A detailed analysis of 16S rRNA gene sequencing and conventional PCR-based testing for the diagnosis of bacterial pathogens and discovery of novel bacteria.

This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.

Genome Mining of a Fungal Polyketide Synthase-Nonribosomal Peptide Synthetase Hybrid Megasynthetase Pathway to Synthesize a Phytotoxic N-Acyl Amino Acid.

Guided by the retrobiosynthesis hypothesis, we characterized a fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid megasynthetase pathway to generate 2-trans-4-trans-2-methylsorbyl-d-leucine (1), a polyketide amino acid conjugate that inhibits Arabidopsis root growth. The biosynthesis of 1 includes a PKS-NRPS enzyme to assemble an N-acyl amino alcohol intermediate, which is further oxidized to an N-acyl amino acid (NAAA), demonstrating a new biosynthetic logic for synthesizing NAAAs and expanding the chemical space of products encoded by fungal PKS-NRPS clusters.

Nano-Interfacial Supramolecular Adhesion of Metal-Organic Framework-Based Separator Enables High-Safety and Wide-Temperature-Range Lithium Batteries.

Polyolefin separators are the most commonly used separators for lithium batteries; however, they tend to shrink when heated, and their Li+ transference number (t Li +) is low. Metal-organic frameworks (MOFs) are expected to solve the above problems due to their high thermal stability, abundant pore structure, and open metal sites. However, it is difficult to prepare high-porosity MOF-based membranes by conventional membrane preparation methods. In this study, a high-porosity free-standing MOF-based safety separator, denoted the BCM separator, is prepared through a nano-interfacial supramolecular adhesion strategy. The BCM separator has a large specific surface area (450.22 m2 g-1) and porosity (62.0%), a high electrolyte uptake (475 wt%), and can maintain its morphology at 200 °C. The ionic conductivity and t Li + of the BCM separator are 1.97 and 0.72 mS cm-1, respectively. Li//LiFePO4 cells with BCM separators have a capacity retention rate of 95.07% after 1100 cycles at 5  C, a stable high-temperature cycling performance of 300 cycles at 80 °C, and good capacity retention at -40 °C. Li//NCM811 cells with BCM separators exhibit significantly improved rate performance and cycling performance. Pouch cells with BCM separators can work at 120 °C and have good safety at high temperature.

Bacteriophage LHE83 targeting OmpA as a receptor exhibited synergism with spectinomycin against Escherichia coli.

Understanding the characteristics of bacteriophages is crucial for the optimization of phage therapy. In this study, the biological and genomic characteristics of coliphage LHE83 were determined and its synergistic effects with different types of antibiotics against E. coli E82 were investigated. Phage LHE83 displayed a contractile tail morphology and had a titer of 3.02 × 109 pfu/mL at an optimal MOI of 0.01. Meanwhile, phage LHE83 exhibited good physical and chemical factors tolerance. The 1-step growth analysis revealed a latent period of approx. 10 min with a burst size of 87 pfu/infected cell. Phage LHE83 belongs to the genus Dhakavirus. Its genome consists of 170,464 bp with a 40% GC content, and a total of 268 Open Reading Frames (ORF) were predicted with no detected virulent or resistant genes. ORF 213 was predicted to encode the receptor binding protein (RBP) and confirmed by the antibody-blocking assay. Furthermore, a phage-resistant strain E. coli E82R was generated by co-culturing phage LHE83 with E. coli E82. Genomic analysis revealed that OmpA served as the receptor for phage LHE83, which was further confirmed by phage adsorption assay using E. coli BL21ΔOmpA, E. coli BL21ΔOmpA: OmpA and E. coli BL21:OmpA strains. Additionally, a synergistic effect was observed between phage LHE83 and spectinomycin against the drug-resistant strain E. coli E82. These results provide a theoretical basis for understanding the interactions between phages, antibiotics, and host bacteria, which can assist in the clinical application of phages and antibiotics against drug-resistant bacteria.

High-Valence Metal Doping Induced Lattice Expansion for M-FeNi LDH toward Enhanced Urea Oxidation Electrocatalytic Activities.

The precise design of low-cost, efficient, and definite electrocatalysts is the key to sustainable renewable energy. The urea oxidation reaction (UOR) offers a promising alternative to the oxygen evolution reaction for energy-saving hydrogen generation. In this study, by tuning the lattice expansion, a series of M-FeNi layered double hydroxides (M-FeNi LDHs, M: Mo, Mn, V) with excellent UOR performance are synthesized. The hydrolytic transformation of Fe-MIL-88A is assisted by urea, Ni2+ and high-valence metals, to form a hollow M-FeNi LDH. Owing to the large atomic radius of the high-valence metal, lattice expansion is induced, and the electronic structure of the FeNi-LDH is regulated. Doping with high-valence metal is more favorable for the formation of the high-valence active species, NiOOH, for the UOR. Moreover, the hollow spindle structure promoted mass transport. Thus, the optimal Mo-FeNi LDH showed outstanding UOR electrocatalytic activity, with 1.32 V at 10 mA cm-2 . Remarkably, the Pt/C||Mo-FeNi LDH catalyst required a cell voltage of 1.38 V at 10 mA·cm-2 in urea-assisted water electrolysis. This study suggests a new direction for constructing nanostructures and modulating electronic structures, which is expected to ultimately lead to the development of a class of auxiliary electrocatalysts.

α-Pyrone Derivatives from Calcarisporium arbuscula Discovered by Genome Mining.

A highly reducing polyketide synthase (HRPKS) gene cluster from the genome of Calcarisporium arbuscula was identified through genome mining. Heterologous expression of this cluster led to the production of four new α-pyrone compounds, calcapyrones A (1) and B (2), along with their biosynthetic intermediates calcapyrones C (3) and D (4). The structures of these compounds were elucidated on the basis of extensive spectroscopic experiments, and the absolute configurations of the 7,8-diol moieties in 1 and 2 were assigned using Snatzke's method. The biosynthetic pathway of 1 and 2 was established through in vivo and in vitro experiments.

Nano-Brush Structure for Rapid Label-Free Differentiation of Alzheimer's Disease Stages and Direct Capture of Neuron-Derived Exosomes from Human Blood Plasma.

The measurement of the neurofilament light chain (NFL) in human blood plasma/serum is a promising liquid biopsy for Alzheimer's disease (AD) diagnosis, offering advantages over conventional neuroimaging techniques recommended in clinical guidelines. Here, a controllable nano-brush structure comprising upstanding silicon nanowires coated with indium tin oxide was employed as the sensing substrate. This nano-brush structure was modified with an NFL antibody (NFLAb) via silane coupling and then further connected as the extended gate in a field-effect transistor (EGFET). Notable signal differences emerged within a 2 min timeframe, enabling the label-free differentiation in human blood plasmas among four distinct cohorts: healthy controls, subjective cognitive decline, mild cognitive impairment, and dementia due to AD. Our study indicates that achieving a surface roughness exceeding 400 nm on the modified nano-brush structure enables the effective electrical sensing in our EGFETs. These distinct electrical responses measured via the NFLAb-modified nano-brush EGFETs can be attributed to the combined effects of the captured NFLs and NFL-specific neuron-derived exosomes (NDEs) found in dementia patients, as confirmed by electron spectroscopy for chemical analysis, atomic force microscopy, and scanning electron microscopy. Finally, the potential of quantitatively detecting NDEs on the NFLAb-modified nano-brush structure was demonstrated using spiked solutions containing NFL-specific NDEs from IMR-32 neuroblast cells, wherein concentration-dependent changes were observed in the EGFETs output signal. Our findings show that the NFLAb-modified nano-brush EGFET enables rapid, label-free differentiation between healthy individuals and patients at varying stages of AD.

Parathyroid hormone enhances the therapeutic effect of mesenchymal stem cells on temporomandibular joint osteoarthritis in rats.

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the joint, which is characterized by injury to the articular cartilage, as well as changes in the synovial and subchondral bone. TMJOA has a high incidence rate, without any effective treatment. Despite the therapeutic potential of mesenchymal stem cells (MSCs) in various diseases, their efficacy in treating TMJOA is constrained by the local hypoxic conditions and elevated reactive oxygen species (ROS) environment within the damaged temporomandibular joint. In recent years, many studies have reported that parathyroid hormone (PTH) can effectively treat TMJOA, and has an important impact on MSC differentiation. Therefore, we hypothesized that PTH may influence the potential of MSCs, thereby improving their therapeutic effect on TMJOA. METHODS: First, we isolated and cultured rat bone marrow MSCs, and evaluated their proliferation and differentiation after adding PTH. Next, the in vitro environment of hypoxia and high ROS was established by hypoxia condition and H2O2 treatment, and the resistance of PTH-treated MSCs to hypoxia and ROS was subsequently investigated. Finally, PTH-treated MSCs were used to treat TMJOA in a rat model to evaluate the efficacy of PTH. RESULTS: PTH enhanced the proliferation ability of MSCs, promoted the osteogenic differentiation of MSCs, and improved the tolerance of MSCs to hypoxia and ROS. Finally, the therapeutic effect of PTH-treated MSCs on TMJOA was significantly improved. CONCLUSION: PTH enhances the therapeutic effect of MSCs on TMJOA in rats.

Monodispersed Pt Sites Supported on NiFe-LDH from Synchronous Anchoring and Reduction for High Efficiency Overall Water Splitting.

Precise design of low-cost, efficient and definite electrocatalysts is the key to sustainable renewable energy. Herein, this work develops a targeted-anchored and subsequent spontaneous-redox strategy to synthesize nickel-iron layered double hydroxide (LDH) nanosheets anchored with monodispersed platinum (Pt) sites (Pt@LDH). Intermediate metal-organic frameworks (MOF)/LDH heterostructure not only provides numerous confine points to guarantee the stability of Pt sites, but also excites the spontaneous reduction for PtII . Electronic structure, charge transfer ability and reaction kinetics of Pt@LDH can be effectively facilitated by the monodispersed Pt moieties. As a result, the optimized Pt@LDH that with the 5% ultra-low content Pt exhibits the significant increment in electrochemical water splitting performance in alkaline media, which only afford low overpotentials of 58 mV at 10 mA cm-2 for hydrogen evolution reaction (HER) and 239 mV at 10 mA cm-2 for oxygen evolution reaction (OER), respectively. In a real device, Pt@LDH can drive an overall water-splitting at low cell voltage of 1.49 V at 10 mA cm-2 , which can be superior to most reported similar LDH-based catalysts. Moreover, the versatility of the method is extended to other MOF precursors and noble metals for the design of ultrathin LDH supported monodispersed noble metal electrocatalysts promoting research interest in material design.

Actinomycotic osteomyelitis in the maxilla and the zygomatic bone: a case report and literature review / 口腔疾病防治

Objective@# To investigate the clinical features, diagnosis and treatment of osteomyelitis of the jaw caused by an actinomycotic infection and to provide a reference for clinical diagnosis and treatment.@*Methods@#A case of osteomyelitis in the bilateral maxilla and the left zygomatic bone and arch caused by a mixed bacterial infection dominated by Actinomycetes was reviewed and analyzed in combination with the literature. @*Results @#The patient had left upper posterior tooth pain with repeated left facial swelling for 7 months. The patient's left face was swollen before surgery, the left maxillary alveolar bone was necrotic, and the upper palate showed fistula discharge. A maxillofacial magnetic resonance imaging scan excluded tumors and other space-occupying lesions. According to CBCT images, the initial diagnoses were left infraorbital space infection and osteomyelitis of the bilateral maxillary, the left zygomatic bone, the left zygomatic arch and the lateral orbital wall. Necrosis of the left maxilla and the zygomatic bone was excised, the focus was cleared and the focal tooth was extracted under general anesthesia. Histopathological results confirmed osteomyelitis and actinomycotic infection. Anti-inflammatory therapy with penicillin sodium was given before surgery, and piperacillin sodium and tazobactam sodium, dexamethasone sodium phosphate, tranexamic acid and mecobalamine were given after surgery. The patients' 6-month follow-up results showed that the maxillofacial shape was basically symmetrical; no ulceration, pus or abnormal secretion was found in the skin or intraoral mucosa; and the surgical area showed good recovery. A review of the relevant literature showed that Actinomyces is an opportunistic pathogen, and factors such as trauma and dental infection have been implicated in the pathogenesis of osteomyelitis. In addition to surgery, antibiotics are used to treat the disease and multidisciplinary symptomatic treatment combined with supportive treatment is required to achieve a better prognostic effect. @*Conclusion @# Actinomycotic osteomyelitis occurring in the maxilla and the zygomatic bone is an extremely rare disease that can be diagnosed by clinical manifestations, bacteriological examination and biopsy. Appropriate and effective penicillin drugs should be given at the initial stage of treatment, more sensitive antibiotics should be selected according to the results of the drug sensitivity test, and the lesions should be surgically removed when the patient's condition improves. Active symptomatic and supportive treatment should be performed during the treatment period.

Rational regulation of acetylene adsorption and separation for ultra-microporous copper-1,2,4-triazolate frameworks by halogen hydrogen bonds.

It is well known that the introduction of exposed fluorine (F) sites into metal-organic frameworks (MOFs) can effectively promote acetylene (C2H2) adsorption via C-H⋯F hydrogen bonds. However, such super strong hydrogen bonding interactions usually lead to very high acetylene adsorption enthalpy and thus require more energy during the adsorbent regeneration process. As the same group elements, chlorine (Cl), bromine (Br) and iodine (I) also can act as hydrogen bond acceptors but with relatively weak forces. So, it is speculated that the decoration of Cl, Br or I sites on the pore surface of MOF adsorbents may enhance acetylene adsorption but with lower energy consumption. Herein, ultra-microporous MOFs constructed by Cu4X4 (X = Cl, Br, I) motifs and 1,2,4-triazolate linkers, namely, [Cu8X4(TRZ)4]n (TRZ = 3,5-diethyl-1,2,4-triazole or detrz for SNNU-313-X, and 3,5-dipropyl-1,2,4-triazole or dptrz for SNNU-314-X), provide an ideal platform to investigate the effect of C-H⋯X (X = Cl, Br, I) hydrogen bonding on C2H2 adsorption and purification performance. Benefiting from the small pore size and pore environment, the C2H2 uptake and separation properties of this series of MOFs are systematically regulated. Detailed gas adsorption results show that with the same organic linker, the C2H2 uptake and separation (C2H2/C2H4 and C2H2/CO2) performance decrease clearly with the electronegativity of halogen ions (SNNU-313-Cl > SNNU-313-Br > SNNU-313-I). With the same halogen ion, the gas adsorption decreases with the bulk of decorated alkyl groups (SNNU-313-Cl > SNNU-314-Cl). Remarkably, SNNU-313/314 series MOF adsorbents exhibit moderate C2H2 uptake capacity and high separation ability, but the C2H2 adsorption enthalpies are much lower than those of MOF materials with exposed F sites. Dynamic fixed-bed column breakthrough experiments and Grand Canonical Monte Carlo (GCMC) simulations further indicate the critical effects of halogen hydrogen bonds on acetylene adsorption and separation. Overall, this work demonstrated an effective regulation of acetylene adsorption and separation by rational C-H⋯X hydrogen bonding, which may provide a new route for the exploration of energy-efficient acetylene adsorbent materials.

Discovery and biosynthesis of macrophasetins from the plant pathogen fungus Macrophomina phaseolina.

3-Decalinoyltetramic acids (DTAs) are a class of natural products with chemical diversity and potent bioactivities. In fungal species there is a general biosynthetic route to synthesize this type of compounds, which usually features a polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) and a lipocalin-like Diels-Alderase (LLDAse). Using a synthetic biology approach, combining the bioinformatics analysis prediction and heterologous expression, we mined a PKS-NRPS and LLDAse encoding gene cluster from the plant pathogenic fungus Macrophomina phaseolina and characterized the cluster to be responsible for the biosynthesis of novel DTAs, macrophasetins. In addition, we investigated the biosynthesis of these compounds and validated the accuracy of the phylogeny-guided bioinformatics analysis prediction. Our results provided a proof of concept example to this approach, which may facilitate the discovery of novel DTAs from the fungal kingdom.

Flavoprotein StnP2 Catalyzes the ß-Carboline Formation during the Streptonigrin Biosynthesis.

ß-Carboline (ßC) alkaloids constitute a large family of indole alkaloids that exhibit diverse pharmacological properties, such as antitumor, antiviral, antiparasitic, and antimicrobial activities. Here, we report that a flavoprotein StnP2 catalyzes the dehydrogenation at C1-N2 of a tetrahydro-ß-carboline (THßC) generating a 3,4-dihydro-ß-carboline (DHßC), and the DHßC subsequently undergoes a spontaneous dehydrogenation to ßC formation involved in the biosynthesis of the antitumor agent streptonigrin. Biochemical characterization showed that StnP2 catalyzed the highly regio- and stereo-selective dehydrogenation, and StnP2 exhibits promiscuity toward different THßCs. This study provides an alternative kind of enzyme catalyzing the biosynthesis of ßC alkaloids and enhances the importance of flavoproteins.

Genome Mining Discovery of a New Benzazepine Alkaloid Pseudofisnin A from the Marine Fungus Neosartorya pseudofischeri F27-1.

l-Kynurenine (Kyn) is an intermediate in the kynurenine pathway and is also found to be a building block or biosynthetic precursor to bioactive natural products. Recent studies revealed that l-Kyn can be incorporated via nonribosomal peptide synthetase (NRPS) biosynthetic routes to generate 1-benzazepine-containing compounds, while 1-benzazepine is a pharmaceutically important scaffold that is rarely found in natural products. Using a core biosynthetic enzyme-guided genome-mining approach, we discovered a biosynthetic gene cluster from Neosartorya pseudofischeri and identified that it encodes for the biosynthesis of pseudofisnins, novel 1-benzazepine-containing compounds. The biosynthetic pathway of pseudofisnins was elucidated through in vivo and in vitro experiments. The methyltransferase PseC from the pathway was biochemically characterized to be an iterative methyltransferase that catalyzes off-NRPS line di-methylation on an amine group.

Combinatorial Biosynthesis of Terpenoids through Mixing-and-Matching Sesquiterpene Cyclase and Cytochrome P450 Pairs.

Terpenoids are an important class of natural products with diverse structures and bioactivities. Their hydrocarbon scaffolds are mainly derived from the terpenes produced by terpene cyclases (TCs). Otherwise, new hydrocarbon scaffolds can be achieved through oxidative rearrangement catalyzed by oxygenases such as P450s. Herein, we report the functional characterization of α/ß-trans-bergamotene-producing TCs and their multifunctional P450 partners mined from different fungal species. In addition, novel sesquiterpenoids with hydrocarbon scaffolds different from bergamotenes were generated by combinatorial biosynthesis through mixing-and-matching these TC and P450 pairs. Our results provide a successful example of expanding the chemical diversity of terpenoids by combining genome mining and synthetic biology.

Micropore Regulation in Ultrastable [Sc3O]-Organic Frameworks for Acetylene Storage and Purification.

High storage capacity, high separation selectivity, and high structure stability are essential for an idea gas adsorbent. However, it is not easy to achieve all three at the same time, even for the promising metal-organic framework (MOF) adsorbents. We demonstrate herein that robust [Sc3O]-organic frameworks could be regulated by a micropore combination strategy for high-performance acetylene adsorption. Under the same solvent system with formic acid as a modulator, similar tritopic ligands extend [Sc3O(COO)6] trigonal-prismatic clusters to generate SNNU-5-Sc and SNNU-150-Sc adsorbents. Notably, the two Sc-MOFs can keep their architectures over 24 h in water at different pH values (2-12) or at 90 °C. Modulated by the linker symmetry, the final stacking metal-organic polyhedral cages produce open window sizes of about 10 Å for SNNU-5-Sc and 5 Å + 7 Å for SNNU-150-Sc. Due to such micropore combinations, SNNU-5-Sc exhibits a top-level C2H2 uptake of 211.2 cm3 g-1 (1 atm and 273 K) and SNNU-150-Sc shows high C2H2/CH4, C2H2/C2H4, and C2H2/CO2 selectivities of 80.65, 4.03, and 8.19, respectively, under ambient conditions. Dynamic breakthrough curves obtained on a fixed-bed column and grand canonical Monte Carlo (GCMC) simulations further support their prominent acetylene storage and purification performance. High framework stability, storage capacity, and separation selectivity make SNNU-5-Sc and SNNU-150-Sc ideal acetylene adsorbents in practical applications.

The regulation of interleukin-7/CD 127 signaling pathway on CD 8+T cells in patients with myasthenia gravis / 中华神经科杂志

Objective:To investigate the modulatory function of interleukin-7 (IL-7)/CD 127 signaling pathway on CD 8+T cells in patients with myasthenia gravis (MG). Methods:Fifty-seven treatment-naive MG patients who were hospitalized in Department of Neurology, Nanyang Central Hospital between 2017 and 2020 as well as 35 healthy controls were enrolled. Peripheral blood was collected, while plasma and peripheral blood mononuclear cells were isolated. Plasma IL-7 and soluble CD 127 (sCD 127) were measured by enzyme linked immunosorbent assay (ELISA). Membrane-bound CD 127 (mCD 127) percentage in CD 8+T cells was measured by flow cytometry. The differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type and their correlation with Quantitative Myasthenia Gravis (QMG) score were analyzed. Purified CD 8+T cells from MG patients were stimulated with recombinant human IL-7 (5 μg/L). Changes of sCD 127 and mCD 127 level were analyzed. Levels of perforin, granzyme B, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) in the cultured supernatants were measured by ELISA. Immune checkpoint molecules mRNA in CD 8+T cells was semi-quantified by real-time fluorescence quantitative polymerase chain reaction. Results:Plasma IL-7 level was up-regulated in MG patients compared with controls [(293.4±74.7) pg/ml vs (233.8±70.8) pg/ml, t=3.78, P<0.001], while sCD 127 level was down-regulated in MG patients compared with controls [(102.7±13.7) pg/ml vs (131.2±20.9) pg/ml, t=7.91, P<0.001]. Peripheral CD 8+T cells percentage was up-regulated in MG patients compared with controls (35.4%±7.1% vs 30.2%±7.5%, t=3.31, P=0.001), and mCD 127+CD 8+T cell percentage was also elevated (45.5%±7.7% vs 34.7%±11.5%, t=5.44, P<0.001). There were no significant differences of above indices between different gender, onset age, afflicting with thymoma, or different Osserman type. There was no significant correlation between above indices and QMG score. There were no significant differences of sCD 127 in cultured supernatants, mCD 127+CD 8+T cell percentage, or immune checkpoint molecules mRNA expression between CD 8+T cells from MG patients with and without IL-7 stimulation. IL-7 stimulation promoted the secretion of perforin [(208.1±67.2) pg/ml vs (168.8±46.2) pg/ml, t=2.16, P=0.038], granzyme B [(941.8±273.9) pg/ml vs (782.4±137.2) pg/ml, t=2.33, P=0.025], and IFN-γ [(19.1±5.2) pg/ml vs (15.3±4.5) pg/ml, t=2.47, P=0.018] by CD 8+T cells. However, there was no remarkable difference of TNF-α production between CD 8+T cells with and without IL-7 stimulation. Conclusion:Elevated IL-7-mediated signaling pathway enhanced the secretion of cytotoxic molecules and cytokines by CD 8+T cells, leading to increased activity of CD 8+T cells in MG patients.

Reductive inactivation of the hemiaminal pharmacophore for resistance against tetrahydroisoquinoline antibiotics.

Antibiotic resistance is becoming one of the major crises, among which hydrolysis reaction is widely employed by bacteria to destroy the reactive pharmacophore. Correspondingly, antibiotic producer has canonically co-evolved this approach with the biosynthetic capability for self-resistance. Here we discover a self-defense strategy featuring with reductive inactivation of hemiaminal pharmacophore by short-chain dehydrogenases/reductases (SDRs) NapW and homW, which are integrated with the naphthyridinomycin biosynthetic pathway. We determine the crystal structure of NapW·NADPH complex and propose a catalytic mechanism by molecular dynamics simulation analysis. Additionally, a similar detoxification strategy is identified in the biosynthesis of saframycin A, another member of tetrahydroisoquinoline (THIQ) antibiotics. Remarkably, similar SDRs are widely spread in bacteria and able to inactive other THIQ members including the clinical anticancer drug, ET-743. These findings not only fill in the missing intracellular events of temporal-spatial shielding mode for cryptic self-resistance during THIQs biosynthesis, but also exhibit a sophisticated damage-control in secondary metabolism and general immunity toward this family of antibiotics.

TerC Is a Multifunctional and Promiscuous Flavoprotein Monooxygenase That Catalyzes Bimodal Oxidative Transformations.

The flavoprotein monooxygenase (FPMO) TerC is encoded by all known cyclopentene biosynthetic gene clusters. It can catalyze oxidative dearomatization toward a series of 6-HM analogues and further induces different skeletal distortions to form either benzoquinone or pyrone by bimodal reaction cascades, which is only governed by the C7 substitutions. Beyond our study demonstrated bimodal reaction cascades and advanced the biosynthetic knowledge of fungal cyclopentenes, this work also sets the stage for the bioengineering of 6-HM polyketides.

Cobalt phosphide nanorings towards efficient electrocatalytic nitrate reduction to ammonia.

High-quality CoP nanorings (CoP NRs) are easily achieved using a phosphorating treatment of CoOOH nanorings, and reveal high activity towards the hydrogen evolution reaction and the nitrate electrocatalytic reduction reaction due to substantial coordinately unsaturated active sites, a high surface area, and available mass transfer pathways. Consequently, the CoP NRs can achieve a faradaic efficiency of 97.1% towards NO3--to-NH3 conversion and provide an NH3 yield of 30.1 mg h-1 mg-1cat at a -0.5 V potential.