Global research trends and prospects of cellular metabolism in colorectal cancer.

BACKGROUND: An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer (CRC). However, no work is currently available to synthesize the field through bibliometrics. AIM: To analyze the development in the field of "glucose metabolism" (GM), "amino acid metabolism" (AM), "lipid metabolism" (LM), and "nucleotide metabolism" (NM) in CRC by visualization. METHODS: Articles within the abovementioned areas of GM, AM, LM and NM in CRC, which were published from January 1, 1991, to December 31, 2022, are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19. RESULTS: The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields. Meanwhile, China and the United States were two of the most prominent contributors in these four areas. In addition, Gang Wang, Wei Jia, Maria Notarnicola, and Cornelia Ulrich ranked first in publication numbers, while Jing-Yuan Fang, Senji Hirasawa, Wei Jia, and Charles Fuchs were the most cited authors on average in these four fields, respectively. "Gut microbiota" and "epithelial-mesenchymal transition" emerged as the newest burst words in GM, "gut microbiota" was the latest outburst word in AM, "metastasis", "tumor microenvironment", "fatty acid metabolism", and "metabolic reprogramming" were the up-to-date outbreaking words in LM, while "epithelial-mesenchymal transition" and "apoptosis" were the most recently occurring words in NM. CONCLUSION: Research in "cellular metabolism in CRC" is all the rage at the moment, and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC. Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

Association of dietary live microbe intake with diabetic kidney disease in patients with type 2 diabetes mellitus in US adults: a cross-sectional study of NHANES 1999-2018.

AIMS: Several studies have reported dietary microorganisms' beneficial effects on human health. We aimed to detect the potential association between dietary live microbe intake and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 1999 to 2018. METHODS: According to the Sanders classification system of dietary live microbes, the study participants were divided into three groups: low, medium, and high live microbe groups. In patients with T2DM, DKD was assessed by glomerular filtration rate (< 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration algorithm), proteinuria (urinary albumin to creatinine ratio ≥ 30 mg/g), or both. Weighted univariate and multivariate logistic regression and subgroup analyses were conducted to investigate the independent association between dietary live microbe and DKD. RESULTS: The study included 3836 participants, of whom 1467 (38.24%) had DKD for the diagnosis. Our study demonstrated that participants in the high dietary live microbe group were more likely to be older, female, non-Hispanic White, have higher education levels, have a lower prevalence of smoking, have a high poverty-income ratio, have higher energy intake, lower haemoglobin (HbA1c) and serum creatinine levels, and lower risk of progression. After adjustment for covariates, patients in the high dietary live microbe group had a low prevalence of DKD, whereas no significant association with DKD was found between the medium and low dietary live microbe groups. No statistically significant interaction was observed in all subgroup analyses except for HbA1c (p for interaction < 0.05). CONCLUSIONS: Our results indicate that high dietary live microbe intake was associated with a low DKD prevalence.

Association between the composite dietary antioxidant index and chronic kidney disease: evidence from NHANES 2011-2018.

Objectives: There is growing evidence that antioxidant-rich diets protect against chronic kidney disease (CKD). However, the relationship between the Composite Dietary Antioxidant Index (CDAI), an important measure of an antioxidant diet, and CKD has received little attention. Therefore, here we investigated the relationship between the CDAI and CKD through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data. Methods: The CDAI was calculated based on the intake of six dietary antioxidants. A survey-based multivariate linear regression analysis was performed to analyze the independent relationship between the CDAI and CKD. Weighted multivariate regression and subgroup analyses were conducted to explore the relationship between the CDAI and CKD. Results: A total of 6874 NHANES participants represented 181.9 million non-institutionalized US residents (mean age, 46.43 ± 0.38 years; 49.87% female; 40.62% non-Hispanic white; 20.24% non-Hispanic black; and 13.94% Mexican American). The weighted linear regression model with full adjustment for confounding variables was -0.0155 (-0.0417, 0.0107) for Q2 (P for trend <0.0001), -0.0052 (-0.0346, 0.0242) for Q3 (P for trend <0.0001), and -0.0305 (-0.0491, -0.0120) for Q4 (P for trend = 0.0094) upon comparison with the lowest quartile of the CDAI. None of the interactions in any subgroup analysis were statistically significant except for individuals with a history of diabetes or the aged population (≥60 years) (P for interaction <0.05). Conclusions: The CDAI was positively associated with a lower prevalence of CKD in adults in the United States. Further large-scale prospective studies are required to analyze the role of the CDAI in CKD.

Brain-Targeting Emodin Mitigates Ischemic Stroke via Inhibiting AQP4-Mediated Swelling and Neuroinflammation.

Failure to achieve target-specific delivery to ischemic brain sites has hampered the clinical efficacy of newly developed therapies for ischemic stroke. Emodin, an active ingredient isolated from traditional Chinese medicine, has been indicated to alleviate ischemic stroke; however, the underlying mechanism remains unclear. In this study, we aimed to achieve brain-targeted delivery of emodin to maximize its therapeutic efficacy and elucidate the mechanisms by which emodin alleviates ischemic stroke. A polyethylene glycol (PEG)/cyclic Arg-Gly-Asp (cRGD)-modified liposome was used to encapsulate emodin. TTC, HE, Nissl staining, and immunofluorescence staining were employed to evaluate the therapeutic efficacy of brain-targeting emodin in MCAO and OGD/R models. Inflammatory cytokine levels were determined using ELISA. Immunoprecipitation, immunoblotting, and RT-qPCR were utilized for clarifying the changes in key downstream signaling. Lentivirus-mediated gene restoration was employed to verify the core effector of emodin for relieving ischemic stroke. Encapsulating emodin in a PEG/cRGD-modified liposome enhanced its accumulation in the infarct region and substantially raised its therapeutic efficacy. Furthermore, we demonstrated that AQP4, the most abundant water transporter subunit expressed in astrocytes, plays a crucial role in mediating the mechanisms by which emodin inhibits astrocyte swelling, neuroinflammatory blood-brain barrier (BBB) breakdown in vivo and in vitro, and brain edema in general. Our study unveiled the critical target of emodin responsible for alleviating ischemic stroke and a localizable drug delivery vehicle in the therapeutic strategy for ischemic stroke and other brain injuries.

YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosis via aberrant glycolysis associated with EGFR/PKM2/HIF-1α pathway.

Objectives: Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD. Materials and methods: We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells. Gene levels were assessed by Western blotting, RT-qPCR, immunofluorescence staining and immunohistochemistry. Molecular interactions were determined by RNA pull-down, co-immunoprecipitation, ubiquitination assay and dual-luciferase reporter analysis. Results: YY1, ARAP1-AS2, ARAP1, HIF-1α, glycolysis and fibrosis genes expressions were upregulated and ARAP1 knockdown could inhibit dimeric PKM2 expression and partly restore tetrameric PKM2 formation, while downregulate HIF-1α accumulation and aberrant glycolysis and fibrosis in in-vivo and in-vitro DKD models. ARAP1 knockdown attenuates renal injury and renal dysfunction in diabetic mice. ARAP1 maintains EGFR overactivation in-vivo and in-vitro DKD models. Mechanistically, YY1 transcriptionally upregulates ARAP1-AS2 and indirectly regulates ARAP1 and subsequently promotes EGFR activation, HIF-1α accumulation and aberrant glycolysis and fibrosis. Conclusion: Our results first highlight the role of the novel regulatory mechanism of YY1 on ARAP1-AS2 and ARAP1 in promoting aberrant glycolysis and fibrosis by EGFR/PKM2/HIF-1α pathway in DKD and provide potential therapeutic strategies for DKD treatments.

Perceived rather than objective weight status is associated with suicidal behaviors among Chinese adolescents: a school-based study.

BACKGROUND: We aimed to explore the relationship between body mass index (BMI) and body weight perception (BWP) with suicidal behaviors among mainland Chinese adolescents. METHODS: A nationally representative sample (N = 10 110) of Chinese adolescents was assessed in this study. Suicidal behaviors (ideation, plan and attempt) were evaluated by four self-reported questions. Generalized linear mixed model was used to estimate the adjusted odds ratios (ORs) for the association between BWP/BMI with suicidal behaviors. RESULTS: The prevalence of suicidal ideation, suicidal plan and suicidal attempt was 12, 5 and 2.1%, respectively. After adjusting potential covariates, perceiving oneself as obese was significantly associated with increased risks of suicidal ideation (OR: 2.4, 95% confidence intervals, CI: 1.6-4.0, P = 0.001), suicidal plan (OR: 3.1, 95% CI: 1.5-6.3, P = 0.002) and suicidal attempt (OR: 3.7, 95% CI: 1.5-9.1, P = 0.001) compared with perceiving as normal weight among male adolescents; the effect attenuated to null among female adolescents. Perceiving oneself as underweight and overweight both exhibited significant adverse effect on suicidal behaviors (only suicidal ideation and suicidal plan) compared with perceiving oneself as normal weight among male adolescents, but not among female adolescents. The actual measured BMI was not significantly associated with suicidal behaviors among neither gender. CONCLUSIONS: Self-perception of their body image rather than actual measured weight may have a gender-specific adverse effect on suicidal behaviors among Chinese adolescents.

Genetically predicted body fat mass and distribution with diabetic kidney disease: A two-sample Mendelian randomization study.

The aim of this study is to apply a Mendelian randomization (MR) design to investigate the potential causal associations between the body mass index (BMI), body fat mass such as trunk fat mass and waist circumference (WC), and diabetic kidney disease (DKD). A two-sample MR study was conducted to obtain exposure and outcome data from previously published studies. The instrumental variables for BMI, trunk fat mass, and WC were selected from genome-wide association study datasets based on summary-level statistics. The random-effects inverse-variance weighted (IVW) method was used for the main analyses, and the weighted median and MR-Egger approaches were complementary. In total, three MR methods suggested that genetically predicted BMI, trunk fat mass, and WC were positively associated with DKD. Using IVW, we found evidence of causal relationships between BMI [odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.47-2.69; p = 7.89 × 10-6], trunk fat mass (OR = 1.80; 95% CI, 1.28-2.53; p = 6.84 × 10-4), WC (OR = 2.48; 95% CI, 1.40-4.42; p = 1.93 × 10-3), and DKD. MR-Egger and weighted median regression also showed directionally similar estimates. Both funnel plots and MR-Egger intercepts showed no directional pleiotropic effects involving the aforementioned variables and DKD. Our MR analysis supported the causal effect of BMI, trunk fat mass, and WC on DKD. Individuals can substantially reduce DKD risk by reducing body fat mass and modifying their body fat distribution.

Predictive Efficacy of a Radiomics Random Forest Model for Identifying Pathological Subtypes of Lung Adenocarcinoma Presenting as Ground-Glass Nodules.

Purpose: To establish and verify the ability of a radiomics prediction model to distinguish invasive adenocarcinoma (IAC) and minimal invasive adenocarcinoma (MIA) presenting as ground-glass nodules (GGNs). Methods: We retrospectively analyzed 118 lung GGN images and clinical data from 106 patients in our hospital from March 2016 to April 2019. All pathological classifications of lung GGN were confirmed as IAC or MIA by two pathologists. R language software (version 3.5.1) was used for the statistical analysis of the general clinical data. ITK-SNAP (version 3.6) and A.K. software (Analysis Kit, American GE Company) were used to manually outline the regions of interest of lung GGNs and collect three-dimensional radiomics features. Patients were randomly divided into training and verification groups (ratio, 7:3). Random forest combined with hyperparameter tuning was used for feature selection and prediction modeling. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate model prediction efficacy. The calibration curve was used to evaluate the calibration effect. Results: There was no significant difference between IAC and MIA in terms of age, gender, smoking history, tumor history, and lung GGN location in both the training and verification groups (P>0.05). For each lung GGN, the collected data included 396 three-dimensional radiomics features in six categories. Based on the training cohort, nine optimal radiomics features in three categories were finally screened out, and a prediction model was established. We found that the training group had a high diagnostic efficacy [accuracy, sensitivity, specificity, and AUC of the training group were 0.89 (95%CI, 0.73 - 0.99), 0.98 (95%CI, 0.78 - 1.00), 0.81 (95%CI, 0.59 - 1.00), and 0.97 (95%CI, 0.92-1.00), respectively; those of the validation group were 0.80 (95%CI, 0.58 - 0.93), 0.82 (95%CI, 0.55 - 1.00), 0.78 (95%CI, 0.57 - 1.00), and 0.92 (95%CI, 0.83 - 1.00), respectively]. The model calibration curve showed good consistency between the predicted and actual probabilities. Conclusions: The radiomics prediction model established by combining random forest with hyperparameter tuning effectively distinguished IAC from MIA presenting as GGNs and represents a noninvasive, low-cost, rapid, and reproducible preoperative prediction method for clinical application.

Directing osteogenic differentiation of BMSCs by cell-secreted decellularized extracellular matrixes from different cell types.

Cell-secreted decellularized extracellular matrixes (D-ECM) are promising for conferring bioactivity and directing cell fate to facilitate tissue regeneration. A cell sheet is a good shape for obtaining D-ECM after decellularization. In this study, cell sheets derived from bone marrow mesenchymal stem cells (BMSCs), MC3T3 osteoblasts, and L929 fibroblasts were decellularized, the three types of D-ECMs obtained were investigated for their capabilities in inducing osteogenic differentiation of re-seeded BMSCs. The D-ECMs were found to be rich in collagen and glycosaminoglycan, at the same time, showing the presence of growth factors, such as vascular endothelial growth factor and bone morphogenetic protein. These all supported the proliferation of BMSCs well, however, they influenced the osteogenic differentiation of BMSCs to different extents. The D-ECM prepared from the BMSC sheet was found to promote the osteogenic differentiation of re-seeded BMSCs the most in vitro, as well as displaying the potential to induce ectopic osteogenesis when being subcutaneously implanted. The results suggested that D-ECMs would be promising for bone tissue engineering applications, however, they favored osteogenesis to different extents, which was closely related to the cell types.

Photoluminescent polyphosphazene nanoparticles for in situ simvastatin delivery for improving the osteocompatibility of BMSCs.

Nanomedicines have found promising applications in regulating the biological behaviors of cells because of the cell endocytosis effect. To enhance the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs), which is one of the key issues in relation to bone regeneration, a biodegradable simvastatin-bearing polyphosphazene prodrug was synthesized and made into nanoparticles (NPs). At the same time, photoluminescent tryptophan ethyl ester and hydrolyzable glycine ethyl ester were introduced as co-substituted side groups onto the polyphosphazene backbone. The resultant polymer, poly(simvastatin-co-ethyl tryptophanato-co-ethyl glycinato)phosphazene (PTGP-SIM), displayed the expected features of photoluminescence, degradability and sustained SIM release. Endocytosis of PTGP-SIM NPs by BMSCs and the location of internalized NPs, were visualized via the inherent photoluminescence features of PTGP-SIM. Thus, simvastatin was released inside the cells directly along with polymer degradation and could play a role in promoting osteogenic differentiation efficiently at quite a low local concentration. From the results, the present study suggested a very promising biomaterial for use as a flexible and functional carrier for bioactive components, which could find wide applications in relation to tissue regeneration.

Glucose deprivation induces chemoresistance in colorectal cancer cells by increasing ATF4 expression.

AIM: To investigate the role of activating transcription factor 4 (ATF4) in glucose deprivation (GD) induced colorectal cancer (CRC) drug resistance and the mechanism involved. METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA and protein expression of drug resistance gene 1 (MDR1), respectively. RESULTS: GD protected CRC cells from drug-induced apoptosis (oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug re-sensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.

The complete mitochondrial genome of Heliconius pachinus (Insecta: Lepidoptera: Nymphalidae).

The complete mitochondrial genome of Heliconius pachinus has been reconstructed from the whole-genome Illumina sequencing data. The circular genome is 15,369 bp in length, and comprises the typical components: 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs) and 1 D-loop region. PCGs are mostly initiated with either the ATN codons (COII, COIII, Cytb, ND2, ND3, ND4, ND4L, ND5, ND6, ATP6 & ATP8) or the TTG codon (ND1); the COI gene may use the unusual CGA as its initiation codon, as suggested for other lepidopteran species. Some PCGs harbor TAG (ND3) or incomplete termination codon T (COI, COII & ND4), while the others use TAA as their termination codons. The nucleotide composition is highly asymmetric (39.2% A, 42.0% T, 7.7% G, 11.1% C) with an overall GC content of 18.8%.

Design, synthesis and biological evaluation of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3ß (GSK-3ß).

Glycogen synthase kinase-3ß (GSK-3ß) plays a key role in type II diabetes and Alzheimer's diseases, to which non-ATP competitive inhibitors represent an effectively therapeutical approach due to their good specificity. Herein, a series of small molecules benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of GSK-3ß have been designed and synthesized. The in vitro evaluation performed by luminescent assay showed most BTZ derivatives have inhibitory effects in micromolar scale. Among them compounds 6l, 6t and 6v have the IC50 values of 25.0 µM, 27.8 µM and 23.0 µM, respectively. Moreover 6v is devoid of any inhibitory activity in the assays to other thirteen protein kinases. Besides, SAR is analyzed and a hypothetical enzymatic binding mode is proposed by molecular docking study, which would be useful for new candidates design.

Cohort Profile: the China-Anhui Birth Cohort Study.

The China-Anhui Birth Cohort Study (C-ABCS) was set up to examine the delayed, cumulative and interactive effects of maternal environmental exposures on birth outcomes and children's development. The C-ABCS recruited pregnant women from six major cities of Anhui province, China, between November 2008 and October 2010. A range of data (including demographic, obstetric, occupational, nutritional and psychosocial factors) were collected by both interviews and laboratory tests. In each trimester, women's blood samples were drawn, and pregnancy complications were abstracted from physician's medical records. By the end of 2011, birth outcomes/birth defects were observed/identified by clinicians within 12 months after the delivery of 11,421 singleton live births of six cities and those outcomes among the remaining 2033 live births are still being observed. In addition, 4668 children from Ma'anshan city will be further followed up during the pre-school period till they reach adolescence to obtain the data on familial environmental exposures as well as children's physical, psychological, behavioural and sexual development. The interview data and information on laboratory examinations are available on request from archives in the Anhui Provincial Key Laboratory of Population Health & Aristogenics.

Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3ß inhibitors through virtual screening.

Glycogen synthase kinase-3ß (GSK-3ß) is an important serine/threonine kinase that has been proved as a key target for neurodegenerative diseases and diabetes. Up to date, most of known inhibitors are bound to the ATP-binding pocket of GSK-3ß, which might lead widespread effects due to the high homology between kinases. Recently, some of its non-ATP competitive inhibitors had been confirmed having therapeutical effects owing to their high selectivity. This finding opens a new pathway to study hopeful drugs for treatment of these diseases. However, it is still a challenge nowadays on how to efficiently find non-ATP competitors. Here, we successfully discovered a novel scaffold of benzothiazepinones (BTZs) as selective non-ATP competitive GSK-3ß inhibitors through virtual screening approach. A 3D receptor model of substrate binding site of GSK-3ß was constructed and applied to screen against drug-like Maybridge database through Autodock program. BTZ compounds were top ranked as efficient hits and were then synthesized for further screening. Among them, the representative compound 4j showed activity to GSK-3ß (IC(50): 25 µM) in non-ATP competitive mechanism, and nearly no inhibitory effect on other 10 related protein kinases. Overall, the results point out that BTZ compounds might be useful in treatment of Alzheimer's disease and diabetes mellitus as novel GSK-3ß inhibitors. It also suggests, on the other hand, that virtual screening would provide a valuable tool in combination with in vitro assays for the identification of novel selective and potent inhibitors.

[Effects of different ways in repairing scrotum of pigs with full-thickness burn on apoptosis and bcl-2 protein expression of spermatogenic cells].

OBJECTIVE: To observe the effects of different ways in repairing scrotum of pigs with full-thickness burn on spermatogenesis of testis. METHODS: Twenty male Guizhou miniature pigs were divided into normal control (NC), natural-healing (NH), flap-repairing (FR), and skin-grafting (SG) groups according to the random number table, with 5 pigs in each group. Pigs in NC group were not subjected to any injury. Scrotum of pigs in the latter three groups were inflicted with full-thickness burn. Wounds in NH group healed naturally. Wounds in FR group were repaired with inguinal region flap, and those in SG group with full-thickness skin from lower abdomen. Appearance of scrotum in the latter three groups was observed right after injury, and three months post injury or surgery (PIM or PSM). Specimens of testes of pigs in the latter three groups were obtained in PIM or PSM 3 to detect apoptosis of spermatogenic cells with TUNEL, and bcl-2 protein expression with immunohistochemistry. The same indexes were observed and determined in pigs of NC group. Data were processed with one-way analysis of variance and LSD test. RESULTS: (1) Scrotum of pigs in NC group had skin folds with contraction function. Scrotum of pigs became hard with a leathery appearance right after burn in the other three groups. In PIM or PSM 3, wounds of pigs in NH group healed with scar, and the testes were squeezed into inguinal region. Scrotal skin of pigs in FR group was thick with testes in the scrotum, and that of pigs in SG group was thin with testes in the scrotum. (2) Spermatogenic cells in each level in NC group were arranged regularly, with few apoptotic spermatocytes and spermatoblasts. In NH, FR, and SG groups, seminiferous epithelium was thinner with most of the spermatogenic cells showing apoptosis, and they were mainly spermatogonia and spermatocytes. Apoptotic index of spermatogenic cells in NH, FR, SG, and NC groups was respectively (46.3 ± 3.3)%, (40.9 ± 3.5)%, (20.6 ± 2.3)%, (7.5 ± 1.9)%, and the difference among them was statistically significant (F = 405.65, P < 0.01). There were significant statistical differences among the former three groups (with P values below 0.01). (3) bcl-2 protein expression in NH, FR, SG, and NC groups was respectively (52 ± 5)%, (53 ± 4)%, (64 ± 5)%, (75 ± 5)%, and the difference among them was statistically significant (F = 56.63, P < 0.01). There was no significant statistical difference in bcl-2 expression between NH group and FR group (P = 0.66), and it was lower in both groups as compared with SG group (with P values below 0.01). CONCLUSIONS: Either scar healing, flap transplantation, or SG in repairing scrotum with full-thickness burn in pigs inhibits spermatogenesis, but repair with SG produces less deleterious effect on the testis.

Periconceptional folic acid supplementation among women attending antenatal clinic in Anhui, China: data from a population-based cohort study.

OBJECTIVES: to examine the rate of periconceptional and optimal folic acid supplementation, and to characterise their patterns and determinants among antenatal women in central China. DESIGN: data from 4290 women in the Anhui Birth Defects and Child Development Cohort Study recruited between October 2008 and September 2009 were analysed. SETTING: seven Maternal and Child Health Centres of two cities (Hefei and Maanshan) in Anhui province of central China. PARTICIPANTS: women initiating prenatal care were included and asked to complete a structured questionnaire regarding folic acid supplementation. FINDINGS: sixty-eight per cent (2905/4290) of pregnant women reported taking folic acid supplementation periconceptionally (i.e. at some point before or during early pregnancy), and 32.8% (1405/4290) and 65.2% (2797/4290) had taken it before or during early pregnancy, respectively. However, only 16.1% (690/4290) used it optimally (i.e. regularly from four weeks before pregnancy throughout four weeks after pregnancy). Use of periconceptional folic acid was significantly associated with educational level, household income, registered residence, age, gestational age at recruitment, and planning of pregnancy. CONCLUSION: optimal folic acid supplementation was relatively low. IMPLICATIONS FOR PRACTICE: further efforts are needed to inform the population and promote the use of folic acid supplementation.

Battacin (Octapeptin B5), a new cyclic lipopeptide antibiotic from Paenibacillus tianmuensis active against multidrug-resistant Gram-negative bacteria.

Hospital-acquired infections caused by drug-resistant bacteria are a significant challenge to patient safety. Numerous clinical isolates resistant to almost all commercially available antibiotics have emerged. Thus, novel antimicrobial agents, specifically those for multidrug-resistant Gram-negative bacteria, are urgently needed. In the current study, we report the isolation, structure elucidation, and preliminary biological characterization of a new cationic lipopeptide antibiotic, battacin or octapeptin B5, produced from a Paenibacillus tianmuensis soil isolate. Battacin kills bacteria in vitro and has potent activity against Gram-negative bacteria, including multidrug-resistant and extremely drug-resistant clinical isolates. Hospital strains of Escherichia coli and Pseudomonas aeruginosa are the pathogens most sensitive to battacin, with MICs of 2 to 4 µg/ml. The ability of battacin to disrupt the outer membrane of Gram-negative bacteria is comparable to that of polymyxin B, the last-line therapy for infections caused by antibiotic-resistant Gram-negative bacteria. However, the capacity of battacin to permeate bacterial plasma membranes is less extensive than that of polymyxin B. The bactericidal kinetics of battacin correlate with the depolarization of the cell membrane, suggesting that battacin kills bacteria by disrupting the cytoplasmic membrane. Other studies indicate that battacin is less acutely toxic than polymyxin B and has potent in vivo biological activity against E. coli. Based on the findings of the current study, battacin may be considered a potential therapeutic agent for the treatment of infections caused by antibiotic-resistant Gram-negative bacteria.

Quantitative analysis of multiple methylated genes in plasma for the diagnosis and prognosis of hepatocellular carcinoma.

This study was aimed to evaluate the clinical value of plasma methylation analysis of a panel of four genes (APC, GSTP1, RASSF1A, and SFRP1), which was identified by our previous work, for the noninvasive diagnosis of hepatocellular carcinoma (HCC). The methylation status of these four genes in 150 plasma samples from 72 patients with HCC, 37 benign live diseases and 41 normal controls was detected with methylation-sensitive restriction enzymes-based quantitative PCR (MSRE-qPCR) method. The plasma methylation levels of APC, GSTP1, RASSF1A, and SFRP1 were significantly higher in HCCs than those in normal or benign controls (P<0.05). Although the area under the receiver-operation characteristic curve (AUC-ROC) for individual gene was moderate (range, from 0.800 to 0.881), the combination analysis of these four genes resulted in an increased AUC of 0.933 with 92.7% sensitivity, 81.9% specificity, 90.5% positive predictive value (PPV), and 87.2% negative predictive value (NPV) in discriminating HCC from normal control. The combination analysis also indicated an increased AUC of 0.877 when compared with individual gene (from 0.666 to 0.850) in discriminating HCC from benign control, and the consultant sensitivity, specificity, PPV, and NPV was 84.7%, 81.1%, 89.7%, and 73.2%, respectively. Patients with elevated plasma methylation levels of APC or RASSF1A showed poorer overall survival than those with low levels (P<0.05). Cox multivariate analysis demonstrated methylated RASSF1A in plasma to be an independent prognostic factor for overall survival (hazard ratio=3.262, 95% CI: 1.476-7.209, P=0.003). These data showed that quantitative analysis of multiple methylated genes in plasma may be a promising tool for noninvasive diagnosis of HCC; and methylated plasma RASSF1A appears to be a prognostic marker of HCC.