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1.
Cancer Cell Int ; 24(1): 198, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38835077

Translationally controlled tumor protein (TCTP), also known as histamine-releasing factor (HRF) or fortilin, is a highly conserved protein found in various species. To date, multiple studies have demonstrated the crucial role of TCTP in a wide range of cellular pathophysiological processes, including cell proliferation and survival, cell cycle regulation, cell death, as well as cell migration and movement, all of which are major pathogenic mechanisms of tumorigenesis and development. This review aims to provide an in-depth analysis of the functional role of TCTP in tumor initiation and progression, with a particular focus on cell proliferation, cell death, and cell migration. It will highlight the expression and pathological implications of TCTP in various tumor types, summarizing the current prevailing therapeutic strategies that target TCTP.

2.
J Microbiol Biotechnol ; 34(6): 1-10, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38755002

This study aimed to develop and assess a chitosan biomedical antibacterial gel ZincOxideGrapheneOxide/Chitosan/ß-Glycerophosphate (ZnO-GO/CS/ß-GP) loaded with nano-zinc oxide (ZnO) and graphene oxide (GO), known for its potent antibacterial properties, biocompatibility, and sustained drug release. ZnO nanoparticles (ZnO-NPs) were modified and integrated with GO sheets to create 1% and 3% ZnO-GO/CS/ß-GP thermo-sensitive hydrogels based on ZnO-GO to Chitosan (CS) mass ratio. Gelation time, pH, structural changes, and microscopic morphology were evaluated. The hydrogel's antibacterial efficacy against Porphyromonas gingivalis, biofilm biomass, and metabolic activity was examined alongside its impact (MC3T3-e1). The findings of this study revealed that both hydrogel formulations exhibited temperature sensitivity, maintaining a neutral pH. The ZnO-GO/CS/ß-GP formulation effectively inhibited P. gingivalis bacterial activity and biofilm formation, with a 3% ZnO-GO/CS/ß-GP antibacterial rate approaching 100%. MC3T3-e1 cells displayed good biocompatibility when cultured in the hydrogel extract.The ZnO-GO/CS/ß-GP thermo-sensitive hydrogel demonstrates favorable physical and chemical properties, effectively preventing P. gingivalis biofilm formation. It exhibits promising biocompatibility, suggesting its potential as an adjuvant therapy for managing and preventing peri-implantitis, subject to further clinical investigations.

3.
Stress ; 27(1): 2357338, 2024 Jan.
Article En | MEDLINE | ID: mdl-38807493

Virtual reality based physical stress (VRPS) paradigms could eliminate the influence of social factors on participants, and it may be a desirable tool to explore the impact of personality traits on stress levels. In this study, we attempt to explore the effects of VRPS on stress response among individuals with different personality traits. Forty male participants with an average age of 22.79 ± 0.41 years were divided into two groups based on Harm Avoidance (HA) scores of Tridimensional Personality Questionnaire (TPQ), referred to as the Low-HA group and the High-HA group. The stress levels of the participants were assessed using salivary α-amylase (sAA) activity and heart rate variability (HRV) indices pre- and post-stress. The influence of personality traits on stress response among different groups was analyzed. VRPS significantly affected the sAA activity and HRV indicators of both groups. During and after stress, there were significant differences in sAA activity and HRV indicators between the two groups. The sAA levels and HRV indices of the Low-HA group were lower than those of the High-HA group. Furthermore, sAA levels and HRV indices were correlated with the scores of TPQ. VRPS scenarios elicit different stress responses on individuals with different harm avoidance personality traits. Stress evaluation based on VR scenarios presents potential in personality trait assessments, particularly for distinguishing between individuals with low and high HA tendencies.


Heart Rate , Personality , Salivary alpha-Amylases , Stress, Psychological , Virtual Reality , Humans , Male , Personality/physiology , Heart Rate/physiology , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Young Adult , Salivary alpha-Amylases/metabolism , Salivary alpha-Amylases/analysis , Saliva/chemistry , Adult , Stress, Physiological/physiology , Surveys and Questionnaires , Harm Reduction
4.
Bioorg Med Chem Lett ; 107: 129777, 2024 Jul 15.
Article En | MEDLINE | ID: mdl-38692522

Inflammation is the body's defense response to stimuli. When the homeostatic balance is disturbed, disease may result. Flavonoids have clear anti-inflammatory effects and the isopentenyl group significantly enhances the pharmacological activity of flavonoids. Therefore, isopentenyl flavonoids have the potential to serve as lead compounds for the development of anti-inflammatory drugs. Throughout this research, eight natural compounds were synthesized, including 5,7-dihydroxy-4'-methoxy-8-prenylflavonoid (1), 4'-O-Methylatalantoflavone (2), Kushenol W (3) and Racemoflavone (5), which were totally synthesized for the first time. Additionally, three flavonols: Licoflavonol (6), 3,5,7,3',4'-pentahydroxy-6-prenylflavonol (7) and Macarangin (8), can be one-step synthesized by direct C-isopentenylation. In the process, an economical and efficient C-isopentenylation method was also simultaneously explored that could facilitate the efficient synthesis of natural products. These compounds were evaluated for their potential anti-inflammatory activities via the NLRP3 signaling pathway. Notably, Macarangin (8) manifested the most potent inhibitory effect. The SAR (Structure-Activity Relationships) also showed the introduction of the isopentenyl group was determined to enhance these effects, whereas simple flavonoid frameworks or cyclization of isopentenyl groups all diminished anti-inflammatory activity.


Flavonoids , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Flavonoids/pharmacology , Flavonoids/chemistry , Flavonoids/chemical synthesis , Inflammasomes/metabolism , Inflammasomes/drug effects , Structure-Activity Relationship , Molecular Structure , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Animals , Biological Products/pharmacology , Biological Products/chemistry , Biological Products/chemical synthesis , Mice , Dose-Response Relationship, Drug , Humans
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124449, 2024 Sep 05.
Article En | MEDLINE | ID: mdl-38754206

To explore the intrinsic mechanism of pure organic room temperature and clustering-induced phosphorescence and investigate mechanochromism and structural-function relationships, here, 4-(2-(9H-carbazol-9-yl)phenyl)-2-amino-6-methoxypyridine-3,5-dicarbonitrile (Lo-CzAD), 4-(3-(9H-carbazol-9-yl)phenyl)-2-amino-6-methoxypyridine-3,5-dicarbonitrile (Lm-CzAD), and 4-(4-(9H-carbazol-9-yl)phenyl)-2-amino-6-methoxypyridine-3,5-dicarbonitrile (Lp-CzAD) were designed and synthesized by choosing self-made carbazole and 3, 5-dicyanopyridine (DCP) unit as electron acceptor and electron donor in sequence. Compared with crystals Lm-CzAD and Lp-CzAD, crystal Lo-CzAD shows better room temperature phosphorescence (RTP) performance, with RTP lifetimes of 187.16 ms, as well as afterglows 1s, which are attributed to twisted carbazole unit and donor-acceptor (D-A) molecular conformation, big crystal density and spin orbit coupling constant ξ (S1 â†’ T1 and S1 â†’ T2), as well as intermolecular H type stacking and small ξ (S0 â†’ T1). By choosing urea and PPh3 as host materials and tuning doping ratio, four doping systems were successfully constructed, significantly improving RTP performance of Lo-CzAD and Lp-CzAD, as well as showing different fluorescence and RTP. The lifetimes and afterglows of pure organic Urea/Lo-CzAD and Urea/Lp-CzAD systems are up to 478.42 ms, 5 s, 261.66 ms and 4.5 s in turn. Moreover, Lo-CzAD and Lp-CzAD show time-dependent RTP in doping systems due to monomer and aggregate dispersion, as well as clustering-induced phosphorescence. Based on the different luminescent properties, multiple information encryptions were successfully constructed.

6.
Int J Biol Macromol ; 270(Pt 2): 132458, 2024 Jun.
Article En | MEDLINE | ID: mdl-38772458

The salient gelling feature of alginate via forming the egg-box structure with calcium ions has received extensive interests for different applications. Owing to the interfacial incompatibility of rigid inorganic solids with soft polymers, the requirement of overall stereocomplexation with calcium released from uniformly distributed solids in alginate remains a challenge. In this study, a novel alginate-incorporated calcium source was proposed to tackle the intractable dispersion for the preparation of injectable alginate hydrogels. Calcium phosphate synthesis in alginate solution yielded CaP-alginate hybrids as a calcium source. The physicochemical characterization confirmed the CaP-alginate hybrid was a nano-scale alginate-hydroxyapatite complex. The colloidally stable CaP-alginate hybrids were uniformly dispersed in alginate solutions even under centrifugation. The calcium-induced gelling of the CaP-alginate hybrids-loaded alginate solutions formed soft yet tough hydrogels including transparent sheets and knittable threads, confirming the homogeneous gelation of the hydrogel. The gelation time, injectability and mechanical properties of the hydrogels could be adjusted by changing preparation parameters. The prepared hydrogels showed uniform porous structure, excellent swelling, wetting properties and cytocompatibility, showing a great potential for applications in different fields. The present strategy with organic/inorganic hybridization could be exemplarily followed in the future development of functional hydrogels especially associated with the interface integration.


Alginates , Durapatite , Hydrogels , Hydrogels/chemistry , Alginates/chemistry , Durapatite/chemistry , Biocompatible Materials/chemistry , Injections , Animals , Mechanical Phenomena , Mice
7.
Talanta ; 276: 126259, 2024 May 14.
Article En | MEDLINE | ID: mdl-38761664

Hypoxanthine is a promising index for evaluating the freshness of various aquatic products. Combined the hydrogels containing upconversion nanoparticles (UCNPs), Co3O4 NPs, and N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt/4-amino-antipyrine (TOPS/4-AAP) with a smartphone, a portable sensor was developed for the convenient, sensitive detection of hypoxanthine. With the H2O2 from xanthine oxidase (XOD)-catalyzed reactions of hypoxanthine, the fluorescence of UCNPs was effectively quenched by the purple product produced from the oxidization of TOPS/4-AAP catalyzed by Co3O4 NPs exhibiting peroxidase activity, among which the color change could be transformed into digital signals for quantification of hypoxanthine. The Green value in the RGB analysis of the fluorescence image was negatively proportional to hypoxanthine concentration in the range of 2.5-20 mg/L with a detection limit of 0.69 mg/L and a quantitation limit of 2.30 mg/L. Finally, this sensor was applied for hypoxanthine detection in real aquatic products, showing potential application for freshness evaluation of aquatic products.

8.
Cell Res ; 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38605178

The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca2+ signals predict hourly time, via a group decision-making mechanism coupled with a spatially modular time feature representation in the SCN. Specifically, we developed a high-speed dual-view two-photon microscope for volumetric Ca2+ imaging of up to 9000 GABAergic neurons in adult SCN slices, and leveraged machine learning methods to capture emergent properties from multiscale Ca2+ signals as a whole. We achieved hourly time prediction by polling random cohorts of SCN neurons, reaching 99.0% accuracy at a cohort size of 900. Further, we revealed that functional neuron subtypes identified by contrastive learning tend to aggregate separately in the SCN space, giving rise to bilaterally symmetrical ripple-like modular patterns. Individual modules represent distinctive time features, such that a module-specifically learned time predictor can also accurately decode hourly time from random polling of the same module. These findings open a new paradigm in deciphering the design principle of the biological clock at the system level.

9.
Nano Lett ; 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38607185

The enhanced Coulomb interaction in two-dimensional semiconductors leads to tightly bound electron-hole pairs known as excitons. The large binding energy of excitons enables the formation of Rydberg excitons with high principal quantum numbers (n), analogous to Rydberg atoms. Rydberg excitons possess strong interactions among themselves as well as sensitive responses to external stimuli. Here, we probe Rydberg exciton resonances through photocurrent spectroscopy in a monolayer WSe2 p-n junction formed by a split-gate geometry. We show that an external in-plane electric field not only induces a large Stark shift of Rydberg excitons up to quantum principal number 3 but also mixes different orbitals and brightens otherwise dark states such as 3p and 3d. Our study provides an exciting platform for engineering Rydberg excitons for new quantum states and quantum sensing.

10.
Se Pu ; 42(4): 360-367, 2024 Apr.
Article Zh | MEDLINE | ID: mdl-38566425

The macroporous anion exchange chromatographic medium (FastSep-PAA) was prepared through grafting polyallylamine (PAA) onto polyacrylate macroporous microspheres (FastSep-epoxy). The effects of the synthesis conditions, including the PAA concentration, reaction time, and reaction solution pH, on the ion exchange (IC) of the medium were investigated in detail. When the PAA concentration, reaction time, and reaction solution pH were increased, the IC of the medium increased, and optimal synthesis conditions were then selected in combination with changes of protein binding capacity. A scanning electron microscope was used to examine the surface morphology of the medium. The medium possessed high pore connectivity. Furthermore, the pore structure of the medium was preserved after the grafting of PAA onto the macroporous microspheres. This finding demonstrates that the density of the PAA ligands does not appear to have any discernible impact on the structure of the medium; that is, no difference in the structure of the medium is observed before and after the grafting of PAA onto the microspheres. The pore size and pore-size distribution of the medium before and after grafting were determined by mercury intrusion porosimetry and the nitrogen adsorption method to investigate the relationship between pore size (measured in the range of 300-1000 nm) and protein adsorption. When the pore size of the medium was increased, its protein binding capacity did not exhibit any substantial decrease. An increase in pore size may hasten the mass transfer of proteins within the medium. Among the media prepared, that with a pore size of 400 nm exhibited the highest dynamic-binding capacity (DBC: 70.3 g/L at 126 cm/h). The large specific surface area of the medium and its increased number of protein adsorption sites appeared to positively influence its DBC. When the flow rate was increased, the protein DBC decreased in media with original pore sizes of less than 700 nm. In the case of the medium with an original pore size of 1000 nm, the protein DBC was independent of the flow rate. The protein DBC decreased by 3.5% when the flow rate was increased from 126 to 628 cm/h. In addition, the protein DBC was maintained at 57.7 g/L even when the flow velocity was 628 cm/h. This finding reveals that the diffusion rate of protein molecules at this pore size is less restricted and that the prepared medium has excellent mass-transfer performance. These results confirm that the macroporous polymer anion exchange chromatographic medium developed in this study has great potential for the high-throughput separation of proteins.


Polyamines , Proteins , Chromatography, Ion Exchange/methods , Adsorption , Proteins/chemistry , Anions
11.
Inflammation ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38668837

Sleep deprivation (SD) has been associated with several adverse effects, including cognitive deficit. Emerging evidence suggests microglia-associated neuroinflammation is a potential trigger of cognitive deficit after SD. Stimulator of interferon genes (STING) constitutes an important factor in host immune response to pathogenic organisms and is found in multiple cells, including microglia. STING is involved in neuroinflammation during neuronal degeneration, although how STING signaling affects SD-induced neuroinflammation remains unexplored. In the present study, the chronic sleep restriction (CSR) model was applied to examine the effects of STING signaling on cognition. The results revealed that cGAMP, a high-affinity and selective STING agonist, significantly improved cognitive deficit, alleviated neural injury, and relieved neuroinflammation in CSR mice by activating the STING-TBK1-IRF3 pathway. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) was upregulated in CSR mice treated with cGAMP, and this effect was abolished by STING knockout. TREM2 upregulation induced by cGAMP regulated the microglia from pro-inflammatory state to anti-inflammatory state, thereby relieving neuroinflammation in CSR mice. These findings indicate cGAMP-induced STING signaling activation alleviates SD-associated neuroinflammation and cognitive deficit by upregulating TREM2, providing a novel approach for the treatment of SD-related nerve injury.

12.
Emerg Microbes Infect ; 13(1): 2337677, 2024 Dec.
Article En | MEDLINE | ID: mdl-38578315

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

13.
Plants (Basel) ; 13(8)2024 Apr 10.
Article En | MEDLINE | ID: mdl-38674475

Climate change inevitably affects vegetation growth in the Tibetan Plateau (TP). Understanding the dynamics of vegetation phenology and the responses of vegetation phenology to climate change are crucial for evaluating the impacts of climate change on terrestrial ecosystems. Despite many relevant studies conducted in the past, there still remain research gaps concerning the dominant factors that induce changes in the start date of the vegetation growing season (SOS). In this study, the spatial and temporal variations of the SOS were investigated by using a long-term series of the Normalized Difference Vegetation Index (NDVI) spanning from 2001 to 2020, and the response of the SOS to climate change and the predominant climatic factors (air temperature, LST or precipitation) affecting the SOS were explored. The main findings were as follows: the annual mean SOS concentrated on 100 DOY-170 DOY (day of a year), with a delay from east to west. Although the SOS across the entire region exhibited an advancing trend at a rate of 0.261 days/year, there were notable differences in the advancement trends of SOS among different vegetation types. In contrast to the current advancing SOS, the trend of future SOS changes shows a delayed trend. For the impacts of climate change on the SOS, winter Tmax (maximum temperature) played the dominant role in the temporal shifting of spring phenology across the TP, and its effect on SOS was negative, meaning that an increase in winter Tmax led to an earlier SOS. Considering the different conditions required for the growth of various types of vegetation, the leading factor was different for the four vegetation types. This study contributes to the understanding of the mechanism of SOS variation in the TP.

14.
Sci Total Environ ; 928: 172534, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38636852

Soil aggregates are crucial for reducing soil erosion and enhancing soil organic carbon sequestration. However, knowledge regarding influences of different slope positions on compositions and carbon content for different soil aggregates is limited. Soil samples were collected from various slope positions including dip slope, anti-dip slope and valley depression in the Longtan karst valley of Southwest China. Contents of macroaggregate (> 0.25 mm), microaggregate (0.053-0.25 mm) and silt and clay fraction (< 0.053 mm), and aggregate-associated carbon contents under the three slope positions were measured. Compared to the anti-dip slope, the mean weight diameter under the dip slope and valley depression decreased by 28.48 % and 58.79 %, respectively, while the geometric mean diameter decreased by 39.01 % and 62.57 %, respectively. The mean carbon content in silt and clay fraction was 27.59 % and 21.00 % lower than the macroaggregate- and microaggregate-associated carbon content, respectively. Under the valley depression and dip slope, soil organic carbon contents in bulk soil (37.67 % and 10.36 %, respectively), microaggregate (37.56 % and 4.95 %), and silt and clay fraction (39.99 % and 12.84 %, respectively) were significantly lower than those under the anti-dip slope. However, the difference in macroaggregate-associated carbon content among the three slope positions was not significant. The silt and clay fraction was the major contributor to soil carbon pool in bulk soil in the study area because of its high content. Compared to the anti-dip slope, contribution of macroaggregates to soil carbon pool under the dip slope and valley depression decreased by 25.53 % and 47.95 %, respectively, whereas the contribution of silt and clay fraction increased by 22.68 % and 42.66 %, respectively. These results suggested that the anti-dip slope surpassed both the dip slope and valley depression in carbon sequestration and soil and water conservation in karst regions.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 315: 124227, 2024 Jul 05.
Article En | MEDLINE | ID: mdl-38608557

Low cost and strong fluorescence emission are two important guarantees for luminogens used as light conversion agents. By one-pot multicomponent approach and inexpensive starting materials, three dicyanopyridine (DP) derivatives named as DCP (2-amino-6-methoxy-4-phenylpyridine-3,5-dicarbonitrile), DCO (2-amino-6-methoxy-4-(4-methoxyphenyl) pyridine-3,5-dicarbonitrile) and DCC (2-amino-4-(4-cyanophenyl)-6-methoxypyridine-3,5-dicarbonitrile) were designed and synthesized. Meanwhile, the ACQ-to-AIE transformation was successfully realized by altering substituent groups rather than traditional rotor-stator theory. Based on crystal analysis and theoretical calculations, the ACQ-to-AIE transformation is attributed to the tunable stacking modes and intermolecular weak interactions. Owing to matched fluorescence emission, low lost, high yield, and AIE activity, DCC is used as light conversion agents and doped in EVA matrix. The light conversion quality confirms that DCC can not only convert ultraviolet light, but also significantly improve the transmittance of 25 %/40 % EVA, whose photosynthetic photon flux density at 400-500 nm and 600-700 nm increased to 30.67 %/30.21 % and 25.37 %/37.82 % of the blank film, respectively. After 20 h of UV irradiation (365 nm, 40 W), the fluorescence intensities of DCC films can maintain 92 % of the initial values, indicating good photostability in the doping films. This work not only provides an excellent and low-cost light conversion agent, but also has important significance for ACQ-to-AIE transformation of luminogens.

16.
Food Chem ; 451: 139428, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38678665

For some aquatic products, pH has been considered a useful index to reflect the changes in materials during the loss of freshness. Based on the inner filter effect (IFE) between deprotonated phenol red (PR) and upconversion nanoparticles (UCNPs), UCNPs coated with PR-doped SiO2 shell were embedded in agarose hydrogel to develop a smartphone-assisted method for pH sensing. With the enhancement of pH response using a phase transfer agent (i.e., tetra butyl ammonium hydroxide, TBAH), the proposed senor realized the colorimetric and fluorescence detection of pH in the range of pH 6.6-8 and pH 6-8, respectively. The sensor also showed satisfied reversibility when switched between pH 6 and 8 for at least 5 cycles. Moreover, this sensor displayed great sensitivity, stability, and portability in analyzing actual fish, shrimp, and shellfish samples, providing a new sight for evaluating the freshness of aquatic products.


Fishes , Hydrogels , Phenolsulfonphthalein , Silicon Dioxide , Smartphone , Hydrogels/chemistry , Hydrogen-Ion Concentration , Silicon Dioxide/chemistry , Animals , Phenolsulfonphthalein/chemistry , Seafood/analysis , Nanoparticles/chemistry , Shellfish/analysis , Colorimetry
17.
Int J Biol Macromol ; 268(Pt 1): 131833, 2024 May.
Article En | MEDLINE | ID: mdl-38663703

The emergence and widespread of multidrug-resistant Gram-negative bacteria have posed a severe threat to human health and environmental safety, escalating into a global medical crisis. Utilization of antibiotic adjuvants is a rapid approach to combat bacterial resistance effectively since the development of new antimicrobial agents is a formidable challenge. NhaA, driven by proton motive force, is a crucial secondary transporter on the cytoplasmic membrane of Escherichia coli. We found that 2-Aminoperimidine (2-AP), which is a specific inhibitor of NhaA, could enhance the activity of colistin against sensitive E. coli and reverse the resistance in mcr-1 positive E. coli. Mechanistic studies indicated that 2-AP induced dysfunction in cytoplasmic membrane through the suppression of NhaA, leading to metabolic inhibition and ultimately enhancing the sensitivity of E. coli to colistin. Moreover, 2-AP restored the efficacy of colistin against resistant E. coli in two animal infection models. Our findings reveal the potential of NhaA as a novel target for colistin adjuvants, providing new possibilities for the clinical application of colistin.


Colistin , Escherichia coli Proteins , Escherichia coli , Colistin/pharmacology , Escherichia coli/drug effects , Escherichia coli Proteins/metabolism , Animals , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Drug Resistance, Bacterial/drug effects , Mice , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology
18.
bioRxiv ; 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38585864

Several neuronal populations in the brain transmit both the excitatory and inhibitory neurotransmitters, glutamate, and GABA, to downstream neurons. However, it remains largely unknown whether these opposing neurotransmitters are co-released onto the same postsynaptic neuron simultaneously or are independently transmitted at different time and locations (called co-transmission). Here, using whole-cell patch-clamp recording on acute mouse brain slices, we observed biphasic miniature postsynaptic currents, i.e., minis with time-locked excitatory and inhibitory currents, in striatal spiny projection neurons (SPNs). This observation cannot be explained by accidental coincidence of monophasic miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively), arguing for the co-release of glutamate and GABA. Interestingly, these biphasic minis could either be an mEPSC leading an mIPSC or vice versa. Although dopaminergic axons release both glutamate and GABA in the striatum, deletion of dopamine neurons did not eliminate biphasic minis, indicating that the co-release originates from another neuronal type. Importantly, we found that both types of biphasic minis were detected in other neuronal subtypes in the striatum as well as in nine out of ten additionally tested brain regions. Our results suggest that co-release of glutamate and GABA is a prevalent mode of neurotransmission in the brain.

19.
Chem Commun (Camb) ; 60(31): 4222-4225, 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38525969

A N2-bridged tetranuclear Sc(III)-Ni(0) complex featuring a Ni → Sc interaction and a 4-membered [Sc-N-C-Ni] ring was synthesized and characterized. Bimetallic reactivity was demonstrated via reactions with a series of unsaturated compounds containing NC, CN, CC, CO and NN bonds.

20.
Animals (Basel) ; 14(6)2024 Mar 10.
Article En | MEDLINE | ID: mdl-38539951

Zoo animals, harboring zoonotic gastrointestinal protozoal diseases, pose potential hazards to the safety of visitors and animal keepers. This study involved the collection and examination of 400 fresh fecal samples from 68 animal species, obtained from five zoos. The aim of this study was to determine the occurrence, genetic characteristics, and zoonotic potential of common gastrointestinal protists. PCR or nested PCR analysis was conducted on these samples to detect four specific parasites: Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi, and Blastocystis spp. The overall prevalence of Cryptosporidium spp was 0.5% (2/400), G. duodenalis was 6.0% (24/400), Blastocystis spp. was 24.5% (98/400), and E. bieneusi was 13.5% (54/400). G. duodenalis, Blastocystis spp., and E. bieneusi were detected in all of the zoos, exhibiting various zoonotic genotypes or subtypes. G. duodenalis-positive samples exhibited three assemblages (D, E, and B). Blastocystis spp. subtypes (ST1, ST2, ST3, ST4, ST5, ST8, ST10, ST13, and ST14) and one unknown subtype (ST) were identified. A total of 12 genotypes of E. bieneusi were identified, including SC02, BEB6, Type IV, pigEBITS 7, Peru8, PtEb IX, D, CD9, EbpC, SCBB1, CM4, and CM7. Moreover, significant differences in the positive rates among different zoos were observed (p < 0.01). The findings indicate that zoo animals in China are affected by a range of intestinal protozoa infections. Emphasizing molecular identification for specific parasite species or genotypes is crucial for a better understanding of the zoonotic risk. Preventing and controlling parasitic diseases in zoos is not only vital for zoo protection and management but also holds significant public health implications.

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