Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain. METHODS: We prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota. RESULTS: Compared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa. CONCLUSIONS: The study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.

CoMI: consensus mutual information for tissue-specific gene signatures.

BACKGROUND: The gene signatures have been considered as a promising early diagnosis and prognostic analysis to identify disease subtypes and to determine subsequent treatments. Tissue-specific gene signatures of a specific disease are an emergency requirement for precision medicine to improve the accuracy and reduce the side effects. Currently, many approaches have been proposed for identifying gene signatures for diagnosis and prognostic. However, they often lack of tissue-specific gene signatures. RESULTS: Here, we propose a new method, consensus mutual information (CoMI) for analyzing omics data and discovering gene signatures. CoMI can identify differentially expressed genes in multiple cancer omics data for reflecting both cancer-related and tissue-specific signatures, such as Cell growth and death in multiple cancers, Xenobiotics biodegradation and metabolism in LIHC, and Nervous system in GBM. Our method identified 50-gene signatures effectively distinguishing the GBM patients into high- and low-risk groups (log-rank p = 0.006) for diagnosis and prognosis. CONCLUSIONS: Our results demonstrate that CoMI can identify significant and consistent gene signatures with tissue-specific properties and can predict clinical outcomes for interested diseases. We believe that CoMI is useful for analyzing omics data and discovering gene signatures of diseases.

A Photosensitizer-Free Radical Cascade for Synthesizing CF3-Containing Polycyclic Quinazolinones with Visible Light.

Herein, we report an efficient photoinduced radical tandem trifluoromethylation/cyclization reaction of N-cyanamide alkenes for the synthesis of functionalized quinazolinones. Importantly, the reaction is carried out under mild conditions without any additional photosensitizer, metal, or extra additives. A series of trifluoromethyl quinazolinones were prepared efficiently with good yields and excellent functional group tolerance. Preliminary mechanistic experiments were conducted to indicate that the transformation proceeds via a possible mechanism involving photoexcited EDA complex and chain propagation.

[Keyhole Approach Endoscopic Surgery versus Stereotactic Aspiration plus Urokinase in Treating Basal Ganglia Hypertensive Intracerebral Hemorrhage].

Objective To compare the short-and long-term effect of two minimal invasive surgical therapies including keyhole approach endoscopic surgery(KAES)and stereotactic aspiration plus urokinase(SAU)in treating basal ganglia hypertensive intracerebral hemorrhage(hICH). Methods The clinical data of 117 hICH patients(63 received KAES and 54 received SAU)were retrospectively analyzed.The operation time,blood loss during surgery,and drainage time were compared between two groups.The residual hematoma volume,hematoma clearance rate(HCR),Glasgow coma scale(GCS)score,and National Institute of Health Stroke Scale(NIHSS)score were recorded at baseline and in the ultra-early stage,early stage,and sub-early stage after surgery.The 30-day mortality and serious adverse events were assessed and the 6-month modified Rankin scale(mRS)score was rated.Results Baseline data showed no significant difference between these two groups.Compared with the SAU group,the KAES group had significantly longer operation time,more intraoperative blood loss,and shorter drainage time(all P<0.001).In the ultra-early stage after surgery,HCR was significantly higher in the KAES group(P<0.001),whereas in the early and sub-early stage,HCR showed no significant differences(all P>0.05).In the ultra-early and early stage,the GCS and NIHSS scores showed no significant differences between two groups(all P>0.05),whereas in the sub-early stage,the NIHSS score was better in the SAU group(P=0.034).The 30-day mortality and incidences of serious adverse events showed no significant difference(all P>0.05).The good recovery(mRS≤3)at 6-months follow-up showed no significant difference between the two groups(P=0.413).Conclusions Both KAES and SAU are safe and effective in treating basal ganglia hICH.In the ultra-early stage after surgery,KAES achieves better residual hematoma volume and HCR,and patients undergoing SAU quickly catch up.The short-and long-term effectiveness of SAU is comparable or even superior to KAES.

Dehydrogenative Silylation of Alkenes for the Synthesis of Substituted Allylsilanes by Photoredox, Hydrogen-Atom Transfer, and Cobalt Catalysis.

A synergistic catalytic method combining photoredox catalysis, hydrogen-atom transfer, and proton-reduction catalysis for the dehydrogenative silylation of alkenes was developed. With this approach, a highly concise route to substituted allylsilanes has been achieved under very mild reaction conditions without using oxidants. This transformation features good to excellent yields, operational simplicity, and high atom economy. Based on control experiments, a possible reaction mechanism is proposed.

Organocatalytic Regiodivergent C-C Bond Cleavage of Cyclopropenones: A Highly Efficient Cascade Approach to Enantiopure Heterocyclic Frameworks.

Here a highly efficient cascade approach is reported that combines a cycloaddition reaction with a regioselective strain-release process to afford diverse heterocyclic frameworks through bifunctional catalysis. The cooperation of hydrogen-bonding network activation and a regiodivergent strain-assisted effect is the key to promoting this complex chemical transformation, leading to the generation of two different ring systems in high yields with excellent stereoselectivities. The reaction proceeded by a mechanism involving a "spring-loaded" intermediate with switchable C-C bond cleavages achieved by controllable ring-strain release. This reaction was also amenable to gram scale synthesis with only 0.1 mol % catalyst loading.

Sc(OTf)3 Catalyzed [4 + 2]-Annulation Reaction between Electron-Rich Phenols and Donor-Acceptor Cyclopropanes: Synthesis of Polysubstituted Dihydronaphthols.

On the basis of the Lewis acid-catalyzed Friedel-Crafts alkylation between 1-acyl-2-arylcyclopropanecarboxylate esters and electron-rich phenols, a Sc(OTf)3 catalyzed cascade [4 + 2]-annulation reaction was developed for the direct synthesis of polysubstituted dihydronaphthols from phenols. In this reaction, the structure of products is dominated by the directing effect of the substituent groups on phenols. Meanwhile, a one-pot Friedel-Crafts alkylation/oxidative cyclization reaction was also developed for the synthesis of spiro-fused 2,5-cyclohexadienones.

PPh3O as an Activating Reagent for One-Pot Stereoselective Syntheses of Di- and Polybrominated Esters from Simple Aldehydes.

An efficient one-pot method for the syntheses of di- and polybrominated esters from readily available aldehydes is reported. The direct use of the in situ generated byproduct PPh3O in the following reactions greatly improves the efficiency of the cascade. Also, the substrate scope of the reaction is proved to be broad.

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates.

A new and efficient synthetic method to obtain fully-substituted hexahydroisoindolinones was developed by using bifunctional tertiary amine-thioureas as powerful catalysts. As far as we know, there is no efficient synthetic method developed toward fully-substituted hexahydroisoindolinones. The products were obtained in good yield and diastereoselectivity. The one-pot cascade quadruple protocol features readily available starting materials, simple manipulation, mild conditions and good atom economy.

An Approach to Preparing Ni-P with Different Phases for Use as Supercapacitor Electrode Materials.

Herein, we describe a simple two-step approach to prepare nickel phosphide with different phases, such as Ni2 P and Ni5 P4 , to explain the influence of material microstructure and electrical conductivity on electrochemical performance. In this approach, we first prepared a Ni-P precursor through a ball milling process, then controlled the synthesis of either Ni2 P or Ni5 P4 by the annealing method. The as-prepared Ni2 P and Ni5 P4 are investigated as supercapacitor electrode materials for potential energy storage applications. The Ni2 P exhibits a high specific capacitance of 843.25 F g(-1) , whereas the specific capacitance of Ni5 P4 is 801.5 F g(-1) . Ni2 P possesses better cycle stability and rate capability than Ni5 P4 . In addition, the Fe2 O3 //Ni2 P supercapacitor displays a high energy density of 35.5 Wh kg(-1) at a power density of 400 W kg(-1) and long cycle stability with a specific capacitance retention rate of 96 % after 1000 cycles, whereas the Fe2 O3 //Ni5 P4 supercapacitor exhibits a high energy density of 29.8 Wh kg(-1) at a power density of 400 W kg(-1) and a specific capacitance retention rate of 86 % after 1000 cycles.

Enantioselective Amine-Catalyzed [4 + 2] Annulations of Allene Ketones and 2,3-Dioxopyrrolidine Derivatives: Synthesis of 4H-Pyran Derivatives.

An efficient cinchona alkaloid-derived amine catalyzed asymmetric [4 + 2] cycloaddition is successfully developed. 4H-Pyran fused pyrrolin-2-one products are readily obtained in moderate to high yields with good enantioselectivites by employing allene ketones and 2,3-dioxopyrrolidine derivatives as substrates.

Ultra-early versus delayed coil treatment for ruptured poor-grade aneurysm.

INTRODUCTION: The timing of definitive aneurysm treatment (coiling or clipping) in poor-grade (Hunt-Hess IV or V) subarachnoid haemorrhage (SAH) patients has been a controversial topic. The purpose of this retrospective study was to analyse whether ultra-early coiling of ruptured intracranial aneurysms improves the clinical outcomes of poor-grade SAH patients. METHODS: The records of patients with aneurysmal SAH who were treated with endovascular coiling were retrieved. The patients were classified into two groups: group A (patients coiled within 24 h of SAH) and group B (patients coiled ≥ 24 h after SAH). For each group, the patient demographics, Fisher grade, aneurysm characteristics and clinical outcomes were recorded. Outcomes were measured at 6 months using the modified Rankin Scale (mRS). RESULTS: Thirty-one patients were coiled within 24 h of SAH (group A), and fourteen patients were coiled ≥24 h after SAH (group B). Groups A and B had similar clinical and angiographic characteristics. The clinical outcomes showed that a total of 58.1% of the patients (18 of 31) in group A were independent (mRS 0-2) compared with 21.4% of the patients (3 of 14) in group B (P = .028). Univariate analysis demonstrated that ultra-early coiling (P = .028) proved to be an independent predictor of better clinical outcomes (mRS 0-2). CONCLUSIONS: Ultra-early (<24 h after SAH) coiling of ruptured aneurysms was associated with improved clinical outcomes compared to coiling at ≥24 h in poor-grade SAH patients. Larger, prospective studies are required to adequately assess the outcome differences between these two groups.

Organocatalyzed Michael-Michael cascade reaction: asymmetric synthesis of polysubstituted chromans.

An enantioselective cascade Michael-Michael reaction between chalcones enolates and nitromethane catalyzed by a bifunctional thiourea is developed. This reaction provides a mild but efficient approach to chiral benzopyrans bearing three consecutive stereocenters in high yields with excellent stereoselectivities, and the benzopyrans can be easily transformed to the corresponding tricyclic product.

Photoredox Catalyzed [3 + 2]-Annulation Reaction of Pyridinium 1,4-Zwitterionic Thiolates with Alkenes: Synthesis of Dihydrothiophenes.

Pyridinium 1,4-zwitterionic thiolates are usually used to develop ionic annulation reactions. However, radical reactions were rare. We developed a photoredox catalyzed [3 + 2]-annulation reaction of pyridinium 1,4-zwitterionic thiolates with alkenes, disclosed the new reactivity of pyridinium 1,4-zwitterionic thiolate, and provided a new synthetic method for dihydrothiophene.

Synthesis of benzo[f][1,2]thiazepine 1,1-dioxides based on the visible-light-mediated aza Paternò-Büchi reaction of benzo[d]isothiazole 1,1-dioxides with alkenes.

A new two-step, one-pot synthesis of benzo[f][1,2]thiazepine 1,1-dioxides was developed, which contains a visible-light mediated aza Paternò-Büchi reaction of benzo[d]isothiazole 1,1-dioxides with alkenes and a Lewis acid catalyzed ring-expansion of azetidine. In this work, the mechanism of the aza Paternò-Büchi reaction was also investigated.

Sc(OTf)3 catalyzed intramolecular single-electron transfer of 2-alkyl-1,4-benzoquinones: synthesis of 6-chromanols from donor-acceptor cyclopropanes.

A Sc(OTf)3 catalyzed intramolecular cyclization reaction of 2-alkyl-1,4-benzoquinone derived from D-A cyclopropane was discovered. This reaction involves single-electron transfer, proton-transfer, an aromatization driven spin center shift, and radical coupling processes, and offers an efficient method for the synthesis of 6-chromanols from D-A cyclopropanes.

Visible-Light-Mediated Intermolecular [2 + 2]-Cycloaddition Reaction of 3-Alkylideneindolin-2-one with Alkenes via Triplet Energy Transfer for the Synthesis of 3-Spirocyclobutyl Oxindoles.

[2 + 2]-Cycloaddition is the most straightforward approach to the construction of cyclobutanes. In this paper, the intermolecular [2 + 2]-cycloaddition reaction of 3-alkylideneindolin-2-ones with alkenes was achieved. This reaction can be used in the synthesis of 3-spirocyclobutyl oxindoles, polycyclic oxindoles, and late stage modification of some drug molecules.

Transcriptomic analysis of World Trade Center particulate Matter-induced pulmonary inflammation and drug treatments.

Over 400,000 people are estimated to have been exposed to World Trade Center particulate matter (WTCPM) since the attack on the Twin Towers in Lower Manhattan on September 11, 2001. Epidemiological studies have found that exposure to dust may cause respiratory ailments and cardiovascular diseases. However, limited studies have performed a systematic analysis of transcriptomic data to elucidate the biological responses to WTCPM exposure and the therapeutic options. Here, we developed an in vivo mouse exposure model of WTCPM and administered two drugs (i.e., rosoxacin and dexamethasone) to generate transcriptomic data from lung samples. WTCPM exposure increased the inflammation index, and this index was significantly reduced by both drugs. We analyzed the transcriptomics derived omics data using a hierarchical systems biology model (HiSBiM) with four levels, including system, subsystem, pathway, and gene analyses. Based on the selected differentially expressed genes (DEGs) from each group, WTCPM and the two drugs commonly affected the inflammatory responses, consistent with the inflammation index. Among these DEGs, the expression of 31 genes was affected by WTCPM exposure and consistently reversed by the two drugs, and these genes included Psme2, Cldn18, and Prkcd, which are involved in immune- and endocrine-related subsystems and pathways such as thyroid hormone synthesis, antigen processing and presentation, and leukocyte transendothelial migration. Furthermore, the two drugs reduced the inflammatory effects of WTCPM through distinct pathways, e.g., vascular-associated signaling by rosoxacin, whereas mTOR-dependent inflammatory signaling was found to be regulated by dexamethasone. To the best of our knowledge, this study constitutes the first investigation of transcriptomics data of WTCPM and an exploration of potential therapies. We believe that these findings provide strategies for the development of promising optional interventions and therapies for airborne particle exposure.

Organocatalytic aza-Michael-Michael cascade reactions: a flexible approach to 2,3,4-trisubstituted tetrahydroquinolines.

Cascading like dominos: An efficient and highly enantioselective synthesis of 2,3,4-trisubstituted tetrahydroquinolines through cascade aza-Michael-Michael reactions was developed. Tetrahydroquinolines were obtained in excellent yields, high enantioselectivities, and good diastereoselectivities, and could be easily transformed into ring-fused tetrahydroquinolines (see scheme).

Concise construction of the tetracyclic core of lycorine-type alkaloids and the formal synthesis of α-lycorane based on asymmetric bifunctional thiourea-catalyzed cascade reaction.

A concise and stereoselective construction of the tetracyclic core of lycorine-type alkaloids and the formal synthesis of α-lycorane has been achieved. The feature of the current method is the employment of a bifunctional thiourea-catalyzed cascade reaction as a powerful tool to construct the skeleton of the natural product, which is a challenging yet very rarely explored strategy. As a result, the tetracyclic core is efficiently synthesized in just three simple operations involving two consecutive cascade reactions.