Helicobacter macacae MazF interplays with Escherichia coli homologs and enhances antibiotic tolerance.

BACKGROUND: Toxin-antitoxin systems are highly variable, even among strains of the same bacterial species. The MazEF toxin-antitoxin system is found in many bacteria and plays important roles in various biological processes such as antibiotic tolerance and phage defense. However, no interplay of MazEF systems between different species was reported. MATERIALS AND METHODS: MazEF toxin-antitoxin system of Helicobacter macacae was examined in three Escherichia coli strains with and without endogenous MazEF knockout. In vivo toxicity, antibiotic tolerance, and live/dead staining followed by flowcytometry analysis were performed to evaluate the functionality and interplay of the toxin-antitoxin system between the two species. RESULTS: Controlled ectopic expression of MazF of H. macacae (MazFhm) in E. coli did not affect its growth. However, in endogenous MazEF knockout E. coli strains, MazFhm expression caused a sharp growth arrest. The toxicity of MazFhm could be neutralized by both the antitoxin of MazE homolog of H.macacae and the antitoxin of MazE of E. coli, indicating interplay of MazEF toxin-antitoxin systems between the two species. Induced expression of MazFhm enhanced tolerance to a lethal dose of levofloxacin, suggesting enhanced persister formation, which was further confirmed by live/dead cell staining. CONCLUSIONS: The MazEF toxin-antitoxin system of H. macace enhances persister formation and thus antibiotic tolerance in E. coli. Our findings reveal an interplay between the MazEF systems of H. macacae and E. coli, emphasizing the need to consider this interaction while evaluating the toxicity and functionality of MazF homologs from different species in future studies.

Transition-metal-mediated benzylation of C60 with benzyl chlorides.

Benzyl bromides have been widely used for fullerene functionalization. However, the use of benzyl chlorides, a more affordable but less reactive counterpart of benzyl bromides, has been rarely reported. Herein, a new metal-mediated benzylation of C60 with benzyl chlorides is presented. In this method, with the combinatorial use of Mn powder and Cu(OAc)2, various benzyl chloride derivatives could react with C60 to afford 1,4-dibenzylated products in 12-53% yields. A mechanistic study by in situ visible near infrared (vis-NIR) spectroscopy and various control experiments suggests that, unlike the conventional anionic pathway that uses benzyl bromides, the transition-metal-mediated benzylation of C60 with benzyl chlorides proceeds via a metal-mediated iterative single electron transfer process.

FGF10 mitigates doxorubicin-induced myocardial toxicity in mice via activation of FGFR2b/PHLDA1/AKT axis.

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10+/- mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26rtTA; tet(O)sFgfr2b) were used to determine the effect of Fgf10 hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10+/- mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10+/+ control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment.

Enhanced recovery after surgery care to reduce surgical site wound infection and postoperative complications for patients undergoing liver surgery.

This study comprehensively assessed the effect of enhanced recovery after surgery (ERAS) on wound infection and postoperative complications in patients undergoing liver surgery. The PubMed, EMBASE, MEDLINE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang electronic databases were searched to collect published studies on the use of ERAS in liver surgery until December 2022. Literature selection was performed independently by two investigators according to the inclusion and exclusion criteria, and quality evaluation and data extraction were performed. RevMan 5.4 software was used in this study. Compared with the control group, the ERAS group showed a significantly lower incidence of postoperative wound infection (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.41-0.84, P = .004) and overall postoperative complication rate (OR: 0.43, 95% CI: 0.33-0.57, P < .001) and significantly shorter postoperative hospital stay (mean difference: -2.30, 95% CI: -2.92 to -1.68, P < .001). Therefore, ERAS was safe and feasible when applied to liver resection, reducing the incidence of wound infection and total postoperative complications, and shortening the length of hospital stay. However, further studies are required to investigate the impact of ERAS protocols on clinical outcomes.

2D→3D Polycatenated Cu(I) Coordination Polymer: Photocatalytic Property and Protective Activity on COPD by Reducing the INF-γ Production.

Reported here is a new [Cu4I4] cluster-based coordination polymer, namely [Cu4I4(bib)2]n·n(DMF) (1, bib = 1,4-bis(imidazolyl)butane, DMF = N,N'-dimethylformamide), which was synthesized by the self-assemble reaction of CuI, bib and KI under solvothermal conditions. Remarkably, compound 1 shows promising photocatalytic performance toward to the degradation of MB solution under visible light irradiation. For the COPD treatment, the ELISA detection kit was conducted to determine the content of INF-γ released by the respiratory tract mucosal epithelial cells. In addition to this, the activation levels of the NF-κB signaling pathway were still need to be assessed by the real time RT-PCR after the compound treatment.

[Establishment of Hospice and Palliative Care Training Platform for Volunteers].

To let the general public,regardless of gender,age,career and education background,understand the core concept of hospice and palliative care,practice in their lives,and then spread to and serve as many people as possible,the hospice and palliative care team of Peking Union Medical College Hospital established the professional hospice and palliative care training platform for volunteers in 2021.This article reviews the training design,content,methods,and results of the platform.It is concluded that the platform has theory-based training design,logical and complete training content,suitable training method for volunteers,and satisfactory training results.The establishment of this hospice and palliative care training platform for volunteers has excellent feasibility.Efforts should be made to further explore the performance and long-term development strategy of the training platform.

[Student Satisfaction Survey of Postgraduate Programs of Clinical Medicine at Regional Medical Schools and the Influencing Factors].

Objective: To investigate the status quo of satisfaction with postgraduate education of clinical medicine and the influencing factors, so as to provide references for promoting improvements in the education model and the program quality of medical personnel training. Methods: A self-developed Clinical Medicine Postgraduate Program Quality Satisfaction Questionnaire was used to conduct a survey among 1907 postgraduate students of clinical medicine, and multivariate linear regression was used to analyze the influencing factors of postgraduate students' satisfaction with the quality of the program. Results: The overall satisfaction rate with the quality of the postgraduate clinical medical program was 81.44%, and the satisfaction score ranking of different dimensions from the highest to the lowest were 14 (12, 15) for supervisors, 19 (17, 22) for curriculum and instruction, 18 (16, 23) for management and survices, and 12 (10, 14) for research environment. The results of multiple stepwise regression analysis showed that the course evaluation method 〔partial regression coefficient ( Β)=0.048, 95% CI: 0.002-0.095, P=0.042〕 and teacher's teaching methodology ( Β=0.041, 95% CI: 0.010-0.072, P=0.011) of the dimension of curriculum and instruction, research outcomes ( B=0.033, 95% CI: 0.002-0.064, P=0.038) of the research environmrnt dimension, the supervisor's research ability ( B=0.035, 95% CI: 0.005-0.065, P=0.022) of the supervisor's ability dimention were important factors influencing the satisfaction with the quality of postgraduate clinical medical training. Conclusion: Satisfaction with the quality of postgraduate clinical medical training still needs further improvement. Regional medical schools should adopt diversified course evaluation methods, appropriately use modern instructional methods, increase investment in research funding, encourage research outputs, and help the supervisors continuously update their teaching and research philosophies.

Reactions of [60]Fullerene with Acetone under Basic Condition: Nucleophilic Ring Opening of the [5,6]-Cyclopropane in C60 and Formation of the Substituted Methano[60]Fulleroids.

The reactions of C60 with acetone were carried out under basic condition in the presence of 1.0 M TBAOH (tetra-n-butylammonium hydroxide) methanol solution and ArCH2Br (Ar = Ph or o-BrPh), where methano[60]fulleroids with a novel 1,1,4,9,9,25-configuration were obtained and structurally characterized by single crystal diffraction. The product was formed via the ring-opening reaction of the [5,6]-cyclopropane by the nucleophilic addition of MeO-, which is different from the reactions of other ketones reported previously.

Polychlorinated biphenyls affects anaerobic methane production from waste activated sludge through suppressing hydrolysis-acidification and methanation processes.

The widespread existence of polychlorinated biphenyls (PCB) in wastewater results in the retention of abundant PCB in waste activated sludge (WAS), which has become a global concern. Till now, the effects of PCB on methane production during WAS anaerobic digestion was still limited. This study aimed to investigate whether and how PCB affects methane production. Results showed that the increased PCB concentration led to the less methane produced. At the highest concentrations of PCB (100 mg/kg DS) in this study, the methane production (112 ±â€¯6 L CH4/kg VS) was significantly reduced by 26.6 ±â€¯0.1% compared to the control (153 ±â€¯7 L CH4/kg VS). Correspondingly, VS destruction at the studied concentrations showed the similar trend. In addition, the dewaterability evaluation indicated that the PCB resulted in the deteriorative sludge dewaterability. The mechanism studies suggested that the decreased methane production with the increased levels of PCB was attributed to the suppression on hydrolysis-acidification and methanation processes. This also was supported by the decreasing key enzymes activities associated with methane production (protease, cellulase, acetate kinase (AK) and coenzyme F420). The relative activity of F420 at 100 mg/kg DS of PCB even reduced to 78% ±â€¯3%.

RNF123 has an E3 ligase-independent function in RIG-I-like receptor-mediated antiviral signaling.

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytoplasmic sensors crucial for recognizing different species of viral RNAs, which triggers the production of type I interferons (IFNs) and inflammatory cytokines. Here, we identify RING finger protein 123 (RNF123) as a negative regulator of RIG-I and MDA5. Overexpression of RNF123 inhibits IFN-ß production triggered by Sendai virus (SeV) and encephalomyocarditis picornavirus (EMCV). Knockdown or knockout of endogenous RNF123 potentiates IFN-ß production triggered by SeV and EMCV, but not by the sensor of DNA viruses cGAS RNF123 associates with RIG-I and MDA5 in both endogenous and exogenous cases in a viral infection-inducible manner. The SPRY and coiled-coil, but not the RING, domains of RNF123 are required for the inhibitory function. RNF123 interacts with the N-terminal CARD domains of RIG-I/MDA5 and competes with the downstream adaptor VISA/MAVS/IPS-1/Cardif for RIG-I/MDA5 CARD binding. These findings suggest that RNF123 functions as a novel inhibitor of innate antiviral signaling mediated by RIG-I and MDA5, a function that does not depend on its E3 ligase activity.

Synthesis of (MeO)2Bn2C70: Regiochemistry of 2-fold Additions to C70 with Addends That Are Preferential for Ortho Addition and Capable of Para Addition.

Three C70 tetraadducts, 2,10-(MeO)2-5,9-Bn2C70 (6), 1,56-Bn2-2,57-(MeO)2C70 (7, 2 o'clock isomer), and 1,41-Bn2-2,58-(MeO)2C70 (8, 12 o'clock isomer), were obtained from the reaction of C70 with MeO- and BnBr (benzyl bromide). The structures of 6-8 were resolved via single-crystal X-ray diffraction and spectroscopic characterizations. Computational calculations on the electrophilic Fukui functions fk+, the stability of reaction intermediates, and activation barriers for the key processes of the reaction were performed to rationalize the regioselectivity of the reaction. A conversion of the 5 and 12 o'clock intermediates to the 2 o'clock intermediate was proposed to account for the regioselectivity related to the 2-fold additions at the two distinctive polar regions of C70. Electrochemical study showed a similar electron deficiency for the 2 and 12 o'clock isomers, while the 2,5,9,10-tetraadduct was more electron deficient with respect to the 2 and 12 o'clock isomers.

iRhom2 deficiency relieves TNF-α associated hepatic dyslipidemia in long-term PM2.5-exposed mice.

Accumulating researches reported that particulate matter (PM2.5) is a risk factor for developing various diseases, including metabolic syndrome. Recently, inactive rhomboid protein 2 (iRhom2) was considered as a necessary modulator for shedding of tumor necrosis factor-α (TNF-α) in immune cells. TNF-α, a major pro-inflammatory cytokine, was linked to various pathogenesis of diseases, including dyslipidemia. Here, wild type (WT) and iRhom2-knockout (iRhom2-/-) mice were used to investigate the effects of iRhom2 on PM2.5-induced hepatic dyslipidemia. The hepatic histology, inflammatory response, glucose tolerance, serum parameters and gene expressions were analyzed. We found that long-term inhalation of PM2.5 resulted in hepatic steatosis. And a significant up-regulation of iRhom2 in liver tissues was observed, accompanied with elevated TNF-α, TNF-α converting enzyme (TACE), TNFα receptor (TNFR)2 and various inflammatory cytokines expressions. Additionally, PM2.5 treatment caused TG and TC accumulation in serum and liver, probably attributed to changes of genes modulating lipid metabolism. Intriguingly, hepatic injury and dyslipidemia were attenuated by iRhom2-/- in mice with PM2.5 challenge. In vitro, iRhom2-knockdwon reduced TNF-α expressions and its associated inflammatory cytokines in Kupffer cells, implying that liver-resident macrophages played an important role in regulating hepatic inflammation and lipid metabolism in cells treated with PM2.5. The findings indicated that long-term PM2.5 exposure caused hepatic steatosis and dyslipidemia through triggering inflammation, which was, at least partly, dependent on iRhom2/TNF-α pathway in liver-resident macrophages.

Reductive Activation of C70 Equatorial Carbons and Structurally Characterized C70 δ-Adduct with Closed [5,6]-Ring Fusion.

The C70 δ-adducts with closed [5,6]-ring fusion are an important type of compound in classifying bond delocalization in the equatorial belt of C70. However, the formation of such compounds is severely restricted due to the low reactivity of the carbon atoms in the flat equatorial region. Such a restriction is lifted when reduced anionic C70 species are used, where the inert equatorial carbon atoms are activated.

Regiocontrolled Electrosynthesis of [60]Fullerene Bisadducts: Photovoltaic Performance and Crystal Structures of C60 o-Quinodimethane Bisadducts.

C60 o-quinodimethane bisadducts [C60(QM)2] are promising electron acceptors for bulk heterojuction (BHJ) organic solar cells (OSCs). However, previous production of C60(QM)2 often resulted in excessive regioisomers, which were difficult to purify and might consequently obscure the structure-performance study of the organofullerene acceptors. Herein, the electrosynthesis of C60(QM)2 is reported. The reaction exhibits a strong regiocontrol with generation of fewer regioisomers. Pure regioisomers of cis-2, trans-3, and e C60(QM)2 are obtained, and the structures are solved with single-crystal X-ray diffraction. Interestingly, the cis-2 and trans-3 regioisomers exhibit better photovoltaic performance than the e regioisomer in the OSCs based on poly(3-hexylthiophene) (P3HT), which can be correlated with their structural difference.

Vis-Near-IR Spectroscopic and Time-Dependent DFT Study of Reduced Singly Bonded C60 Species.

Reduced fullerenes and fullerene derivatives exhibit intense absorptions in the vis-near-IR (vis-NIR) region. The absorptions are sensitive toward the addition pattern, number of addends, and oxidation state of the fullerene species and are used as an important benchmark for identifying anionic fullerene species. Similar absorptions are also shown for the reduced singly bonded C60 species, which are electronically different from reduced fullerene derivatives. However, much less work has been carried out on the vis-NIR spectroscopic study of the anionic singly bonded C60 species, likely due to the difficulty in controlled production of these species. Herein, we report the vis-NIR spectroscopic study of the mono- and dianions of the singly bonded C60 species (RC60(-), R(-)C60(-), and RC60(2-•)), which are selectively generated by controlled-potential bulk electrolysis (CPE) of the singly bonded C60 dimer and C60 oxazolino heterocycles. Time-dependent density functional theory (TD-DFT) calculations were performed to rationalize the experimental results.

Estrogen regulates the expression of small-conductance Ca-activated K+ channels in colonic smooth muscle cells.

AIM: This study aimed to determine the effects of small-conductance Ca(2+)-activated K(+) (SK) channels in colonic relaxation and the regulation of SK channels by estrogen. METHODS: The contractile activity of muscle strips from male rats was estimated, and drugs including vehicle (DMSO), 17ß-estradiol (E2), or apamin (SK blocker) were added, respectively. In a further experiment, muscle strips were preincubated with apamin before exposure to E2. The levels of the SK2 and SK3 protein expression in the colonic smooth muscle cells (SMCs) were detected. SMCs were treated with ICI 182780 (estrogen receptor [ER] antagonist) plus E2, BSA-E2, PPT (ERα agonist), or DPN (ERß agonist). SK3 mRNA and protein expression levels were detected. RESULTS: The muscle strips responded to E2 with a decrease and to apamin with a transient increase in tension. Preincubation with apamin partially prevented E2-induced relaxation. Two SK channel subtypes, SK2 and SK3, were coexpressed with α-actin in colonic SMCs. The quantitative ratio of the SK transcriptional expression in colonic SMCs was SK3 > SK2. The SK3 expression was upregulated by E2, and was downregulated by ICI 182780, but was not influenced by BSA-E2. Furthermore, the effect of PPT on the expression of SK3 was almost the same as that of E2, while DPN did not influence the protein expression of SK3. CONCLUSION: These findings indicate that SK3 is involved in the E2-induced relaxing effect on rat colonic smooth muscle. Furthermore, E2 upregulates the expression of SK3 in rat SMCs, and that this effect is mediated via the ERα receptor.

Identification and differential expression of hepatopancreas microRNAs in red swamp crayfish fed with emodin diet.

Using high-throughput Illumina Solexa system, the differential miRNA expressions from hepatopancreas in red swamp crayfish (Procambarus clarkii) fed with diets containing 0 (control) and 75 mg emodin kg(-1) (trial) were identified, respectively. As a result, 13,335,928 raw reads from the control sample and 14,938,951 raw reads from the trial sample were obtained while 13,053,344 (98.77%) and 14,517,522 (98.34%) small RNA were identified, respectively. 106 mature miRNAs (belonging to 68 miRNA gene families) were identified. 35 miRNAs displayed significantly differential expressions between two libraries. Of these, comparing to the control library, 6 miRNAs were significantly up-regulated and 29 miRNAs were significantly down-regulated. Moreover, 5 novel miRNAs (2 from control sample, 3 from trial sample) and target genes were predicted. GO analysis suggested that these miRNAs might be involved in innate immune response, growth, metabolism, cellular process, biological regulation and stimulus response. Our knowledge from this study could contribute to a better understanding of the miRNAs roles in regulating innate immune response and the study of miRNA function in crayfish.

Neuroregeneration in the nucleus ambiguus after recurrent laryngeal nerve avulsion in rats.

OBJECTIVES: The objective was to investigate neuroregeneration, the origins of newborn cells and the proliferation of neuronal and glial cells in the nucleus ambiguus (NA) after ipsilateral recurrent laryngeal nerve (RLN) avulsion. METHODS: All of the animals received a CM-Dil injection in the left lateral ventricle. Forty-five adult rats were subjected to a left RLN avulsion injury, while 9 rats were used as controls. 5-Bromo-2-deoxyuridine (BrdU) was injected intraperitoneally. Neuron quantification and immunohistochemical analysis were performed in the brain stems at different time points after RLN injury. RESULTS: After RLN avulsion, CM-Dil labeled neural progenitor cells (NPCs) migrated to the ipsilateral NA and differentiated into astrocytes but not into neurons. In the NA, the neuronal cells re-expressed nestin. Only a small number of neuronal and glial cells in the NA showed BrdU immunoreactivity. CONCLUSIONS: After RLN avulsion, the NPCs in the ependymal layer of the fourth ventricle or central canal are activated, migrate to the lesion in the NA and differentiate exclusively into astrocytes. The newborn neural stem cells in the NA may arise from the mature region neurons. The presence of both cell types in the NA may play a role in repairing RLN injuries.

Optimization of nursing interventions for postoperative mental status recovery in patients with cerebral hemorrhage.

BACKGROUND: Hypertensive cerebral hemorrhage (HCH), the most common chronic diseases, has become a topic of global public health discussions. AIM: To investigate the role of rehabilitative nursing interventions in optimizing the postoperative mental status recovery phase and to provide clinical value for future rehabilitation of patients with HCH. METHODS: This randomized controlled study included 120 patients with cerebral HCH who were contained to our neurosurgery department between May 2021-May 2023 as the participants. The participants have randomly sampled and grouped into the observation and control groups. The observation group received the rehabilitation nursing model, whereas the control group have given conventional nursing. The conscious state of the patients was assessed at 7, 14, 21, and 30 d postoperatively. After one month of care, sleep quality, anxiety, and depression were compared between the two groups. Patient and family satisfaction were assessed using a nursing care model. RESULTS: The results showed that the state of consciousness scores of the patients in both groups significantly increased (P < 0.05) after surgical treatment. From the 14th day onwards, differences in the state of consciousness scores between the two groups of patients began to appear (P < 0.05). After one month of care, the sleep quality, anxiety state, and depression state of patients were significantly better in the observation group than in the control group (P < 0.05). Satisfaction with nursing care was higher in the observation group than in the control group (P < 0.05). CONCLUSION: The rehabilitation nursing model has a more complete system compared to conventional nursing, which can effectively improve the postoperative quality of life of patients with cerebral hemorrhage and improve the efficiency of mental state recovery; however, further analysis and research are needed to provide more scientific evidence.

Circular DNAzyme-Switched CRISPR/Cas12a Assay for Electrochemiluminescent Response of Demethylase Activity.

DNA nanostructure provides powerful tools for DNA demethylase activity detection, but its stability has been significantly challenged. By virtue of circular DNA with resistance to exonuclease degradation, herein, the circular DNAzyme duplex with artificial methylated modification was constructed to identify the target and output the DNA activators to drive the CRISPR/Cas12a, constructing an "on-off-on" electrochemiluminescence (ECL) biosensor for monitoring the activity of the O6-methylguanine-DNA methyltransferase (MGMT). Specifically, the circular DNAzyme duplex consisted of the chimeric RNA-DNA substrate ring with double activator sequences and two single-stranded DNAzymes, whose catalytic domains were premodified with the methyl groups. When the MGMT was present, the methylated DNAzymes were repaired and restored the catalytic activity to cleave the chimeric RNA-DNA substrates, followed by the output of DNA activators to initiate the CRISPR/Cas12a. Subsequently, the ECL signals of silver nanoparticle-modified SnO2 nanospheres (Ag@SnO2) were recovered by releasing the ferrocene-labeled quenching probes (Fc-DNA) from the electrode surface because of the trans-cleavage activity of CRISPR/Cas12a, thus achieving the specific and sensitive ECL detection of MGMT from 2.5 × 10-4 to 2.5 × 102 ng/mL with a low limit (9.69 × 10-5 ng/mL). This strategy affords novel ideas and insights into research on how to project stable nucleic acid probes to detect DNA demethylases beyond traditional methods.