Microbial extracellular vesicles contribute to antimicrobial resistance.

With the escalating global antimicrobial resistance crisis, there is an urgent need for innovative strategies against drug-resistant microbes. Accumulating evidence indicates microbial extracellular vesicles (EVs) contribute to antimicrobial resistance. Therefore, comprehensively elucidating the roles and mechanisms of microbial EVs in conferring resistance could provide new perspectives and avenues for novel antimicrobial approaches. In this review, we systematically examine current research on antimicrobial resistance involving bacterial, fungal, and parasitic EVs, delineating the mechanisms whereby microbial EVs promote resistance. Finally, we discuss the application of bacterial EVs in antimicrobial therapy.

Synthesis of functional polyacrylamide (co)polymers by organocatalyzed post-polymerization modification of non-activated esters.

The broad application of polyacrylamides (PAMs) has greatly promoted the development of new synthetic methods to prepare PAM-based functional (co)polymers regarding their traditional preparation via the direct polymerization of various acrylamide monomers. Herein, we have explored the post-polymerization modification of the poly(2,2,2-trifluoroethyl acrylate) (PTFEA) homopolymer, a typical non-activated ester, and various amines using the organo-catalytic system involving 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,2,4-triazole (TA). The reaction kinetics (e.g., the optimized reaction solvent, temperature, time, initial molar ratio of amines to esters and the molar ratio of DBU to TA) were carefully studied with the modulus substrate of iso-propylamine as the formed poly(iso-propyl acrylamide) (PNIPAM) representing the most investigated PAM. The full and partial amidation of the esters in PTFEA could be precisely regulated just by controlling the kinetic conditions to give (co)polymers with designable compositions and structures. We have demonstrated that the poly(N-acryloyl pyrrolidine) obtained by the post-polymerization modification of non-activated ester and pyrrolidine exhibited a noticeable phase transition, which confirmed the robustness and versatility of the post-polymerization modification. The described method paves the way for the synthesis of various (co)polymers with amide side chains from readily available polymer precursors.

Facilitation of Behavioral and Cortical Emergence from Isoflurane Anesthesia by GABAergic Neurons in Basal Forebrain.

General anesthesia shares many similarities with natural sleep in behavior and electroencephalogram (EEG) patterns. The latest evidence suggests that general anesthesia and sleep-wake behavior may share overlapping neural substrates. The GABAergic neurons in the basal forebrain (BF) have recently been demonstrated to play a key role in controlling wakefulness. It was hypothesized that BF GABAergic neurons may participate in the regulation of general anesthesia. Here, using in vivo fiber photometry, we found that the activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia, having obviously decreased during the induction of anesthesia and being gradually restored during the emergence from anesthesia, in Vgat-Cre mice of both sexes. Activation of BF GABAergic neurons with chemogenetic and optogenetic approaches decreased sensitivity to isoflurane, delayed induction, and accelerated emergence from isoflurane anesthesia. Optogenetic activation of BF GABAergic neurons decreased EEG δ power and the burst suppression ratio (BSR) during 0.8% and 1.4% isoflurane anesthesia, respectively. Similar to the effects of activating BF GABAergic cell bodies, photostimulation of BF GABAergic terminals in the thalamic reticular nucleus (TRN) also strongly promoted cortical activation and behavioral emergence from isoflurane anesthesia. Collectively, these results showed that the GABAergic BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthesia via the GABAergic BF-TRN pathway. Our findings may provide a new target for attenuating the depth of anesthesia and accelerating emergence from general anesthesia.SIGNIFICANCE STATEMENT The basal forebrain (BF) is a key brain region controlling sleep-wake behavior. Activation of GABAergic neurons in the BF potently promotes behavioral arousal and cortical activity. Recently, many sleep-wake-related brain structures have been reported to participate in the regulation of general anesthesia. However, it is still unclear what role BF GABAergic neurons play in general anesthesia. In this study, we aim to reveal the role of BF GABAergic neurons in behavioral and cortical emergence from isoflurane anesthesia and elucidate the underlying neural pathways. Understanding the specific role of BF GABAergic neurons in isoflurane anesthesia would improve our understanding of the mechanisms of general anesthesia and may provide a new strategy for accelerating emergence from general anesthesia.

The Effect of Computer-Assisted Cognitive Remediation Therapy on Cognitive Function, Social Function and Quality of Life in Patients with Vascular Dementia.

Objective: Our study aimed to investigate the effects of computer-assisted cognitive remediation therapy (CCRT) on cognitive function, social function and quality of life in patients with vascular dementia (VD). Methods: Ninety-eight patients with VD were treated with CCRT in four 45-minute sessions per week over a course of 40 sessions to exercise four cognitive functions, including flexibility, working memory, plan execution and social cognition. The Mini-Mental State Examination (MMSE), Social Disability Screening Schedule (SDSS), Personal and Social Performance Scale (PSP), and Generic Quality of Life Inventory-74 (GQOL-74) were used to assess before and after treatment. Results: (1) The scores of orientation (5.60 ± 1.35), calculation (2.20 ± 0.79), verbal ability (7.10 ± 0.36), spatial ability (0.78 ± 0.42), immediate memory (2.42 ± 0.53), short-term memory (1.17 ± 0.78) and MMSE (23.36 ± 2.98) were all improved after treatment (P < 0.05) compared with those before treatment; (2) The scores of SDSS, PSP and Activities of Daily Living (ADL) after treatment were 8.23 ± 0.94, 81.36 ± 14.23, and 32.7 ± 12.1, and all of which improved (P < 0.05); (3) The scores of physical health were 68.24 ± 7.44, mental health were 69.75 ± 7.15, social function were 69.08 ± 7.43, material life were 37.46 ± 4.85 and the total score were 230.79 ± 9.56, all of which improved (P < 0.05). Conclusion: For patients with VD, CCRT can improve their cognitive function, social function, daily life ability and quality of life.

The effects of Mesona chinensis Benth gum on the pasting, rheological, and microstructure properties of different types of starches.

The effect of Mesona chinensis Benth gum (MCG) on pasting, rheological and texture properties of different types of starches (tubers, cereals, and beans) were investigated. Pasting results showed that the pasting temperatures (PT) of native cereal and beans starch were higher, and MCG decreased the PT of starch granules by competing water with starch granules for water. MCG increased the peak viscosity and breakdown viscosity of native starches except potato starch, and effectively promoted the short-term retrogradation of all kinds of starches. Rheological results also revealed MCG increased apparent viscosity and dynamic modulus of native starch gels, given that the compacter network structures could be formed after adding MCG. The compacter network structures also contribute to the enhancement of gel strength and hardness, and the decreased spin relaxation time of starch gels. The information provided in this paper could help people to understand the different effects of MCG on the various starch, which had certain significance for starch-MCG product development.

TGF-ß-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine.

TGF-ß signaling is necessary for CD8+ T cell differentiation into tissue resident memory T cells (TRM). Although higher frequency of CD8+ TRM cells in the tumor microenvironment is associated with better prognosis, TGF-ß-blockade typically improves rather than worsens outcomes. Here we show that in a mouse melanoma model, in the tumor-draining lymph nodes (TDLN) rather than in the tumors themselves, stem-like CD8+ T cells differentiate into TRMs in a TGF-ß and tumor antigen dependent manner. Following vaccination against a melanoma-specific epitope, most tumour-specific CD8+ T cells are maintained in a stem-like state, but a proportion of cells lost TRM status and differentiate into CX3CR1+ effector CD8+ T cells in the TDLN, which are subsequently migrating into the tumours. Disruption of TGF-ß signaling changes the dynamics of these developmental processes, with the net result of improving effector CD8+ T cell migration into the tumours. In summary, TDLN stem-like T cells transiently switch from a TGF-ß-dependent TRM differentiation program to an anti-tumor migratory effector development upon vaccination, which transition can be facilitated by targeted TGF-ß blockade.

Regulation of wakefulness by astrocytes in the lateral hypothalamus.

The lateral hypothalamus (LH) is an important brain region mediating sleep-wake behavior. Recent evidence has shown that astrocytes in central nervous system modulate the activity of adjacent neurons and participate in several physiological functions. However, the role of LH astrocytes in sleep-wake regulation remains unclear. Here, using synchronous recording of electroencephalogram/electromyogram in mice and calcium signals in LH astrocytes, we show that the activity of LH astrocytes is significantly increased during non-rapid eye movement (NREM) sleep-to-wake transitions and decreased during Wake-to-NREM sleep transitions. Chemogenetic activation of LH astrocytes potently promotes wakefulness and maintains long-term arousal, while chemogenetic inhibition of LH astrocytes decreases the total amount of wakefulness in mice. Moreover, by combining chemogenetics with fiber photometry, we show that activation of LH astrocytes significantly increases the calcium signals of adjacent neurons, especially among GABAergic neurons. Taken together, our results clearly illustrate that LH astrocytes are a key neural substrate regulating wakefulness and encode this behavior through surrounding GABAergic neurons. Our findings raise the possibility that overactivity of LH astrocytes may be an underlying mechanism of clinical sleep disorders.

Mesona chinensis polysaccharide accelerates the short-term retrogradation of debranched waxy corn starch.

The effect of non-starch polysaccharides on the structural and functional properties of native starch have been extensively studied. However, the effect of non-starch polysaccharides on the structural characteristics of debranched starch, a kind of enzymatic modified starch, remains unclear. The aim of this study is to investigate the effects of Mesona chinensis polysaccharide (MP) on starch retrogradation and structural properties of debranched waxy corn starch (DWS). The results showed that only appropriate addition of MP (0.5 or 1%) can effectively promote the short-term retrogradation of DWS, while excessive MP (3 or 5%) had a negative effect. Gel hardness results revealed that the short-term retrogradation (24 h) of DWS could be divided into two phases. The retrogradation of DWS-MP gels mainly occurred at first stage (0-4 h), which was demonstrated by the rapid increase of gel hardness and relative crystallinity in this stage. In the second stage (4-24 h), DWS-MP gels were more likely to undergo the aggregation of starch granules as proved by SEM and particle size results. The degree of short-range ordered decreased during the total retrogradation stage. Overall, this work aims to provide an insight into the effect of non-starch polysaccharides on the short-term retrogradation of DWS.

Regulation of wakefulness by GABAergic dorsal raphe nucleus-ventral tegmental area pathway.

The dorsal raphe nucleus (DRN) has previously been proved to be involved in the regulation of the sleep-wake behavior. DRN contains several neuron types, such as 5-HTergic and GABAergic neurons. GABAergic neurons, which are the second largest cell subtype in the DRN, participate in a variety of neurophysiological functions. However, their role in sleep-wake regulation and the underlying neural circuitry remains unclear. Herein, we used fiber photometry and synchronous electroencephalogram (EEG)/electromyography (EMG) recording to demonstrate that DRN GABAergic neurons exhibit high activities during wakefulness and low activities during NREM sleep. Short-term optogenetic activation of DRN GABAergic neurons reduced the latency of NREM-to-wake transition and increased the probability of wakefulness, while long-term optogenetic activation of these neurons significantly increased the amount of wakefulness. Chemogenetic activation of DRN GABAergic neurons increased wakefulness for almost 2 h and maintained long-lasting arousal. In addition, inhibition of DRN GABAergic neurons with chemogenetics caused a reduction in the amount of wakefulness. Finally, similar to the effects of activating the soma of DRN GABAergic neurons, optogenetic stimulation of their terminals in the ventral tegmental area (VTA) induced instant arousal and promoted wakefulness. Taken together, our results illustrated that DRN GABAergic neurons are vital to the induction and maintenance of wakefulness, which promote wakefulness through the GABAergic DRN-VTA pathway.

Changes in polysaccharides structure and bioactivity during Mesona chinensis Benth storage.

Mesona chinensis Benth has been consumed as a functional food for many years. It is widely believed that storage times affect its health benefits. In this study, Mesona chinensis Benth polysaccharides with two different storage times (fresh and storage for 1 year) were prepared, namely, FMP and AMP. The physicochemical properties and bioactivity were comparatively assessed. Results indicated that FMP was mainly composed of galacturonic acid, galactose, and glucose with a molecular weight of 44.39 kDa. AMP was composed of galacturonic acid, galactose, and fructose with a molecular weight of 64.34 kDa. However, the principal structural characteristics of polysaccharides remained stable. Furthermore, assays of antioxidant activity showed that Mesona chinensis Benth polysaccharide had an antioxidant effect against DPPH radical, ABTS radical cation, among which FMP was stronger. Additionally, flow cytometry indicated that the apoptosis rate of FMP and AMP on HepG2 tumor cells was 22.50 ± 1.25% and 15.49 ± 1.30%, respectively. In general, antioxidant and antitumor activities of Mesona chinensis Benth polysaccharides were decreased as the storage for 1 year. The change of physicochemical properties was responsible for the enhanced bioactivities. These results explained how polysaccharides contributed to the decreased health benefits of Mesona chinensis Benth during storage.

Modification of starch by polysaccharides in pasting, rheology, texture and in vitro digestion: A review.

Starch is a copolymer with unique physicochemical characteristics, is known for its low cost, easy degradability, renewable and easy availability. However, natural starches have some undesirable properties such as poor solubility, poor functional properties, lower resistant starch content with reduced retrogradation, and poor stability under various temperatures, pH, which limit their application in food. Different modification methods are used to improve its performance and expand its application. Numerous studies have been conducted to investigate why the addition of small amounts of polysaccharides affects the properties of starch pastes and gels. The application of polysaccharide-modified starch can be seen in the pasting, rheology, texture and in vitro digestive properties of starch gels. The main influencing factors include different starches, different specific polysaccharides, and different methods of preparation of composite pastes and gels. This paper reviews the changes in the properties of starch in terms of pasting, rheology, texture and in vitro digestion after modification with polysaccharides and the mechanism of polysaccharide action on starch.

Isolation, Characterization and Antioxidant Activity of Yam Polysaccharides.

This study aimed to characterize the structure of Chinese yam (Dioscoreae Rhizoma) polysaccharide (CYP) and to investigate its protective effect against H2O2-induced oxidative damage in IEC-6 cells. The chemical composition and structural characteristics of the samples were analyzed by chemical and instrumental methods, including high-performance gel permeation chromatography, high-performance anion-exchange chromatography (HPAEC), Fourier transformed infrared (FT-IR), ultraviolet (UV), and scanning electron microscopy (SEM). Antioxidant activity was evaluated by establishing a cellular model of oxidative damage. The molecular weight of CYP was 20.89 kDa. Analysis of the monosaccharide composition revealed that CYP was primarily comprised of galactose (Gal), glucose (Glu), and galacturonic acid (GalA), and the ratio between them was 28.57:11.28:37.59. Pretreatment with CYP was able to improve cell viability, superoxide dismutase (SOD) activity, and reduce intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content after H2O2 injury. CYP also attenuated oxidative damage in cells through the mitogen-activated protein kinase (MAPK) signaling pathway. This study showed that CYP was an acidic heteropolysaccharide with a good protective effect against oxidative damage, and it thus has good prospects in food and biopharmaceutical industries.

Dry heat treatment induced the gelatinization, rheology and gel properties changes of chestnut starch.

The effects of continuous dry heat treatment (CT) and repeated dry heat treatment (RT) on gel and structural properties of chestnut starch (CS) were investigated. CT and RT both reduced the swelling degree of starch and showed significant variations in pasting viscosity, viscoelasticity, gel strength and hardness varying from high to low after dry heat treatment, and CT was lower than that of RT. Neither dry heat treatment nor gelatinization produced new functional groups, and both reduced short-range ordered degree. There were significant decrease in spin-spin relaxation time (T2) with dry heat treatment (CT and RT), which made the starch in the samples closely combine with water. These results are helpful to better understand the changes of physicochemical properties of starch gel products during dry heat treatment and provide some theoretical references for the application of CS in food industry.

Preparation and characterization of hyacinth bean starch film incorporated with TiO2 nanoparticles and Mesona chinensis Benth polysaccharide.

Hyacinth bean starch (HBS) was used to prepare nanocomposite films with the reinforcement agent of nanotitanium oxide (TiO2-N) and Mesona chinensis Benth polysaccharide (MCP). The effects of TiO2-N and MCP on the moisture combination, rheological properties of film-forming solutions (FFS) and physiochemical properties of films were investigated. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) revealed that HBS, TiO2-N and MCP had good compatibility, while no novel absorption peak in FTIR spectra, and characteristic peaks of TiO2-N were found in XRD patterns of composite films. Contact angle of HBS/TiO2-N/M3 film increased from 65.6° to 90.9°, which illustrated that TiO2-N and MCP effectively enhanced hydrophobicity of films. TiO2-N and MCP positively affected anti-UV light ability of HBS films by resisting most of invisible light. Furthermore, stable and compact network structures were formed by the synergistic effect of TiO2-N and MCP, thereby elongation to break was increased from 17.123% to 28.603% significantly, and heat resistance was enhanced clearly. This study prepared a nanocomposite HBS-based films based TiO2-N and MCP, which had guiding significance for development of functional films and combination of polysaccharides and metallic oxide.

Hybrid Copolymerization of Ethylene Oxide and tert-Butyl Methacrylate with Organocatalyst.

Hybrid copolymerization of structurally different, reactivity and mechanism distinct monomers (e.g., cyclic and vinyl type monomers) is of great interest and challenge for both academic research and practical application. Herein, ethylene oxide-co-tert-butyl methacrylate-co-poly(ethylene glycol) benzyl methacrylate (EO-co-BMA-co-bPEO), a statistical copolymer was synthesized via hybrid copolymerization of EO and BMA using an uncharged, non-nucleophilic organobase t-BuP4 as the catalyst. Detailed characterizations indicate that hybrid copolymerization of ethylene oxide and vinyl monomer forms a statistical copolymer concurrently with the transesterification of tert-butyl group and oligomer PEO anions. The application of the copolymer as all solid lithium-ion battery polymer electrolyte was investigated by detecting the ionic conductivity (σ) with electrical impedance spectrum measurement.

The role of alkali in sweet potato starch-Mesona chinensis Benth polysaccharide gels: Gelation, rheological and structural properties.

According to the Chinese traditional black jelly production process, a critical step to ensure the quality of jelly is to add alkali to it. In this study, the effects of sodium carbonate (Na2CO3) and sodium bicarbonate (NaHCO3) on the pasting, rheological, textural, and structural properties of sweet potato starch (SPS)-Mesona chinensis Benth polysaccharide (MCP) gels were evaluated. Adding Na2CO3 at low concentration reduced the final viscosity (FV) of SPS-MCP gels, whereas adding it at a high concentration increased the FV. Adding NaHCO3 can increase the FV of SPS-MCP gels in a concentration-dependent manner. Rheological results indicated that adding NaHCO3 at a low concentration decreased the storage modulus of SPS-MCP gels, whereas adding it at a high concentration increased the storage modulus. The storage modulus of SPS-MCP gels increased with increasing concentration of NaHCO3. The addition of Na2CO3 and NaHCO3 improved the textural properties of SPS-MCP gels and decreased the water mobility. Infrared results indicated that adding alkali can enhance the hydrogen bonding between SPS and MCP. Scanning electron microscopy results suggested that alkali can reduce the size of gels, and make the structure more compact.

Interaction between rice starch and Mesona chinensis Benth polysaccharide gels: Pasting and gelling properties.

Interactions between starch and non-starch polysaccharides are very important for predicting and controlling the structure and function of starch-.based products. In this study, the effects of Mesona chinensis Benth polysaccharide (MCP) on the pasting, rheological, structural, and water mobility properties of rice starch (RS)-MCP gels were evaluated. Results indicated that MCP can increase the pasting viscosity, and gel properties of RS-MCP gels. Rheological results showed that RS-MCP gels exhibited shear-thinning behavior and that MCP can enhance the viscoelasticity of RS-MCP gels. Fourier-transform infrared spectra results indicated no covalent interaction between RS and MCP, and MCP could increase the degree of short-range order of RS-MCP gels. MCP also enhanced the water-retention capacity of RS-MCP gels. Scanning electron microscopy results suggested that MCP could decrease the pore sizes of RS gels and the microstructure of RS gels became more ordered at 0.1 % concentration of MCP. The results suggested that the amylose and MCP molecules interacted through hydrogen bonds and electrostatic forces, which enhanced the gelling properties of RS-MCP gels. Overall, this study shows the potential applications of MCP, and also provides the theoretical basis of interactions in starch-hydrocolloids systems.

Studying the Ring-Opening Polymerization of 1,5-Dioxepan-2-one with Organocatalysts.

Three different organocatalysts, namely, 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris (dimethylamino) phosphoranylidenamino]-2Λ5,4Λ5-catenadi(phosphazene) (t-BuP4), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), have been used as 1,5-dioxepan-2-one (DXO) ring-opening polymerization (ROP) catalysts at varied reaction conditions. 1H NMR spectra, size exclusion chromatography (SEC) characterizations, and kinetic studies prove that the (co)polymerizations are proceeded in a controlled manner with the three organocatalysts. It is deduced that t-BuP4 and DBU catalysts are in an initiator/chain end activated ROP mechanism and TBD is in a nucleophilic ROP mechanism.