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.

Acyl Cyanides as Bifunctional Reagent: Application in Copper-Catalyzed Cyanoamidation and Cyanoesterification Reaction.

Cu-catalyzed domino decyanation and cyanation reaction of acyl cyanides with amines or alcohols have been developed. The cyano sources were generated in situ via C-CN cleavage yielding the corresponding cyano substituted amides or esters in moderate to excellent yields. This approach features a cheap copper catalyst, domino decyanation and cyanation reaction, readily available starting materials, broad substrate scope, operational simplicity, and the potential for further transformation of the cyano group.

Characterization of a p.R76H mutation in Cx50 identified in a Chinese family with congenital nuclear cataract.

BACKGROUND/PURPOSE: A three-generation Chinese family with autosomal dominant congenital nuclear cataract was recruited. This study aimed to identify the disease-causing gene for nuclear cataract with functional dissections of the identified mutant. METHODS: Detailed clinical data and family history were recorded. Candidate gene sequencing was performed to identify the disease-causing mutation. Recombinant connexin50 (Cx50) wild type and mutant constructs were synthesized. Triton X-100 solubility and subcellular localization of the recombinant Cx50 proteins were analyzed in HeLa cells. Apoptosis was assayed as the percentage of fragmented nuclei in transfected cells. RESULTS: All affected individuals in the family displayed clear phenotypes of dense nuclear cataracts. A c.227 G > A variation was found in the coding region of Cx50, which arginine residue at position 76 was substituted by histidine (p.R76H). This mutation was co-segregated with the disease in the family, and was not observed in 110 unrelated Chinese controls. No statistically significant differences were found in the Triton X-100 solubility and apoptosis rate between wild type and mutant Cx50 in HeLa cells. However, Cx50 mutant was unable to form gap junctional plaques between adjacent cells as the wild type proteins did. CONCLUSION: This study identified a novel cataract phenotype caused by the p.R76H mutation in Cx50, providing evidence of further phenotypic heterogeneity associated with this mutation. Functional analysis showed that the mutation affected the formation of gap junction channels and led to opacity in the lens.

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.

Groundwater irrigation induced variations in DOM fluorescence and arsenic mobility.

Dissolved organic matter (DOM) plays a predominant role in groundwater arsenic (As) mobility. However, the temporal-spatial variations in DOM fluorescent characteristics and their effects on As mobility induced by groundwater irrigation remain unclear. To address these issues, groundwater from multilevel and irrigation wells in Zones I and II (with low- and high-As groundwater irrigation, respectively) from the Hetao Basin, China, were monitored in both non-irrigation (NIG) and irrigation (IG) seasons. Upon irrigation, the irrigation return increased the relative abundance of protein- and humic-like DOM in shallow groundwater from Zone I with Ca-type groundwater and Zone II with Na-type groundwater irrigation, respectively. The introduced dissolved oxygen by irrigation return decreased As concentrations by 22 % and 6 % on average in shallow groundwater from Zones I and II, respectively. However, the pumping-induced lateral recharge of lower- and higher-As groundwater led to an average 17 % decrease and 38 % increase in As concentrations in deeper groundwater from the two zones, respectively. The increased degradation of protein-like DOM may also contribute to the elevated As concentrations in deep groundwater from Zone II. The study provides insights into the dependence of irrigation-induced variations in DOM fluorescence and As concentrations on geochemicals of irrigation groundwater and aquifer hydrogeological conditions.

Transformation of dissolved organic matter and related arsenic mobility at a surface water-groundwater interface in the Hetao Basin, China.

Porewater arsenic mobility above the groundwater table has been recognized as a potential cause of arsenic-rich groundwater, but the processing pathways of dissolved organic matter (DOM) in that hyporheic zone and their effect on porewater arsenic release remain poorly understood. To address these issues, two porewater profiles were sampled in a surface water-groundwater interaction zone from the Hetao Basin, China, to monitor the porewater geochemistry and DOM molecular characteristics. The results show that the porewater arsenic, Fe(II), and DOC concentrations were all significantly higher than those of the intruding pond water, and were located above the conservative mixing model lines. This indicates a net release of these solutes from the sediment. By comparing the porewater with pond water DOM, we found that the carboxyl-rich alicyclic molecules (CRAM) were selectively preserved, carbohydrates and aliphatics/proteins were preferentially consumed, and low O/C-ratio compounds with high bioproduction index (I_bioprod) and terrestrial index (I_terr) were produced. The transformation of CHO to CHOS compounds also represented a pathway of recalcitrant DOM production. The produced recalcitrant organic compounds mostly contributed to the elevated porewater DOC concentrations, but their contribution decreased along the filtration path. The consumption of labile DOM compounds would be responsible for Fe(III) hydroxide reduction and arsenic release. The generated recalcitrant DOM may also be a driver of porewater arsenic mobility by acting as electron shuttles. This study highlights the importance of the hyporheic zone in shaping shallow groundwater DOM composition and the potential contribution to arsenic enrichment.

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.

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.

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.

Paleochannel of the Yellow River within the Zoige Basin and its environmental significance on the NE Tibetan Plateau.

Paleochannel sedimentary sequences can provide abundant information on regional environmental changes. A typical paleochannel (paleo-oxbow lake type) section of the Yellow River was identified within the Zoige Basin on the NE Tibetan Plateau. A multi-index approach was used to accurately identify sediments of different genetic types, such as riverbed deposits of the Yellow River, paleo-oxbow lake deposits, and overbank flood deposits (OFD) in the section. Based on optically stimulated luminescence (OSL) and AMS 14C dates, we examined the environmental evolution recorded by the section. The results show that: (1) The section is a record of environmental change since 4.17 ± 0.49 ka. During 4.17 ± 0.49 to 3.24 ± 0.26 ka, the ancient Yellow River occupied the channel. At 3.24 ± 0.26 ka, the paleochannel experienced a neck cutoff, and the fluvial environment began to change into the oxbow lake environment. After 2.45 ± 0.11 ka, the paleo-oxbow lake gradually disappeared. Subalpine meadow soil has developed at this site since 1.31 ± 0.05 ka. (2) Paleoenvironmental proxies indicate that the Zoige Basin was warmer and wetter before ~3.00 ka, and became drier and colder after ~3.00 ka, which may be mainly related to the weakening of the East Asian summer monsoon (EASM) and the strengthening of the Westerlies. (3) Two episodes of extreme overbank flooding occurred at 2.96 ± 0.24 to 2.87 ± 0.27 ka and 1.84 ± 0.20 to 1.70 ± 0.16 ka, correlated with climate shift period from the mid-Holocene climatic optimum to the late Holocene and the Dark Age Cold Period (DACP), respectively. Due to the relatively cold and dry climate in these periods, glaciers generally advanced on the Tibetan Plateau, and the contribution of snow and ice meltwater weakened. Therefore, the strong rainfall caused by the abnormal atmospheric circulation may be the main cause of these extreme overbank flooding.

Combined lumbar muscle block and perioperative comprehensive patient-controlled intravenous analgesia with butorphanol in gynecological endoscopic surgery.

BACKGROUND: Laparoscopic surgery has become a common surgical approach for the clinical treatment of intra-abdominal lesions in recent years. We hypothesized that lumbar block with postoperative patient-controlled intravenous analgesia (PCIA) by butorphanol after gynecological surgery under general anesthesia would be more effective than PCIA by butorphanol alone. AIM: To investigate the effect of lumbar block with PCIA by butorphanol after gynecological surgery under general anesthesia. METHODS: This study assessed 120 women scheduled for laparoscopic surgery at our hospital between May 2017 and May 2020. They were divided using a random number table into a research group (those who received quadratus lumborum block combined with PCIA analgesia by butorphanol) and a control group (those who received only PCIA analgesia by butorphanol), with 60 patients in each group. Demographic factors, visual analog scale scores for pain, serum inflammatory markers, PCIA compressions, Ramsay scores, and adverse events were compared between groups using a t-test, analysis of variance, or χ 2 test, as appropriate. RESULTS: There were no significant differences in demographic factors between groups (all P > 0.05). The visual analog scale scores of the research group in the resting state 12 h and 24 h postoperatively were significantly lower than those of the control group (P < 0.05). Two hours after surgery, there were no significant differences in the levels of serum tumor necrosis factor-α, interleukin (IL)-6, or IL-8 between groups (P > 0.05). The serum tumor necrosis factor-α levels of the research group 24 h postoperatively were significantly lower than those of the control group (P < 0.05). The levels of serum IL-6 and IL-8 in the study group 24 h and 48 h postoperatively were significantly lower than those in the control group (P < 0.05). CONCLUSION: Lumbar block with PCIA with butorphanol after gynecological surgery under general anesthesia significantly improves the analgesic effect and reduces the degree of inflammation, instances of PCIA compression, and adverse reactions.

Spatial variation in dissolved phosphorus and interactions with arsenic in response to changing redox conditions in floodplain aquifers of the Hetao Basin, Inner Mongolia.

Increasing numbers of studies have reported groundwater with naturally high phosphorous (P) and arsenic (As) concentrations, which can potentially threaten the environment and human health. However, the cycling of P and its interactions with As in groundwater under changing redox conditions remain largely unknown. In this study, 83 groundwater samples and 14 sediment samples were collected from the Hetao Basin, Inner Mongolia, for systematic hydrogeochemical investigation and complementary geochemical evaluation. The results showed that P cycling in floodplain aquifers was tightly constrained by redox conditions. Under oxic/suboxic conditions, mineralization of organic matter and weathering of P-bearing minerals were the two dominant processes that mobilized considerable amounts of P in groundwater. When redox conditions became reducing, Fe(III)-oxide reduction dominated, resulting in enrichment of both P and As in groundwater. In Fe(III)-reducing conditions, secondary Ca/Fe(II)-minerals might serve as an important sink for P. When redox conditions became SO42--reducing, preferential adsorption and incorporation of P over As on Fe(II)-sulfides might constrain the As immobilization pathway, resulting in immediate retardation of P and hysteretic immobilization of As. This P-immobilization pathway in natural aquifers has not been described before. This study provides novel insights into P cycling and As enrichment in groundwater systems. Understanding the roles of Fe(II)- and S(-II)-minerals in the immobilization of and interaction between P and As in response to SO42- reduction may help to inspire effective in-situ remediation of contaminated groundwater, in which P and As coexist and remain mobile for decades or longer.

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.

Mutation Analysis of Families with Autosomal Dominant Congenital Cataract: A Recurrent Mutation in the CRYBA1/A3 Gene Causing Congenital Nuclear Cataract.

PURPOSE: To identify the CRYBA1/A3 mutation spectrum and analyze the genotype-phenotype correlations in Chinese families with congenital cataract. METHODS: Family history and clinical data of 47 unrelated families with autosomal dominant congenital cataract (ADCC) were recorded. CRYBA1/A3 gene sequencing was applied to identify the causative mutation. Haplotypes were constructed using closely linked microsatellite markers and intragenic single-nucleotide polymorphisms (SNPs) to compare the affected haplotype in three families. RESULTS: Nuclear cataract was the most common type of ADCC in Chinese families, accounting for 42.6% (20/47). A recurrent CRYBA1/A3 deletion mutation (ΔG91) was identified in three families (6.4%) with nonprogressive nuclear congenital cataract. Different haplotypes segregated with the mutation in each family. CONCLUSIONS: A recurrent ΔG91CRYBA1/A3 mutation occurs independently in 6.4% of the Chinese families with autosomal dominant nuclear cataracts and most likely represents a mutational hot spot, which underscores the relations between nonprogressive nuclear cataract and CRYBA1/A3.

Modified Si-Ni-San Decoction Ameliorates Central Fatigue by Improving Mitochondrial Biogenesis in the Rat Hippocampus.

The traditional Chinese medicine (TCM) decoction Si-Ni-San (SNS) has been utilised for millennia to improve physiological coordination of the functions of the liver and spleen, which are regarded as the main pathological organs of central fatigue in TCM. This study evaluates the effect of a modified SNS (MSNS) formula on central fatigue in rats and explores molecular changes associated with hippocampal mitochondrial biogenesis. Central fatigue was induced through a 21-day sleep deprivation protocol. We assessed MSNS's effects on behaviour, blood and liver biomarkers, and mitochondrial ultrastructure. We found that MSNS could reverse various signs of central fatigue such as its effects on hippocampal gene and protein expression levels of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1). We also observed evidence of MSNS decreasing central fatigue, such as decreasing creatine kinase activity, decreasing levels of malondialdehyde and blood urea nitrogen, increasing lactate dehydrogenase and superoxide dismutase activities, increasing mitochondrial DNA copy number, and reversing mitochondrial ultrastructure changes. These findings suggest that MSNS can ameliorate central fatigue and that its molecular mechanism involves mitochondrial biogenesis enhancement mediated by hippocampal SIRT1, PGC-1α, and NRF1.

Selection and characterization of vaccine strain for Enterovirus 71 vaccine development.

Enterovirus 71 (EV71) has recently emerged as an important neurotropic virus in Asia because effective medications and prophylactic vaccine against EV71 infection are not available. Based on the success of inactivated poliovirus vaccine, the Vero cell-based chemically inactivated EV71 vaccine candidate could be developed. Identification of EV71 vaccine strain which can grow to high titer in Vero cell and induce cross-genotype virus neutralizing antibody responses represents the first step in vaccine development. In this report we describe the characterization and validation of a clinical isolate E59 belonging to B4 sub-genotype based on VP1 genetic analysis. Before selected as the vaccine strain, the genetic stability of E59 in passage had been analyzed based on the nucleotide sequences obtained from the Master Virus Seed, Working Seed banks and the virus harvested from the production lots, and found to be identical to those found in the original isolate. These results indicate that E59 vaccine strain has strong genetic stability in passage. Using this vaccine strain the prototype EV71 vaccine candidate was produced from 20L of Vero cell grown in serum-containing medium. The production processes were investigated, characterized and quantified to establish the potential vaccine manufacturing process including the time for virus harvest, the membrane for diafiltration and concentration, the gel-filtration chromatography for the down-stream virus purification, and the methods for viral inactivation. Finally, the inactivated virion vaccine candidate containing sub-microgram of viral proteins formulated with alum adjuvant was found to induce strong virus neutralizing antibody responses in mice and rabbits. Therefore, these results provide valuable information for cell-based EV71 vaccine development.