure sores (RR = 0.14, 95% CI: 0.04, 0.44; P = .001). However, early mobilization did not reduce the ICU mortality rate (RR = 1.31, 95% CI: 0.97, 1.76; P = .074), improve the handgrip strength (WMD = 4.03 kg, 95% CI: -0.68, 8.74; P = .094), and shorten the duration of mechanical ventilation (WMD = 0.20 days, 95% CI: -0.10, 0.50; P = .194). CONCLUSION: This study indicated that early mobilization was effective in preventing the occurrence of ICU-AW, shortening the length of ICU and hospital stay, and improving the functional mobility. However, it had no effect on the ICU mortality rate and ventilator-free days. RELEVANCE TO CLINICAL PRACTICE: ICU-AW is a common neuromuscular complication of critical illness, and it is predictive of adverse outcomes. Early mobilization of critically ill patients is a candidate intervention to reduce the incidence and severity of ICU-AW. Some clinical studies have demonstrated this, whereas others found opposite results. The aim of our study is to assess if early mobilization and rehabilitation in the ICU could reduce the ICU-AW, improve functional recovery, improve muscle strength, shorten length of ICU and hospital stay, and reduce the mortality rate.

Recurrent PAX 6 mutation in a Chinese family with congenital aniridia, progressive cataracts and mental retardation.

BACKGROUND: One prominent pathological feature of congenital aniridia is hypoplasia of the iris, often accompanied by other eye abnormalities. The objective of this study is to identify gene mutations responsible for autosomal dominance in a Chinese family with congenital aniridia, progressive cataracts and mental retardation. METHODS: A total of 11 family members, including 6 affected and 5 unaffected individuals were recruited. Whole exome sequencing was performed on the proband and Sanger sequencing was applied to identify the causal mutation in the other family members and control samples. RESULTS: A heterozygous mutation, c. 112delC (p. Arg38fs) in PAX 6, was identified in the family that was associated with congenital aniridia, progressive cataracts and mental retardation. The mutation was exclusively observed in all affected individuals but not in unaffected family members or unrelated healthy controls without aniridia recruited from Beijing Tongren Hospital. Bioinformatics analysis indicated that the mutation c. 112delC (p. Arg38fs) in PAX 6 affected sugar phosphate backbone construction, leading to half reduction of the full-length protein. Other symptoms such as lens opacity, keratitis, lens dislocation, ciliary body hypoplasia, foveal hypoplasia and mental development retardation were also observed in this family. CONCLUSION: These results provided a new insight into the effects of PAX 6 as a mutational hotspot, with a symptom complex that includes congenital aniridia, progressive cataracts and mental retardation. These findings suggested the cognitive treatment of PAX 6-mutated individuals could be considered earlier clinically, combined with medication or surgery of congenital aniridia and progressive cataracts.

NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128.

Long noncoding RNAs (lncRNA) have been recognized as significant regulators in the progression of atherosclerosis (AS). Oxidized low-density lipoprotein (ox-LDL) can induce macrophage inflammation and oxidative stress, that serves important roles in AS. However, the exact function of lncRNA NEAT1 and its possible molecular mechanism in AS remain unclear. Here, we concentrated on the roles and molecular mechanisms of NEAT1 in AS development. In our current study, we observed that NEAT1 was elevated by ox-LDL in a dose-dependent and time-dependent manner. RAW264.7 cell survival was greatly enhanced, and cell apoptosis was significantly inhibited by LV-shNEAT1 transfection. In addition, knockdown of NEAT1 in RAW264.7 cells repressed CD36 expression and foam cell formation while NEAT1 overexpression shown an opposite process. Moreover, NEAT1 downregulation inhibited inflammation molecules including IL-6, IL-1ß, and TNF-α. Meanwhile, silencing of NEAT1 can also suppress reactive oxygen species (ROS) and malondialdehyde (MDA) levels with an enhancement of superoxide dismutase (SOD) activity in RAW264.7 cells. MicroRNAs are some short RNAs, and they can regulate multiple biological functions in many diseases including AS. Here, we found that miR-128 expression was remarkably decreased in ox-LDL-incubated RAW264.7 cells. Interestingly, miR-128 mimics was able to reverse AS-correlated events induced by overexpression of NEAT1. By using bioinformatics analysis, miR-128 was predicted as a target of NEAT1 and the correlation between them was validated in our study. Taken these together, it was implied that NEAT1 participated in ox-LDL-induced inflammation and oxidative stress in AS development through sponging miR-128.