Large-scale rare variant burden testing in Parkinson's disease.

Parkinson's disease has a large heritable component and genome-wide association studies have identified over 90 variants with disease-associated common variants, providing deeper insights into the disease biology. However, there have not been large-scale rare variant analyses for Parkinson's disease. To address this gap, we investigated the rare genetic component of Parkinson's disease at minor allele frequencies <1%, using whole genome and whole exome sequencing data from 7184 Parkinson's disease cases, 6701 proxy cases and 51 650 healthy controls from the Accelerating Medicines Partnership Parkinson's disease (AMP-PD) initiative, the National Institutes of Health, the UK Biobank and Genentech. We performed burden tests meta-analyses on small indels and single nucleotide protein-altering variants, prioritized based on their predicted functional impact. Our work identified several genes reaching exome-wide significance. Two of these genes, GBA1 and LRRK2, have variants that have been previously implicated as risk factors for Parkinson's disease, with some variants in LRRK2 resulting in monogenic forms of the disease. We identify potential novel risk associations for variants in B3GNT3, AUNIP, ADH5, TUBA1B, OR1G1, CAPN10 and TREML1 but were unable to replicate the observed associations across independent datasets. Of these, B3GNT3 and TREML1 could provide new evidence for the role of neuroinflammation in Parkinson's disease. To date, this is the largest analysis of rare genetic variants in Parkinson's disease.

Nickel/Photoredox Dual-Catalyzed Regiodivergent Aminoalkylation of Unactivated Alkyl Halides.

A mild and regiodivergent aminoalkylation of unactivated alkyl halides is disclosed via a dual photoredox/nickel catalysis. Bipyridyl-type ligands without an ortho-substituent control the site-selective coupling at the original position, while ortho-disubstituted ligands tune the site-selectivity at a remote, unprefunctionalized position. Mechanistic studies combined with DFT calculations give insight into the mechanism and the origins of the ligand-controlled regioselectivity. Notably, this redox-neutral, regiodivergent alkyl-alkyl coupling features mild conditions, broad substrate scope for both alkyl coupling partners, and excellent site-selectivity and offers a straightforward way for α-alkylation of tertiary amines to synthesize structurally diverse alkylamines and value-added amino acid derivatives.

Synthesis, structure-activity relationship, and biological evaluation of quinolines for development of anticancer agents.

Tetrahydro-ß-carbolines (THßCs) are a kind of natural alkaloids with multiple pharmaceutical activities. Herein, a focused compound library derived from THßCs was synthesized and their anticancer activities were studied in several cancer cell lines. Among them, three compounds showed considerable anticancer activities with low micromolar to submicromolar IC50 values. The abilities to induce apoptosis and alter mitochondrial membrane potential levels, which are comparable to those of the commercial anticancer drug adriamycin, were confirmed by one representative compound (21) on the B16/F10 cell line. Our preliminary structure-activity relationship studies indicated that alkylamines with suitable lengths are very important for potency improvement.

Touch-Programmable Metasurface for Various Electromagnetic Manipulations and Encryptions.

Previous programmable metasurfaces integrated with diodes or varactors require external instructions for field programmable gate arrays (FPGAs), which usually rely on computer-inputs or pre-loaded algorithms. But the complicated external devices make the coding regulation process of the programmable metasurfaces cumbersome and difficult to use. To simplify the process and provide a new interaction manner, a touch-programmable metasurface (TPM) based on touch sensing modules is proposed to realize various electromagnetic (EM) manipulations and encryptions. By simply touching the meta-units of the TPM, the state of the diodes can be changed. Through the touch controls, the TPM can achieve independent and direct manipulations of meta-units and efficient inputs of coding patterns without using a FPGA or other control modules. Various coding patterns are demonstrated to achieve diverse scattering-field control and flexible near-field EM information encryptions, which verifies the feasibility of the TPM design. The presented TPM will have wide application prospects in imaging displays, wireless communications, and EM information encryptions.

Ultraviolet-sensing metasurface for programmable electromagnetic scattering field manipulation by combining light control with a microwave field.

Combining digital information science with metasurface technology is critical for achieving arbitrary electromagnetic wave manipulation. However, there is a scarcity of contemporary scholarly studies on this subject. In this paper, we propose an Ultraviolet (UV) sensing metasurface for programmable electromagnetic scattering field manipulation by combining light control with a microwave field. The active sensing of UV light and the real-time reaction of the scattering are achieved by integrating four UV sensors on the metasurface. On the metasurface, a UV sensor ML8511 and a voltage driver module are coupled to control each row of the Positive-Intrinsic-Negative (PIN) diodes. Due to the light sensing capability of the UV sensor, the on or off state of the PIN diode integrated into the programmable metasurface can be switched efficiently through the change of light. When the incident wave changes, various discrete data are transmitted to the FPGA. Then the FPGA performs the corresponding voltage distribution to control the state of the PIN diode. Finally, different metasurface coding sequences are generated to realize different electromagnetic functions. As a result, the spatial distribution of sensing light by sensors can be used to determine the electromagnetic field and connect sensing optical information with the microwave field. The simulation and measured results show that this design is feasible. This work provides a dimension for electromagnetic waves modulation.

Diverse Functionalization of Tetrahydro-ß-carbolines or Tetrahydro-γ-carbolines via Oxidative Coupling Rearrangement.

We report herein diverse functionalization of tetrahydro-ß-carbolines (THßCs) or tetrahydro-γ-carbolines (THγCs) via oxidative coupling rearrangement. The treatment of THßCs or THγCs with t-BuOOH (TBHP) afforded 3-peroxyindolenines, followed by HCl catalyzed indolation to form unexpected 2-indolyl-3-peroxyindolenines. Further rearrangement of these peroxides allows for rapid access to a skeletally diverse chemical library in good to excellent yields.

Light-controllable metasurface for microwave wavefront manipulation.

Applying multiple physical fields to artificial manipulate electromagnetic waves is a highly stirring research. In this paper, we creatively combine light control with microwave scattering, realizing an optically coding metasurface for beam deflection based on anomalous reflection. A photoresistor and a voltage-driven module are connected to control each row of PIN-diode-loaded unit cells, endowing the reflection phase of the elements with a strong dependence on light. Owing to the high sensitivity of photoresistor, the digital element state "0" or "1" can be switched effectively via light variation sensed by the photoresistor. By modulating the light signal, the arrangement of digital elements can be reprogrammed, generating the specific scattering field. Therefore, the electromagnetic field can be determined by the spatial distribution of light, which induces the connect with the optical information and microwave field. The simulated and experimental results demonstrate the feasibility of our design. This light-steering approach provides a dimension for electromagnetic wave modulation.

Facile access to evodiakine enabled by aerobic copper-catalyzed oxidative rearrangement.

Oxidation as a fundamentally important method for the synthesis of complex structures is difficult to achieve in a selective manner. Evodiakine, a complex natural product possessing an unprecedented ring system (6/5/5/7/6), has a high oxidation state without a practical solution. Herein, we report the first synthesis of evodiakine via aerobic copper-catalyzed late-stage functionalization of evodiamine.

Identification by comparative transcriptomics of core regulatory genes for higher alcohol production in a top-fermenting yeast at different temperatures in beer fermentation.

Undesirable flavor caused by excessive higher alcohols restrains the development of the wheat beer industry. To clarify the regulation mechanism of the metabolism of higher alcohols in wheat beer brewing by the top-fermenting yeast Saccharomyces cerevisiae S17, the effect of temperature on the fermentation performance and transcriptional levels of relevant genes was investigated. The strain S17 produced 297.85 mg/L of higher alcohols at 20 °C, and the production did not increase at 25 °C, reaching about 297.43 mg/L. Metabolite analysis and transcriptome sequencing showed that the metabolic pathways of branched-chain amino acids, pyruvate, phenylalanine, and proline were the decisive factors that affected the formation of higher alcohols. Fourteen most promising genes were selected to evaluate the effects of single-gene deletions on the synthesis of higher alcohols. The total production of higher alcohols by the mutants Δtir1 and Δgap1 was reduced by 23.5 and 19.66% compared with the parent strain S17, respectively. The results confirmed that TIR1 and GAP1 are crucial regulatory genes in the metabolism of higher alcohols in the top-fermenting yeast. This study provides valuable knowledge on the metabolic pathways of higher alcohols and new strategies for reducing the amounts of higher alcohols in wheat beer.

Two-dimensional speckle tracking to image ventricular-arterial coupling in uremia.

OBJECTIVE: To study ventricular-arterial coupling(VAC) in uremic patients by application of two-dimensional speckle tracing imaging (2DSTI). METHODS: One hundred uremic patients were divided into two groups based on left ventricular ejection fraction (LVEF): group 1 with LVEF ≥ 5%, and group 2 with LVEF < 55%. Forty healthy subjects were recruited as a control group. Conventional echocardiography was performed; VAC components and myocardial performance index were calculated. Longitudinal strain (LS) of 17 segments was measured using 2DSTI. Mean base (LSBA ), papillary muscle (LSPM ), and apex values (LSAP ) were calculated. RESULTS: Compared to subjects in the control group and group 1, subjects in group 2 exhibited decreased LV end-diastolic volume (EDV), end-systolic volume (ESV), LV mass index (LVMI), and VAC (P < 0.05). EF, fractional shortening (FS), end-systolic elastance (Ees) were significantly higher in group 2 (P < 0.05). SLBA , SLPM , and SLAP differed significantly among the groups (all P < 0.05). SLBA , SLPM , and SLAP correlated positively with Ees, EF, and FS (all P < 0.05) but negatively with arterial elastance (Ea), VAC, systemic vascular resistance index (SVRI), and rate-pressure product (RPP) (all P < 0.05). Multiple regression analysis revealed that relative wall thickness (RWT), LVMI, LSAP , and stroke works (SW) were independent predictors of VAC (b' = -0.443, 0.537, -0.470, and -0.491, all P < 0.05). CONCLUSIONS: In patients with uremia, LV myocardial LS gradually decreased as LV systolic dysfunction decreased. VAC correlated negatively with left ventricular LS, and LSAP was an independent predictor for VAC.

Nomogram for predicting preoperative lymph node involvement in patients with invasive micropapillary carcinoma of breast: a SEER population-based study.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. This study was to identify risk factors accounting for IMPC of the breast and to develop a nomogram to preoperatively predict the probability of lymph node involvement. METHODS: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation sets. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. A logistic regression model was used to construct the nomogram in the training set and then varified in the validation set. Nomogram performance was quantified with respect to discrimination and calibration using R 3.4.1 software. RESULTS: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. Logistic regression analysis indicated larger lesions, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95% confidential interval (CI) 0.692 to 0.777), demonstrating a good prediction performance. Calibration curve for the nomogram was plotted and the slope was close to 1, which demonstrated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, with AUC of 0.748 (95% CI 0.701 to 0.767). CONCLUSIONS: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinicalpathologic parameters was established, which could accurately preoperatively predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients.

Genetic engineering to alter carbon flux for various higher alcohol productions by Saccharomyces cerevisiae for Chinese Baijiu fermentation.

Higher alcohols significantly influence the quality and flavor profiles of Chinese Baijiu. ILV1-encoded threonine deaminase, LEU1-encoded α-isopropylmalate dehydrogenase, and LEU2-encoded ß-isopropylmalate dehydrogenase are involved in the production of higher alcohols. In this work, ILV1, LEU1, and LEU2 deletions in α-type haploid, a-type haploid, and diploid Saccharomyces cerevisiae strains and ILV1, LEU1, and LEU2 single-allele deletions in diploid strains were constructed to examine the effects of these alterations on the metabolism of higher alcohols. Results showed that different genetic engineering strategies influence carbon flux and higher alcohol metabolism in different manners. Compared with the parental diploid strain, the ILV1 double-allele-deletion diploid mutant produced lower concentrations of n-propanol, active amyl alcohol, and 2-phenylethanol by 30.33, 35.58, and 11.71%, respectively. Moreover, the production of isobutanol and isoamyl alcohol increased by 326.39 and 57.6%, respectively. The LEU1 double-allele-deletion diploid mutant exhibited 14.09% increased n-propanol, 33.74% decreased isoamyl alcohol, and 13.21% decreased 2-phenylethanol production, which were similar to those of the LEU2 mutant. Furthermore, the LEU1 and LEU2 double-allele-deletion diploid mutants exhibited 41.72 and 52.18% increased isobutanol production, respectively. The effects of ILV1, LEU1, and LEU2 deletions on the production of higher alcohols by α-type and a-type haploid strains were similar to those of double-allele deletion in diploid strains. Moreover, the isobutanol production of the ILV1 single-allele-deletion diploid strain increased by 27.76%. Variations in higher alcohol production by the mutants are due to the carbon flux changes in yeast metabolism. This study could provide a valuable reference for further research on higher alcohol metabolism and future optimization of yeast strains for alcoholic beverages.

Reduced production of diacetyl by overexpressing BDH2 gene and ILV5 gene in yeast of the lager brewers with one ILV2 allelic gene deleted.

Diacetyl causes an unwanted buttery off-flavor in lager beer. The production of diacetyl is reduced by modifying the metabolic pathway of yeast in the beer fermentation process. In this study, BDH2 and ILV5 genes, coding diacetyl reductase and acetohydroxy acid reductoisomerase, respectively, were expressed using a PGK1 promoter in Saccharomyces cerevisiae, which deleted one ILV2 allelic gene. Diacetyl contents and fermentation performances were examined and compared. Results showed that the diacetyl content in beer was remarkably reduced by 16.52% in QI2-KP (one ILV2 allelic gene deleted), 55.65% in QI2-B2Y (overexpressed BDH2 gene and one ILV2 allelic gene deleted), and 69.13% in QI2-I5Y (overexpressed ILV5 gene and one ILV2 allelic gene deleted) compared with the host strain S2. The fermentation ability of mutant strains was similar to that of S2. Results of the present study can lead to further advances in this technology and its broad application in scientific investigations and industrial beer production.

[A novel disposable circumcision device versus conventional surgery in the treatment of redundant prepuce and phimosis].

OBJECTIVE: To compare the clinical effect of a novel disposable circumcision device Ring with that of conventional circumcision in the treatment of redundant prepuce and phimosis. METHODS: Totally, 750 patients with redundant prepuce or phimosis underwent Ring circumcision (group A, n = 450) or conventional circumcision (group B, n = 300). We recorded the operation time, intraoperative blood loss, Visual Analogue Scale (VAS) intraoperative pain scores, postoperative complications, wound healing time, and patients' satisfaction with postoperative penile appearance, followed by comparison of the collected data between the two groups of patients. RESULTS: All the operations were successfully completed. Group A, as compared with B, showed significantly shorter operation time (ï¼»3.78 ± 0.42ï¼½ vs ï¼»26.24 ± 3.99ï¼½ min, P <0.05), less intraoperative blood loss (ï¼»2.39 ± 1.01ï¼½ vs ï¼»10.80 ± 3.57ï¼½ ml, P <0.05), lower pain scores intraoperatively (0.14 ± 0.36 vs 2.30 ± 1.46, P <0.05), 6 hours postoperatively (0.32 ± 0.78 vs 3.03 ± 1.56, P <0.05) and at the ring removal (3.35 ± 1.42 vs 2.78 ± 1.43, P <0.05), shorter wound healing time (ï¼»7.61 ± 1.60ï¼½ vs ï¼»8.57 ± 1.37ï¼½ d, P <0.05), higher satisfaction with postoperative penile appearance (97.8% ï¼»440/450ï¼½ vs 86% ï¼»258/300ï¼½, P <0.05), and lower incidence of postoperative bleeding or hematoma (0.89% ï¼»4/450ï¼½ vs 3% ï¼»9/300ï¼½, P <0.05). No statistically significant differences were observed between groups A and B in the nocturnal pain score before the ring removal (1.45±1.02 vs 1.38 ± 0.92, P >0.05) or the postoperative incidence rate of edema (0.89% ï¼»4/450ï¼½ vs 2.33% ï¼»7/300ï¼½, P >0.05). There were no significant postoperative infections or delayed incision healing except for 1 case of wound dehiscence in each group. CONCLUSIONS: Ring circumcision, with its advantages of shorter operation time, less blood loss and pain, higher safety, and better postoperative penile appearance, is easily accepted by the patients and deserves wide clinical application.

[A novel disposable ring versus the suture device in circumcision].

OBJECTIVE: To investigate the clinical effect of a novel disposable ring versus that of the suture device in circumcision for redundant prepuce and phimosis. METHODS: We randomly assigned 470 male patients with redundant prepuce or phimosis to receive circumcision with a novel disposable ring (the DR group, n = 235) or the suture device (the SD group, n = 235) and compared the operation time, intraoperative blood loss, pain scores, wound healing time, and postoperative complications and penile appearance between the two groups of patients. RESULTS: All the operations were completed smoothly. Compared with the SD group, the DR group showed significantly shorter operation time (ï¼»7.49 ± 1.84ï¼½ vs ï¼»3.83 ± 0.42ï¼½ min, P <0. 05), less intraoperative blood loss (ï¼»3.34 ± 2.59ï¼½ vs ï¼»2.41 ± 1.01ï¼½ ml, P <0.05), lower intraoperative pain score (0.57 ± 0.76 vs 0.20 ± 0.47, P <0.05) and 6-hour postoperative pain score (3.42 ± 1.12 vs 0.48 ± 0.94, P <0.05), shorter wound healing time (ï¼»12.05 ± 2.80ï¼½ vs ï¼»7.79 ± 1.65ï¼½ d, P <0.05), lower incidence rates of postoperative glans congestion or edema (36.17% ï¼»85/235ï¼½ vs 2.56% ï¼»6/235ï¼½, P <0.05), dysuria or strenuous urination (34.04% ï¼»80/235ï¼½ vs 2.13% ï¼»5/235ï¼½, P <0.05) and bleeding or hematoma (5.11% ï¼»12/235ï¼½ vs 1.28% ï¼»3/235ï¼½, P <0.05), and higher satisfaction with postoperative penile appearance (90.6% ï¼»213/235ï¼½ vs 95.8% ï¼»228/235ï¼½, P <0.05). There were no statistically significant differences between the SD and DR groups in the pain scores at the sixth night after operation (1.31 ± 0.96 vs 1.34 ± 1.07, P >0.05) or while the staples scraping the underpants or at the ring removal (3.49 ± 1.22 vs 3.36 ± 1.41, P >0.05). No obvious postoperative infection or delayed healing was observed except for 3 cases of wound dehiscence (1 in the DR and 2 in the SD group) and 8 cases of delayed removal of the staples in the SD group. CONCLUSIONS: The novel disposable ring, with its advantages of short operation time, less bleeding and pain, good penile appearance, high safety, and simple operation, is obviously superior to the suture device in circumcision and deserves to be applied and popularized clinically. .

Reduced production of ethyl carbamate for wine fermentation by deleting CAR1 in Saccharomyces cerevisiae.

Ethyl carbamate (EC), a pluripotent carcinogen, is mainly formed by a spontaneous chemical reaction of ethanol with urea in wine. The arginine, one of the major amino acids in grape musts, is metabolized by arginase (encoded by CAR1) to ornithine and urea. To reduce the production of urea and EC, an arginase-deficient recombinant strain YZ22 (Δcarl/Δcarl) was constructed from a diploid wine yeast, WY1, by successive deletion of two CAR1 alleles to block the pathway of urea production. The RT-qPCR results indicated that the YZ22 almost did not express CAR1 gene and the specific arginase activity of strain YZ22 was 12.64 times lower than that of parent strain WY1. The fermentation results showed that the content of urea and EC in wine decreased by 77.89 and 73.78 %, respectively. Furthermore, EC was forming in a much lower speed with the lower urea during wine storage. Moreover, the two CAR1 allele deletion strain YZ22 was substantially equivalent to parental strain in terms of growth and fermentation characteristics. Our research also suggested that EC in wine originates mainly from urea that is produced by the arginine.

Efficient Tailoring of Upconversion Selectivity by Engineering Local Structure of Lanthanides in Na(x)REF(3+x) Nanocrystals.

Efficient tailoring of upconversion emissions in lanthanide-doped nanocrystals is of great significance for extended optical applications. Here, we present a facile and highly effective method to tailor the upconversion selectivity by engineering the local structure of lanthanides in Na(x)REF(3+x) nanocrystals. The local structure engineering was achieved through precisely tuning the composition of nanocrystals, with different [Na]/[RE] ([F]/[RE]) ratio. It was found that the lattice parameter as well as the coordination number and local symmetry of lanthanides changed with the composition. A significant difference in the red to green emission ratio, which varied from 1.9 to 71 and 1.6 to 116, was observed for Na(x)YF(3+x):Yb,Er and Na(x)GdF(3+x):Yb,Er nanocrystals, respectively. Moreover, the local structure-dependent upconversion selectivity has been verified for Na(x)YF(3+x):Yb,Tm nanocrystals. In addition, the local structure induced upconversion emission from Er(3+) enhanced 9 times, and the CaF2 shell grown epitaxially over the nanocrystals further promoted the red emission by 450 times, which makes it superior as biomarkers for in vivo bioimaging. These exciting findings in the local structure-dependent upconversion selectivity not only offer a general approach to tailoring lanthanide related upconversion emissions but also benefit multicolor displays and imaging.

Paradigms and challenges for bioapplication of rare earth upconversion luminescent nanoparticles: small size and tunable emission/excitation spectra.

Rare earth (RE) materials, which are excited in the ultraviolet and emit in the visible light spectrum, are widely used as phosphors for lamps and displays. In the 1960's, researchers reported an abnormal emission phenomenon where photons emitted from a RE element carried more energy than those absorbed, owing to the sequential energy transfer between two RE ions--Yb(3+)-sensitized Er(3+) or Tm(3+)--in the solid state. After further study, researchers named this abnormal emission phenomenon upconversion (UC) emission. More recent approaches take advantage of solution-based synthesis, which allows creation of homogenous RE nanoparticles (NPs) with controlled size and structure that are capable of UC emission. Such nanoparticles are useful for many applications, especially in biology. For these applications, researchers seek small NPs with high upconversion emission intensity. These UCNPs have the potential to have multicolor and tunable emissions via various activators. A vast potential for future development remains by developing molecular antennas and energy transfer within RE ions. We expect UCNPs with optimized spectra behavior to meet the increasing demand of potential applications in bioimaging, biological detection, and light conversion. This Account focuses on efforts to control the size and modulate the spectra of UCNPs. We first review efforts in size control. One method is careful control of the synthesis conditions to manipulate particle nucleation and growth, but more recently researchers have learned that the doping conditions can affect the size of UCNPs. In addition, constructing homogeneous core/shell structures can control nanoparticle size by adjusting the shell thickness. After reviewing size control, we consider how diverse applications impose different requirements on excitation and/or emission photons and review recent developments on tuning of UC spectral profiles, especially the extension of excitation/emission wavelengths and the adjustment and purification of emission colors. We describe strategies that employ various dopants and others that build rationally designed nanostructures and nanocomposites to meet these goals. As the understanding of the energy transfer in the UC process has improved, core/shell structures have been proved useful for simultaneous tuning of excitation and emission wavelengths. Finally, we present a number of typical examples to highlight the upconverted emission in various applications, including imaging, detection, and sensing. We believe that with deeper understanding of emission phenomena and the ability to tune spectral profiles, UCNPs could play an important role in light conversion studies and applications.

Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer.

Long non-coding RNAs (lncRNAs) have been proved to serve as a critical role in cancer development and progression. However, little is known about the pathological role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer patients. The aims of this study are to measure the expression of lncRNA MALAT1 in pancreatic cancer patients and to explore the clinical significance of the lncRNA MALAT1. Using qRT-PCR, the expression of lncRNA MALAT1 was measured in 126 pancreatic cancer tissues and 15 adjacent non-cancerous tissues. In the present study, our results indicated that lncRNA MALAT1 was highly expressed in pancreatic cancer compared with adjacent non-cancerous tissues (P < 0.001), and positively correlated with clinical stage (early stages vs. advanced stages, P < 0.001), tumor size (<2 vs. ≥2 cm, P = 0.004), lymph node metastasis (negative vs. positive, P < 0.001), and distant metastasis (absent vs. present, P = 0.001) in pancreatic cancer patients. Furthermore, we also found that lncRNA MALAT1 overexpression was an unfavorable prognostic factor in pancreatic cancer patients (P < 0.001), regardless of clinical stage, tumor size, lymph node metastasis, and distant metastasis. Finally, increased lncRNA MALAT1 expression was an independent poor prognostic factor for pancreatic patients through multivariate analysis (P = 0.018). In conclusion, overexpression of lncRNA MALAT1 serves as an unfavorable prognostic biomarker in pancreatic cancer patients.

Enhanced production of 2,3-butanediol by overexpressing acetolactate synthase and acetoin reductase in Klebsiella pneumoniae.

Mutants with overexpression of α-acetolactate synthase (ALS), α-acetolactate decarboxylase, and acetoin reductase (AR), either individually or in combination, were constructed to improve 2,3-butanediol (2,3-BD) production in Klebsiella pneumoniae. The recombinant strains were characterized in terms of the enzyme activity, 2,3-BD yield, and expression levels. The recombinant K. pneumoniae strain (KG-rs) that overexpressed both ALS and AR showed an improved 2,3-BD yield. When cultured in the media with five different carbon sources (glucose, galactose, fructose, sucrose, and lactose), the mutant exhibited higher 2,3-BD productivity and production than the parental strain in all the tested carbon sources except for lactose. The 2,3-BD production of KG-rs in a batch fermentation with glucose as the carbon source was 12% higher than that of the parental strain.