Search

5-Hydroxymethylfurfural (5-HMF) exists in a wide range of sugar-rich foods and traditional Chinese medicines. The role of 5-HMF in antiviral innate immunity and its mechanism have not been reported previously. In this study, we reveal for the first time that 5-HMF upregulates the production of retinoic acid-inducible gene I (RIG-I)-mediated type I interferon (IFN) as a response to viral infection. IFN-β and IFN-stimulated chemokine gene expressions induced by the vesicular stomatitis virus (VSV) are upregulated in RAW264.7 cells and primary peritoneal macrophages after treatment with 5-HMF, a natural product that appears to inhibit the efficiency of viral replication. Meanwhile, 5-HMF-pretreated mice show enhanced innate antiviral immunity, increased serum levels of IFN-β, and reduced morbidity and viral loads upon infection with VSV. Thus, 5-HMF can be seen to have a positive effect on enhancing type I IFN production. Mechanistically, 5-HMF upregulates the expression of RIG-I in macrophages, resulting in an acceleration of the RIG-I signaling pathway activation. Additionally, STAT1 and STAT2 phosphorylations, along with the expression of IFN-stimulated chemokine genes induced by IFN-α/β, were also enhanced in macrophages cotreated with 5-HMF. In summary, these findings indicate that 5-HMF not only can induce type I IFN production but also can enhance IFN-JAK/STAT signaling, leading to a novel immunomodulatory mechanism against viral infection. In conclusion, our study reveals a previously unrecognized effect of 5-HMF in the antiviral innate immune response and suggests new potential of utilizing 5-HMF for controlling viral infection.

Clinical efficacy of treatments against non-obstructive azoospermia (NOA), which affects 1% of men, are currently limited by the incomplete understanding of NOA pathogenesis and normal spermatogenic microenvironment. Here, we profile >80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. We show that Sertoli cells, which form the scaffold in the testicular microenvironment, are severely damaged in NOA patients and identify the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature, but exhibit abnormal immune responses, while the cells in idiopathic NOA (iNOA) are physiologically immature. Furthermore, we find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic methods and therapeutic targets for NOA., Non-obstructive azoospermia affects 1% of men. Here, authors perform single-cell transcriptomic analysis of human testicular cells from healthy donors and non-obstructive azoospermia patients and find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from patients.

Urolithiasis has become more prevalent throughout China.Knowing stone composition helps identify their possible underlying etiology of urolithiasis, provide appropriate individualized treatment and prevent stone recurrence.To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone localization and geographical region on stone composition.We used Fourier transform infrared spectroscopy to analyse urinary stones from consecutive patients at 46 hospitals in seven geographic areas of China between June 1, 2010 and May 31, 2015.Chi-squared tests and logistic regression analyses were performed to determine associations between stone composition and sex, age, body mass index (BMI), stone location, and geographic region.The most common stone components were calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), brushite (1.7%), and cystine (0.9%). CaOx and urate occurred more frequently in males, whereas carbapatite and struvite were more common in females (p

Previous studies evaluating the role of magnesium supplementation as a preventative strategy for preeclampsia showed inconsistent results. We performed a meta-analysis or randomized controlled trials (RCTs) to evaluate the influence of oral magnesium supplementation on the incidence of preeclampsia in pregnant women. Relevant studies were obtained by search of Medline, Embase, and Cochrane's Library databases. A random effects model was used to pool the results. Influences of study characteristics of the outcome were evaluated by predefined subgroup analyses. Seven RCTs with 2653 pregnant women were included. Pooled results showed that oral magnesium supplementation during pregnancy significantly reduced the risk of preeclampsia (risk ratio [RR]: 0.76, 95% confidence interval [CI]: 0.59 to 0.98, P = 0.04) with no significant heterogeneity (P for Cochrane's Q test = 0.42, I2 = 1%). The result was not significant for the outcome of severe preeclampsia (RR: 0.54, 95% CI: 0.18 to 1.69, P = 0.29; I2 = 0%), although only two studies were available. Subgroup analysis showed that oral magnesium supplementation did not significantly reduce the risk of preeclampsia in normal pregnant women (RR: 0.91, 95% CI: 0.67 to 1.25, P = 0.57), but the preventative effect was significant in studies with normal and high-risk pregnant women (RR: 0.54, 95% CI: 0.35 to 0.83, P = 0.005; P for subgroup difference = 0.04). In conclusion, oral supplementation of magnesium may reduce the risk of preeclampsia, which may be more remarkable in high-risk pregnant women.

Chronic periodontitis caused by Porphyromonas gingivalis (P. gingivalis) infection generally lasts for a lifetime. The long-term existence and development of P. gingivalis infection gradually aggravate the accumulation of inflammatory signals and toxic substances in the body. Recent evidence has revealed that P. gingivalis infection may be relevant to some central nervous system (CNS) diseases. The current work collects information and tries to explore the possible relationship between P. gingivalis infection and CNS diseases, including the interaction or pathways between peripheral infection and CNS injury, and the underlying neurotoxic mechanisms.

Parastomal hernia and fecal incontinence cause severe distress to the rectal cancer patients with stoma after abdominoperineal resection. We attempted a new colostomy technique through the gap between the abdominal oblique internal and external muscles to prevent parastomal hernia and improve quality of life. This cohort study retrospectively examined clinical data from a total of 114 consecutive rectal cancer patients who underwent laparoscopic abdominoperineal resection in our center from March 2016 to March 2018 after propensity score matching. Group A included 57 patients who underwent colostomy through the gap between the abdominal oblique internal and oblique external muscles, while group B included 57 patients who underwent extraperitoneal colostomy. Patients’ quality of life was evaluated using Fecal Incontinence Quality of Life (FIQL) Scale. Group A had a lower incidence of parastomal hernia (0% vs. 15.7%, p = 0.004) and higher quality of life, especially in lifestyle, coping/behavior and embarrassment domains (all p values

Non-obstructive azoospermia (NOA) affects 1% of men. However, the unknowns of NOA pathogenesis and even normal spermatogenic microenvironment establishment severely limit the clinical efficacy of NOA treatment. We profiled > 80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. Sertoli cells, which form the scaffold in the testicular microenvironment, exhibited the most obvious damages in NOA patients. We identified the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature but with abnormal immune response, while the cells in idiopathic NOA (iNOA) are basically physiologically immature. Furthermore, inhibition of Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic methods and therapeutic targets for NOA.

The gene encoding transmembrane protein 100 (TMEM100) was first discovered to be transcribed by the murine genome. It has been recently proven that TMEM100 contributes to hepatocellular carcinoma and non-small-cell lung carcinoma (NSCLC). This study investigates the impact of TMEM100 expression on gastric cancer (GC). TMEM100 expression was remarkably downregulated in GC samples compared to the surrounding non-malignant tissues (p in vivo examination of TMEM100 activity revealed that its upregulation prohibits the pulmonary metastasis of GC cells and increases the sensitivity of xenograft tumors to 5-FU treatment. In conclusion, TMEM100 serves as a tumor suppressor in GC and could be used as a promising target for the treatment of GC and as a predictor of GC clinical outcome.

Adaptation refers to the general phenomenon that a neural system dynamically adjusts its response property according to the statistics of external inputs. In response to a prolonged constant stimulation, neuronal firing rates always first increase dramatically at the onset of the stimulation; and afterwards, they decrease rapidly to a low level close to background activity. This attenuation of neural activity seems to be contradictory to our experience that we can still sense the stimulus after the neural system is adapted. Thus, it prompts a question: where is the stimulus information encoded during the adaptation? Here, we investigate a computational model in which the neural system employs a dynamical encoding strategy during the neural adaptation: at the early stage of the adaptation, the stimulus information is mainly encoded in the strong independent firings; and as time goes on, the information is shifted into the weak but concerted responses of neurons. We find that short-term plasticity, a general feature of synapses, provides a natural mechanism to achieve this goal. Furthermore, we demonstrate that with balanced excitatory and inhibitory inputs, this correlation-based information can be read out efficiently. The implications of this study on our understanding of neural information encoding are discussed.