PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton, modulating emotional behavior.

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function. Synaptic abnormalities, such as defects in the density and morphology of postsynaptic dendritic spines, underlie the pathology of various neuropsychiatric disorders. Protocadherin 17 (PCDH17) is associated with major mood disorders, including bipolar disorder and depression. However, the molecular mechanisms by which PCDH17 regulates spine number, morphology, and behavior remain elusive. In this study, we found that PCDH17 functions at postsynaptic sites, restricting the number and size of dendritic spines in excitatory neurons. Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety- and depression-like behaviors in mice. Mechanistically, PCDH17 interacts with actin-relevant proteins and regulates actin filament (F-actin) organization. Specifically, PCDH17 binds to ROCK2, increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3 (Ser3). Inhibition of ROCK2 activity with belumosudil (KD025) ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression, suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development. Hence, these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior, providing pathological insights into the neurobiological basis of mood disorders.

[Application of micro-bolus injection and piezoelectric sensors to improve the safety of radiopharmaceuticals bolus injection].

Radiopharmaceutical dynamic imaging typically necessitates intravenous injection via the bolus method. However, manual bolus injection carries the risk of handling errors as well as radiological injuries. Hence, there is potential for automated injection devices to replace manual injection methods. In this study, the effect of micro-bolus pulse injection technology was compared and verified by radioactive experiments using a programmable injection pump, and the overall bubble recognition experiment and rat tail vein simulation injection verification were performed using the piezoelectric sensor preloading method. The results showed that at the same injection peak speed, the effective flushing volume of micro-bolus pulse flushing (about 83 µL/pulse) was 49.65% lower than that of uniform injection and 25.77% lower than that of manual flushing. In order to avoid the dilution effect of long pipe on the volume of liquid, the use of piezoelectric sensor for sealing preloading detection could accurately predict the bubbles of more than 100 µL in the syringe. In the simulated injection experiment of rat tail vein, when the needle was placed in different tissues by preloading 100 µL normal saline, the piezoelectric sensor fed back a large difference in pressure attenuation rate within one second, which was 2.78% in muscle, 17.28% in subcutaneous and 54.71% in vein. Micro-bolus pulse injection method and piezoelectric sensor sealing preloading method have application potential in improving the safety of radiopharmaceutical automatic bolus injection.

Development and External Validation of a Nomogram for Predicting the Effect of RTX on the Treatment of Membranous Nephropathy.

Introduction: Rituximab (RTX) has been shown to be effective in inducing immunological remission in patients with membranous nephropathy (MN). Some patients required more than one course of RTX to achieve immunological remission. Identifying patients who need more courses of RTX to achieve immunological remission is beneficial for better physician-patient communication, the assessment of treatment course, and the evaluation of medical costs. This study aims to establish a practical model to predict the probability of immunological remission after receiving one cycle of RTX. Methods: This study enrolled 106 patients from the First Affiliated Hospital of Zhengzhou University in the modeling group and 30 patients from Henan Provincial Hospital of Traditional Chinese Medicine in the external validation group. Patients in the modeling group were divided into responders or nonresponders according to whether they achieved immunological remission or not after following up for 6 months. A nomogram was established based on the results of logistic regression analysis. The predictive performance of the nomogram was evaluated by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCAs). Results: In the modeling group, 75 (70.8%) patients achieved immunological remission within 6 months after receiving one cycle of RTX. Significant differences were observed between nonresponders and responders. Risk factors used in nomogram included PLA2R antibody, hemoglobin, and gender. The AUC value of nomogram was 0.797 (95% CI 0.701-0.894, P<0.001). The calibration curves demonstrated acceptable agreement between the predicted outcomes by the nomogram and the actual values. DCA curves showed good positive net benefits in the predictive model. The external validation also demonstrated the reliability of the prediction nomogram. Conclusion: A predictive nomogram including PLA2R antibody, hemoglobin, and gender may provide a basis to predict the doses of RTX needed in MN patients.

Research on irradiated food status and consumer acceptance: A Chinese perspective.

China is currently the world's largest producer of food irradiation. Despite the long-standing (about 100 years) evidence supporting the safety of food irradiation, consumers' acceptance of irradiated foods remains limited. This study aimed to investigate the development of food irradiation in China and identify the barriers that keep consumers away from irradiated foods. This was accomplished by exploring the relevant policies of food irradiation, the size and distribution of irradiation facilities in China, and analyzing their relationships between consumer characteristics and the acceptance of irradiated food. To achieve these objectives, we conducted an online survey of participants from Hubei, China (N = 264). The results reveal that irradiation facilities are mainly distributed in large coastal cities such as the Bohai Bay, the Yangtze River Delta, and the Greater Bay Area. Furthermore, the study identified that consumer' acceptance of irradiated food is directly related to their level of understanding. Approximately 22% of the sampled consumers reported that they would not accept that they have consumed irradiated food and most of them (41%) stated that they would not purchase irradiated food if they were aware of buying irradiated food. Specifically, consumers expressed discomfort with consuming irradiated food under unknown circumstances. This trend is more prevalent among female, low-educated, and older consumers, with 40% of the sampled population indicating that they would not buy irradiated food. Given the strong correlation between knowledge and acceptance of irradiated foods, the study suggests that policy reform should prioritize enhancing the understanding of irradiated food, particularly among female, low-educated, and older consumers.

Synthesis, anti-aging and mechanism of magnolol derivatives.

Magnolol (M), a hydroquinone containing an allyl side chain, is one of the major active components of Houpoea officinalis for antioxidation and anti-aging. To enhance the antioxidant activity of magnolol, the different sites of magnolol were structurally modified in this experiment, and a total of 12 magnolol derivatives were obtained. Based on the preliminary exploration of the anti-aging effect of magnolol derivatives in a Caenorhabditis elegans (C. elegans) model. Our results indicate that the active groups of magnolol exerting anti-aging effects were allyl groups and hydroxyl on the phenyl. Meanwhile, the anti-aging effect of the novel magnolol derivative M27 was found to be significantly superior to that of magnolol. To investigate the effect of M27 on senescence and the potential mechanism of action, we investigated the effect of M27 on senescence in C. elegans. In this study, we investigated the effect of M27 on C. elegans physiology by examining body length, body curvature and pharyngeal pumping frequency. The effect of M27 on stress resistance in C. elegans was explored by acute stress experiments. The mechanism of M27 anti-aging was investigated by measuring ROS content, DAF-16 nuclear translocation, sod-3 expression, and lifespan of transgenic nematodes. Our results indicate that M27 prolonged the lifespan of C. elegans. Meanwhile, M27 improved the healthy lifespan of C. elegans by improving pharyngeal pumping ability and reducing lipofuscin accumulation in C. elegans. M27 increased resistance to high temperature and oxidative stress in C. elegans by reducing ROS. M27 induced DAF-16 translocation from cytoplasm to nucleus in transgenic TJ356 nematodes and upregulated the expression of sod-3 (a gene downstream of DAF-16) in CF1553 nematodes. Furthermore, M27 did not extend the lifespan of daf-16, age-1, daf-2, and hsp-16.2 mutants. This work suggests that M27 may ameliorate aging and extend lifespan in C. elegans through the IIS pathway.

[Application of automatic injection device based on automatic hemostasis in injection of radiopharmaceutical bolus injection].

In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.

CMKLR1 Antagonist Alpha-NETA Protects against Diabetic Nephropathy in Mice.

INTRODUCTION: Diabetic nephropathy (DN) is a common complication in diabetic patients. Chemerin, a novel adipokine, has been associated with renal damage in DN. The chemerin chemokine-like receptor 1 (CMKLR1) has been reported to participate in DN. In this study, we aimed to investigate the effect of a CMKLR1 antagonist, 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA), on DN. METHODS: To induce diabetes, 8-week-old male C57BL/6J mice were given a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Diabetic mice were randomly assigned to receive daily doses of 0, 5, or 10 mg/kg α-NETA for 4 weeks. RESULTS: α-NETA dose-dependently induced body weight and reduced fasting blood glucose levels in STZ-induced diabetic mice. Furthermore, α-NETA significantly reduced the expressions of renal injury markers, including serum creatinine, kidney weight/body weight, urine volume, total proteins, and albumin in the urine, and increased creatinine clearance. Periodic acid-Schiff staining also indicated that α-NETA could effectively ameliorate renal injuries in DN mice. In addition, α-NETA inhibited renal inflammation and the expressions of chemerin and CMKLR1 in mice with DN. CONCLUSION: In summary, our findings suggested that α-NETA has beneficial effects on the management of DN. Specifically, α-NETA effectively ameliorated renal damage and inflammation in a dose-dependent manner in mice with DN. Thus, targeting the chemerin and CMKLR1 axis with α-NETA may be a promising therapeutic strategy for the treatment of DN.

Tenascin-C promotes the proliferation and fibrosis of mesangial cells in diabetic nephropathy through the ß-catenin pathway.

OBJECTIVE: To mechanistically assess the involvement of tenascin-C (TNC) in diabetic nephropathy (DN). METHODS: Renal specimens from DN patients were histopathologically examined, and their TNC expression patterns were evaluated via immunohistochemistry. Additionally, the hereditarily diabetic C57BL/KsJ db/db mice were induced to develop DN via adaptive feeding, and then their renal levels of TNC and ß-catenin were assessed via western blotting and immunohistochemistry. Furthermore, the TNC and ß-catenin levels in primary rat mesangial cells (RMCs) cultured with high glucose levels were assessed via western blotting. In parallel, RMCs cultured with TNC in the presence or absence of the ß-catenin blocker ICG-001 were analyzed for their fibronectin and collagen I levels via immunostaining, and for their fibronectin, α-SMA, vimentin, PDGFR-ß, PCNA, and ß-catenin levels via western blotting. RESULTS: The TNC levels in the specimens were associated with the pathological classification. In these DN specimens, TNC protein was highly detected in the MCs and slightly in the tubulointerstitium. Renal TNC (P < 0.05) and ß-catenin (P < 0.001) were upregulated in db/db vs. db/m mice. High-glucose treatment upregulated TNC (P < 0.01) and ß-catenin (P < 0.05) in RMCs. TNC treatment upregulated fibronectin (P < 0.05), α-SMA (P < 0.01), vimentin (P < 0.05), PCNA (P < 0.05), and ß-catenin (P < 0.05) in RMCs, as assessed via western blotting. Immunohistochemical analysis confirmed the fibronectin upregulation and showed collagen I upregulation. Western-blot results also showed that levels of fibronectin (P < 0.001), α-SMA (P < 0.01), vimentin (P < 0.001), PCNA (P < 0.05), PDGFR-ß (P < 0.05), and ß-catenin (P < 0.01) were lower in RMCs co-treated with TNC and ICG-001 than in TNC-treated cells. Immunofluorescence analysis confirmed the decreased fibronectin level and showed that the collagen I level was also decreased by ICG-001. CONCLUSION: TNC is upregulated in DN and induces MC proliferation and fibrosis through the ß-catenin pathway.

New Insights into the Lactic Acid Resistance Determinants of Listeria monocytogenes Based on Transposon Sequencing and Transcriptome Sequencing Analyses.

Listeria monocytogenes is a foodborne pathogen that can tolerate a variety of extreme environments. In particular, its acid resistance (AR) capability is considered one of the key factors threating food safety. Here, we employed a microbial functional genomic technology termed transposon sequencing (Tn-seq), leading to the identification of two genes involved in cell wall peptidoglycan biosynthesis (murF) and phosphate transport (lmo2248) that play key roles in lactic acid resistance (LAR) of L. monocytogenes. Deletion of lmo2248 significantly impaired the ability of LAR in L. monocytogenes, demonstrating the accuracy of the Tn-seq results. Transcriptome analysis revealed that 31.7% of the L. monocytogenes genes on the genome were differentially expressed under lactic acid (LA) treatment, in which genes involved in phosphate transport were influenced most significantly. These findings shed light on the LAR mechanisms of L. monocytogenes, which may contribute to the development of novel strategies against foodborne pathogens. IMPORTANCE Listeria monocytogenes is a Gram-positive foodborne pathogen with high lethality and strong stress resistance, and its strong acid tolerance leads to many foodborne illnesses occurring in low-pH foods. Lactic acid is a generally recognized as safe (GRAS) food additive approved for use by the FDA. However, the genetic determinants of lactic acid resistance in L. monocytogenes have not been fully identified. In this study, the lactic acid resistance determinants of L. monocytogenes were comprehensively identified by Tn-seq on a genome-wide scale. Two genes, murF (cell wall peptidoglycan biosynthesis) and lmo2248 (phosphate transport), were identified to play an important role in the lactic acid resistance. Moreover, genome-wide transcriptomic analysis showed that phosphotransferase system (PTS)-related genes play a key role at the transcriptional level. These findings contribute to a better understanding of the lactic acid resistance mechanism of L. monocytogenes and may provide unique targets for the development of other novel antimicrobial agents.

Botany, ethnopharmacology, phytochemistry and pharmacology of Erodii Herba Geranii Herba-An review.

ETHNOPHARMACOLOGICAL RELEVANCE: As a commonly used traditional Chinese herbal medicine, Erodii Herba Geranii Herba (Geranium wilfordii Maxim., Geranium carolinianum L. and Erodium stephanianum Willd.), which was known as Laoguancao (Chinese:), has high medicinal value. It has been used to dispel rheumatism, dredge the meridians, activate blood circulation, remove blood stasis, clear heat and detoxify, and stop diarrhea and dysentery. It's also used to treat eczema, sores, carbuncles, boils caused by accumulation of damp toxin. AIM OF THE REVIEW: This review aimed to provide a systematic and comprehensive analysis of the current research progress in terms of the botany, ethnopharmacology, phytochemistry and pharmacological activities of Erodii Herba Geranii Herba, and discuss expectations for prospective research and implementation about this herb. MATERIALS AND METHODS: Information on Erodii Herba Geranii Herba was gathered via the Internet (using Google Scholar, Baidu Scholar, Pubmed, Elsevier, ACS, Medline Plus, CNKI and Web of Science) and libraries. Additionally, information was also obtained from local books and brilliant scholars in ethnopharmacology. RESULTS: More than isolated 240 chemical compounds were recorded, and main compositions are tannins, flavones, organic acids and volatile oil. The pharmacoactives of Erodii Herba Geranii Herba and its active constituents are diverse, including antibacterial, antiviral, antioxidant, liver and kidney protection, anti-inflammatory and analgesic, other activities. Among them, the antibacterial, antiviral, anti-inflammatory, analgesic, antidiarrheal and other pharmacological activities of it are consistent with traditional applications. CONCLUSIONS: All kinds of research conducted on Erodii Herba Geranii Herba, especially in field of ethnopharmacological use, phytochemicals and pharmacology have been reviewed. There are plenty of active compounds with varied effects in Erodii Herba Geranii Herba. However, some traditional applications and pharmacological activities of Erodii Herba Geranii Herba have not been scientifically evaluated or convincing due to incomplete methods and ambiguous results, as well as the lack of clinical data. In order to verify the pharmacological activity, clinical efficacy and safety of it, a systematic and comprehensive research evaluation is also required. As an important traditional Chinese medicine, Erodii Herba Geranii Herba should be further explored to promote the development of new drugs and therapeutics for various diseases. How to make better use of it should be paid more attention to.

Function and inhibition of Haspin kinase: targeting multiple cancer therapies by antimitosis.

OBJECTIVES: Haploid germ cell-specific nuclear protein kinase (Haspin) is a serine/threonine kinase as an atypical kinase, which is structurally distinct from conventional protein kinases. KEY FINDINGS: Functionally, Haspin is involved in important cell cycle progression, particularly in critical mitosis regulating centromeric sister chromatid cohesion during prophase and prometaphase, and subsequently ensuring proper chromosome alignment during metaphase and the normal chromosome segregation during anaphase. However, increasing evidence has demonstrated that Haspin is significantly upregulated in a variety of cancer cells in addition to normal proliferating somatic cells. Its knockdown or small molecule inhibition could prevent cancer cell growth and induce apoptosis by disrupting the regular mitotic progression. Given the specificity of its expressed tissues or cells and the uniqueness of its current known substrate, Haspin can be a promising target against cancer. Consequently, selective synthetic and natural inhibitors of Haspin have been widely developed to determine their inhibitory power for various cancer cells in vivo and in vitro. SUMMARY: Here our perspective includes a comprehensive review of the roles and structure of Haspin, its relatively potent and selective inhibitors and Haspin's preliminary studies in a variety of cancers.

Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis.

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown. Therefore, we further explored its possible mechanism. We subcutaneously injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)-/- (KO) mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated with hirudin in the presence of high glucose/lipopolysaccharides and ATP to measure the release of interleukin-18 and interleukin-1ß. Kidney injury induced by STZ injection was significantly ameliorated by hirudin through inhibiting Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury both in vivo and in vitro. We also found that hirudin regulated the expression of Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy to treat DN.

Fufang Xueshuantong Improves Diabetic Cardiomyopathy by Regulating the Wnt/ß-Catenin Pathway.

Diabetic cardiomyopathy (DCM) is one of the main complications of diabetic patients and the major reason for the high prevalence of heart failure in diabetic patients. Fufang Xueshuantong (FXST) is a traditional Chinese medicine formula commonly used in the treatment of diabetic retinopathy and stable angina pectoris. However, the role of FXST in DCM has not yet been clarified. This study was conducted to investigate the effects of FXST on diabetic myocardial lesions and reveal its molecular mechanism. The rats were intraperitoneally injected with 65 mg/kg streptozotocin (STZ) to induce diabetes mellitus (DM). DM rats were given saline or FXST. The rats in the control group were intraperitoneally injected with an equal amount of sodium citrate buffer and gavaged with saline. After 12 weeks, echocardiography, heart weight index (HWI), and myocardial pathological changes were determined. The expression of transforming growth factor-beta1 (TGF-ß1), collagen I, and collagen III was examined using immunofluorescence staining and western blot. The expressions of Wnt/ß-catenin signaling pathway-related proteins and mRNA were detected by western blot and real-time PCR. The results showed that FXST significantly improved cardiac function, ameliorated histopathological changes, and decreased HWI in the DM rats. FXST significantly inhibited the expression of myocardial TGF-ß1, collagen I, and collagen III in DM rats. Furthermore, FXST significantly inhibited the Wnt/ß-catenin pathway. Taken together, FXST has a protective effect on DCM, which might be mediated by suppressing the Wnt/ß-catenin pathway.

[Association between fruit intake during pregnancy and blood glucose metabolism].

OBJECTIVE: To examine the association between fruit intake and blood glucose metabolism. METHODS: Healthy singleton pregnant women with 6-14 weeks of gestation were selected in a maternal-and-child health care institution in Chengdu from February to July 2017. Dietary information was obtained by 3-day 24-hour dietary recall during each trimester, and the average daily total fruit intake per person were calculated. According to the Dietary guidelines for Chinese pregnant women(2016), insufficient rates of fruits were calculated, and the participants were divided into insufficient intake group, suitable intake group and higher intake group. Multiple linear regression was used to analyze the association between fruit intake during pregnancy and fasting blood glucose, 1-h plasma glucose and 2-h plasma glucose. Log-binomial regression model was used to analyze the association between fruit intake during pregnancy and the risk of gestational diabetes mellitus(GDM). RESULTS: Valid samples of 1453 cases in early pregnancy, 1049 cases in middle pregnancy were included, the age was(28.5±4.0)years old. The average fruit intake during the early and middle pregnancy(M(P25, P75)) were 279.7(180.8, 415.2) g/d and 232.0(100.0, 390.0) g/d, respectively. The insufficient rates were 18.8% and 43.2%, respectively. After adjusting for age, pre-pregnancy BMI, education level, family income, family history of diabetes, parity, physical activity, energy, vegetables, grains, red meat, and beverages, multiple linear regression result showed that compared with the insufficient fruit intake group, in the suitable fruit intake group, the fasting blood glucose level was decreased(ß=-0.071, 95%CI-0.111--0.003). Results of log binomial regression analysis showed that when compared with the fruit suitable intake group during the second trimester, the insufficient intake group may increase the risk of GDM(RR=1.13, 95% CI 1.11-1.58); no association between fruit intake during the early pregnancy and blood glucose metabolism was observed. CONCLUSION: Fruit intake during pregnancy is associated with blood glucose metabolism. The appropriate amount of fruit intake may improve fasting blood glucose and insufficient intake of fruits during the second trimester may increase the risk of GDM.

Synergistic Antibacterial Mechanism of Mannosylerythritol Lipid-A and Lactic Acid on Listeria monocytogenes Based on Transcriptomic Analysis.

Mannosylerythritol lipids-A (MEL-A) is a novel biosurfactant with multiple biological effects. The synergistic antibacterial activity and mechanism of MEL-A and lactic acid (LA) against Listeria monocytogenes were investigated. The synergistic effect resulted in a significant increase in the antibacterial rate compared to LA treatment alone. Genome-wide transcriptomic analysis was applied to deeply investigate the synergistic antibacterial mechanism. Gene Ontology (GO) enrichment analysis showed that the synergy between MEL-A and LA affected many potential cellular responses, including the sugar phosphotransferase system, carbohydrate transport, and ribosomes. KEGG enrichment analysis showed that the PTS system and ribosome-related pathways were significantly enriched. In addition, synergistic treatment affected locomotion and membrane-related cellular responses in GO enrichment analysis and carbohydrate metabolism and amino acid metabolism pathways in KEGG enrichment analysis compared to LA treatment alone. The accuracy of the transcriptome analysis results was verified by qPCR (R2 = 0.9903). This study will provide new insights for the prevention and control of L. monocytogenes.

Functional Genomics Identified Novel Genes Involved in Growth at Low Temperatures in Listeria monocytogenes.

Listeria monocytogenes (Lm) is a foodborne pathogen that can cause severe human illness. Standard control measures for restricting bacterial growth, such as refrigeration, are often inadequate as Lm grows well at low temperatures. To identify genes involved in growth at low temperatures, a powerful functional genomics method Tn-seq was performed in this study. This genome-wide screening comprehensively identified the known and novel genetic determinants involved in low-temperature growth. A novel gene lmo1366, encoding rRNA methyltransferase, was identified to play an essential role in Lm growth at 16°C. In contrast, the inactivation of lmo2301, a gene encoding the terminase of phage A118, significantly enhanced the growth of Lm at 16°C. The deletion of lmo1366 or lmo2301 resulted in cell morphology alterations and impaired the growth rate in milk and other conditions at low temperatures. Transcriptomic analysis revealed that the Δlmo1366 and Δlmo2301 mutants exhibited altered transcriptional patterns compared to the wild-type strain at 16°C with significant differences in genes involved in ribosome structural stability and function, and membrane biogenesis, respectively. This work uncovered novel genetic determinants involved in Lm growth at 16°C, which could lead to a better understanding of how bacteria survive and multiply at low temperatures. Furthermore, these findings could potentially contribute to developing novel antibacterial strategies under low-temperature conditions. IMPORTANCE Listeria monocytogenes is a Gram-positive pathogen that contributes to foodborne outbreaks due to its ability to survive at low temperatures. However, the genetic determinants of Lm involved in growth at low temperatures have not been fully defined. Here, the genetic determinants involved in the low-temperature growth of Lm were comprehensively identified on a genome-wide scale by Tn-seq. The gene lmo1366, encoding rRNA methyltransferase, was identified essential for growth under low-temperature conditions. On the other hand, the gene lmo2301, encoding terminase of phage A118, plays a negative role in bacterial growth at low temperatures. The transcriptomic analysis revealed the potential mechanisms. These findings lead to a better understanding of how bacteria survive and multiply at low temperatures and could provide unique targets for novel antibacterial strategies under low-temperature conditions.

Enterocins: Classification, Synthesis, Antibacterial Mechanisms and Food Applications.

Enterococci, a type of lactic acid bacteria, are widely distributed in various environments and are part of the normal flora in the intestinal tract of humans and animals. Although enterococci have gradually evolved pathogenic strains causing nosocomial infections in recent years, the non-pathogenic strains have still been widely used as probiotics and feed additives. Enterococcus can produce enterocin, which are bacteriocins considered as ribosomal peptides that kill or inhibit the growth of other microorganisms. This paper reviews the classification, synthesis, antibacterial mechanisms and applications of enterocins, and discusses the prospects for future research.

Soy foods and nuts consumption during early pregnancy are associated with decreased risk of gestational diabetes mellitus: a prospective cohort study.

AIMS: To study the relationship of soy foods and nuts consumption during early pregnancy with the risk of gestational diabetes mellitus (GDM). METHODS: This was a prospective observational study conducted in Southwest China. Dietary information was assessed through 3-day 24-h dietary recalls at 6-14 gestational weeks. For soy foods and nuts, non-consumers were used as the reference category and the consumers were categorized into tertiles. GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 gestational weeks. Log-binomial models were used to assess the effects of soy foods and nuts on GDM. RESULTS: Of the 1495 pregnant women, 529 were diagnosed with GDM. Median (IQRs) intakes of soy foods and nuts were 2.9 (0.0, 10.3) and 5.0 (0.0, 15.0) g/d, respectively. Our study found that, compared with the non-consumers, the highest tertile of soy foods intake was associated with a decrease in risk of GDM (RR = 0.73, 95%CI: 0.54-0.99, p = .049). Similarly, compared with the non-consumers, a negative relationship between the highest tertile of nuts intake and GDM risk was identified (RR = 0.65, 95%CI: 0.48-0.89, p = .007). CONCLUSIONS: Consumption of soy foods and nuts are independently inversely associated with the risk of GDM during early pregnancy.

The Lipoteichoic Acid-Related Proteins YqgS and LafA Contribute to the Resistance of Listeria monocytogenes to Nisin.

Listeria monocytogenes is a major pathogen contributing to foodborne outbreaks with high mortality. Nisin, a natural antimicrobial, has been widely used as a food preservative. However, the mechanisms of L. monocytogenes involved in nisin resistance have not yet to be fully defined. A mariner transposon library was constructed in L. monocytogenes, leading to the identification of 99 genes associated with the innate resistance to nisin via Transposon sequencing (Tn-seq) analysis. To validate the accuracy of the Tn-seq results, we constructed five mutants (ΔyqgS, ΔlafA, ΔvirR, ΔgtcA, and Δlmo1464) in L. monocytogenes. The results revealed that yqgS and lafA, the lipoteichoic acid-related genes, were essential for resistance to nisin, while the gtcA and lmo1464 mutants showed substantially enhanced nisin resistance. Densely wrinkled, collapsed surface and membrane breakdown were shown on ΔyqgS and ΔlafA mutants under nisin treatment. Deletion of yqgS and lafA altered the surface charge, and decreased the resistance to general stress conditions and cell envelope-acting antimicrobials. Furthermore, YqgS and LafA are required for biofilm formation and cell invasion of L. monocytogenes. Collectively, these results reveal novel mechanisms of nisin resistance in L. monocytogenes and may provide unique targets for the development of food-grade inhibitors for nisin-resistant foodborne pathogens. IMPORTANCE Listeria monocytogenes is an opportunistic Gram-positive pathogen responsible for listeriosis, and is widely present in a variety of foods including ready-to-eat foods, meat, and dairy products. Nisin is the only licensed lantibiotic by the FDA for use as a food-grade inhibitor in over 50 countries. A prior study suggests that L. monocytogenes are more resistant than other Gram-positive pathogens in nisin-mediated bactericidal effects. However, the mechanisms of L. monocytogenes involved in nisin resistance have not yet to be fully defined. Here, we used a mariner transposon library to identify nisin-resistance-related genes on a genome-wide scale via transposon sequencing. We found, for the first time, that YqgS and LafA (Lipoteichoic acid-related proteins) are required for resistance to nisin. Subsequently, we investigated the roles of YqgS and LafA in L. monocytogenes stress resistance, antimicrobial resistance, biofilm formation, and virulence in mammalian cells.

Starchy vegetable intake in the first trimester is associated with a higher risk of gestational diabetes mellitus: a prospective population-based study.

OBJECTIVE: The purpose of this study was to evaluate the association between starchy vegetable consumption and subgroup consumption in the first trimester and the risk of gestational diabetes mellitus (GDM). METHODS: A prospective study (n = 1444) was conducted in China. Dietary information was assessed by 24-hour dietary recalls for three days and then we calculated the consumption of total starchy vegetable and its subgroups, including (1) potato and (2) other starchy vegetable (pumpkin, lotus root, yam, taro, water chestnut, pea, and cowpea). GDM was diagnosed according to the results of 75-g two-hour oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. A modified log-binomial regression was used to estimate RRs and 95% CIs of GDM risk. RESULTS: Among the 1444 participants in our study, 520 were diagnosed with GDM. The adjusted RRs (95% CIs) for GDM from the lowest to the highest quartiles of total starchy vegetable consumption were 1.00 (reference), 1.29 (1.06, 1.57), 1.13 (0.93, 1.40), and 1.26 (1.02, 1.56), respectively; p for trend = .032. For potato, the RR of GDM risk was 1.32 for the highest potato intake quartile compared with the lowest quartile (95% CI 1.07-1.64, p for trend = .003). In addition, we did not observe an association between other starchy vegetable intakes and GDM risk. CONCLUSIONS: A higher consumption of total starchy vegetables and potatoes in the first trimester is associated with a greater risk of GDM.