Changes in the first postoperative night bispectral index of patients after thyroidectomy with different types of primary anesthetic management: a randomized controlled trial.

Despite major advances in anesthesia management and developments in anesthetic agents, postoperative sleep disturbances remain dissatisfactory for many patients. We hypothesized that propofol might have a subtle influence on sleep after thyroidectomy compared to sevoflurane. A randomized, single-blinded, controlled trial was conducted at the First Hospital of China Medical University from October 2014 to October 2015. One hundred and twenty-four patients undergoing thyroidectomy were enrolled and received sevoflurane (sevoflurane group) or propofol (propofol group) as anesthesia maintenance. Major assessments were made during the operation (different types of anesthetic management) and on the first postoperative night (sleep status). The primary outcome was postoperative sleep status, measured by the BIS-Vista monitor on the first night after surgery between propofol and sevoflurane groups. A total of 105 patients (79 women, 26 men; mean age 49 years; range 18-65 years) were included in the final study sample. All patients in both groups showed one of the five sleep patterns classified by this trial. The BIS-area under the curve was decreased, the sleep efficiency index was significantly increased, and the durations of postoperative sleep and sleep stage N3 were increased by 110.5 and 36.5 min per patient, respectively, in the propofol compared to the sevoflurane group. Propofol might preserve sleep time immediately after thyroidectomy. Clinical Trials.gov identifier: NCT 02146976.

Remote Ischemia Preconditioning Attenuates Blood-Spinal Cord Barrier Breakdown in Rats Undergoing Spinal Cord Ischemia Reperfusion Injury: Associated with Activation and Upregulation of CB1 and CB2 Receptors.

BACKGROUND/AIMS: Remote ischemic preconditioning (RIPC) has protective effects on spinal cord ischemia reperfusion (I/R) injury, but the potential mechanisms remain unclear. In our study, the effects and underlying mechanisms of RIPC on blood-spinal cord barrier (BSCB) breakdown following I/R injury were investigated. METHODS: animals underwent intraperitoneal administration with cannabinoid-1 (CB1) receptor antagonist AM251, cannabinoid-2 (CB2) receptor antagonist AM630 or vehicle 15 minutes before three 3-minute occlusion-reperfusion cycles on the right femoral artery or a sham operation. 30 minutes after the preconditioning, aortic arch was exposed with or without 14-minute occlusion. Neurological function was assessed with Tarlov scoring system. The disruption of BSCB was assessed by measuring Evans Blue (EB) extravasation. The expression of tight junction protein occludin was determined by western blot analyses. The expression and localization of CB1 and CB2 receptors were assessed by western blot and immunofluorescence. RESULTS: RIPC attenuated the motor dysfunction, BSCB disruption and downregulation of occludin after I/R injury, which were impaired by blocking CB1 and CB2 receptors. Moreover, RIPC upregulated the elevated perivascular expression of CB1 and CB2 receptors following I/R injury. CONCLUSIONS: These results indicated that RIPC, through activation and upregulation of CB1 and CB2 receptors, was involved in preserving the integrity of BSCB after spinal cord I/R injury.

miR-320a affects spinal cord edema through negatively regulating aquaporin-1 of blood-spinal cord barrier during bimodal stage after ischemia reperfusion injury in rats.

BACKGROUND: Spinal cord edema is a serious complication and pathophysiological change after ischemia reperfusion (IR) injury. It has been demonstrated closely associated with bimodal disruption of blood-spinal cord barrier (BSCB) in our previous work. Aquaporin (AQP)1 plays important but contradictory roles in water homeostasis. Recently, microRNAs (miRs) effectively regulate numerous target mRNAs during ischemia. However, whether miRs are able to protect against dimodal disruption of BSCB by regulating perivascular AQP1 remains to be elucidated. RESULTS: Spinal water content and EB extravasation were suggested as a bimodal distribution in directly proportion to AQP1, since all maximal changes were detected at 12 and 48 h after reperfusion. Further TEM and double immunofluorescence showed that former disruption of BSCB at 12 h was attributed to cytotoxic edema by up-regulated AQP1 expressions in astrocytes, whereas the latter at 48 h was mixed with vasogenic edema with both endothelial cells and astrocytes involvement. Microarray analysis revealed that at 12 h post-injury, ten miRs were upregulated (>2.0 fold) and seven miRs were downregulated (<0.5 fold) and at 48 h, ten miRs were upregulated and eleven were downregulated compared to Sham-operated controls. Genomic screening and luciferase assays identified that miR-320a was a potential modulator of AQP1 in spinal cord after IR in vitro. In vivo, compared to rats in IR and negative control group, intrathecal infusion of miR-320a mimic attenuated IR-induced lower limb motor function deficits and BSCB dysfunction as decreased EB extravasation and spinal water content through down-regulating AQP1 expressions, whereas pretreated with miR-320a AMO reversed above effects. CONCLUSION: These findings indicate miR-320a directly and functionally affects spinal cord edema through negatively regulating AQP1 of BSCB after IR.

MiR-27a ameliorates inflammatory damage to the blood-spinal cord barrier after spinal cord ischemia: reperfusion injury in rats by downregulating TICAM-2 of the TLR4 signaling pathway.

BACKGROUND: Spinal cord ischemia reperfusion (IR) injury causes inflammation and subsequently increases blood-spinal cord barrier leakage and Toll-like receptor 4 (TLR4) pathway activation. MicroRNAs (miRs) effectively regulate numerous target mRNAs during ischemia. However, their roles during IR injury are poorly understood. We investigated miRs involvement, particularly miR-27a, in TLR4 pathway-mediated inflammatory responses after IR. METHOD: We used a genomics approach to examine changed miRs of rats that had undergone 14 minutes of ischemia, followed by 24 or 72 hours of reperfusion. Quantitative RT-PCR was used to identify and confirm the miRs involved in regulating TLR4 pathway activation. We scanned miR databases for potential miR targets and confirmed these targets by quantitative RT-PCR. The miR mimic and anti-miR oligonucleotides (AMOs) were intrathecally injected at 12-hour intervals beginning three days before the ischemia. The effects of miRs on the TLR4 pathway and downstream cytokines were analyzed by PCR, western blotting, and ELISA. Double immunofluorescence staining was perfumed to determine the relationship between the targets and TLR4. Blood-spinal cord barrier (BSCB) permeability was examined using Evans blue (EB) dye. RESULTS: A microarray analysis revealed that at 24 hours post-injury, three miRs were upregulated (>2.0 fold) and 15 miRs were downregulated (<0.5 fold), and at 72 hours, four miRs were upregulated and 14 were downregulated compared to their levels in sham-operated controls. We focused on miR-27a, which is predicted to contain sequences complementary to the 3'-untranslated region (UTR) of Toll-like receptor adaptor molecule 2 (TICAM-2). Double immunostaining indicated that TLR4 activation correlated with changes in TICAM-2 expression. Compared to the rats in the IR and negative control groups, intrathecal infusion of the miR-27a mimic attenuated IR-induced TLR4 activation and inflammatory damage to the BSCB, which was shown as decreased EB extravasation and lower levels of nuclear factor kappa-B (NF-κB) and lnterleukin (IL)-1ß at 24 and 72 hours after reperfusion, whereas pretreatment with miR-27a AMO aggravated these injuries. CONCLUSIONS: We present the first evidence that miRs play an important role in spinal cord IR injury. We identified TICAM-2 as a novel target of miR-27a. miR-27a upregulation attenuates IR-induced inflammatory damage to the BSCB by negatively regulating TICAM-2 of the TLR4 signaling pathway and inhibiting the NF-κB/IL-1ß pathway. These results provide new therapeutic targets for IR injury treatment.

Integrative Analysis of the Microbiome and Metabolome of Broiler Intestine: Insights into the Mechanisms of Probiotic Action as an Antibiotic Substitute.

Antibiotic substitutes have become a research focus due to restrictions on antibiotic usage. Among the antibiotic substitutes on the market, probiotics have been extensively researched and used. However, the mechanism by which probiotics replace antibiotics remains unclear. In this study, we aimed to investigate this mechanism by comparing the effects of probiotics and antibiotics on broiler growth performance and intestinal microbiota composition. Results shown that both probiotics and antibiotics increased daily weight gain and reduced feed conversion rate in broilers. Analysis of ileum and cecum microorganisms via 16S rRNA gene sequencing revealed that both interventions decreased intestinal microbial diversity. Moreover, the abundance of Bacteroides increased in the mature ileum, while that of Erysipelatoclostridium decreased in the cecum in response to both probiotics and antibiotics. The main metabolites of probiotics and antibiotics in the intestine were found to be organic acids, amino acids, and sugars, which might play comparable roles in growth performance. Furthermore, disaccharides and trisaccharides may be essential components in the ileum that enable probiotics to replace antibiotics. These findings provide important insights into the mechanisms underlying the use of probiotics as antibiotic substitutes in broiler breeding.

Neurotoxins and pore forming toxins in sea anemones: Potential candidates for new drug development.

There are two kinds of toxins in sea anemones: neurotoxins and pore forming toxins. As a representative of the sodium channel toxin, the neurotoxin ATX II in neurotoxin mainly affects the process of action potential and the release of transmitter to affect the inactivation of the sodium channel. As the representatives of potassium channel toxins, BgK and ShK mainly affect the potassium channel current. EqTx and Sticholysins are representative of pore forming toxins, which can form specific ion channels in cell membranes and change the concentration of internal and external ions, eventually causing hemolytic effects. Based on the above mechanism, toxins such as ATX II can also cause toxic effects in tissues and organs such as heart, lung and muscle. As an applied aspect it was shown that sea anemone toxins often have strong toxic effects on tumor cells, induce cancer cells to enter the pathway of apoptosis, and can also bind to monoclonal antibodies or directly inhibit relevant channels for the treatment of autoimmune diseases.

Natural history and malignant potential of simple ovarian cysts in postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: Postmenopausal ovarian masses are not uncommon, and the incidence of ovarian cancer rises sharply after menopause. OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the natural history and malignant potential of postmenopausal simple ovarian cysts. EVIDENCE REVIEW: PubMed, MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), ClinicalTrials.gov , and ISRCTN (International Standard Randomized Controlled Trial Number Register) were searched from inception to January 31, 2022. Meta-analyses were conducted using R software. FINDINGS: Twelve cohort studies with 1,672 participants and 1,513 ovarian cysts were included. The rates of simple cysts remaining unchanged (38.90%; 95% CI, 19.79%-59.85%; P < 0.01) or disappearing (34.17%; 95% CI, 19.13%-50.93%; P < 0.01) were the highest during conservative observation. The surgery rate for the simple cyst was 19.04% (95% CI, 8.19%-32.92%; P < 0.01). The malignancy rate (including borderline tumors) was very low, approximately 1/10,000 (95% CI, 0% to 0.23%; P = 0.79). CONCLUSIONS: Simple ovarian cysts in postmenopausal women were most likely to remain unchanged or disappear during follow-up. The malignancy rate was approximately 1 in 10,000. Personal preference is the most common reason for surgery.

Degradation of indole via a two-component indole oxygenase system from Enterococcus hirae GDIAS-5.

Animal farming copiously generates indoles, which contribute to odor and pose a challenge for deodorization. While biodegradation is widely accepted, there is a lack of suitable indole-degrading bacteria for animal husbandry. In this study, we aimed to construct genetically engineered strains with indole-degrading abilities. Enterococcus hirae GDIAS-5 is a highly efficient indole-degrading bacterium, which functions via a monooxygenase YcnE presumably contributes to indole oxidation. However, the efficiency of engineered Escherichia coli expressing YcnE for indole degradation is lower than that of GDIAS-5. To improve its efficacy, the underlying indole-degradation mechanisms in GDIAS-5 were analyzed. An ido operon that responds to a two-component indole oxygenase system was identified. In vitro experiments showed that the reductase component of YcnE, YdgI, can improve the catalytic efficiency. The reconstruction of the two-component system in E. coli exhibited higher indole removal efficiency than GDIAS-5. Furthermore, isatin, the key intermediate metabolite in indole degradation, might be degraded via a novel isatin-acetaminophen-aminophenol pathway involving an amidase whose coding gene is located near the ido operon. The two-component anaerobic oxidation system, upstream degradation pathway, and engineering strains investigated in this study provide important insights into indole degradation metabolism and offer efficient resources for achieving bacterial odor elimination.

Cytoskeletal protein SPTA1 mediating the decrease in erectile function induced by high-fat diet via Hippo signaling pathway.

BACKGROUND: The mechanism of high-fat diet (HFD)-induced decrease in erectile function has not been elucidated, and in previous studies, spectrin alpha, erythrocytic 1 (SPTA1) is a cytoskeletal protein that regulates cellular function, which belongs to a family of proteins that can affect cell and tissue growth and development by regulating YAP, an effector on the Hippo signaling pathway, but its particular role has not been elucidated. OBJECTIVE: To explore the role of SPTA1 in the abnormality of erectile function induced by HFD. METHODS: We analyzed the penile tissues of mice on normal diet and HFD by transcriptomics and screened for differentially expressed genes, further identified closely related target genes in rat penile tissues, and verified target gene expression in in vitro construction of high-glucose (HG)-treated corpus cavernosum endothelial cells (CCECs) and corpus cavernosum smooth muscle cells (CCSMCs) models. The distribution of target genes in various cell populations in penile tissues was retrieved by single-cell sequencing Male Health Atlas database. Moreover, interfering with target genes was further applied to explore the mechanisms involved in erectile function decline. RESULTS: Transcriptomic analysis screened out down-regulated differential gene SPTA1; Western blot and immunohistochemistry results showed that SPTA1 expression significantly decreased in the penile tissues of Sprague-Dawley (SD) rats in the HFD group. Immunofluorescence staining showed a positive expression of CD31 and VWF in CCECs and a positive expression of α-SMA in CCSMCs. The expression level of SPTA1 protein significantly decreased in the HG group of CCECs and CCSMCs. The expression of SPTA1 mRNA significantly decreased in CCSMCs while significantly increased in CCECs. SPTA1 may have various expression patterns and biological functions in different cell populations. Real-time quantitative PCR results showed that the siSPTA1 transfected in CCSMCs had a significant interference effect compared with the control siNC. Transfection of siSPTA1 into CCSMCs resulted in the significant down-regulation of mRNA and protein expression of eNOS, and significant up-regulation of YAP, Caspase-1, GSDMD, GSDMD-N IL-18, and IL-1ß protein expression levels. The expression level of CCSMCs contractile-type protein α-SMA was significantly down-regulated. CONCLUSIONS: The down-regulation of SPTA1 in SD rats fed with HFD may induce cell pyroptosis and lead to the decrease of erectile function by activating the Hippo pathway; these findings may provide new therapeutic targets for improving erectile function.

[Correlation of BCL-6, MYC and p53 gene abnormalities with immunological subtypes and prognosis of diffuse large B-cell lymphoma].

OBJECTIVE: To investigate BCL-6, MYC and p53 genes abnormalities in diffuse large B-cell lymphoma (DLBCL) and correlate the result with immunosubtypes and prognosis. METHODS: Interphase fluorescence in situ hybridization (I-FISH) was performed to detect the BCL-6, MYC and p53 genes. Immunohistochemistry (Envision method) was used to measure the expressions of CD3, CD10, CD20, BCL-6, MUM -1, BCL-2 and Ki-67 genes in DLBCL. The patients were classified into germinal center B cell-like (GCB) and non-GCB subtypes according to Hans' algorithm. RESULTS: BCL-6 rearrangement was detected in 10 of 46 DLBCL cases. The presence of gene rearrangement had no correlation with BCL-6 protein expression (P= 0.245). Overall survival (OS, P= 0.138) and progression-free survival (PFS, P= 0.095) were not influenced by BCL-6 rearrangement. All MYC rearrangements were detected in GCB type DLBCL. Deletion of p53 gene was detected in 14 cases and was significantly associated with shorter OS (P= 0.046) and PFS (P= 0.043). CONCLUSION: I-FISH is a rapid, accurate and sensitive method for detecting BCL-6, MYC and p53 abnormalities. No correlation was found between BCL-6 gene rearrangement and BCL-6 protein expression. MYC translocation was more common in GCB type DLBCL compared with non-GCB type ones. Patients with p53 deletion had a poorer prognosis. The p53 gene may provide a useful indicator for the prognosis of DLBCL.

[Comparison of allelic frequencies of 15 short tandem repeat loci between chronic myeloid leukemia patients and non-related healthy individuals].

OBJECTIVE: To compare allelic frequencies of 15 short tandem repeat (STR) loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) between chronic myeloid leukemia (CML) patients and non-related healthy individuals from Changzhou region in order to predict genes related with the CML. METHODS: Blood samples were collected from 745 healthy subjects and 132 CML patients with complete remission. Genotypes were determined with gene scan technology and multiplex PCR with fluorescence-labeled primers. Allelic polymorphisms of 15 STR loci were compared between the two groups. Potential genes related with CML were predicted with statistical analysis of differences in allelic frequencies. RESULTS: Allelic frequencies of 3 loci, including CSF1PO, vWA and TPOX, showed a significant difference (P<0.05) between the two groups. CONCLUSION: CSF1PO, vWA and TPOX loci may be related with CML, albeit that the exact biologic mechanisms is unclear.

Indole metabolism mechanisms in a new, efficient indole-degrading facultative anaerobe isolate Enterococcus hirae GDIAS-5.

Indole is an inter-species and inter-kingdom signaling molecule widespread in the natural world. A large amount of indole in livestock wastes makes it difficult to be degraded, which causes serious malodor. Identifying efficient and eco-friendly ways to eliminate it is an urgent task for the sustainable development of husbandry. While bioconversion is a widely accepted means, the mechanism of indole microbial degradation is little understood, especially under anaerobic conditions. Herein, a new Enterococcus hirae isolate GDIAS-5, effectively degraded 100 mg/L indole within 28 h aerobically or 5 days anaerobically. Three intermediates (oxindole, isatin, and catechol) were identified in indole degradation, and catechol was further degraded by a meta-cleavage catabolic pathway. Two important processes for GDIAS-5 indole utilization were discovered. One is Fe(III) uptake and reduction, which may be a critical process that is coupled with indole oxidation, and the other is the entire pathway directly involved in indole oxidation and metabolism. Furthermore, monooxygenase ycnE responsible for indole oxidation via the indole-oxindole-isatin pathway was identified for the first time. Bioinformatic analyses showed that ycnE from E. hirae formed a phylogenetically separate branch from monooxygenases of other species. These findings provide new targets and strategies for synthetic biological reconstruction of indole-degrading bacteria.

Tin bisulfide nanoplates anchored onto flower-like bismuth tungstate nanosheets for enhancement in the photocatalytic degradation of organic pollutant.

The development of efficient heterojunctions through a simple and facile method is an effective way to enhance the photocatalytic performance of bismuth-based oxide semiconductors for industrial applications. Here, the novel flower-like type II SnS2/Bi2WO6 heterostructure consisting of bismuth tungstate (Bi2WO6) nanosheets and tin bisulfide (SnS2) nanoplates was successfully designed and synthesized. The crystal structure, composition, morphology, and photoelectric properties of the heterostructure were systematically characterized. In addition, the photocatalytic activity of SnS2/Bi2WO6 was analyzed and compared with Bi2WO6 or SnS2 alone or physical mixture of SnS2 and Bi2WO6. 2%SnS2/Bi2WO6 presents a 3.1 times greater degradation rate constant (0.0065 min-1) than that of Bi2WO6 (0.0021 min-1) under low visible light irradiation (5.3 mW·cm-2, a 44 W LED), while SnS2 alone exhibits no photocatalytic effect toward glyphosate. Furthermore, 2%SnS2/Bi2WO6 maintains 93% of its original photocatalytic activity even after four cycles. The possible photocatalytic degradation pathway of glyphosate and photocatalytic mechanism are also proposed. The excellent photocatalytic performance of SnS2/Bi2WO6 is attributed to the decoration of SnS2 nanoplates on the surface of Bi2WO6, appropriate (113)/(020) ratio, increased visible-light absorption, and effective separation of photoinduced carriers. This paper reports a new methodology that can act as a reference basis to design and develop visible-light responsive photocatalysts with outstanding photocatalytic performance for carbon dioxide reduction, water splitting, and pollutant degradation.

Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer.

Colorectal cancer is one of the most serious tumors and berberine can inhibit the recurrence and transformation of colorectal adenoma into colorectal cancer. However, the direct binding target proteins of berberine in inhibiting colorectal cancer remain unclear. In this study, the chemical proteomics method was used and demonstrated that berberine is directly bound to pyruvate kinase isozyme type M2 (PKM2) in colorectal cancer cells. The triangular N-O-O triangular structure of berberine contributed to hydrophobic interaction with I119 amino acid residues and π-π interaction with F244 amino acid residues of PKM2 protein. Moreover, berberine was shown to inhibit the reprogramming of glucose metabolism and the phosphorylation of STAT3, down regulate the expression of Bcl-2 and Cyclin D1 genes, ultimately inhibiting the progression of colorectal cancer. This study uncovered the direct binding target protein and mechanism of berberine to improve metabolic reprogramming in colorectal cancer, which is helpful to guide the optimization of berberine.

[Effects of simvastatin plus all-trans retinoic acid on WT1/hDMP1 gene expression profiles of human promyelocytic leukemia cell line NB4].

OBJECTIVE: To investigate the effects of simvastatin (SV) plus all-trans retinoic acid (ATRA) on the proliferation, differentiation, apoptosis and WT1/hDMP1 gene expression profiles of human promyelocytic leukemia cell line NB4. METHODS: The NB4 cell was incubated with simvastatin and ATRA alone or in combination. And the NB4 cell without any treatment was adopted as a normal control. The cells of different groups were collected at 24, 48 and 72 h post-incubation. Their morphological changes were observed after Wright staining. The method of MTT was employed to assay the growth inhibition rate and flow cytometry was used to detect the early-stage ratios of apoptosis and cell necrosis. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the WT1/hDMP1 gene expression levels. RESULTS: The cell inhibition rates increased gradually (F = 7.15, P = 0.000) at 15, 10 and 5 µmol/L SV respectively. And so did the expression levels of CD11b (F = 3.41, P = 0.014) and Annexin-V (F = 43.38, P = 0.000). However the expression levels of WT1 decreased gradually (F = 5.35, P = 0.001) reversely with the elevated levels of hDMP1 (F = 22.61, P = 0.000). Furthermore the NB4 cell exhibited the most significant changes at 15 µmol/L SV. After a 72-hour incubation, the expression levels of CD11b (89.46% ± 9.13%)and hDMP1 (626.9 ± 56.9) in NB4 cells at 15 µmol/L SV plus 0.5 µmol/L ATRA were significantly higher than those with ATRA(71.27% ± 7.27%, P = 0.000 and 421.8 ± 38.3, P = 0.003 in each) and SV alone(62.41% ± 6.37%, P = 0.003 and 241.4 ± 21.9, P = 0.003 in each). A combination of 15 µmol/L SV with 0.5 µmol/L ATRA displayed obvious interactions with the expressions of CD11b and hDMP1 (F = 4.09, P = 0.025 and F = 29.58, P = 0.000 in each). And there was no significant interaction for cell inhibition rates and Annexin-V expression. CONCLUSION: Simvastatin in vitro inhibits the proliferation of NB4 cell, induces its differentiation and promotes its apoptosis. And the lowered expression of WT1 has a dose-dependent correlation with the elevated expression of hDMP1. It indicates that simvastatin has the synergistic in vitro anti-promyelocytic potency.

Chemoenzymatic access to enantiopure N-containing furfuryl alcohol from chitin-derived N-acetyl-D-glucosamine.

BACKGROUND: Chiral furfuryl alcohols are important precursors for the synthesis of valuable functionalized pyranones such as the rare sugar L-rednose. However, the synthesis of enantiopure chiral biobased furfuryl alcohols remains scarce. In this work, we present a chemoenzymatic route toward enantiopure nitrogen-containing (R)- and (S)-3-acetamido-5-(1-hydroxylethyl)furan (3A5HEF) from chitin-derived N-acetyl-D-glucosamine (NAG). FINDINGS: 3-Acetamido-5-acetylfuran (3A5AF) was obtained from NAG via ionic liquid/boric acid-catalyzed dehydration, in an isolated yield of approximately 31%. Carbonyl reductases from Streptomyces coelicolor (ScCR) and Bacillus sp. ECU0013 (YueD) were found to be good catalysts for asymmetric reduction of 3A5AF. Enantiocomplementary synthesis of (R)- and (S)-3A5HEF was implemented with the yields of up to > 99% and the enantiomeric excess (ee) values of > 99%. Besides, biocatalytic synthesis of (R)-3A5HEF was demonstrated on a preparative scale, with an isolated yield of 65%. CONCLUSIONS: A two-step process toward the chiral furfuryl alcohol was successfully developed by integrating chemical catalysis with enzyme catalysis, with excellent enantioselectivities. This work demonstrates the power of the combination of chemo- and biocatalysis for selective valorization of biobased furans.

[The Mutated Gene Sequenced by NGS and the Correlation of Their Coexistent Mutual Exclusiveness in NPM1 Mutated Acute Myeloid Leukemia].

OBJECTIVE: To analyze the clinicobiological heterogeneity of NPM1 mutated (NPM1mut) acute myeloid leukemia (AML) detected by next generation sequencing (NGS) and their coexistence and mutual exclusivity relationship in the AML subtype. METHODS: The NGS data based on 112 genes related to blood disease in 238 newly diagnosed patients with NPM1mut were collected. The χ2 test and non-parametric test were used to analyze the distribution correlation between the genes in the mutational spectrum. RESULTS: Among all the patients, at least one co-mutation was detected out. The median number per case of the mutated genes, including NPM1mut was 4.5 (range 2－14), among them, there were 5.0 (range 2－10) for NPM1mut/FLT3-ITD+ and 4.0 (range 2－14) for NPM1mut/FLT3-ITD- cases, but it was no significant difference between the two groups (P=0.378). A total of 240 NPM1 mutational events were detected out in entire 238 NPM1mut patients, of which 10 (4.2%) were missense mutations, and were all found in NPM1mut/FLT3-ITD- patients. Most (9/10, 90%) of these NPM1 missense mutations were accompanied by AML subtype-defining cytogenetic or molecular abnormalities, of which 7 patients were in low risk or 2 in high risk. The most common NPM1mut coexisting mutations were DNMT3A (104, 43.7%), followed were FLT3-ITD (95, 39.9%) and FAT1 (57, 23.9%), FLT3-ITD and DNMT3A showed significant coexistence (P=0.005). FLT3-ITD showed significantly reciprocal exclusivity with FLT3-nonITD (P<0.001), NRAS (P<0.001), PTPN11 (P=0.017) and IDH1 (P=0.005), and showed an exclusivity inclination with KRAS (P=0.073). In addition, FLT3-nonITD along with KRAS (P=0.035), NRAS along with KRAS (P=0.008) and PTPN11 (P=0.039) coexisted significantly. CONCLUSION: Prognoses of AML involving less common NPM1 missense mutations should be stated on a case by case basis. The mutational landscape and co-occurrence and mutual exclusivity correlations of NPM1mut AML provide a mechanism explaining biological diversity and clinical heterogeneity in this AML subset.

Phenothiazine-anthraquinone donor-acceptor molecules: synthesis, electronic properties and DFT-TDDFT computational study.

Two donor-acceptor molecules with different pi-electron conjugative units, 1-((10-methyl-10H-phenothiazin-3-yl)ethynyl)anthracene-9,10-dione (AqMp) and 1,1'-(10-methyl-10H-phenothiazine-3,7-diyl)bis(ethyne-2,1-diyl)dianthracene-9,10-dione (Aq2Mp), have been synthesized and investigated for their photochemical and electrochemical properties. Density functional theory (DFT) calculations provide insights into their molecular geometry, electronic structures, and properties. These studies satisfactorily explain the electrochemistry of the two compounds and indicate that larger conjugative effect leads to smaller HOMO-LUMO gap (Eg) in Aq2Mp. Both compounds show ICT and pi --> pi* transitions in the UV-visible range in solution, and Aq2Mp has a bathochromic shift and shows higher oscillator strength of the absorption, which has been verified by time-dependent DFT (TDDFT) calculations. The differences between AqMp and Aq2Mp indicate that the structural and conjugative effects have great influence on the electronic properties of the molecules.