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1.
Cell ; 181(2): 293-305.e11, 2020 04 16.
Article in English | MEDLINE | ID: mdl-32142653

ABSTRACT

Pulmonary tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), manifests with a persistent cough as both a primary symptom and mechanism of transmission. The cough reflex can be triggered by nociceptive neurons innervating the lungs, and some bacteria produce neuron-targeting molecules. However, how pulmonary Mtb infection causes cough remains undefined, and whether Mtb produces a neuron-activating, cough-inducing molecule is unknown. Here, we show that an Mtb organic extract activates nociceptive neurons in vitro and identify the Mtb glycolipid sulfolipid-1 (SL-1) as the nociceptive molecule. Mtb organic extracts from mutants lacking SL-1 synthesis cannot activate neurons in vitro or induce cough in a guinea pig model. Finally, Mtb-infected guinea pigs cough in a manner dependent on SL-1 synthesis. Thus, we demonstrate a heretofore unknown molecular mechanism for cough induction by a virulent human pathogen via its production of a complex lipid.


Subject(s)
Cough/physiopathology , Glycolipids/metabolism , Nociceptors/physiology , Virulence Factors/metabolism , Adult , Animals , Cell Line , Cough/etiology , Cough/microbiology , Female , Glycolipids/physiology , Guinea Pigs , Host-Pathogen Interactions , Humans , Lipids/physiology , Lung/microbiology , Macrophages/microbiology , Male , Mice , Mycobacterium tuberculosis/metabolism , Mycobacterium tuberculosis/pathogenicity , Primary Cell Culture , Tuberculosis/microbiology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/physiopathology , Virulence Factors/physiology
2.
Plant Cell ; 36(5): 1913-1936, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38242836

ABSTRACT

Low temperature is a major environmental factor limiting plant growth and crop production. Epigenetic regulation of gene expression is important for plant adaptation to environmental changes, whereas the epigenetic mechanism of cold signaling in rice (Oryza sativa) remains largely elusive. Here, we report that the histone deacetylase (HDAC) OsHDA716 represses rice cold tolerance by interacting with and deacetylating the transcription factor OsbZIP46. The loss-of-function mutants of OsHDA716 exhibit enhanced chilling tolerance, compared with the wild-type plants, while OsHDA716 overexpression plants show chilling hypersensitivity. On the contrary, OsbZIP46 confers chilling tolerance in rice through transcriptionally activating OsDREB1A and COLD1 to regulate cold-induced calcium influx and cytoplasmic calcium elevation. Mechanistic investigation showed that OsHDA716-mediated OsbZIP46 deacetylation in the DNA-binding domain reduces the DNA-binding ability and transcriptional activity as well as decreasing OsbZIP46 protein stability. Genetic evidence indicated that OsbZIP46 deacetylation mediated by OsHDA716 reduces rice chilling tolerance. Collectively, these findings reveal that the functional interplay between the chromatin regulator and transcription factor fine-tunes the cold response in plant and uncover a mechanism by which HDACs repress gene transcription through deacetylating nonhistone proteins and regulating their biochemical functions.


Subject(s)
Cold Temperature , Gene Expression Regulation, Plant , Histone Deacetylases , Oryza , Plant Proteins , Protein Stability , Transcriptional Activation , Oryza/genetics , Oryza/enzymology , Oryza/metabolism , Oryza/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Transcriptional Activation/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Plants, Genetically Modified , Acetylation
3.
Proc Natl Acad Sci U S A ; 121(7): e2318822121, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38319967

ABSTRACT

The maintenance of cholesterol homeostasis is crucial for normal function at both the cellular and organismal levels. Two integral membrane proteins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and Scap, are key targets of a complex feedback regulatory system that operates to ensure cholesterol homeostasis. HMGCR catalyzes the rate-limiting step in the transformation of the 2-carbon precursor acetate to 27-carbon cholesterol. Scap mediates proteolytic activation of sterol regulatory element-binding protein-2 (SREBP-2), a membrane-bound transcription factor that controls expression of genes involved in the synthesis and uptake of cholesterol. Sterol accumulation triggers binding of HMGCR to endoplasmic reticulum (ER)-localized Insig proteins, leading to the enzyme's ubiquitination and proteasome-mediated ER-associated degradation (ERAD). Sterols also induce binding of Insigs to Scap, which leads to sequestration of Scap and its bound SREBP-2 in the ER, thereby preventing proteolytic activation of SREBP-2 in the Golgi. The oxygenated cholesterol derivative 25-hydroxycholesterol (25HC) and the methylated cholesterol synthesis intermediate 24,25-dihydrolanosterol (DHL) differentially modulate HMGCR and Scap. While both sterols promote binding of HMGCR to Insigs for ubiquitination and subsequent ERAD, only 25HC inhibits the Scap-mediated proteolytic activation of SREBP-2. We showed previously that 1,1-bisphosphonate esters mimic DHL, accelerating ERAD of HMGCR while sparing SREBP-2 activation. Building on these results, our current studies reveal specific, Insig-independent photoaffinity labeling of HMGCR by photoactivatable derivatives of the 1,1-bisphosphonate ester SRP-3042 and 25HC. These findings disclose a direct sterol binding mechanism as the trigger that initiates the HMGCR ERAD pathway, providing valuable insights into the intricate mechanisms that govern cholesterol homeostasis.


Subject(s)
Phytosterols , Sterols , Sterols/metabolism , Endoplasmic Reticulum-Associated Degradation , Sterol Regulatory Element Binding Protein 1/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Cholesterol/metabolism , Hydroxymethylglutaryl CoA Reductases/metabolism , Carbon/metabolism , Diphosphonates
4.
Brief Bioinform ; 25(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38385874

ABSTRACT

The three-dimensional (3D) structure of bacterial chromosomes is crucial for understanding chromosome function. With the growing availability of high-throughput chromosome conformation capture (3C/Hi-C) data, the 3D structure reconstruction algorithms have become powerful tools to study bacterial chromosome structure and function. It is highly desired to have a recommendation on the chromosome structure reconstruction tools to facilitate the prokaryotic 3D genomics. In this work, we review existing chromosome 3D structure reconstruction algorithms and classify them based on their underlying computational models into two categories: constraint-based modeling and thermodynamics-based modeling. We briefly compare these algorithms utilizing 3C/Hi-C datasets and fluorescence microscopy data obtained from Escherichia coli and Caulobacter crescentus, as well as simulated datasets. We discuss current challenges in the 3D reconstruction algorithms for bacterial chromosomes, primarily focusing on software usability. Finally, we briefly prospect future research directions for bacterial chromosome structure reconstruction algorithms.


Subject(s)
Bacteria , Chromosome Structures , Prokaryotic Cells , Chromosomes, Bacterial/genetics , Algorithms , Escherichia coli/genetics
5.
Proc Natl Acad Sci U S A ; 120(44): e2309986120, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37878718

ABSTRACT

Extinction of threat memory is a measure of behavioral flexibility. In the absence of additional reinforcement, the extinction of learned behaviors allows animals and humans to adapt to their changing environment. Extinction mechanisms and their therapeutic implications for maladaptive learning have been extensively studied. However, how aging affects extinction learning is much less understood. Using a rat model of olfactory threat extinction, we show that the extinction of olfactory threat memory is impaired in aged Sprague-Darley rats. Following extinction training, long-term depression (LTD) in the piriform cortex (PC) was inducible ex vivo in aged rats and was NMDA receptor (NMDAR)-independent. On the other hand, adult rats acquired successful olfactory threat extinction, and LTD was not inducible following extinction training. Neuronal cFos activation in the posterior PC correlated with learning and extinction performance in rats. NMDAR blockade either systemically or locally in the PC during extinction training prevented successful extinction in adult rats, following which NMDAR-dependent LTD became inducible ex vivo. This suggests that extinction learning employs NMDAR-dependent LTD mechanisms in the PC of adult rats, thus occluding further LTD induction ex vivo. The rescue of olfactory threat extinction in aged rats by D-cycloserine, a partial NMDAR agonist, suggests that the impairment in olfactory threat extinction of aged animals may relate to NMDAR hypofunctioning and a lack of NMDAR-dependent LTD. These findings are consistent with an age-related switch from NMDAR-dependent to NMDAR-independent LTD in the PC. Optimizing NMDAR function in sensory cortices may improve learning and flexible behavior in the aged population.


Subject(s)
Piriform Cortex , Receptors, N-Methyl-D-Aspartate , Humans , Rats , Animals , Aged , Receptors, N-Methyl-D-Aspartate/metabolism , Depression , Piriform Cortex/metabolism , Learning/physiology , Neuronal Plasticity/physiology
6.
Nat Mater ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39300286

ABSTRACT

Platinum (Pt) oxides are vital catalysts in numerous reactions, but research indicates that they decompose at high temperatures, limiting their use in high-temperature applications. In this study, we identify a two-dimensional (2D) crystalline Pt oxide with remarkable thermal stability (1,200 K under nitrogen dioxide) using a suite of in situ methods. This 2D Pt oxide, characterized by a honeycomb lattice of Pt atoms encased between dual oxygen layers forming a six-pointed star structure, exhibits minimized in-plane stress and enhanced vertical bonding due to its unique structure, as revealed by theoretical simulations. These features contribute to its high thermal stability. Multiscale in situ observations trace the formation of this 2D Pt oxide from α-PtO2, providing insights into its formation mechanism from the atomic to the millimetre scale. This 2D Pt oxide with outstanding thermal stability and distinct surface electronic structure subverts the previously held notion that Pt oxides do not exist at high temperatures and can also present unique catalytic capabilities. This work expands our understanding of Pt oxidation species and sheds light on the oxidative and catalytic behaviours of Pt oxide in high-temperature settings.

7.
Infect Immun ; 92(1): e0022923, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38099659

ABSTRACT

Legionella is a common intracellular parasitic bacterium that infects humans via the respiratory tract, causing Legionnaires' disease, with fever and pneumonia as the main symptoms. The emergence of highly virulent and azithromycin-resistant Legionella pneumophila is a major challenge in clinical anti-infective therapy. The CRISPR-Cas acquired immune system provides immune defense against foreign nucleic acids and regulates strain biological functions. However, the distribution of the CRISPR-Cas system in Legionella and how it regulates gene expression in L. pneumophila remain unclear. Herein, we assessed 915 Legionella whole-genome sequences to determine the distribution characteristics of the CRISPR-Cas system and constructed gene deletion mutants to explore the regulation of the system based on growth ability in vitro, antibiotic sensitivity, and intracellular proliferation of L. pneumophila. The CRISPR-Cas system in Legionella was predominantly Type II-B and was mainly concentrated in the genome of L. pneumophila ST1 strains. The Type II-B CRISPR-Cas system showed no effect on the strain's growth ability in vitro but significantly reduced resistance to azithromycin and decreased proliferation ability due to regulation of the lpeAB efflux pump and the Dot/Icm type IV secretion system. Thus, the Type II-B CRISPR-Cas system plays a crucial role in regulating the virulence of L. pneumophila. This expands our understanding of drug resistance and pathogenicity in Legionella, provides a scientific basis for the prevention of Legionnaires' disease outbreaks and the rational use of clinical drugs, and facilitates effective treatment of Legionnaires' disease.


Subject(s)
Legionella pneumophila , Legionella , Legionnaires' Disease , Humans , Legionnaires' Disease/microbiology , Azithromycin/pharmacology , CRISPR-Cas Systems , Legionella pneumophila/genetics
8.
J Cell Biochem ; 125(1): 115-126, 2024 01.
Article in English | MEDLINE | ID: mdl-38079224

ABSTRACT

Asperosaponin VI (ASA VI) is a bioactive triterpenoid saponin extracted from Diptychus roots, of Diptyl, and has previously shown protective functions in rheumatoid arthritis and sepsis. This study investigates the effects and molecular mechanisms of ASA VI on skeletal muscle regeneration in a cardiotoxin (CTX)-induced skeletal muscle injury mouse model. Mice were subjected to CTX-induced injury in the tibialis anterior and C2C12 myotubes were treated with CTX. Muscle fiber histology was analyzed at 7 and 14 days postinjury. Apoptosis and autophagy-related protein expression were evaluated t s by Western blot, and muscle regeneration markers were quantified by quantitative polymerase chain reaction. Docking studies, cell viability assessments, and glycogen synthase kinase-3ß (GSK-3ß) activation analyses were performed to elucidate the mechanism. ASA VI was observed to improve muscle interstitial fibrosis, remodeling, and performance in CTX-treated mice, thereby increased skeletal muscle size, weight, and locomotion. Furthermore, ASA VI modulated the expression of apoptosis and autophagy-related proteins through GSK-3ß inhibition and activated the transcription of regeneration genes. Our results suggest that ASA VI mitigates skeletal muscle injury by modulating apoptosis and autophagy via GSK-3ß signaling and promotes regeneration, thus presenting a probable therapeutic agent for skeletal muscle injury.


Subject(s)
Muscle, Skeletal , Saponins , Mice , Animals , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Muscle, Skeletal/metabolism , Apoptosis , Saponins/pharmacology
9.
J Am Chem Soc ; 146(35): 24257-24264, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39172734

ABSTRACT

The C-H hydroxylation of the pyridine C3 position is a highly desirable transformation but remains a great challenge due to the inherent electronic properties of this heterocycle core which bring difficulties in chemical reactivity and regioselectivity. Herein we present an efficient method for formal C3 selective hydroxylation of pyridines via photochemical valence isomerization of pyridine N-oxides. This metal-free transformation features operational simplicity and compatibility with a diverse array of functional groups, and the resulting hydroxylated products are amenable to further elaboration to synthetically useful building blocks. The synthetic utility of this strategy is further demonstrated in the effective late-stage functionalization of pyridine-containing medicinally relevant molecules and versatile derivatizations of 3-pyridinols.

10.
J Am Chem Soc ; 146(31): 21769-21777, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39072677

ABSTRACT

Aryl amines are one of the most common moieties in biologically active molecules, and approximately 37% of drug candidates contain aromatic amines. Recent advancements in medicinal chemistry, coined "escaping from flatland", have led to a greater focus on accessing highly functionalized C (sp3)-rich amines to improve the physicochemical and pharmacokinetic properties of compounds. This article presents a modular and operationally straightforward three-component alkyl Petasis boron-Mannich (APBM) reaction that utilizes ubiquitous starting materials, including amines, aldehydes, and alkyl boronates. By adaptation of this transformation to high-throughput experimentation (HTE), it offers rapid access to an array of diverse C(sp3)-rich complex amines, amenable for rapid identification of drug candidates.

11.
Plant Biotechnol J ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39024414

ABSTRACT

Polyamines (PAs) are pleiotropic bioorganic molecules. Cellular PA contents are determined by a balance between PA synthesis and degradation. PAs have been extensively demonstrated to play vital roles in the modulation of plant developmental processes and adaptation to various environmental stresses. In this review, the latest advances on the diverse roles of PAs in a range of developmental processes, such as morphogenesis, organogenesis, growth and development, and fruit ripening, are summarized and discussed. Besides, the crosstalk between PAs and phytohormones or other signalling molecules, including H2O2 and NO, involved in these processes is dwelled on. In addition, the attempts made to improve the yield and quality of grain and vegetable crops through altering the PA catabolism are enumerated. Finally, several other vital questions that remain unanswered are proposed and discussed. These include the mechanisms underlying the cooperative regulation of developmental processes by PAs and their interplaying partners like phytohormones, H2O2 and NO; PA transport for maintaining homeostasis; and utilization of PA anabolism/catabolism for generating high-yield and good-quality crops. This review aims to gain new insights into the pleiotropic role of PAs in the modulation of plant growth and development, which provides an alternative approach for manipulating and engineering valuable crop varieties that can be used in the future.

12.
Plant Biotechnol J ; 22(4): 833-847, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37965680

ABSTRACT

Major polyamines include putrescine, spermidine, spermine and thermospermine, which play vital roles in growth and adaptation against environmental changes in plants. Thermospermine (T-Spm) is synthetised by ACL5. The function of ACL5 in rice is still unknown. In this study, we used a reverse genetic strategy to investigate the biological function of OsACL5. We generated several knockout mutants by pYLCRISPR/Cas9 system and overexpressing (OE) lines of OsACL5. Interestingly, the OE plants exhibited environmentally-dependent leaf rolling, smaller grains, lighter 1000-grain weight and reduction in yield per plot. The area of metaxylem vessels of roots and leaves of OE plants were significantly smaller than those of WT, which possibly caused reduction in leaf water potential, resulting in leaf rolling with rise in the environmental temperature and light intensity and decrease in humidity. Additionally, the T-Spm contents were markedly increased by over ninefold whereas the ethylene evolution was reduced in OE plants, suggesting that T-Spm signalling pathway interacts with ethylene pathway to regulate multiple agronomic characters. Moreover, the osacl5 exhibited an increase in grain length, 1000-grain weight, and yield per plot. OsACL5 may affect grain size via mediating the expression of OsDEP1, OsGS3 and OsGW2. Furthermore, haplotypes analysis indicated that OsACL5 plays a conserved function on regulating T-Spm levels during the domestication of rice. Our data demonstrated that identification of OsACL5 provides a theoretical basis for understanding the physiological mechanism of T-Spm which may play roles in triggering environmentally dependent leaf rolling; OsACL5 will be an important gene resource for molecular breeding for higher yield.


Subject(s)
Oryza , Spermine/analogs & derivatives , Oryza/metabolism , Spermine/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , Ethylenes/metabolism , Edible Grain/genetics , Edible Grain/metabolism , Gene Expression Regulation, Plant/genetics
13.
BMC Microbiol ; 24(1): 7, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38172646

ABSTRACT

BACKGROUND: Hosts, parasites, and microbiota interact with each other, forming a complex ecosystem. Alterations to the microbial structure have been observed in various enteric parasitic infections (e.g. parasitic protists and helminths). Interestingly, some parasites are associated with healthy gut microbiota linked to the intestinal eubiosis state. So the changes in bacteria and metabolites induced by parasite infection may offer benefits to the host, including protection from other parasitesand promotion of intestinal health. The only ciliate known to inhabit the hindgut of grass carp, Balantidium ctenopharyngodoni, does not cause obvious damage to the intestinal mucosa. To date, its impact on intestinal microbiota composition remains unknown. In this study, we investigated the microbial composition in the hindgut of grass carp infected with B. ctenopharyngodoni, as well as the changes of metabolites in intestinal contents resulting from infection. RESULTS: Colonization by B. ctenopharyngodoni was associated with an increase in bacterial diversity, a higher relative abundance of Clostridium, and a lower abundance of Enterobacteriaceae. The family Aeromonadaceae and the genus Citrobacter had significantly lower relative abundance in infected fish. Additionally, grass carp infected with B. ctenopharyngodoni exhibited a significant increase in creatine content in the hindgut. This suggested that the presence of B. ctenopharyngodoni may improve intestinal health through changes in microbiota and metabolites. CONCLUSIONS: We found that grass carp infected with B. ctenopharyngodoni exhibit a healthy microbiota with an increased bacterial diversity. The results suggested that B. ctenopharyngodoni reshaped the composition of hindgut microbiota similarly to other protists with low pathogenicity. The shifts in the microbiota and metabolites during the colonization and proliferation of B. ctenopharyngodoni indicated that it may provide positive effects in the hindgut of grass carp.


Subject(s)
Balantidium , Carps , Gastrointestinal Microbiome , Animals , Bacteria/genetics , Virulence
14.
Opt Express ; 32(5): 7044-7052, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38439395

ABSTRACT

The carrier transport performances play key roles in the photoelectric conversion efficiency for photovoltaic effect. Hence, the low carrier mobility and high photogenerated carrier recombination in ferroelectric materials depress the separation of carriers. This work designs a ferroelectric polarization-interface-free PN junction composed with P-type semiconductor BiFeO3 (BFO) derived from the variable valence of Fe and N-type semiconductor BiFe0.98Ti0.02O3 (BFTO) through Ti donor doping. The integration of the ferroelectricity decides the PN junction without polarization coupling like the traditional heterojunctions but only existing carrier distribution differential at the interface. The carrier recombination in PN junction is significantly reduced due to the driving force of the built-in electric field and the existence of depletion layer, thereby enhancing the switching current 3 times higher than that of the single ferroelectric films. Meanwhile, the carrier separation at the interface is significantly engineered by the polarization, with open circuit voltage and short circuit current of photovoltaic effect increased obviously. This work provides an alternative strategy to regulate bulk ferroelectric photovoltaic effects by carrier transport engineering in the polarization-interface-free ferroelectric PN junction.

15.
Langmuir ; 40(10): 5026-5039, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38420691

ABSTRACT

Metal-organic frameworks (MOFs) are a type of multifunctional material with organic-inorganic doped metal complexes that have a lot of unsaturated metal sites and a consistent network structure. MOFs work has great performance for enhancing the mass transfer, signal, and sensitivity as well as analyte enrichment. This study highlights the recent advancements of MOFs-based sensors for pollutant detection in a water environment and summarizes the effect of various synthetic materials on the performance of MOFs-based sensors. The related challenges and optimization techniques have been discussed. Then the research results of various MOFs sensors in the detection of wastewater pollutants are analyzed. Finally, the challenges facing MOFs-based water sensor development and the outlook for future research are discussed.

16.
Environ Sci Technol ; 58(27): 12272-12280, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38934332

ABSTRACT

Environmentally benign cerium-based catalysts are promising alternatives to toxic vanadium-based catalysts for controlling NOx emissions via selective catalytic reduction (SCR), but conventional cerium-based catalysts unavoidably suffer from SO2 poisoning in low-temperature SCR. We develop a strongly sulfur-resistant Ce1+1/TiO2 catalyst by spatially confining Ce atom pairs to different anchoring sites of anatase TiO2(001) surfaces. Experimental results combined with theoretical calculations demonstrate that strong electronic interactions between the paired Ce atoms upshift the lowest unoccupied states to an energy level higher than the highest occupied molecular orbital (HOMO) of SO2 so as to be catalytically inert in SO2 oxidation but slightly lower than HOMO of NH3 so that Ce1+1/TiO2 has desired ability toward NH3 activation required for SCR. Hence, Ce1+1/TiO2 shows higher SCR activity and excellent stability in the presence of SO2 at low temperatures with respect to supported single Ce atoms. This work provides a general strategy to develop sulfur-resistant catalysts by tuning the electronic states of active sites for low-temperature SCR, which has implications for practical applications with energy-saving requirements.


Subject(s)
Cerium , Sulfur , Cerium/chemistry , Sulfur/chemistry , Catalysis , Oxidation-Reduction , Temperature
17.
Nature ; 560(7718): 350-354, 2018 08.
Article in English | MEDLINE | ID: mdl-30061620

ABSTRACT

Prized for their ability to rapidly generate chemical complexity by building new ring systems and stereocentres1, cycloaddition reactions have featured in numerous total syntheses2 and are a key component in the education of chemistry students3. Similarly, carbon-carbon (C-C) cross-coupling methods are integral to synthesis because of their programmability, modularity and reliability4. Within the area of drug discovery, an overreliance on cross-coupling has led to a disproportionate representation of flat architectures that are rich in carbon atoms with orbitals hybridized in an sp2 manner5. Despite the ability of cycloadditions to introduce multiple carbon sp3 centres in a single step, they are less used6. This is probably because of their lack of modularity, stemming from the idiosyncratic steric and electronic rules for each specific type of cycloaddition. Here we demonstrate a strategy for combining the optimal features of these two chemical transformations into one simple sequence, to enable the modular, enantioselective, scalable and programmable preparation of useful building blocks, natural products and lead scaffolds for drug discovery.


Subject(s)
Carbon/chemistry , Chemistry Techniques, Synthetic , Cycloaddition Reaction , Biological Products/chemical synthesis , Biological Products/chemistry , Drug Discovery
18.
Cereb Cortex ; 33(4): 1489-1503, 2023 02 07.
Article in English | MEDLINE | ID: mdl-35437602

ABSTRACT

Aging is associated with cognitive decline and memory loss in humans. In rats, aging-associated neuronal excitability changes and impairments in learning have been extensively studied in the hippocampus. Here, we investigated the roles of L-type calcium channels (LTCCs) in the rat piriform cortex (PC), in comparison with those of the hippocampus. We employed spatial and olfactory tasks that involve the hippocampus and PC. LTCC blocker nimodipine administration impaired spontaneous location recognition in adult rats (6-9 months). However, the same blocker rescued the spatial learning deficiency in aged rats (19-23 months). In an odor-associative learning task, infusions of nimodipine into either the PC or dorsal CA1 impaired the ability of adult rats to learn a positive odor association. Again, in contrast, nimodipine rescued odor associative learning in aged rats. Aged CA1 neurons had higher somatic expression of LTCC Cav1.2 subunits, exhibited larger afterhyperpolarization (AHP) and lower excitability compared with adult neurons. In contrast, PC neurons from aged rats showed higher excitability and no difference in AHP. Cav1.2 expression was similar in adult and aged PC somata, but relatively higher in PSD95- puncta in aged dendrites. Our data suggest unique features of aging-associated changes in LTCCs in the PC and hippocampus.


Subject(s)
Nimodipine , Piriform Cortex , Humans , Rats , Animals , Aged , Nimodipine/metabolism , Piriform Cortex/metabolism , Pyramidal Cells/physiology , Hippocampus/physiology , Calcium Channels, L-Type/metabolism , Aging/physiology
19.
Article in English | MEDLINE | ID: mdl-38940810

ABSTRACT

Background: Plasma exchange is the most commonly applied method for treating severe hepatitis. As a kind of invasive treatment, plasma exchange may have various complications during treatment. Therefore, effective nursing should be implemented during plasma exchange treatment to prevent the incidence of complications. Objective: To compare the effects of traditional nursing methods versus evidence-based nursing practices on the quality of life and anxiety of patients with liver injury. Design: This was a retrospective study. Patient data were obtained from patient records. Setting: This study was carried out in the Department of Gastroenterology, Second Hospital of Hebei Medical University. Participants: One hundred and twenty severe hepatitis patients with 89 cases of early hepatic failure and 31 cases of middle hepatic failure admitted to our department from January 2020 to December 2022 were chosen, followed by randomly separating into a control group and an observation group. Interventions: The control group adopted nursing, while the observation group received evidence-based nursing including psychological nursing, nursing during treatment and post-treatment nursing. Primary Outcome Measures: (1) liver function (2) emotional state assessed by Self-rating Anxiety Scale (SAS) along with Self-rating Depression Scale (SDS) (3) coagulation function, (4) quality of life assessed by Short-Form 36 (SF-36) scale (5) nursing satisfaction, and (6) incidence of complications. Results: In contrast to the control group, the occurrence of complications in the observation group was significantly lower (P < .05). At 1-month review, the quality of life score in the observation group was higher in contrast to the control group (P < .05). In contrast to the control group, the nursing satisfaction of patients in the observation group was better (P < .05), alanine aminotransferase and total bilirubin levels in the observation group were lower, while albumin levels were higher (P < .05), the anxiety and depression scores of the observation group were lessened (P < .05), and the required time of coagulation function indexes in the observation group was shorter (P < .05). Conclusion: The application of evidence-based nursing to artificial liver therapy in patients with liver failure can effectively promote the liver function and coagulation index of patients, help to relieve negative emotions, and promote the quality of life of patients. This study may provide clinical reference for the nursing of artificial liver therapy in patients with liver failure.

20.
Nano Lett ; 23(7): 2958-2963, 2023 Apr 12.
Article in English | MEDLINE | ID: mdl-37011415

ABSTRACT

Here we use low-temperature and variable-temperature scanning tunneling microscopy to study the pnictide superconductor, Ba1-xSrxNi2As2. In the low-temperature phase (triclinic phase) of BaNi2As2, we observe the unidirectional charge density wave (CDW) with Q = 1/3 on both the Ba and NiAs surfaces. On the NiAs surface of the triclinic BaNi2As2, there are structural-modulation-induced chain-like superstructures with distinct periodicities. In the high-temperature phase (tetragonal phase) of BaNi2As2, the NiAs surface appears as the periodic 1 × 2 superstructure. Interestingly, in the triclinic phase of Ba0.5Sr0.5Ni2As2, the unidirectional CDW is suppressed on both the Ba/Sr and NiAs surfaces, and the Sr substitution stabilizes the periodic 1 × 2 superstructure on the NiAs surface, which enhance the superconductivity in Ba0.5Sr0.5Ni2As2. Our results provide important microscopic insights for the interplay among the unidirectional CDW, structural modulation, and superconductivity in this class of pnictide superconductors.

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