Amino acid metabolism and MAP kinase signaling pathway play opposite roles in the regulation of ethanol production during fermentation of sugarcane molasses in budding yeast.

Sugarcane molasses is one of the main raw materials for bioethanol production, and Saccharomyces cerevisiae is the major biofuel-producing organism. In this study, a batch fermentation model has been used to examine ethanol titers of deletion mutants for all yeast nonessential genes in this yeast genome. A total of 42 genes are identified to be involved in ethanol production during fermentation of sugarcane molasses. Deletion mutants of seventeen genes show increased ethanol titers, while deletion mutants for twenty-five genes exhibit reduced ethanol titers. Two MAP kinases Hog1 and Kss1 controlling the high osmolarity and glycerol (HOG) signaling and the filamentous growth, respectively, are negatively involved in the regulation of ethanol production. In addition, twelve genes involved in amino acid metabolism are crucial for ethanol production during fermentation. Our findings provide novel targets and strategies for genetically engineering industrial yeast strains to improve ethanol titer during fermentation of sugarcane molasses.

On-Surface Growth of Single-Layered Homochiral 2D Covalent Organic Frameworks by Steric Hindrance Strategy.

Investigation of chirality in on-surface synthesis is of significance not only for fabricating atomically precise covalently bonded chiral species but also for unveiling chiral phenomena involving chemical reactions. In this contribution, we present the growth of single-layered homochiral 2D covalent organic frameworks (COFs) on surfaces based on a steric hindrance strategy, by which both the chiral expression of the prochiral precursor and the newly formed C═N bonds are successfully steered. When coupling a tritopic monomer with the prochiral ditopic molecule with phenyl substituents, two enantiomers of the precursor are randomly integrated in the product via variable C═N linkages, resulting in distorted hexagonal frameworks without chiral expression. After equipping the prochiral precursor with more hindered bulky substituents, highly regular homochiral 2D COFs are fabricated, in which only one of the enantiomers of the prochiral precursor is integrated, and all C═N linkages possess the same configuration. Structural analysis based on high resolution scanning tunneling microscopy images and theoretical simulations indicate that the homochiral 2D COFs are generated through an enantioselective on-surface polymerization driven by the steric hindrance effect. This result not only benefits understanding and controlling chirality in on-surface synthesis but also provides a new approach for the growth of highly regular COFs on surfaces.

On-Surface Synthesis of Highly Ordered Covalent Sierpinski Triangle Fractals.

The Sierpinski triangle (ST) is a well-known fractal structure. Synthesis of stable molecular STs with robust covalent linkages is attractive but challenging. Here, we demonstrate the formation of a series of high-quality covalent STs via the on-surface dehydration reaction of 1,3-benzenediboronic acid with the presence of water as an equilibrium regulator at ambient atmosphere. Extended molecular fractals up to third generation are obtained, as disclosed by scanning tunnel microscope. The covalent STs show intriguing bright and dark contrasts irrespective of the fractal generations, which is related with epitaxial relationship of fractal structure to the underlying graphite lattice, as supported by theoretical simulations.

Concentration-Directed Polymorphic Surface Covalent Organic Frameworks: Rhombus, Parallelogram, and Kagome.

Polymorphic single-layered covalent organic frameworks (sCOFs) via on-surface synthesis have been investigated by employing the tetradentate monomer 1,3,6,8-tetrakis(p-formylphenyl)pyrene with D2h symmetry and ditopic linear diamine building blocks. Three kinds of well-ordered sCOFs, including rhombus, parallelogram, and Kagome networks, are observed on the graphite surface by scanning tunnel microscopy. The pore size and periodicity of sCOFs are tunable by employing diamine monomers with different lengths. Statistical analysis reveals that two types of quadrate networks are preferred at high concentration, whereas the occupancy of Kagome networks increases at low concentration. This trend can be understood by the differences in the network density of three kinds of networks. The reversibility and the self-sorting ability of the dynamic covalent reaction make it possible to control the polymorphic distribution similar to the principle demonstrated in supramolecular self-assembly.

Simultaneous construction of two linkages for the on-surface synthesis of imine-boroxine hybrid covalent organic frameworks.

The orthogonality between the Schiff base reaction and the boronic acid dehydration reaction is explored during the on-surface synthesis process. By activating the above two reactions in one-step and employing asymmetrical substituted monomers and the 3-fold symmetric monomer 1,3,5-tris(4-aminophenyl)benzene (TAPB), highly ordered imine-boroxine hybrid single-layered covalent organic frameworks (sCOFs) have been successfully constructed on HOPG by a gas-solid interface reaction method and characterized by scanning tunnelling microscopy (STM). In particular, the reaction between the meta-substituted monomer and TAPB generates sCOFB with a windmill structure, which is the first sCOF with surface chirality so far reported. The demonstration of the one-step synthesis of multiple linkages to form sCOFs can further enlarge the sCOF family and expand the design routes for functional 2D organic nanomaterials.

The intramolecular H-bonding effect on the growth and stability of Schiff-base surface covalent organic frameworks.

The introduction of intramolecular H-bonding by adding -OH functionalities adjacent to the Schiff base centers is considered to be a useful strategy to enhance the stability and crystallinity of bulk covalent organic frameworks (COFs). However, the influence of intramolecular H-bonding on the synthesis of surface COFs (SCOFs) have been barely explored. Herein, SCOFs based on the Schiff-base reaction between 1,3,5-tris(4-aminophenyl)benzene (TAPB) and terephthalaldehydes with symmetry or asymmetrically substituted hydroxyl functional groups are designed. In the absence of a solvent, hydroxyl substituents can be easily oxidized; thus argon protection is required to obtain high-quality SCOFs. Besides, an extended network with uniform pores can be achieved in spite of the symmetry of substituents. Both experimental results and theoretical calculations show that the influence of intramolecular hydrogen bonding on surface synthesis is not as important as that in bulk phase synthesis because the substrate itself can lead to the complanation of adsorbed molecules. The existence of intramolecular H-bonding can enhance the stability of the network in both acid and alkali environments.

[Combined intravenous and intrathecal vancomycin in treatment of patients with intracranial infections after craniotomy].

OBJECTIVE: To explore the efficacy and safety of combined intravenous and intrathecal vancomycin in treatment of patients with intracranial infection after craniotomy. METHODS: Clinical data of a total of 60 consecutive patients with intracranial infections after cranial operation admitted to Department of Neurosurgery of Nanfang Hospital of Southern Medical University from June 1st 2013 to June 1st 2015 were retrospectively analyzed. The patients were divided into two groups: intravenous injection only (n = 25) and combined intravenous and intrathecal injection (n = 35). In both groups of patients intravenously given vancomycin hydrochloride 500 kU every 6 hours as well as third or fourth generation of cephalosporins or meropenem. In combined intravenous and intrathecal injection group, in addition to 20 mg vancomycin was slowly injected via lumbar puncture after release of cerebrospinal fluid (CSF) once a day. The clinical efficacy and complications of the two groups were compared. RESULTS: The recovery rate in the combined intravenous and intrathecal injection group was significantly higher than that in the intravenous injection only group (94.3% vs. 76.0%, χ (2) = 4.220, P = 0.040). Lowering of white blood cell count in combined intravenous and intrathecal injection group was significantly earlier than that of the intravenous injection only group (time to become normal: 8 days vs. 13 days). The time of recovery in combined intravenous and intrathecal injection group was significantly shorter than that of the intravenous injection only group (days: 9.9±0.7 vs. 13.4±1.1, t = -2.716, P = 0.009). There were 3 patients who experienced nerve root irritation symptoms in combined intravenous and intrathecal injection group. Symptomatic treatment was given and injection speed was slowed down for these patients. There were no severe complications, such as coma, epilepsy or death in both groups. CONCLUSIONS: Combined intravenous and intrathecal injection of vancomycin could be a safe and effective therapy for intracranial infection after craniotomy.

Isomeric routes to Schiff-base single-layered covalent organic frameworks.

With graphene-like topology and designable functional moieties, single-layered covalent organic frameworks (sCOFs) have attracted enormous interest for both fundamental research and application prospects. As the growth of sCOFs involves the assembly and reaction of precursors in a spatial defined manner, it is of great importance to understand the kinetics of sCOFs formation. Although several large families of sCOFs and bulk COF materials based on different coupling reactions have been reported, the synthesis of isomeric sCOFs by exchanging the coupling reaction moieties on precursors has been barely explored. Herein, a series of isomeric sCOFs based on Schiff-base reaction is designed to understand the effect of monomer structure on the growth kinetics of sCOFs. The distinctly different local packing motifs in the mixed assemblies for the two isomeric routes closely resemble to those in the assemblies of monomers, which affect the structural evolution process for highly ordered imine-linked sCOFs. In addition, surface diffusion of monomers and the molecule-substrate interaction, which is tunable by reaction temperature, also play an important role in structural evolutions. This study highlights the important roles of monomer structure and reaction temperature in the design and synthesis of covalent bond connected functional nanoporous networks.

[Preliminary clinical evaluations of bevacizumab for recurrent malignant glioma in Chinese patients].

OBJECTIVE: To explore the clinical efficacies of bevacizumab (BEV) for high-grade glioma (HGG) in Chinese patients and evaluate its profiles of adverse events and usage safety. METHODS: A total of 15 HGG cases, including glioblastoma multiform (GBM) (n = 12) and anaplastic astrocytoma (AA) (n = 3), were selected to receive the treatments of BEV (10 mg/kg, q2w) and temozolomide (TMZ, 150 mg/m(2), 5 d/28 d). Their radiological responses, clinical status, progression-free survival (PFS) and overall survival (OS) were evaluated. Also their adverse events and severity were recorded and analyzed. RESULTS: According to the RANO criteria, during the short period (<3 months), 11 cases had significant radiological and clinical responses. However, only 4 cases responded during a follow-up period of beyond 3 months. Three cases had retrogression after BEV chemotherapy. At 6 months post-treatment, 8 cases (53.3%) survived without lesion progression and the median PFS was 8 ± 5 months. During a longer follow-up (>6 months), 8 patients had tumor retrogression, including 5 deaths. The median overall survival period was 24 ± 10 months. The adverse events included hypertension (n = 2), wound-healing complication (n = 1), vomiting (n = 2) and cerebro-spinal fluid leakage (n = 1). All complications were cured by activate supportive measures. CONCLUSION: After BEV treatment, most patients obtain more significant short-term responses with good toleration. For re-operative cases, the usage of BEV should be deferred to one month post-operation so as to avoid the occurrence of wound-healing complications.

[Operative strategies for bilateral brain contusion and laceration].

OBJECTIVE: To explore the operative strategies for bilateral brain contusion and laceration and evaluate their clinical significance. METHODS: Based on the clinical manifestations, computed tomography (CT) and intracranial pressure (ICP), different operative strategies were applied to 25 cases of bilateral brain contusion and laceration. The strategies were classified into 6 types according to the principles of decompression and brain protection.All cases received routine treatments at neurosurgical intensive care unit (ICU) ward. And the occurrences of operative complications and 6-month Glasgow outcome scale (GOS) were statistically analyzed. RESULTS: Type 1:4 cases of unilateral decompressive craniectomy without resection of contusion focus; Type 2:8 cases of unilateral decompressive craniectomy with resection of bilateral contusion focus; Type 3:5 cases of bilateral decompressive craniectomy with resection of unilateral brain contusion; Type 4:5 cases of bilateral decompressive craniectomy; Type 5:1 case of bilateral brain contusion resection; Type 6:2 cases of bilateral decompressive craniectomy and brain contusion resection.Postoperative complications such as epilepsy, expanding contusion foci, brain infarction, encephalocele, incisional CSF leakage, intracranial infection, subdural hydroma and hydrocephalus were rare. The 6-month GOS revealed 6 cases of good outcome (n = 6), moderate disability (n = 8), severe disability (n = 3) and vegetative status (n = 5) and death (n = 3). CONCLUSION: Different operative strategies may be applied for severe brain contusion and laceration according to their clinical manifestations, CT findings and ICP values. And the efficacies are improved by operative strategies based on the principles of ICP control, prevention of secondary injury and brain function preservation.

Heteroaromatic imidazo[1,2-a]pyridines synthesis from C-H/N-H oxidative cross-coupling/cyclization.

A novel silver-mediated highly selective C-H/N-H oxidative cross-coupling/cyclization between 2-aminopyridines and terminal alkynes has been demonstrated. This approach provided a simple way to construct heteroaromatic imidazo[1,2-a]pyridines. By using this protocol, the marketed drug zolimidine (antiulcer) could be synthesized easily.