Reverse Separation of Carbon Dioxide and Acetylene in Two Isostructural Copper Pyridine-Carboxylate Frameworks.

Separating acetylene from carbon dioxide is important but highly challenging due to their similar molecular shapes and physical properties. Adsorptive separation of carbon dioxide from acetylene can directly produce pure acetylene but is hardly realized because of relatively polarizable acetylene binds more strongly. Here, we reverse the CO2 and C2H2 separation by adjusting the pore structures in two isoreticular ultramicroporous metal-organic frameworks (MOFs). Under ambient conditions, copper isonicotinate (Cu(ina)2), with relatively large pore channels shows C2H2-selective adsorption with a C2H2/CO2 selectivity of 3.4, whereas its smaller-pore analogue, copper quinoline-5-carboxylate (Cu(Qc)2) shows an inverse CO2/C2H2 selectivity of 5.6. Cu(Qc)2 shows compact pore space that well matches the optimal orientation of CO2 but is not compatible for C2H2. Neutron powder diffraction experiments confirmed that CO2 molecules adopt preferential orientation along the pore channels during adsorption binding, whereas C2H2 molecules bind in an opposite fashion with distorted configurations due to their opposite quadrupole moments. Dynamic breakthrough experiments have validated the separation performance of Cu(Qc)2 for CO2/C2H2 separation.

Effectiveness of an ERAS-based exercise-nutrition management model in enhancing postoperative recovery for thoracoscopic radical resection of lung cancer: A randomized controlled trial.

BACKGROUND: To analyze the effect of an exercise-nutrition management model based on the Enhanced Recovery After Surgery (ERAS) concept on patients undergoing thoracoscopic radical surgery for lung cancer. METHODS: From June 2019 to December 2022, 85 lung cancer patients who underwent thoracoscopic radical lung cancer surgery were randomly divided into 2 groups. The control group, consisting of 42 patients, received routine nursing care during the perioperative period. The study group, comprising 43 patients, implemented an exercise-nutrition management model based on the ERAS concept during the perioperative period. We compared general data, perioperative indicators, compliance, and complications between the 2 groups. Additionally, we assessed the nutritional status using the patient-generated subjective global assessment (PG-SGA), albumin (ALB), prealbumin (PA), and hemoglobin (Hb), as well as lung function, including forced expiratory volume in the first second (FEV1) and maximum voluntary ventilation (MVV), in the patient population following the Piper intervention. RESULTS: In the study group, the times to first defecation and getting out of bed, the duration of thoracic drainage tube indwelling, and the length of hospital stay were shorter than those in the control group. The VAS scores on the 2nd and 3rd postoperative days were lower in the study group than in the control group (P < .05). Medication compliance was higher in the study group compared to the control group (P < .05). Post-intervention, the PG-SGA scores in the study group were lower, while PA, ALB, and Hb levels were higher than those in the control group (P < .05). The MVV, FEV1, and FVC values were higher in the study group than in the control group after the intervention (P < .05). The PFS and mMRC scores were lower in the study group compared to the control group after the intervention, and the QLQ-C30 scores were higher (P < .05). The incidence of complications was 6.98% in the study group, which was not significantly different from 11.90% in the control group (P > .05). CONCLUSION: The exercise-nutrition management model, based on the ERAS concept, exhibits significant perioperative effects in patients undergoing thoracoscopic radical resection of lung cancer, improving their nutritional status and reducing complications.

Synthesis of narrow-spectrum anti-mycobacterial molecules without effect on the diversity of gut microbiota in mice based on the structure of rifampicin.

Rifampicin (RIF) is a broad-spectrum antimicrobial agent that is also a first-line drug for treating tuberculosis (TB). Based on the naphthyl ring structure of RIF this study synthesized 16 narrow-spectrum antimicrobial molecules that were specifically anti-Mycobacterium tuberculosis (Mtb). The most potent candidate was 2-((6-hydroxynaphthalen-2-yl) methylene) hydrazine-1-carbothioamide (compound 3c) with minimum inhibitory concentration (MIC) of 1 µg/mL against Mtb. Synergistic anti-Mtb test indicated that none of the combinations of 3c with the major anti-TB drugs are antagonistic. Consistent with RIF, compound 3c induced large amounts of reactive oxygen radicals (ROS) in the cells of Mtb. The killing kinetics of compound 3c and RIF are very similar. Furthermore, molecular docking showed that compound 3c was able to access the RIF binding pocket of the ß subunit of Mtb RNA polymerase (RNAP). Experiments in mice showed that compound 3c increased the variety of intestinal flora in mice, while RIF significantly decreased the diversity of intestinal flora in mice. In addition, compound 3c is non-toxic to animal cells with a selection index (SI) much more than 10. The evidence from this study suggests that the further development of 3c could contribute to the development of novel drug for TB treatment.

A systematic review of ginsenoside biosynthesis, spatiotemporal distribution, and response to biotic and abiotic factors in American ginseng.

American ginseng (Panax quinquefolius) has gained recognition as a medicinal and functional food homologous product with several pharmaceutical, nutritional, and industrial applications. However, the key regulators involved in ginsenoside biosynthesis, the spatiotemporal distribution characteristics of ginsenosides, and factors influencing ginsenosides are largely unknown, which make it challenging to enhance the quality and chemical extraction processes of the cultivated American ginseng. This review presents an overview of the pharmacological effects, biosynthesis and spatiotemporal distribution of ginsenosides, with emphasis on the impacts of biotic and abiotic factors on ginsenosides in American ginseng. Modern pharmacological studies have demonstrated that American ginseng has neuroprotective, cardioprotective, antitumor, antidiabetic, and anti-obesity effects. Additionally, most genes involved in the upregulation of ginsenoside biosynthesis have been identified, while downstream regulators (OSCs, CYP450, and UGTs) require further investigation. Futhermore, limited knowledge exists regarding the molecular mechanisms of the impact of biotic and abiotic factors on ginsenosides. Notably, the nonmedicinal parts of American ginseng, particularly its flowers, fibrous roots, and leaves, exhibit higher ginsenoside content than its main roots and account for a considerable amount of weight in the whole plant, representing promising resources for ginsenosides. Herein, the prospects of molecular breeding and metabolic engineering based on multi-omics to improve the unstable quality of cultivated American ginseng and the shortage of ginsenosides are proposed. This review highlights the gaps in the current research on American ginseng and proposes solutions to address these limitations, providing a guide for future investigations into American ginseng ginsenosides.

19 Schiff bases as antimycobacterial agents: synthesis, molecular docking and a plausible mechanism of action.

Aim: To discover novel anti-Mycobacterium tuberculosis (Mtb) drugs, 19 compounds were synthesized; their anti-Mtb effects were evaluated and mechanisms of action were preliminarily explored. Materials & methods: The compounds were synthesized and their anti-Mtb activity was elucidated using resazurin microtiter assays. The plausible target of the potential compound was investigated by microimaging techniques, gas chromatography-mass spectrometry analysis and molecular docking. Results: 19 compounds inhibited Mtb growth with minimum inhibitory concentrations ranging from 1 to 32 µg/ml. Compounds 1-17 showed inhibition of Mtb KatG enzyme. Compound 19, the most potent, might be an inhibitor of Pks13 polyketide synthase. Conclusion: This study suggests that 2-((6-fluoropyridin-3-yl)methylene) hydrazine-1-carbothioamide (19) is a potential anti-Mtb lead compound with a novel mechanism of action.

Globally, more than 1.6 million people die of tuberculosis (TB) and about 11 million new cases occur each year. The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) has made it difficult to effectively treat TB. Therefore, 19 drugs were synthesized and assayed in the laboratory to verify whether they could inhibit the growth of Mtb. All compounds exhibit anti-Mtb effects at relatively low concentrations. Among them, compound 19 had a strong anti-Mtb effect, and its bactericidal effect on Mtb even exceeded that of isoniazid. In addition, it was preliminarily determined that compound 19 is a novel inhibitor of a key enzyme in the biosynthesis of Mtb cell walls. These findings demonstrate a potential new treatment option for TB but more research is needed to confirm the safety of these drugs.

Dendrite-Free Dual-Phase Li-Ba Alloy Anode Enabled by Ordered Array of Built-in Mixed Conducting Microchannels.

The development and application of lithium (Li) anode is hindered by volumetric variation, dendritic Li growth, and parasitic reactions. Herein, a dual-phase Li-barium (Ba) alloy with self-assembled microchannels array is synthesized through a one-step thermal fusion method to investigate the inhibition effect of lithiophilic composite porous array on Li dendrites. The Li-rich Li-Ba alloy (BaLi24) as composite Li electrode exhibits an ordered porous structure of BaLi4 intermetallic compound after delithiation, which acts as a built-in 3D current collector during Li plating/striping process. Furthermore, the lithiophilic BaLi4 alloy scaffold is a mixed conductor, featuring with Li+ ions diffusion capability, which can efficiently transport the reduced Li to the interior of the electrode structure. This unique top-down growth mode can effectively prohibit Li dendrites growth and improve the space utilization of 3D electrode structure. The spin-polarized density functional theory (DFT) calculations suggest that the absorption capability of BaLi4 benefits the deposition of Li metal. As a result, the cell performance with the dual-phase Li-Ba alloy anode is significantly improved.

Mechanisms of the Higher Catalytic Activity of Polymer Forms over Complexes for Non-pyrolytic Mono-1,10-phenanthroline-Coordinated Cu2+ (Cu-N2 Type) in an Oxygen Reduction Reaction.

In this paper, we have thoroughly investigated the ORR mechanism of non-pyrolytic mono-1,10-phenanthroline-coordinated Cu2+ (Cu-N2 type) complexes and polymers by molecular dynamics and quantum mechanics calculation. In contrast to the complex-catalyzed ORR, which follows a direct four-electron pathway along intermediates of Cu(I)-Phen, the polymer-catalyzed ORR follows an indirect four-electron pathway by intermediates of Cu(II)-Phen. By analyzing the structure, spin population, electrostatic potential (ESP), and density of states, we confirmed that the higher ORR catalytic activity of the polymer is due to the conjugation effect of coplanar phenanthroline and Cu(II) in the planar reactants or at the base of the square-pyramidal intermediates. The conjugation effect allows the highest ESP to be located near the active center Cu(II), while the lower ESPs are distributed on the phenanthroline, which is very favorable for the reduction current. This will serve as a theoretical foundation for the development of new highly efficient ORR non-pyrolytic CuN2 polymer catalysts.

Synthesis, antimycobacterial evaluation, and molecular docking study of 1,2,4-triazole derivatives.

Fifteen 1,2,4-triazole derivatives were synthesised in this study and their MIC values against Mycobacterium tuberculosis (Mtb) ranged from 2 to 32 µg/mL. Furthermore, their antimycobacterial activity was positively correlated with the KatG enzyme docking score. Among the 15 compounds, compound 4 showed the strongest bactericidal activity with an MIC of 2 µg/mL. The selectivity index of compound 4 is more than 10, indicating that the compound has low toxicity to animal cells and has the potential to become a drug. Molecular docking indicates that compound 4 can bind firmly to the Mtb KatG active site. The experimental results showed that compound 4 inhibited Mtb KatG and caused the accumulation of ROS in Mtb cells. We speculate that compound 4 causes the accumulation of ROS by inhibiting KatG, and ROS produces oxidative destruction, leading to the death of Mtb. This study provides a new idea for the development of novel anti-Mtb drugs.

A chemical signal that promotes insect survival via thermogenesis.

Cold-activated thermogenesis of brown adipose tissues (BAT) is vital for the survival of animals under cold stress and also inhibits the development of tumours. The development of small-molecule tools that target thermogenesis pathways could lead to novel therapies against cold, obesity, and even cancer. Here, we identify a chemical signal that is produced in beetles in the winter to activate fat thermogenesis. This hormone elevates the basal body temperature by increasing cellular mitochondrial density and uncoupling in order to promote beetle survival. We demonstrate that this hormone activates UCP4- mediated uncoupled respiration through adipokinetic hormone receptor (AKHR). This signal serves as a novel fat-burning activator that utilizes a conserved mechanism to promote thermogenesis not only in beetles, nematode and flies, but also in mice, protecting the mice against cold and tumor growth. This hormone represents a new strategy to manipulate fat thermogenesis.

Discovery of 4-(1,2,4-Oxadiazol-5-yl)azepan-2-one Derivatives as a New Class of Cannabinoid Type 2 Receptor Agonists for the Treatment of Inflammatory Pain.

Selectively targeting the cannabinoid receptor CB2 is an attractive therapeutic strategy for the treatment of inflammatory pain without psychiatric side effects mediated by the cannabinoid receptor CB1. Herein, we report the discovery of 4-(1,2,4-oxadiazol-5-yl)azepan-2-one derivatives as a new class of CB2 agonists. Systematic structure-activity relationship investigations resulted in the identification of the most potent compound 25r. This compound displayed high selectivity for CB2 against CB1 (CB2 EC50 = 21.0 nM, Emax = 87%, CB1 EC50 > 30 µM, ratio CB1/CB2 > 1428) with favorable pharmacokinetic properties. Especially, 25r demonstrated significant efficacy in the analgesic model of rodent inflammatory pain. All the results suggest that compound 25r could serve as a lead compound for treating inflammatory pain and deserves further in-depth studies.

Pd/Co Catalyst with High Pd Atom Utilization Efficiency for Nitrobenzene Hydrogenation at Room Temperature: Experimental and DFT Studies.

Enhancing catalytic performance as well as reducing catalyst cost are the eternal pursuit for the catalysis community. Herein, a simple and effective palladium-doped cobalt (Pd/Co) catalyst with high Pd atom utilization efficiency was synthesized via galvanic replacement reaction for the selective hydrogenation of nitrobenzene with H2 at room temperature, delivering >99 % yield of aniline with up to 158 times higher catalytic activity than commercial palladium powder. Detailed characterizations and DFT calculations revealed that Co-Pd interaction leads to a decrease in electron density of Pd and the distance between Pd atoms that results in the enhanced catalytic performance. Further experiments indicated that the Pd/Co catalyst serves as a highly efficient, selective, and recyclable catalyst for a range of nitroarene substrates. This work might provide a green and sustainable methodology to design and synthesize highly active catalysts with high utilization efficiency of the noble metals in fundamental and applied research.

Quantifying Alignment Deviations for the In-Plane Biaxial Test System via a Shape-Optimised Cruciform Specimen.

The loading coaxiality of an in-plane biaxial test system and the structure of a cruciform specimen markedly affect the test results. However, due to the lack of methods for correcting the loading coaxiality and designing the cruciform specimen, the data scatter of the test results of the in-plane biaxial test systems varies from the laboratory to different tests. To quantify the loading coaxiality of the in-plane biaxial test system, we first developed a model to calculate alignment deviations with strain distribution of the shape-optimised cruciform specimen with Automated Machine Learning (AutoML). Our results demonstrated that 99.2% (54,536 of 54,976) of the quantified errors are less than 5%. Quantifying alignment deviations for an in-plane biaxial test system has been solved. The quantified method of alignment deviations could enhance the reliability of test data, improve assembly efficiency, and aid in constructing failure criteria of materials under biaxial stress.

Designing a Cruciform Specimen via Topology and Shape Optimisations under Equal Biaxial Tension Using Elastic Simulations.

Stress uniformity within the gauge zone of a cruciform specimen significantly affects materials' in-plane biaxial mechanical properties in material testing. The stress uniformity depends on the load transmission of the cruciform specimen from the fixtures to the gauge zone. Previous studies failed to alter the nature of the load transmission of the geometric features using parametric optimisations. To improve stress uniformity in the gauge zone, we optimised the cross-arms to design a centre-reduced cruciform specimen with topology and shape optimisations. The simulations show that the optimised specimen obtains significantly less stress variation and range in the gauge zone than the optimised specimen under different observed areas, directions, and load ratios of von Mises, S11, S22, and S12. In the quantified gauge zone, a more uniform stress distribution could be generated by optimizing specimen geometry, whose value should be estimated indirectly each time through simulations. We found that topology and shape optimisations could markedly improve stress uniformity in the gauge zone, and stress concentration at the cross-arms intersection. We first optimised the cruciform specimen structure by combining topology and shape optimisations, which provided a cost-effective way to improve stress uniformity in the gauge zone and reduce stress concentration at the cross-arms intersection, helping obtain reliable data to perform large strains in the in-plane biaxial tensile test.

Glabridin, a bioactive component of licorice, ameliorates diabetic nephropathy by regulating ferroptosis and the VEGF/Akt/ERK pathways.

BACKGROUND: Glabridin (Glab) is a bioactive component of licorice that can ameliorate diabetes, but its role in diabetic nephropathy (DN) has seldom been reported. Herein, we explored the effect and underlying mechanism of Glab on DN. METHODS: The bioactive component-target network of licorice against DN was by a network pharmacology approach. The protective effect of Glab on the kidney was investigated by a high-fat diet with streptozotocin induced-diabetic rat model. High glucose-induced NRK-52E cells were used for in vitro studies. The effects of Glab on ferroptosis and VEGF/Akt/ERK pathways in DN were investigated in vivo and in vitro using qRT-PCR, WB, and IHC experiments. RESULTS: Bioinformatics analysis constructed a network comprising of 10 bioactive components of licorice and 40 targets for DN. 13 matching targets of Glab were mainly involved in the VEGF signaling pathway. Glab treatment ameliorated general states and reduced FBG, HOMA-ß, and HOMA-insulin index of diabetic rats. The renal pathological changes and the impaired renal function (the increased levels of Scr, BUN, UREA, KIM-1, NGAL, and TIMP-1) were also improved by Glab. Moreover, Glab repressed ferroptosis by increasing SOD and GSH activity, and GPX4, SLC7A11, and SLC3A2 expression, and decreasing MDA and iron concentrations, and TFR1 expression, in vivo and in vitro. Mechanically, Glab significantly suppressed VEGF, p-AKT, p-ERK1/2 expression in both diabetic rats and HG-induced NRK-52E cells. CONCLUSIONS: This study revealed protective effects of Glab on the kidney of diabetic rats, which might exert by suppressing ferroptosis and the VEGF/Akt/ERK pathway.

A case of chlamydia psittaci caused severe pneumonia and meningitis diagnosed by metagenome next-generation sequencing and clinical analysis: a case report and literature review.

BACKGROUND: Psittacosis, which is also known as parrot fever, is Chlamydia psittaci (C. psittaci) caused infectious disease. The clinical manifestations vary from asymptomatic infection to severe atypical pneumonia or even fatal meningitis. Early recognition of psittacosis is difficult because of its nonspecific clinical manifestations. Culture and gene probe techniques for C. psittaci are not available for routine clinical use, which makes the diagnosis difficult too. Although psittacosis has increasingly been recognized and reported in recent years, cure of severe pneumonia complicated with meningitis, with etiologic diagnosis aided by the use of metagenomic next-generation sequencing (mNGS), is still uncommon. So, it is necessary to report and review such potentially fatal case. CASE PRESENTATION: This report describes a 54-year-old woman with C. psittaci caused severe atypical pneumonia and meningitis. She presented with symptoms of fever, dry cough and dyspnea, accompanied by prominent headache. Her condition deteriorated rapidly to respiratory failure and lethargy under the treatment of empirical antibacterial agents, and was treated with invasive mechanical ventilation soon. She denied contact with birds, poultry or horses, but unbiased mNGS of both the bronchoalveolar lavage fluid (BALF) and the cerebrospinal fluid (CSF) identified sequence reads corresponding to C. psittaci infection, and there was no sequence read corresponding to other probable pathogens. Combined use of targeted antimicrobial agents of tetracyclines, macrolides and fluoroquinolones was carried out, and the patient's condition improved and she was discharged home 28 days later. Her status returned close to premorbid condition on day 60 of follow-up. CONCLUSIONS: When clinicians come across a patient with atypical pneumonia accompanied by symptoms of meningitis, psittacosis should be taken into consideration. mNGS is a promising detection method in such condition and is recommended.

Disseminated Tuberculosis Associated Hemophagocytic Lymphohistiocytosis in a Pregnant Woman With Evans syndrome: A Case Report and Literature Review.

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in underdeveloped and developing countries. Disseminated TB may induce uncommon and potentially fatal secondary hemophagocytic lymphohistiocytosis (HLH). Timely treatment with anti-tuberculosis therapy (ATT) and downmodulation of the immune response is critical. However, corticosteroid treatment for TB-associated HLH remains controversial. Herein, we report a successful case of disseminated TB-associated HLH in a pregnant woman with Evans syndrome accompanied by a literature review. Case Presentation: A 26-year-old pregnant woman with Evans syndrome was transferred to the Third Affiliated Hospital of Sun Yat-Sen University because of severe pneumonia. She presented with cough, fever, and aggravated dyspnea. Nested polymerase chain reaction for Mycobacterium tuberculosis (M. tuberculosis) complex in sputum was positive. Sputum smear sample for acid-fast bacilli was also positive. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid identified 926 DNA sequence reads and 195 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 DNA sequence reads corresponding to M. tuberculosis. There was no sequence read corresponding to other potential pathogens. She was initially administered standard ATT together with a low dose of methylprednisolone (40 mg/day). However, her condition deteriorated rapidly with high fever, acute respiratory distress syndrome, pancytopenia, and hyperferritinemia. Bone marrow smears showed hemophagocytosis. And caseating tuberculous granulomas were found in the placenta. A diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy with a higher dose of methylprednisolone (160 mg/day) combined with immunoglobulin and plasma exchange was managed. The patient's condition improved, and she was discharged on day 19. Her condition was good at follow-up with the continuation of the ATT. Conclusions: Clinicians encountering patients with suspected TB accompanied by unexplainable inflammation not responding to ATT should consider complications with HLH. Timely administration of ATT combined with corticosteroids may result in a favorable outcome.

Quantitative relationship between the structures and properties of VOCs and SOA formation on the surfaces of acidic aerosol particles.

In this research, all the efforts, based on a series of molecular dynamics simulations on the interfacial process between VOC-contaminated air and acidic sulfate, were made to find how the structures and properties of VOCs are related to the formation of SOAs. The experimental fractional aerosol coefficients (FACs) were used to quantify the SOA formation and 14 VOC species were chosen based on the atmosphere inventory and the FAC magnitude. Finally, the quantitative relationship (QR) was found through the FAC as a function of the two variables the total valid interactions (Tg) and the diffusion coefficient (D), with R square 0.94. Meanwhile, the effect of water was explored and the QR was proved to be rational and reliable. The QR not only explained the SOA formation capacity of VOCs, but could also predict the SOA formation of new molecules.

Automatic analysis system of calcaneus radiograph: Rotation-invariant landmark detection for calcaneal angle measurement, fracture identification and fracture region segmentation.

BACKGROUND AND OBJECTIVE: Calcaneus is the largest tarsal bone to withstand the daily stresses of weight-bearing. The calcaneal fracture is the most common type in the tarsal bone fractures. After a fracture is suspected, plain radiographs should be taken first. Bohler's Angle (BA) and Critical Angle of Gissane (CAG), measured by four anatomic landmarks in lateral foot radiograph, can guide fracture diagnosis and facilitate operative recovery of the fractured calcaneus. This study aims to develop an analysis system that can automatically locate four anatomic landmarks, measure BA and CAG for fracture assessment, identify fractured calcaneus, and segment fractured regions. METHODS: For landmark detection, we proposed a coarse-to-fine Rotation-Invariant Regression-Voting (RIRV) landmark detection method based on regressive Multi-Layer Perceptron (MLP) and Scale Invariant Feature Transform (SIFT) patch descriptor, which solves the problem of fickle rotation of calcaneus. By implementing a novel normalization approach, the RIRV method is explicitly rotation-invariance comparing with traditional regressive methods. For fracture identification and segmentation, a convolution neural network (CNN) based on U-Net with auxiliary classification head (U-Net-CH) is designed. The input ROIs of the CNN are normalized by detected landmarks to uniform view, orientation, and scale. The advantage of this approach is the multi-task learning that combines classification and segmentation. RESULTS: Our system can accurately measure BA and CAG with a mean angle error of 3.8○ and 6.2○ respectively. For fracture identification and fracture region segmentation, our system presents good performance with an F1-score of 96.55%, recall of 94.99%, and segmentation IoU-score of 0.586. CONCLUSION: A powerful calcaneal radiograph analysis system including anatomical angles measurement, fracture identification, and fracture segmentation can be built. The proposed analysis system can aid orthopedists to improve the efficiency and accuracy of calcaneus fracture diagnosis.