Meroterpenoids with divers' rings systems from Phyllosticta capitalensis and their anti-inflammatory activity.

Four undescribed sesquiterpene-shikimates (1-4), eight undescribed monoterpene-shikimates (5-12), together with two known ones were isolated and identified from the 95% ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Capitalensis A (1) was identified as the first sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid degradation product, while capitalensis B (2) is a sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid with a unique D-ring formed by a C-2-O-C-9' connection. The structures of these previously undescribed compounds were elucidated by multiple techniques, including IR, HR-ESI-MS, and NMR analysis. Furthermore, their absolute configurations were established through the comprehensive approach that involved the calculations of ECD spectra, optical rotation values, and single-crystal X-ray analysis. Moreover, the anti-inflammatory activity of all isolated compounds was evaluated using a lipopolysaccharide (LPS)-induced inflammation model in BV2 microglial cells. Meanwhile, these compounds exhibited activity in inhibiting NO production. Four compounds, capitalensis C (3), capitalensis D (4), 15-hydroxyl tricycloalternarene 5b (13) and guignarenone A (14) showed strong inhibitory effects with IC50 values of 21.6 ± 1.33, 12.2 ± 1.08, 18.6 ± 1.27, and 15.8 ± 1.20 µM, respectively. In addition, the structure-activity relationship of the anti-inflammatory activity of the compounds was discussed.

Chlorophyllin-Containing Copolymers and Their Responsive Properties.

Copper-chlorophyllin is a water-soluble derivative of chlorophylls and shows low cytotoxicity and antimutagenic properties in cultured cells. It has multiple applications, including its use as a photosensitizer in photothermal therapy because of its green light-activated photothermal performance. In this work, it was copolymerized with a poly(ethylene glycol) methacrylic monomer to yield random copolymers by free radical polymerization, which showed dual temperature- and pH-dependent phase transitions in aqueous solutions. The cloud points of the copolymer solutions were raised by lowering the pH of the aqueous solutions due to the protonation of the carboxylic groups on the chlorophyllin moieties, which decreased the overall hydrophilicity of the polymers. At low pH values, complete protonation of the carboxylic acid groups of the chlorophyllin moieties led to an irreversible aggregation of the copolymers in water. The incorporation of chlorophyllin in the copolymer improved its stability over its single molecular form.

A Novel Flp Reporter Mouse Shows That TRPA1 Expression Is Largely Limited to Sensory Neuron Subsets.

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal cation channel that is activated by electrophilic irritants, oxidative stress, cold temperature, and GPCR signaling. TRPA1 expression has been primarily identified in subsets of nociceptive sensory afferents and is considered a target for future analgesics. Nevertheless, TRPA1 has been implicated in other cell types including keratinocytes, epithelium, enterochromaffin cells, endothelium, astrocytes, and CNS neurons. Here, we developed a knock-in mouse that expresses the recombinase FlpO in TRPA1-expressing cells. We crossed the TRPA1Flp mouse with the R26ai65f mouse that expresses tdTomato in a Flp-sensitive manner. We found tdTomato expression correlated well with TRPA1 mRNA expression and sensitivity to TRPA1 agonists in subsets of TRPV1 (transient receptor potential vanilloid receptor type 1)-expressing neurons in the vagal ganglia and dorsal root ganglia (DRGs), although tdTomato expression efficiency was limited in DRG. We observed tdTomato-expressing afferent fibers centrally (in the medulla and spinal cord) and peripherally in the esophagus, gut, airways, bladder, and skin. Furthermore, chemogenetic activation of TRPA1-expressing nerves in the paw evoked flinching behavior. tdTomato expression was very limited in other cell types. We found tdTomato in subepithelial cells in the gut mucosa but not in enterochromaffin cells. tdTomato was also observed in supporting cells within the cochlea, but not in hair cells. Lastly, tdTomato was occasionally observed in neurons in the somatomotor cortex and the piriform area, but not in astrocytes or vascular endothelium. Thus, this novel mouse strain may be useful for mapping and manipulating TRPA1-expressing cells and deciphering the role of TRPA1 in physiological and pathophysiological processes.

A mouse model of repeated traumatic brain injury-induced hearing impairment: Early cochlear neurodegeneration in the absence of hair cell loss.

PURPOSE: Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide. Mounting evidence suggests that even mild TBI injuries, which comprise >75% of all TBIs, can cause chronic post-concussive neurological symptoms, especially when experienced repetitively (rTBI). The most common post-concussive symptoms include auditory dysfunction in the form of hearing loss, tinnitus, or impaired auditory processing, which can occur even in the absence of direct damage to the auditory system at the time of injury. The mechanism by which indirect damage causes loss of auditory function is poorly understood, and treatment is currently limited to symptom management rather than preventative care. We reasoned that secondary injury mechanisms, such as inflammation, may lead to damage of the inner ear and parts of the brain used for hearing after rTBI. Herein, we established a model of indirect damage to the auditory system induced by rTBI and characterized the pathology of hearing loss. METHODS: We established a mouse model of rTBI in order to determine a timeline of auditory pathology following multiple mild injuries. Mice were subject to controlled cortical impact at the skull midline once every 48 h, for a total of 5 hits. Auditory function was assessed via the auditory brainstem response (ABR) at various timepoints post injury. Brain and cochleae were collected to establish a timeline of cellular pathology. RESULTS: We observed increased ABR thresholds and decreased (ABR) P1 amplitudes in rTBI vs sham animals at 14 days post-impact (dpi). This effect persisted for up to 60 days (dpi). Auditory temporal processing was impaired beginning at 30 dpi. Spiral ganglion degeneration was evident at 14 dpi. No loss of hair cells was detected at this time, suggesting that neuronal loss is one of the earliest notable events in hearing loss caused by this type of rTBI. CONCLUSIONS: We conclude that rTBI results in chronic auditory dysfunction via damage to the spiral ganglion which occurs in the absence of any reduction in hair cell number. This suggests early neuronal damage that may be caused by systemic mechanisms similar to those leading to the spread of neuronal death in the brain following TBI. This TBI-hearing loss model provides an important first step towards identifying therapeutic targets to attenuate damage to the auditory system following head injury.

Facile Obtainment of Fluorescent PEG Hydrogels Bearing Pyrene Groups by Frontal Polymerization.

Frontal polymerization (FP) was used to prepare poly(ethylene glycol) methyl ether acrylate (PEGMA) fluorescent polymer hydrogels containing pyrenebutyl pendant groups as fluorescent probes. The polymerization procedure was carried out under solvent-free conditions, with different molar quantities of pyrenebutyl methyl ether methacrylate (PybuMA) and PEGMA, in the presence of tricaprylmethylammonium (Aliquat 336®) persulfate as a radical initiator. The obtained PEGPy hydrogels were characterized by FT-IR spectroscopy, confirming the effective incorporation of the PybuMA monomer into the polymer backbone. The thermal properties of the hydrogels were determined using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). After immersing the hydrogels in deionized water at 25 °C and pH = 7, their swelling behavior was investigated by mass gain at different pH and temperature values. The introduction of PybuMA comonomer into the hydrogel resulted in a decreased swelling ability due to the hydrophobicity of PybuMA. The optical properties of PEGPy were determined by UV-visible absorption and fluorescence spectroscopies. Both monomer and excimer emission bands were observed at 379-397 and 486 nm, respectively, and the fluorescence spectra of the PEGPy hydrogel series were recorded in different solvents to explore the coexistence of monomer and excimer emissions.

Radiotherapy combined with PD-1/PD-L1 inhibitors in NSCLC brain metastases treatment: The mechanisms, advances, opportunities, and challenges.

At present, whole-brain radiation therapy/stereotactic radiosurgery is one of the main local treatments for brain metastasis of non-small-cell lung cancer (NSCLC). Currently, it has been proved that radiotherapy (RT) can regulate the immune response, and small-sample studies have shown that patients with NSCLC brain metastases (BMs) can benefit from RT combined with immunotherapy (IO). However, the efficacy and safety of the combination treatment have not been deeply elaborated. Notably, as a challenge that is still being explored, the timing of RT combined with IO is likely to be an important factor affecting efficacy and prognosis. This article reviews the current application and challenges of RT combined with IO from the perspectives of molecular mechanism, combination timing, safety, and efficacy. The purpose is to provide information on clinical evidence-based medicine of combination between RT with IO. For further investigation, we also discuss the major challenges and prospects of RT combined with IO in NSCLC BMs.

The Pharmacokinetics and Pharmacodynamics of A Novel Recombinant Activated Human Factor VII, GEN-0828, in Hemophilia B Mice.

GEN-0828, a proposed clinical candidate for hemophilia and trauma hemorrhage treatment, is a novel recombinant activated human factor VII (rFVIIa). The purpose of this paper is to compare the pharmacokinetics and pharmacodynamics of GEN-0828 in hemophilia B mice with those of NovoSeven®, the only marketed rFVIIa product worldwide., GEN-0828 and NovoSeven® showed similar affinity bioactivity to recombinant tissue factor (rTF) in vitro. Pharmacodynamics data indicated a generally similar hemostatic efficacy (ED50) of GEN-0828 (10.91 KIU·kg-1) and NovoSeven® (18.91 KIU·kg-1) at the doses studied in hemophilia B mice, while GEN-0828 represented a lower initial effective dosage compared with that of NovoSeven® in terms of both blood loss and APTT. GEN-0828 exhibited linear pharmacokinetic profiles in hemophilia B mice at the 30-338 KIU·kg-1 dose range, the comparative pharmacokinetic study with NovoSeven® indicated better characteristics than NovoSeven® in terms of the appropriate higher maximal concentration (Cmax) and area under the plasma concentration-time curve (AUClast) and longer mean residence time (MRT). In conclusion, GEN-0828 was a promising new type of rFVIIa compound with favourable pharmacokinetic and pharmacodynamic profiles.

Buserelin Inhibits the Immunosuppressive Activity of Regulatory T Cells through the Protein Kinase A Signaling in a Central Precocious Puberty Model.

BACKGROUND: Gonadotropin-releasing hormone analogs (GnRHas) are used for treating central precocious puberty (CPP). However, their roles in the regulation of immune cells especially regulatory T cells (Tregs) remains elusive. Therefore, we characterized buserelin-induced phenotypical and functional changes of Tregs. METHODS: A rat CPP model was established followed by administration of buserelin acetate. Flow cytometry was used to evaluate the expression of functional molecules in splenic Tregs. The suppressive activity of Tregs was determined by the suppression assay. GnRHR expression in Tregs was assessed by flow cytometry analysis and Immunoblotting. Normal Tregs were then stimulated and treated with buserelin acetate in vitro. After that, Foxp3 expression, Treg proliferation, and cytokine production were analyzed by flow cytometry. Intracellular signaling was evaluated by Immunoblotting, and Treg function was determined by the suppression assay. RESULTS: After in vivo buserelin treatment, the frequency of splenic Tregs was decreased, with the reduction in the expression of Foxp3, IL-10, and TGF-ß. The suppressive activity of Tregs was weakened. Buserelin down-regulated Foxp3 expression while promoting the expression of RORγt and IL-17 in Tregs through activating the protein kinase A (PKA) pathway in vitro. The PKA inhibitor H-89 abolished the effect of buserelin and enhanced Treg function. CONCLUSION: Buserelin impaired the immunosuppressive activity of Tregs through the PKA signal pathway. Buserelin-induced activation of PKA signaling down-regulated Foxp3 expression while promoting RORγt expression in Tregs, and subsequently weakened Treg function. Our study indicates the necessity of monitoring Treg activity in CPP patients to avoid potential autoimmunity or inflammation.

Guest-Mediated Reversal of the Tumbling Process in Phosphorus-Dendritic Compounds Containing ß-Cyclodextrin Units: An NMR Study.

The conformational study of dendritic platforms containing multiple ß-cyclodextrin (ßCD) units in the periphery is relevant to determine the availability of ßCD cavities for the formation of inclusion complexes in aqueous biological systems. In this work, we performed a detailed conformational analysis in D2O, via 1D and 2D NMR spectroscopy of a novel class of phosphorus dendritic compounds of the type P3N3-[O-C6H4-O-(CH2)n-ßCD]6 (where n = 3 or 4). We unambiguously demonstrated that a functionalized glucopyranose unit of at least one ßCD unit undergoes a 360° tumbling process, resulting in a deep inclusion of the spacer that binds the cyclodextrin to the phosphorus core inside the cavity, consequently limiting the availability of the inner cavities. In addition, we confirmed through NMR titrations that this tumbling phenomenon can be reversed for all ßCD host units using a high-affinity guest, namely 1-adamantanecarboxylic acid (AdCOOH). Our findings have demonstrated that it is possible to create a wide variety of multi-functional dendritic platforms.

Melatonin Alleviates Acute Gouty Inflammation In Vivo and In Vitro.

The aim of this study was to identify the effects of melatonin on acute gouty inflammation and to investigate the underlying mechanisms. We found significantly lower serum melatonin levels in gout patients in the acute phase than in those in the remission phase or in normal individuals. The mRNA expression of melatonin receptor 2 (MT2) was also lower in gout patients than in normal individuals. To verify the in-vivo role of melatonin, a gouty arthritis model was established by intraarticular injection of monosodium urate (MSU, 1 mg) crystals into the paws of C57BL/6 mice. Joint inflammation in the mouse model was evaluated by measuring the thickness of the right paw/left paw, and the inflammation index was determined by examining infiltrating neutrophils with haematoxylin and eosin (H&E) staining. Melatonin was found to reduce both paw thickness and the inflammation index in the mouse model, and melatonin also reduced the mRNA levels of interleukin-1 beta (IL-1ß), IL-6 and NLR family pyrin domain containing 3 (NLRP3) inflammasome. To mimic gouty inflammation in vitro, mouse peritoneal macrophages were stimulated with lipopolysaccharides (LPS) plus MSU. Melatonin was revealed to reduce IL-1ß secretion by stimulated macrophages. The mRNA expression levels of IL-1ß and IL-6 were also inhibited by melatonin. Western blot analysis showed that the expression of NLRP3, caspase-1 and pro-IL-1ß was also inhibited by melatonin. In conclusion, our study demonstrated that melatonin alleviated gouty inflammation in vivo and in vitro, and the underlying mechanism may involve inhibiting the assembly of the NLRP3 inflammasome.

How Does Information Sharing of a Supervisor Influence Proactive Change Behavior of an Employee? The Chain Mediating Role of Family-Like Employee-Organization Relationship and Relationship Energy.

The proactive change behavior of an employee is the key to promoting organizational innovation. However, the proactive change has a certain risk, and many employees are unwilling to implement initiatively. How to promote the occurrence of a proactive change behavior of an employee has become a hot issue in the theoretical and practical areas. Based on the self-disclosure theory, this study uses the questionnaire survey method, containing a total of 32 items, and uses the 5-point Likert scale (1 = strongly disagree and 5 = strongly agree), with the Mplus and SPSS statistical software to analyze the impact mechanism of work-related information sharing of supervisors on the proactive change behavior of employees through the structural equation model. The regulatory effect of non-work information sharing of leaders is analyzed using the latent regulatory structural equation method. The conclusions are as follows: work-related information sharing positively of supervisors influences the family-like employee-organization relationship of employees; the family-like employee-organization relationship and relationship energy play serial mediating roles in the relationship between work-related information sharing of supervisors and the proactive change behavior of employees; non-work information sharing of supervisors moderates the serial mediating path by enhancing the positive influence of work-related information sharing of supervisors on the family-like employee-organization relationship. Theoretically, this study has complemented and enriched the research on the influence mechanism between the information sharing of supervisors and the proactive change behavior of employees. Practically, this study has important implications for supervisors to promote the proactive change behavior of employees by sharing work-related information and non-work information with employees.

[Contrast-enhanced Ultrasonography and Color Doppler Ultrasonography for Dynamic Assessment of Intracranial Changes in Early MCAO Rats Models].

OBJECTIVE: To assess the value of contrast-enhanced ultrasound (CEUS) and color Doppler ultrasound (DUS) on hemodynamic changes and cerebral perfusion quantitative analyses in Sprague-Dawley (SD) rats with focal permanent ischemic stroke. METHODS: Sixteen SD rats with thin skulls were subjected to establish middle cerebral artery occlusion (MCAO) model. CEUS images were performed before modeling (T 0), immediately after modeling (5-15 min after modeling, T 1), 3 h after modeling (T 2), followed by the measurement of bilateral middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA) using DUS. The peak systolic velocity (PSV), end-diastolic velocity (EDV) and mean velocity (MV) of these arteries were obtained. The brain time-intensity curve was taken as interest region of the whole right brain, and the quantitative parameters of CEUS were obtained, including peak intensity (PI), area under the curve ( AUC), wash in slope (WIS), time to peak (TTP), rise time (RT) and time from peak to one half (TPH). The modified neurological deficit score (mNSS) of the rats was performed 3 h after the modeling, and the data of the rats with a score of 9-11 were statistically analyzed. RESULTS: A total of 12 rats were successfully modeled and completed with mNSS score 9-11. No blood flow signals were observed on the right MCA and ACA in the 12 rats at T 1 and T 2. From T 0 to T 1, PI, AUC and WIS of the right hemisphere decreased sharply with TTP and RT significantly prolonged, and the differences were statistically significant. However, there was no significant difference in hemodynamic parameters at that period of time. From T 1 to T 2, there were no significant changes in CEUS quantitative parameters (except AUCand TPH), while PSV, EDV, MV of LMCA and bilateral PCA showed significant acceleration, and the differences were statistically significant. CONCLUSION: CEUS and DUS can reveal the intracranial hemodynamics and brain tissue perfusion trends of MCAO rats, which could be new methods in assessment of ischemic stroke model at multiple time points.

Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies: a systematic review and meta-analysis.

BACKGROUND: Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs. METHODS: We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model. RESULTS: Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE. CONCLUSIONS: The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

Efficient modification of PAMAM G1 dendrimer surface with ß-cyclodextrin units by CuAAC: impact on the water solubility and cytotoxicity.

The toxicity of the poly(amidoamine) dendrimers (PAMAM) caused by the peripheral amino groups has been a limitation for their use as drug carriers in clinical applications. In this work, we completely modified the periphery of PAMAM dendrimer generation 1 (PAMAM G1) with ß-cyclodextrin (ß-CD) units through the Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) to obtain the PAMAM G1-ß-CD dendrimer with high yield. The PAMAM G1-ß-CD was characterized by 1H- and 13C-NMR and mass spectrometry studies. Moreover, the PAMAM G1-ß-CD dendrimer showed remarkably higher water solubility than native ß-CD. Finally, we studied the toxicity of PAMAM G1-ß-CD dendrimer in four different cell lines, human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa) and pig kidney epithelial cells (LLC-PK1). The PAMAM G1-ß-CD dendrimer did not present any cytotoxicity in cell lines tested which shows the potentiality of this new class of dendrimers.

[Application of Multimodal Transcranial Ultrasound in SD Rats of Cerebral Ischemic Model at Super Early Stage].

OBJECTIVE: To determine the value of applying multimodal ultrasound (mUS) in SD rats of cerebral ischemic model at super early stage (5-15 min after modeling). METHODS: Fifteen focal cerebral ischemic models were established in SD rats with thinning skulls using the suture method. Gray-scale ultrasound, contrast-enhanced ultrasound, and enhanced color Doppler (CECDUS) were performed before and immediately after the modeling to observe the location of the in-cranial suture, perfusion of the right hemisphere, and color flow signal of the middle cerebral artery and the anterior cerebral artery, respectively.A modified neurological deficit score (mNSS) and 2, 3, 5-triphenyltetrazolium chloride (TTC) stains were obtained three hours later to confirm the successful modeling as the gold standard. The positive rate detected by mUS was compared with the gold standard using McNemar tests. RESULTS: One rat died and 14 rats completed the experiment.mUS imaging detected 71% (10/14) positive signals, no significant difference compared with the gold standard (64%, 9/14) ( P>0.05). A hyperechoic double-line at the bottom of the right brain and focal hypoperfused areas in the right hemisphere were observed by gray scale ultrasound and contrast-enhanced ultrasound in the successfully modeled rats, respectively. The CECDUS found no blood flow in the anterior and middle cerebral arteries. Time intensity curve (TIC) analyses indicated significant changes in peak intensity (PI), area under the curve (AUC), wash in slope (WIS), and time to peak (TTP) after successful modeling. CONCLUSION: Multimodal ultrasound can assess modeling success quickly and accurately immediately after the establishment of ischemic model of SD rats.

Increased Plasma Levels of S100A8, S100A9, and S100A12 in Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a skin disorder with an important immunologic profile. S100A8, S100A9, and S100A12 are the members of S100 family that have been reported to play important role in autoimmune diseases, but the characteristics of these three S100 members have not been defined in CSU. AIMS: This study was performed to investigate the levels of these three S100s in patients with CSU and to study whether they were associated with the severity and clinical characteristics of CSU. MATERIALS AND METHODS: The levels of plasma S100A8, S100A9, and S100A12 were measured in 51 CSU patients and 20 healthy controls using enzyme linked immunosorbent assay kits. The values in the patient group and that of the healthy controls were statistically compared. The relationships between the different markers were evaluated by correlation analysis. RESULTS: The plasma levels of S100A8, S100A9, and S100A12 were significantly higher in CSU patients than those in controls. Interestingly, the level of S100A12 was significantly correlated with S100A8 and S100A9 in CSU patients (P < 0.05 and P < 0.001, respectively). In addition, S100A8, S100A9, and S100A12 were all significantly inversely correlated with blood basophil percentage. CONCLUSIONS: Plasma S100A8, S100A9, and S100A12 levels were elevated in CSU patients. They might be useful biomarkers of CSU, with the potential role in the pathogenesis of CSU.

[Combined Process of DNBF-O3-GAC for Nitrogen and Phosphorus and Metabolite Advanced Removal].

To improve the quality of the tailings water from a wastewater treatment plant (WWTP), a denitrification biofilter (DNBF) with a composite filler composed of a new slow-release organic-carbon source (SOC-F), sponge iron, and activated carbon was tested. Studies were conducted in the combined process of DNBF-O3-GAC to explore the efficiency of the advanced removal of nitrogen, phosphorus, and microbial metabolite by using synthetic effluent made from running water and chemicals. Corresponding comparative studies were conducted by using the secondary effluent from the WWTP. The microbial population structure in the biofilm of the denitrification biofilter was analyzed by adopting MiSeq high-throughput sequencing technologies. The results indicated that the combination process achieved high efficiency removal of nitrogen, phosphorus, and microbial metabolite. The average removal rate of NO3--N in the simulated and actual water period reached 88.87% and 79.99%, respectively; the average removal rate of TP reached 87.67% and 65.51%, respectively; and the average removal rate of UV254 reached 45.51% and 49.23%, respectively. Each processing unit had different functions. The changes in NO3--N, TN, TP, and TFe mainly occurred in the denitrification biofilter, and the removal of UV254 and the change in the three-dimensional fluorescence intensity mainly occurred in the ozone-activated carbon reactor. The cluster analysis at the genus level indicated that the denitrification system had sulfur autotrophic denitrifying bacteria and heterotrophic denitrifying bacteria. Sulfur autotrophic denitrification increased obviously in the actual water period when relatively lack of carbon sources, and the proportion of Thiobacillus increased from 7.44% to 29.62%. The complementary effect of sulfur autotrophic denitrification and heterotrophic denitrification had extended the use of the new slow-release carbon source.

The Potential Effect of Oral Microbiota in the Prediction of Mucositis During Radiotherapy for Nasopharyngeal Carcinoma.

BACKGROUND: Oral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis. METHODS: Based on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated. FINDINGS: Our results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema - patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89. INTERPRETATION: Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy.

[Effects of Temperature on the Characteristics of Nitrogen and Phosphorus Removal and Microbial Community in SCSC-S/Fe].

In order to investigate the effect of temperature on the cellulose-degrading bacteria and denitrifying bacteria, the denitrification and phosphorus removal of solid carbon source of cellulose corncob+sulfur/sponge iron nitrogen and phosphorus removal composite system, abbreviated as SCSC-S/Fe, was analyzed under different temperature conditions, and the surface structure and microbial properties of corncob before and after reaction were analyzed by scanning electron microscope (SEM) and MiSeq high-throughput sequencing technologies. The results indicated that when temperature increased from 15, 20, 25 to 30℃, the average TN removal rate of the system increased from 78.88% to 92.70%, the average removal rate of TP increased from 82.58% to 89.15%;microbial properties showed that the surface reaction after corncob was dominated by spherical and rod-shaped microorganisms; the proportion of cellulose-degrading bacteria was 11.01% higher at 30℃ than 20℃, and the proportion of denitrifying bacteria decreased by 21.26%. It can be seen that the cellulose -degrading bacteria were more sensitive to the temperature than the denitrification bacteria, and more obviously affected by the temperature.