Disulfidptosis: A new type of cell death.

Disulfidptosis is a novel form of cell death that is distinguishable from established programmed cell death pathways such as apoptosis, pyroptosis, autophagy, ferroptosis, and oxeiptosis. This process is characterized by the rapid depletion of nicotinamide adenine dinucleotide phosphate (NADPH) in cells and high expression of solute carrier family 7 member 11 (SLC7A11) during glucose starvation, resulting in abnormal cystine accumulation, which subsequently induces andabnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. This review aimed to summarize the underlying mechanisms, influencing factors, comparisons with traditional cell death pathways, associations with related diseases, application prospects, and future research directions related to disulfidptosis.

Upregulation of Spinal MDGA1 in Rats After Nerve Injury Alters Interactions Between Neuroligin-2 and Postsynaptic Scaffolding Proteins and Increases GluR1 Subunit Surface Delivery in the Spinal Cord Dorsal Horn.

Previous studies suggested that postsynaptic neuroligin-2 may shift from inhibitory toward excitatory function under pathological pain conditions. We hypothesize that nerve injury may increase the expression of spinal MAM-domain GPI-anchored molecule 1 (MDGA1), which can bind to neuroligin-2 and thereby, alter its interactions with postsynaptic scaffolding proteins and increase spinal excitatory synaptic transmission, leading to neuropathic pain. Western blot, immunofluorescence staining, and co-immunoprecipitation studies were conducted to examine the critical role of MDGA1 in the lumbar spinal cord dorsal horn in rats after spinal nerve ligation (SNL). Small interfering ribonucleic acids (siRNAs) targeting MDGA1 were used to examine the functional roles of MDGA1 in neuropathic pain. Protein levels of MDGA1 in the ipsilateral dorsal horn were significantly upregulated at day 7 post-SNL, as compared to that in naïve or sham rats. The increased levels of GluR1 in the synaptosomal membrane fraction of the ipsilateral dorsal horn tissues at day 7 post-SNL was normalized to near sham level by pretreatment with intrathecal MDGA1 siRNA2308, but not scrambled siRNA or vehicle. Notably, knocking down MDGA1 with siRNAs reduced the mechanical and thermal pain hypersensitivities, and inhibited the increased excitatory synaptic interaction between neuroligin-2 with PSD-95, and prevented the decreased inhibitory postsynaptic interactions between neuroligin-2 and Gephyrin. Our findings suggest that SNL upregulated MDGA1 expression in the dorsal horn, which contributes to the pain hypersensitivity through increasing the net excitatory interaction mediated by neuroligin-2 and surface delivery of GluR1 subunit in dorsal horn neurons.

Diagnostic value of LungPoint navigation combined with EBUS-GS & ROSE in peripheral pulmonary nodules.

Background & objectives: Recently, there has been a surge to develop new devices and techniques for the diagnosis of peripheral pulmonary lesions such as the combination of LungPoint navigation and endobronchial ultrasound with a guide sheath (EBUS-GS). The present study aimed to explore the diagnostic value of LungPoint navigation in combination with EBUS-GS and rapid on-site evaluation (ROSE) particularly for peripheral pulmonary nodules. Methods: Patients (n=108) with pulmonary nodules (10 mm ≤ nodal diameter ≤30 mm) presenting to Henan Provincial People's Hospital were detected using chest computed tomographic (CT) scanning and bronchoscopy. All patients were evaluated using LungPoint navigation, EBUS-GS and ROSE techniques to evaluate the positive rate of combined diagnosis using the three methods. Results: A total of 108 patients participated in this study and successfully underwent all the three procedures. Of these, 82 patients were accurately diagnosed, making the overall diagnostic rate of 75.9 per cent for combined LungPoint navigation, EBUS-GS, and ROSE analyses. Further subgroup analysis of the diagnostic rate of the three combined techniques were conducted based on the size of the nodules which showed a diagnostic rate of 65.3 per cent for 10 mm ≤ nodule diameter ≤20 mm and 85.7 per cent for 20 mm ≤ nodal diameter ≤30 mm. Of the 108 patients, 85 had solid nodules and 23 had ground-glass nodules; the positive rate of diagnosis of solid nodules was the highest. The patients ultimately were diagnosed with lung cancer with a positive rate of 83.5 per cent. The sensitivity, specificity and positive and negative predicted values for ROSE were 90.3, 78.3, 84.8 and 83.6 per cent, respectively. Interpretation & conclusions: The combined use of the three techniques can effectively shorten the duration of the total diagnosis period and improve the safety of diagnosis without affecting the detection rate.

Aortic Valve Replacement for Patients with Heyde Syndrome: A Literature Review.

Objective To explore the characteristics and clinical outcomes of patients with Heyde syndrome (HS) who undergo aortic valve replacement (AVR). Methods Electronic databases including PubMed, Embase, Ovid, WANFANG, VIP and CNKI were searched to identify all case reports of HS patients undergoing AVR surgery, using different combinations of search terms "Heyde syndrome", "gastrointestinal bleeding", "aortic stenosis", and "surgery". Three authors independently extracted the clinical data including the patients' characteristics, aortic stenosis severity, gastrointestinal bleeding sites, surgical treatments and prognosis. Results Finally, 46 case reports with 55 patients aging from 46 to 87 years, were determined eligible and included. Of them, 1 patient had mild aortic stenosis, 1 had moderate aortic stenosis, 42 had severe aortic stenosis, and 11 were not mentioned. Gastrointestinal bleeding was detected in colon (n=8), jejunum (n=6), ileum (n=4), cecum (n=3), duodenal (n=3) and multiple sites (n=8). No specific bleeding site was identified in 23 patients. Preoperative hemoglobin level ranged from 43 to 117 g/L. All but one of 16 patients showed decreased level of high molecule weight von Willebrand factor. Of the 55 patients, 43 underwent AVR, and 12 received transcatheter AVR. Aortic valves of 14 cases were replaced by mechanical valves, and 33 cases by biological valves. All patients recovered well during the follow-up, except 5 patients. One patient who had perivalvular leakage and gastrointestinal bleeding after AVR underwent the second AVR. Two patients had recurrent gastrointestinal bleeding. Two patients died of life-threatening acute subdural hematoma and multiple organ failure, respectively. Conclusions HS is a rare syndrome characterized by aortic stenosis and gastrointestinal bleeding. AVR is an effective treatment for HS.

Postoperative tight glycemic control significantly reduces postoperative infection rates in patients undergoing surgery: a meta-analysis.

BACKGROUND: The benefit results of postoperative tight glycemic control (TGC) were controversial and there was a lack of well-powered studies that support current guideline recommendations. METHODS: The EMBASE, MEDLINE, and the Cochrane Library databases were searched utilizing the key words "Blood Glucose", "insulin" and "Postoperative Period" to retrieve all randomized controlled trials evaluating the benefits of postoperative TGC as compared to conventional glycemic control (CGC) in patients undergoing surgery. RESULTS: Fifteen studies involving 5053 patients were identified. As compared to CGC group, there were lower risks of total postoperative infection (9.4% vs. 15.8%; RR 0.586, 95% CI 0.504 to 0.680, p <  0.001) and wound infection (4.6% vs. 7.2%; RR 0.620, 95% CI 0.422 to 0.910, p = 0.015) in TGC group. TGC also showed a lower risk of postoperative short-term mortality (3.8% vs. 5.4%; RR 0.692, 95% CI 0.527 to 0.909, p = 0.008), but sensitivity analyses showed that the result was mainly influenced by one study. The patients in the TGC group experienced a significant higher rate of postoperative hypoglycemia (22.3% vs. 11.0%; RR 3.145, 95% CI 1.928 to 5.131, p <  0.001) and severe hypoglycemia (2.8% vs. 0.7%; RR 3.821, 95% CI 1.796 to 8.127, p <  0.001) as compared to CGC group. TGC showed less length of ICU stay (SMD, - 0.428 days; 95% CI, - 0.833 to - 0.022 days; p = 0.039). However, TGC showed a neutral effect on neurological dysfunction (1.1% vs. 2.4%; RR 0.499, 95% CI 0.219 to 1.137, p = 0.098), acute renal failure (3.3% vs. 5.4%, RR 0.610, 95% CI 0.359 to 1.038, p = 0.068), duration of mechanical ventilation (p = 0.201) and length of hospitalization (p = 0.082). CONCLUSIONS: TGC immediately after surgery significantly reduces total postoperative infection rates and short-term mortality. However, it might limit conclusion regarding the efficacy of TGC for short-term mortality in sensitivity analyses. The patients in the TGC group experienced a significant higher rate of postoperative hypoglycemia. This study may suggest that TGC should be administrated under close glucose monitoring in patients undergoing surgery, especially in those with high postoperative infection risk.

Correction: Yan Chen, et al. Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model. Int. J. Mol. Sci. 2014, 15, 2761-2772.

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Tuning the Origin of Magnetic Relaxation by Substituting the 3d or Rare-Earth Ions into Three Isostructural Cyano-Bridged 3d-4f Heterodinuclear Compounds.

Three isostructural cyano-bridged 3d-4f compounds, [YFe(CN)6(hep)2(H2O)4] (1), [DyFe(CN)6(hep)2(H2O)4] (2), and [DyCo(CN)6(hep)2(H2O)4] (3), were successfully assembled by site-targeted substitution of the 3d or rare-earth ions. All compounds have been structurally characterized to display slightly distorted pentagonal-bipyramidal local coordination geometry around the rare-earth ions. Magnetic analyses revealed negligible magnetic coupling in compound 1, antiferromagnetic intradimer interaction in 2, and weak ferromagnetic coupling through dipolar-dipolar interaction in 3. Under an applied direct-current (dc) field, 1 (Hdc = 2.5 kOe, τ0 = 1.3 × 10(-7) s, and Ueff/kB = 23 K) and 3 (Hdc = 2.0 kOe, τ0 = 7.1 × 10(-11) s, and Ueff/kB = 63 K) respectively indicated magnetic relaxation behavior based on a single [Fe(III)]LS ion and a Dy(III) ion; nevertheless, 2 (Hdc = 2.0 kOe, τ0 = 9.7 × 10(-8) s, and Ueff/kB = 23 K) appeared to be a single-molecule magnet based on a cyano-bridged DyFe dimer. Compound 1, which can be regarded as a single-ion magnet of the [Fe(III)]LS ion linked to a diamagnetic Y(III) ion in a cyano-bridged heterodimer, represents one of the rarely investigated examples based on a single Fe(III) ion explored in magnetic relaxation behavior. It demonstrated that the introduction of intradimer magnetic interaction of 2 through a cyano bridge between Dy(III) and [Fe(III)]LS ions negatively affects the energy barrier and χ″(T) peak temperature compared to 3.

Dual agent loaded PLGA nanoparticles enhanced antitumor activity in a multidrug-resistant breast tumor eenograft model.

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic.

[Effectiveness of different maintenance methods for codonopsis radix].

OBJECTIVE: To observe different maintenance methods including vacuum-packing, storage together with tobacco, storage together with fennel, ethanol steam and sulfur fumigation for the protection of Codonopsis Radix against mildew and insect damage, and to analyze the content of polysaccharide and flavonoids of Codonopsis Radix tested in this studies, so as to look for the scientific maintenance methods replacing traditional sulfur fumigation. METHODS: Except for the sulfur fumigation, naturally air-dried Codonopsis Radix was used to investigate the maintenance effectiveness of the above methods, respectively. Mildew was observed by visual inspection, and the content of polysaccharide and flavonoids were determined by ultra-violet and visible spectrophotometer. Comprehensive evaluation was given based on the results of the different maintenance methods. RESULTS: Low-temperature vacuum-packing, ambient-temperature vacuum-packing and sulfur fumigation could keep Codonopsis Radix from mildew and insect damage for one year, but ambient-temperature vacuum-packing showed flatulent phenomenon; ethanol steam could keep Codonopsis Radix from mildew and insects for over half a year; storage together with tobacco or fennel did not have maintenance effect. The difference of polysaccharide and flavonoids contents of all tested Codonopsis Radix was not statistically significant. CONCLUSION: Low temperature vacuum-packing maintenance can replace traditional sulfur fumigation, and it can maintain the quality of Codonopsis Radix to a certain extent.

[Effect of Codonopsis Radix maintained with sulfur fumigation on immune function in mice].

OBJECTIVE: To investigate the immune function of mice being given the extract of Codonopsis Radix maintained with sulfur fumigation. METHODS: Mice were divided into five groups. Except the normal control group, the mice were fed with the extract of Codonopsis Radix maintained with sulfur fumigation at the high,medium and low doses, as well as medium dose of Codonopsis Radix maintained with low-temperature vacuum method, respectively. Mice were treated once a day for 10 continuous days. Weight change,organ indexes, blood cell indices, macrophage phagocytic function, and IL-2 and IFN-γ levels were measured. RESULTS: Compared with normal control group, Codonopsis Radix maintained with sulfur fumigation at medium and high doses inhibited body weight increase of mice; white blood cell count of high dose group was significantly increased; significant increase of macrophage phagocytosis were observed for all groups except the normal control group; and spleen index and IFN-γ level of Codonopsis Radix maintained with sulfur fumigation medium dose group were increased significantly. CONCLUSION: Codonopsis Radix maintained with sulfur fumigation can promote mouse immune function to a certain degree. There was no difference in immune effect between Codonopsis Radix maintained with sulfur fumigation and low-temperature vacuum method during experimental period. However,taking the extract of Codonopsis Radix maintained with sulfur fumigation can exert negative effect on appetite and body weight in mice.

[Association of folate metabolism genes MTRR and MTHFR with complex congenital abnormalities among Chinese population in Shanxi Province, China].

OBJECTIVE: To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers. METHODS: A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420). RESULTS: SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the recessive model, individuals with GG genotype at rs1801394 and CC genotype at rs1801133 had a relatively low risk of developing birth defects, so the two genotypes were protective factors against birth defects. The homozygous recessive genotype at rs1801133, which served as a protective factor, was associated with ectoderm- or endoderm-derived complex congenital abnormalities, while the homozygous recessive genotype at rs1801394, which served as a protective factor, was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital abnormalities. CONCLUSIONS: Among the Chinese population in Shanxi Province, the SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex congenital abnormalities and related to ectoderm, mesoderm or endoderm development.

A Birth Cohort Study of Neurodevelopmental Outcomes from Birth to 2 Years of Age in Preterm Infants under 34 Weeks of Gestation.

Background: The tissues and organs of premature infants are immature and easily damaged by external adverse factors, leading to functional development disorders and abnormalities. Besides, the incidence of premature babies in various countries has an increasing trend, with the incidence rate exceeding 10%. Objective: This study aims to investigate the neurodevelopment and the incidence of various developmental delays, cerebral palsy, autism spectrum disorder, and audio-visual impairment in premature infants under 34 weeks of gestation from birth to 2 years of age, so as to provide the basis for early intervention of premature infants in the clinic. Methods: A cohort of premature infants was established using 263 premature infants with a gestational age of 28-33 + 6 weeks who were born alive from March 1, 2018, to February 28, 2019, in four tertiary hospitals in Shenzhen. In addition, 263 full-term infants of the same sex who were born in the same period in the four hospitals were randomly selected and paired in a ratio of 1 : 1 as the control group. The subjects were assessed for neurodevelopment using the Gesell test scale at 6, 12, 18, and 24 months after birth (premature infants were corrected for months). We calculated the neurodevelopmental indicators of children in each month of age and the incidence of various developmental delays, cerebral palsy, autism spectrum disorder, and audio-visual impairment in the two groups. Results: The results of this study showed that the cohort of premature infants with birth gestational age less than 34 weeks had higher adaptive, fine motor, and personal-social energy domain development quotient (DQ) values from the corrected gestational age of 6 months to the corrected gestational age of 24 months after birth compared with the full-term cohort. And it also achieved catch-up growth in neurological development, but the detection rates of neurodevelopmental abnormalities at the corrected gestational age of 12 and 24 months were higher than those in the full-term cohort. Conclusion: It is important to reduce the disability rate and degree of premature infants by strengthening the systematic management, early promotion and supervision, as well as early intervention for preterm infants with developmental abnormalities who were born at gestational age less than 34 weeks after birth.

[Effects of Nutrients on the Growth of Microcystis aeruginosa and Bacteria in the Phycosphere].

The "bacteria-algae" system plays an important role in water ecosystems. The effects of bacteria in phycospheres on the growth of Microcystis aeruginosa under in-situ nutrient stimulation were studied to explore the bacteria-algae interaction during a cyanobacteria bloom. The results showed that LB medium could inhibit the growth of M. aeruginosa, and the algicidal rate was 86.49%. Sodium acetate, glucose, and sodium citrate could promote M. aeruginosa, and the growth rate was more than 50%. The addition of nutrients in M. aeruginosa could have changed the biocoenosis in the phycosphere and increased the species richness by 16S rRNA gene sequencing, and the number of bacteria in the phycosphere increased dramatically in the LB medium and peptone groups. The physiological and biochemical responses showed that algae suffered serious lipid peroxidation, and superoxide dismutase (SOD) and catalase (CAT) activities first increased significantly and subsequently decreased under the oxidative stress of LB medium or peptone. Scanning electron microscopy (SEM) indicated that the surface of algae cells appeared wrinkled, invaded, and atrophied under LB medium stimulation, whereas bacteria in the phycosphere significantly increased. Furthermore, six strains of algicidal bacteria were isolated from the LB medium and peptone groups, and the algicidal rate of Bacillus sp. A1 was 97.55%, which confirmed that the phycosphere of M. aeruginosa included algicidal bacteria. Therefore, appropriate external nutrient stimulation can produce algicidal bacteria in situ to prevent cyanobacterial blooms.

Inflammation-Related Gene Signature: An Individualized Risk Prediction Model for Kidney Renal Clear Cell Carcinoma.

BACKGROUND: There is much evidence that confirms the inextricable link between inflammation and malignancy. Inflammation-related regulators were involved in the progression of kidney renal clear cell carcinoma (KIRC). However, the predictive role of single gene biomarkers is inadequate, and more accurate prognostic models are necessary. We undertook the current research to construct a robust inflammation-related gene signature that could stratify patients with KIRC. METHODS: The transcriptome sequencing data along with clinicopathologic information of KIRC were obtained from TCGA. A list of inflammation-related genes was acquired from the Molecular Signatures Database. Using the RNA-seq and survival time data from the TCGA training cohort, an inflammation-related gene signature was built using bioinformatic methods, and its performance in predicting patient prognosis was assessed by Kaplan-Meier and ROC curve analyses. Furthermore, we explored the association of risk score with immune score, stromal score, tumor immune-infiltrating cells (TIICs), immunosuppressive molecules, m6A regulators, and autophagy-related biomarkers. RESULTS: Herein, nine inflammation-related hub genes (ROS1, PLAUR, ACVR2A, KLF6, GABBR1, APLNR, SPHK1, PDPN, and ADORA2B) were determined and used to build a predictive model. All sets, including training set, four testing sets, and the entire TCGA group, were divided into two groups (low and high risk), and Kaplan-Meier curves all showed an adverse prognosis for patients in the high-risk group. ESTIMATE algorithm revealed a higher immune score in the high-risk subgroup. CIBERSORT algorithm illustrated that the high-risk group showed higher-level immune infiltrates. Furthermore, LAG3, TIGIT, and CTLA4 were overexpressed in the high-risk subgroup and positively associated with risk scores. Moreover, except for METTL3 and ALKBH5, the other m6A regulators decreased in the high-risk subgroup. CONCLUSIONS: In conclusion, a novel inflammation-related gene signature comprehensively constructed in the current study may help stratify patients with KIRC.

A new specialization in astrocytes: glutamate- and ammonia-induced nuclear size changes.

We observed nuclear swelling in glutamate (Glu)-treated astrocytes that was concomitant with but independent of astrocytic cell swelling. We confirmed Glu-induced nuclear swelling with nuclei isolated from astrocytes. Ammonia is metabolically related to Glu and could induce a nuclear swelling in intact astrocytes but shrinkage in isolated nuclei. Other compounds such as glutamine, aspartate, taurine, glycine, and ATP did not cause any nuclear swelling in isolated nuclei of astrocytes. Surprisingly, Glu and ammonia did not induce nuclear swelling in microglia, C6, HEK 293, or Hep G2 cell lines in cultures and their isolated nuclei. The Glu- and ammonia-induced nuclear size changes appear to be a specific response of astrocytes to these two closely related metabolic compounds.

[Trends in incidence and long-term recurrence rate of pilonidal sinus disease and analysis of associated influencing factors].

OBJECTIVES: To investigate the trends in incidence and long-term recurrence rate of pilonidal sinus disease (PSD) within the German Armed Forces, and analyse the influence of variable factors, such as different surgical methods, body constitution and smoking amount, to incidence and long-term recurrence rate of PSD. METHODS: Information of all the patients being admitted with primary PSD to the surgical departments of three hospitals of the German Armed Forces between 1980 and 1996 was collected and analyzed, 500 patients of which were interviewed. RESULTS: Two of the 500 patients were dead, and every one of the rest 498 patients agreed to take part in the interview. The incidence of PSD rose from 0.3/1000 in 1985 to 2.4/1000 in 2007. The recurrence rates were decreasing within 16 years of treatment from 33% in 1981 via 23% in 1986 to 12% in 1996 (P = 0.01). Recurrence rates of primary open wound healing (16.8%) compared to primary suture (31.0%) differ significantly (P < 0.01). While the mean body weight within the army rose 1 kg per decade, population shows an increase of 1.9 kg per decade though not being an influencing factor on the recurrence rate (P = 0.72). Smoking of more than 20 cigarettes per day proved to be a significant factor on the recurrence rate of PSD (P = 0.015). CONCLUSION: While the recurrence rates-especially of primary open wound treatment-decreased, the incidence of PSD rose nearly tenfold.

[Occurrence of Antibiotic Resistance Genes and Bacterial Community Structure of Different Sludge Samples During Microwave Pretreatment-Anaerobic Digestion].

The waste sludge of municipal wastewater treatment plants is an important reservoir for antibiotic resistance genes (ARG). It is necessary to explore the fate of ARG, microbial community succession, and the correlations between them. Therefore, the distribution of ARG and the microbial community structure of waste sludge from wastewater treatment plants with A2O and A2O-MBR processes during microwave pretreatment and anaerobic digestion were studied in this research. The results showed that the occurrence of ARG and the microbial community structure were quite different in the waste sludge of A2O and A2O-MBR processes. The microwave pretreatment did not change the microbial community much, whereas the community structure of the digested sludge with pretreatment showed significant differences. Anaerobic digestion had a conformity effect on the distribution of ARG and MGE in the digested sludge with or without pretreatment. Among genes, ermF, qnrS, and blaNDM-1 were the most difficult to be reduced ARG and were prone to propagation during anaerobic digestion. The influence of biomass, ammonia nitrogen, and phosphorus on the distribution of ARG and MGE was higher than that of other environmental factors. The sludge characteristics also showed important impacts on the microbial community, especially on some genera with specific functions. These results could help people to better understand the spread and control of ARG during sludge anaerobic digestion.

[Mutual Influence Between Microbial Community, Wastewater Characteristics, and Antibiotic Resistance Genes During Spiramycin Production Wastewater Treatment].

Wastewater from antibiotic production usually contains a huge amount of antibiotic resistance genes (ARG). Therefore, it is essential to study the dissemination and control of antibiotic resistance during the treatment of antibiotic production wastewater. The mutual influence between microbial community evolution, wastewater characteristics, and ARG was investigated using high-throughput sequencing and a variety of statistical analysis methods. Results showed that the influent characteristics had only a marginal influence on the microbial community of each treatment section. Methanogenic bacteria and sulfate-reducing bacteria were the dominant microbes in the anaerobic and anoxic tank. Chemical oxygen demand (COD), NO2--N, and PO43--P exhibited an intimate relationship with the microbial community, whereas biomass, NH4+-N, and COD showed a strong correlation with ARG and mobile genetic elements (MGE). In the sludge, more genera (including pathogenic bacteria) were significantly correlated with ARG and MGE than that in the wastewater, indicating that bacteria in the sludge had a greater chance of acquiring pathogenicity and resistance. Therefore, more attnetion should be given to waste sludge from the treatment plants of antibiotic production wastewater. This research could provide further understanding of antibiotic resistance dissemination and control during wastewater treatment, especially for antibiotic production wastewater.

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients.

BACKGROUND: At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM: To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS: Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS: Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION: The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

Astrocytes express N-methyl-D-aspartate receptor subunits in development, ischemia and post-ischemia.

The expression of the N-methyl-D-aspartate receptor (NMDA-R) in astrocytes is controversial. The receptor is commonly considered neuron-specific. We showed that astrocytes in primary cultures differentially expressed mRNA of NMDA-R subunits, NR1, NR2A and NR2B, in development, ischemia and post-ischemia. One-week-old cultures expressed detectable NR1 mRNA, which fell significantly at 2 weeks and became barely detectable at 4 weeks. NR2A and NR2B mRNA were both significantly up-regulated from 1 to 2 weeks. In 4 weeks, 2 h of ischemia caused a significant up-regulation of NR1 and NR2B mRNA; while 6 h caused down-regulation of NR2A mRNA. Under 3 h of post-ischemia, only NR1 mRNA was increased. Ischemia induced the expression of major NMDA-R effecter, nitric oxide synthase 1, which was unaffected by AMPA-R antagonist CNQX, but dose-dependently inhibited by NMDA-R specific antagonist MK-801. These findings reflected that astrocyte could express inducible functional NMDA receptors without the presence of neurons.