Phycicoccus sonneraticus sp. nov., a Novel Endophytic Actinobacterium Isolated from the Bark of Sonneratia apetala.

A novel endophytic actinobacterial strain, designated MQZ13P-5T, was isolated from a piece of bark of Sonneratia apetala, collected from Guangxi Zhuang Autonomous Region, China. This strain was Gram-stain positive, aerobic, non-spore-forming, non-motile and rod-shaped. Comparative 16S rRNA gene sequence analysis showed that strain MQZ13P-5T was related to the genus Phycicoccus with exhibiting the highest similarity (98.0%) to Phycicoccus endophyticus IP6SC6T. The phylogenetic trees based on 16S rRNA gene sequences and core genes indicated that strain MQZ13P-5T belonged to the genus Phycicoccus and could not be assigned to any described species. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain MQZ13P-5T and type strains of Phycicoccus species were less than 84% and 27%, respectively, below the thresholds for species delineation. This strain showed chemotaxonomic and phenotypic properties consistent with its classification in the genus Phycicoccus. Based on the taxonomic data, strain MQZ13P-5T should represent a novel species of the genus Phycicoccus, for which the name Phycicoccus sonneraticus sp. nov. is proposed, with the type strain MQZ13P-5T (= CGMCC 1.18744T = JCM 34337T).

Development and validation of a risk score for predicting inconsistent condom use with women among men who have sex with men and women.

BACKGROUND: Men who have sex with men and women (MSMW) are the most important bridge population for HIV transmission. Condom use plays an important role for HIV infection. However the predictors for condom ues with females are not well characterized. METHODS: This was a cross-sectional study. Participants were enrolled by four community-based organizations (CBOs) by offline (bathrooms, bars), and online (gay applications, chat room) from April to December 2019. Electronic questionnare was fulfilled after a face-to-face training led by CBOs. We identified predictors of inconsistent condom use with females by creating a risk score based on regression coefficients. We externally validated this score via an independent cross-sectional survey conducted in Zhejiang Province in 2021. A total of 917, 615 MSMW were included in analysis in 2019 and 2021, seperately. RESULTS: Among 917 MSMW, 73.2% reported heterosexual behavior in the prior 6 months and 38.3% reported inconsistent condom use with females (ICUF) over that time. Compared with heterosexual/unsure MSMW, bisexual MSMW reported more male and female sex partners, higher proportion of inconsistent condom use with males, less commercial sex with males (p < 0.05). Four risky predictors of ICUF were identified: Duration of local residence ≦6 months; more than one male partner in the prior 6 months; inconsistent condom use with males in the prior 6 months; and never heard post-exposure prophylaxis (PEP). The proportions of respondents indicating ICUF in the low- (0), medium- (2-4) and high-risk (6-20) groups (according to our risk scoring system) were 11.7% (14/120), 26.9% (96/357), and 78.1% (125/160), respectively (Ptrend < 0.001). In the validation survey, the respective proportions of those reporting ICUF were 13.4% (15/112), 17.8% (24/185) and 87.3% (96/110) (Ptrend < 0.001). CONCLUSIONS: We developed and validated a predictive risk score for ICUF among MSMW; four factors were identified, of which inconsistent condom use with men was the most important. Risk reduction intervention programs should focus on MSM who report inconsistent condom use with males, never heard PEP, having multiple partners and living in local less than 6 months.

Processing Mechanism of Massa Medicata Fermentata Based on the Correlation Analysis of Strains, Chemical Compositions and Anti-Inflammatory Activity.

The traditional Chinese medicine of fermented medicine may be under the involvement of multiple strains and the interaction between these microorganisms. Liu Shenqu (Massa Medicata Fermentata, MMF) is one of the most widely used fermented medicines, whose potential processing mechanism is still unclear. In this work, UPLC/MS and GNPS methods were employed to rapidly predict chemical compositions in MMF. Moreover, the dynamic changes of strains, chemical compositions and anti-inflammatory activity of MMF during fermentation process were investigated, and subsequently strains-chemical compositions-efficacy interactions were revealed by Pearson correlation analysis and partial least squares regression (PLSR) analysis. As a result, 24 components were identified, and the potential strains including Bacillus, Burkholderia_Caballeronia_Paraburkholderia, Enterobacter, Aspergillus heterocaryoticus, Rhizopus arrhizus, Kazachstania bulderi, which related to the production of anti-inflammatory active ingredients were exposed. These results demonstrated chemical compositions-strains-efficacy interactions during fermentation of MMF, and provide reference for the exploration of the processing mechanism of MMF.

Expression Pattern of ALOXE3 in Mouse Brain Suggests Its Relationship with Seizure Susceptibility.

Arachidonic acid (AA), a polyunsaturated fatty acid, is involved in the modulation of neuronal excitability in the brain. Arachidonate lipoxygenase 3 (ALOXE3), a critical enzyme in the AA metabolic pathway, catalyzes the derivate of AA into hepoxilins. However, the expression pattern of ALOXE3 and its role in the brain has not been described until now. Here we showed that the levels of Aloxe3 mRNA and protein kept increasing since birth and reached the highest level at postnatal day 30 in the mouse hippocampus and temporal cortex. Histomorphological analyses indicated that ALOXE3 was enriched in adult hippocampus, somatosensory cortex and striatum. The distribution was restricted to the neurites of function-specific subregions, such as mossy fibre connecting hilus and CA3 neurons, termini of Schaffer collateral projections, and the layers III and IV of somatosensory cortex. The spatiotemporal expression pattern of ALOXE3 suggests its potential role in the modulation of neural excitability and seizure susceptibility. In fact, decreased expression of ALOXE3 and elevated concentration of AA in the hippocampus was found after status epilepticus (SE) induced by pilocarpine. Local overexpression of ALOXE3 via adeno-associated virus gene transfer restored the elevated AA level induced by SE, alleviated seizure severities by increasing the latencies to myclonic switch, clonic convulsions and tonic hindlimb extensions, and decreased the mortality rate in the pilocarpine-induced SE model. These results suggest that the expression of ALOXE3 is a crucial regulator of AA metabolism in brain, and potentially acts as a regulator of neural excitability, thereby controlling brain development and seizure susceptibility.

Valproate-Induced Epigenetic Upregulation of Hypothalamic Fto Expression Potentially Linked with Weight Gain.

Valproate (VPA), a widely-used antiepileptic drug, is a selective inhibitor of histone deacetylase (HDAC) that play important roles in epigenetic regulation. The patient with different diseases receiving this drug tend to exhibit weight gain and abnormal metabolic phenotypes, but the underlying mechanisms remain largely unknown. Here we show that VPA increases the Fto mRNA and protein expression in mouse hypothalamic GT1-7 cells. Interestingly, VPA promotes histone H3/H4 acetylation and the FTO expression which could be reversed by C646, an inhibitor for histone acetyltransferase. Furthermore, VPA weakens the FTO's binding and enhances the binding of transcription factor TAF1 to the Fto promoter, and C646 leads to reverse effect of the VPA, suggesting an involvement of the dynamic of histone H3/H4 acetylation in the regulation of FTO expression. In addition, the mice exhibit an increase in the food intake and body weight at the beginning of 2-week treatment with VPA. Simultaneously, in the hypothalamus of the VPA-treated mice, the FTO expression is upregulated and the H3/H4 acetylation is increased; further the FTO's binding to the Fto promoter is decreased and the TAF1's binding to the promoter is enhanced, suggesting that VPA promotes the assembly of the basal transcriptional machinery of the Fto gene. Finally, the inhibitor C646 could restore the effects of VPA on FTO expression, H3/H4 acetylation, body weight, and food intake; and loss of FTO could reverse the VPA-induced increase of body weight and food intake. Taken together, this study suggests an involvement of VPA in the epigenetic upregulation of hypothalamic FTO expression that is potentially associated with the VPA-induced weight gain.

Transmission and evolution of OXA-48-producing Klebsiella pneumoniae ST11 in a single hospital in Taiwan.

OBJECTIVES: Epidemic spread of OXA-48-producing Klebsiella pneumoniae, mainly mediated by the transmission of a blaOXA-48-carrying plasmid, has threatened global health during the last decade. Since its introduction to Taiwan in 2013, OXA-48 has become the second most common carbapenemase. We described the transmission and evolution of an OXA-producing K. pneumoniae clone in a single hospital. METHODS: Twenty-two OXA-48 K. pneumoniae were isolated between October 2013 and December 2015. Comparative genomic analysis was performed based on the WGS data generated with Illumina and MinION techniques. RESULTS: Seventeen of the 22 OXA-48 K. pneumoniae that belonged to ST11, with the same capsular genotype, KL64, and differed from each other by seven or fewer SNPs, were considered outbreak strains. Eight of the 17 outbreak strains harboured a 65499 bp blaOXA-48-carrying IncL plasmid (called pOXA48). pOXA48 was absent from the remaining nine strains. Instead, a 24.9 kb blaOXA-48-carrying plasmid fragment was integrated into a prophage region of their chromosomes. Transmission routes of the ST11_KL64 K. pneumoniae sublineages, which carried either pOXA48 or chromosomally integrated blaOXA-48, were reconstructed. CONCLUSIONS: Clonal expansion of ST11_KL64 sublineages contributed to the nosocomial outbreak of OXA-48 K. pneumoniae. The chromosome-borne blaOXA-48 lineage emerged during a 2 year period in a single hospital. Dissemination of OXA-48, which is vertically transmitted in K. pneumoniae even in the absence of selective pressure from antimicrobials, deserves public health attention.

Effects and Mechanisms of Acupuncture Combined with Mesenchymal Stem Cell Transplantation on Neural Recovery after Spinal Cord Injury: Progress and Prospects.

Spinal cord injury (SCI) is a structural event with devastating consequences worldwide. Due to the limited intrinsic regenerative capacity of the spinal cord in adults, the neural restoration after SCI is difficult. Acupuncture is effective for SCI-induced neurologic deficits, and the potential mechanisms responsible for its effects involve neural protection by the inhibition of inflammation, oxidation, and apoptosis. Moreover, acupuncture promotes neural regeneration and axon sprouting by activating multiple cellular signal transduction pathways, such as the Wnt, Notch, and Rho/Rho kinase (ROCK) pathways. Several studies have demonstrated that the efficacy of combining acupuncture with mesenchymal stem cells (MSCs) transplantation is superior to either procedure alone. The advantage of the combined treatment is dependent on the ability of acupuncture to enhance the survival of MSCs, promote their differentiation into neurons, and facilitate targeted migration of MSCs to the spinal cord. Additionally, the differentiation of MSCs into neurons overcomes the problem of the shortage of endogenous neural stem cells (NSCs) in the acupuncture-treated SCI patients. Therefore, the combination of acupuncture and MSCs transplantation could become a novel and effective strategy for the treatment of SCI. Such a possibility needs to be verified by basic and clinical research.

Fabrication of a low background signal glucose biosensor with 3D network materials as the electrocatalyst.

Glucose oxidase (GOx) based biosensor is an effective method to determine glucose level. However, the biosensors embedded with high electroactive species suffered from high background signal levels, which leading to relative low sensitivity for glucose sensing. In this work, a novel 3D network materials based glucose biosensor with low background signal was constructed, which demonstrated high sensitivity and selectivity towards glucose assay. Here, the combination of ionic liquid modified graphene sheets (GS-IL) and Au nanorods (Au NRs) acted as high electroactive catalyst, and thiol-containing silica sol-gel served as a nonconductive matrix to self-assembly of GS-IL and Au NRs to form the three-dimensional (3D) network materials. Meanwhile, the doping amount of the sol-gel had significant influences on electrochemical performance of the 3D network materials based biosensor. As a result, optimized 3.75% doping 3D network materials were selected to construct the glucose biosensor, which exhibited low background signal and high sensitivity. This biosensor was successfully applied in monitoring the glucose levels of serum and brain microdialysate samples.

In vivo monitoring of cerebral glucose with an updated on-line electroanalytical system.

Because cerebral species involve rapid events, increasing the temporal resolution to realize in vivo near-real-time measurements is desirable. Here, we aimed to improve the low resolution of our previous on-line electroanalytical system by decreasing the dead volume and reducing molecular dispersion. This updated system has advantages of elevated time resolution and accelerated analysis for on-line monitoring of glucose versus the previous system. Finally, this new system was successfully applied to continuous measurement of cerebral glucose in vivo during global ischemia/reperfusion events. This study is expected to offer a reliable on-line analytical platform for continuous monitoring of important species associated with fast physiological and pathological events in vivo. Graphical abstract.

Bioinformatic analyses of a potential Salmonella-virus-FelixO1 biocontrol phage BPS15S6 and the characterisation and anti-Enterobacteriaceae-pathogen activity of its endolysin LyS15S6.

Foodborne Enterobacteriaceae pathogens, especially Salmonella, still seriously threaten food safety. To establish a foundation for further developing phage- and endolysin-based methods combating these pathogens, in this study, the newly isolated Salmonella-virus-FelixO1 phage BPS15S6 for biocontrol purposes was characterised by genomic bioinformatic analysis, and then its endolysin LyS15S6 was obtained using a prokaryotic expression system, characterised in vitro and evaluated in the antibacterial efficacy. It was shown that BPS15S6 had an 87,609-bp genome with 130 open reading frames and does not appear to carry known lysogeny-associated genes and other damaging genetic determinants and is unlikely to perform generalised transduction. Furthermore, LyS15S6 was determined to possess the high enzymatic activity of 1,001,000 U mg-1 and the broad spectrum of lysing 56 tested Gram-negative strains. The assays of thermostability and optimum pH revealed that LyS15S6 was stable up to 40 °C and more active at pH 7. Notably, we demonstrate that edible ε-poly-L-lysine (EPL) can be used as an outer-membrane permeabiliser to improve the antibacterial performance of endolysins. When combined with 1 µg ml-1 EPL, 2 µM LyS15S6 could cause 3-4 log viable cell reductions of the three tested Enterobacteriaceae pathogens in vitro after 2 h of reaction at 25 °C and 2.56 and 3.14 log reductions of Salmonella ATCC13076 after 15 min of reaction at 25 °C and 2 h of reaction at 8 °C respectively. A new strategy, the combined application of endolysins and edible EPL for combating Enterobacteriaceae pathogens in food, is thus presented in this work.

Cadmium and arsenic accumulation during the rice growth period under in situ remediation.

Rice (Oryza sativa L.) planted in cadmium (Cd)- and arsenic (As)-contaminated soil is considered the main source of dietary Cd and As intake for humans in Southeast Asia and thereby poses a threat to human health. Minimizing the transfer of these pollutants to rice grain is an urgent task for environmental researchers. The main objective of this study was to investigate the effects and the mechanisms of a combined amendment (hydroxyapatite + zeolite + biochar, HZB) on decreasing Cd and As accumulation in rice. In situ remediation and aqueous solution adsorption experiments were conducted. The results showed that after application of HZB, Cd and As concentrations of the exchangeable fraction and TCLP extraction in soil decreased with the growth of rice plants. Cd concentrations in rice tissues were decreased at the tillering, filling and maturing stages after in situ remediation, while As concentrations in rice tissues were decreased only at the maturing stage. When 8 kg·plot-1 (9000 kg ha-1) HZB was applied, concentrations of Cd and inorganic As in brown rice were decreased to 0.18 and 0.16 mg kg-1, respectively, lower than the levels permissible for grain in China, i.e., 0.2 mg kg-1. Application of HZB reduced Cd accumulation in rice tissues, and the suppression of Cd accumulation was significantly greater than that of As. Furthermore, HZB significantly increased rice grain yield. An aqueous solution adsorption experiment demonstrated that HZB could adsorb and covalently bind Cd and As (V) via -OH, -COOH, -Si-O-Si and CO32- groups to produce carboxylates, silicates and carbonates, thereby promoting in situ immobilization of Cd and As in soil solution.

MDH2 is an RNA binding protein involved in downregulation of sodium channel Scn1a expression under seizure condition.

Voltage-gated sodium channel α-subunit type I (NaV1.1, encoded by SCN1A gene) plays a critical role in the excitability of brain. Downregulation of SCN1A expression is associated with epilepsy, a common neurological disorder characterized by recurrent seizures. Here we reveal a novel role of malate dehydrogenase 2 (MDH2) in the posttranscriptional regulation of SCN1A expression under seizure condition. We identified that MDH2 was an RNA binding protein that could bind two of the four conserved regions in the 3' UTRs of SCN1A. We further showed that knockdown of MDH2 or inactivation of MDH2 activity in HEK-293 cells increased the reporter gene expression through the 3' UTR of SCN1A, and MDH2 overexpression decreased gene expression by affecting mRNA stability. In the hippocampus of seizure mice, the upregulation of MDH2 expression contributed to the decrease of the NaV1.1 levels at posttranscriptional level. In addition, we showed that the H2O2 levels increased in the hippocampus of the seizure mice, and H2O2 could promote the binding of MDH2 to the binding sites of Scn1a gene, whereas ß-mercaptoethanol decreased the binding capability, indicating an important effect of the seizure-induced oxidation on the MDH2-mediated downregulation of Scn1a expression. Taken together, these data suggest that MDH2, functioning as an RNA-binding protein, is involved in the posttranscriptional downregulation of SCN1A expression under seizure condition.

Damxungmacin A and B, Two New Amicoumacins with Rare Heterocyclic Cores Isolated from Bacillus subtilis XZ-7.

Two new amicoumacins, named Damxungmacin A (1) and B (2), were isolated from the culture broth of a soil-derived bacterium Bacillus subtilis XZ-7. Their chemical structures were elucidated by spectroscopic studies (UV, IR, NMR and HR-ESI-MS). Compound 1 possessed a 1,4-diazabicyclo[2.2.1]heptane-2-one ring system in its structure, which was reported for the first time, while 2 had a 1-acetylmorpholine-3-one moiety, which was naturally rare. Compound 1 exhibited moderate to weak cytotoxic activities against three human tumor cell lines (A549, HCT116 and HepG2) with IC50 values of 13.33, 14.34 and 13.64 µM, respectively. Meanwhile, compound 1 showed weak antibacterial activities against some strains of Staphylococcus epidermidis, while compound 2 at 16 µg/mL did not show antibacterial activity.

Progesterone and vitamin D combination therapy modulates inflammatory response after traumatic brain injury.

OBJECTIVE: Inflammation is an important component of the response to traumatic brain injury (TBI). Progesterone has been shown to inhibit neuroinflammation following (TBI) and may do so through Toll-like receptor (TLR)-mediated pathways. In vitro studies indicate that 1,25-dihydroxyvitamin D(3) (VDH) may also modulate the inflammatory response through the TLR4 pathway. This study tested the hypothesis that PROG and VDH would exert additive and synergistic neuroprotective effects compared with individual treatment by modulating TLR4/NF-κB-mediated inflammation pathways after TBI in rats. RESEARCH DESIGN AND METHODS: Bilateral medial frontal cortical impact injury was induced in young adult Sprague-Dawley rats. Progesterone (i.p., 16 mg kg-1 body weight) and VDH (1 µg kg-1 body weight) were injected separately or combined at 1 and 6 hours after surgery. Rats were killed 24 hours post-surgery and peri-contusional brain tissue harvested for immunostaining and protein measurement. RESULTS: TLR4, phosphorylation of NF-κB, neuronal loss and astrocyte activation were significantly reduced with combination treatment after TBI compared to each agent given individually. CONCLUSIONS: At 24 hours after TBI, combination therapy shows greater efficacy in reducing neuroinflammation compared to progesterone and VDH given separately, and does so by modulating the TLR4/NF-κB signalling pathway.

[Intratympanic methylprednisolone hemisuccinate injection in treating the refractory noise induced deafness].

OBJECTIVE: To analyze the efficacy of Methylprednisolone hemisuccinate intratympanic injection for refractory noise induced deafness. METHODS: One hundred and twenty cases (215 ears) of noise induced deafness were treated with either hormone group (107 ears) or with non hormone group (108 ears). Following prior interventions, 145 ears went on to receive intratympanic Methylprednisolone hemisuccinate injection twice a week. RESULTS: After Intratympanic therapy, the total effective rate was 46.2%. 32 of 71 ears (45.1%) demonstrated hearing improvement in hormone group and 35 of 74 ears (47.3%) in non hormone group. The difference was statistically insignificant (P = 0.788). CONCLUSION: Intratympanic therapy appears to provide additional treatment benefits for patients with refractory noise induced deafness who have been treated with prior interventions. The outcome is not affected by pretreatment with hormone.

The Clinical Features and Prognosis of Gastric Remnant Carcinoma after Treatment.

BACKGROUND/AIMS: The incidence of gastric remnant carcinoma does not decrease after partial gastrectomy The aim of this study was to evaluate the clinical features and prognosis of gastric remnant carcinoma after treatment. METHODOLOGY: Among 412 gastric carcinoma patients who were admitted to our hospital 21 were found to have gastric remnant carcinoma. We analyzed their clinicopathological features and prognosis. RESULTS: Prognosis did not differ significantly in terms of gender, age, tumor-lymph node-metastasis stage, tumor location, and time interval between first and subsequent operations. However, it was influenced by intensive curative gastrectomy with or without resection of local lymph nodes. CONCLUSION: Long-term follow-up after gastrectomy, appropriate curative resection, as well as prevention and management of hypertensive disease co-mobility are important to improve survival rate of gastric remnant carcinoma operation.

Hydrogen sulfide attenuates depression-like behaviours in Parkinson's disease model rats by improving synaptic plasticity in a hippocampal Warburg effect-dependent manner.

BACKGROUND: Depression is a highly prevalent comorbidity arising in patients with Parkinson's disease (PD). However, depression in patients with PD is poorly treated. Hydrogen sulfide (H2S), a neuromodulator, has the potential to relieve depression. OBJECTIVE: To investigate whether H2S attenuates depression-like behaviours in a rat model of PD and examine the underlying mechanisms. METHODS: We utilised rotenone to develop a PD model with subcutaneous injections in the dorsal cervical region of Sprague-Dawley rats. The depression-like behaviours in the rotenone-induced PD model rats were assessed through forced swimming, tail suspension, open field, novelty-suppressed feeding, and elevated plus-maze tests. The expression of postsynaptic density protein-95 and synapsin-1, related to synaptic plasticity, was detected using Western blot in the hippocampus. The hippocampal ultrastructure, including the synaptic density, length of the synaptic active zone, postsynaptic density thickness, and synaptic gap width, was detected using transmission electron microscopy. RESULTS: We proved that sodium hydrosulfide (NaHS; a donor of H2S) significantly attenuated the depression-like behaviours and disorders of hippocampal synaptic plasticity in rotenone-induced PD rats. Furthermore, inhibition of the hippocampal Warburg effect by 2-deoxyglucose abolished NaHS-enhanced hippocampal synaptic plasticity and reversed NaHS-attenuated depression-like behaviours in the rotenone-induced PD rats. CONCLUSION: H2S attenuates PD-associated depression by improving the hippocampal synaptic plasticity in a hippocampal Warburg effect-dependent manner.

Progesterone and vitamin D: Improvement after traumatic brain injury in middle-aged rats.

Progesterone (PROG) and vitamin D hormone (VDH) have both shown promise in treating traumatic brain injury (TBI). Both modulate apoptosis, inflammation, oxidative stress, and excitotoxicity. We investigated whether 21 days of VDH deficiency would alter cognitive behavior after TBI and whether combined PROG and VDH would improve behavioral and morphological outcomes more than either hormone alone in VDH-deficient middle-aged rats given bilateral contusions of the medial frontal cortex. PROG (16 mg/kg) and VDH (5 µg/kg) were injected intraperitoneally 1 h post-injury. Eight additional doses of PROG were injected subcutaneously over 7 days post-injury. VDH deficiency itself did not significantly reduce baseline behavioral functions or aggravate impaired cognitive outcomes. Combination therapy showed moderate improvement in preserving spatial and reference memory but was not significantly better than PROG monotherapy. However, combination therapy significantly reduced neuronal loss and the proliferation of reactive astrocytes, and showed better efficacy compared to VDH or PROG alone in preventing MAP-2 degradation. VDH+PROG combination therapy may attenuate some of the potential long-term, subtle, pathophysiological consequences of brain injury in older subjects.