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A growing body of research suggests that short-chain fatty acids (SCFAs), metabolites produced by intestinal symbiotic bacteria that ferment dietary fibers (DFs), play a crucial role in the health status of symbiotes. SCFAs act on a variety of cell types to regulate important biological processes, including host metabolism, intestinal function, and immune function. SCFAs also affect the function and fate of immune cells. This finding provides a new concept in immune metabolism and a better understanding of the regulatory role of SCFAs in the immune system, which impacts the prevention and treatment of disease. The mechanism by which SCFAs induce or regulate the immune response is becoming increasingly clear. This review summarizes the different mechanisms through which SCFAs act in cells. According to the latest research, the regulatory role of SCFAs in the innate immune system, including in NLRP3 inflammasomes, receptors of TLR family members, neutrophils, macrophages, natural killer cells, eosinophils, basophils and innate lymphocyte subsets, is emphasized. The regulatory role of SCFAs in the adaptive immune system, including in T-cell subsets, B cells, and plasma cells, is also highlighted. In addition, we discuss the role that SCFAs play in regulating allergic airway inflammation, colitis, and osteoporosis by influencing the immune system. These findings provide evidence for determining treatment options based on metabolic regulation.

Ultra-low loss fiber is promising to support 400 Gbit/s or even 1 Tbit/s ultra-high data-rate optical transmission. Currently, there have been extensive studies on ultra-low loss fibers. In this paper, we make a comprehensive survey on the state of the art of ultra-low loss fiber technology from the aspects of fabrication, industrialization status, and application. Also, as a potential type of ultra-low loss fiber, hollow fiber is introduced. We wish to provide useful technical information to readers and promote the wide application of ultra-low loss fibers.

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P

A major performance index for analyzing a stochastic transport network is the two-terminal capacity reliability Rd, defined as the probability that d units of goods can be successfully transported via stochastic arc capacities from the source to the destination. This paper presents an efficient d-minimal path method to calculate Rd based on some newly obtained results. The proposed method uses a simple method to check d-minimal path candidates and a more efficient approach to remove duplicate d-minimal paths that are the biggest obstacle in solving d-minimal paths, along with an indication of the advantage over the existing methods. Besides, sensitivity analysis is adopted to explore the most important arc whose reliability change affects the network reliability most significantly, which helps supervisor identify and enhance the critical arcs for improving the network reliability more effectively. Computational and application examples demonstrate the efficiency and utility of the method, respectively.

Penile squamous cell carcinoma (PSCC) is a rare malignancy with poor survival after standard treatment. Although genomic alterations of PSCC have been characterized in several latest studies, the association between the formation of somatic landscape and regional lymph node metastasis (LNM), an important predictor for patient survival, has not been comprehensively investigated. Here, we collected formalin-fixed paraffin-embedded tumor tissue and matched normal samples of 32 PSCC patients, including 14 LNM patients and 18 clinically node-negative patients, to implement a whole-exome sequencing. Comparison of genomic features among different lymph node status subgroups was conducted after genomic profiling and its effects on patient survival were explored. Top-ranked recurrent gene mutants in our PSCC cohort were TP53 (13/32), NOTCH1 (12/32), CDKN2A (11/32), TTN (9/32) and FAT1 (8/32), mainly identified in the Notch, Hippo, cell cycle, TP53, RTK-RAS and PI3K pathways. While CDKN2A was confirmed to be the driver gene in all PSCC patients, certain gene mutants were significantly enriched in LNM involved patients, including TP53 (9/14 vs. 4/18, p = 0.029) and GBF1 (4/14 vs. 0/18, p = 0.028). Overall survival stratification of PSCC patients were found to be significantly correlated with mutations of three genes, including PIK3CA (Hazard ratio [HR] = 4.15, p = 0.029), CHD7 (HR = 4.82, p = 0.032) and LAMC3 (HR = 15.9, p < 0.001). PIK3CA and LAMC3 held a higher prevalence in patients with LNM compared to those without LNM (PIK3CA: 3/14 vs. 1/18, LAMC3: 2/14 vs. 1/18). Our finding demonstrated that genomic divergence exists across PSCC patients with different lymph node statuses, and it may be correlated with their survival outcome. It helps delineate somatic evolution during tumor progression and perfect potential therapeutic intervention in this disease.

Feature selection is of particular importance in the field of drug discovery. Many methods have been put forward for feature selection during recent decades. Among them, evolutionary computation has gained increasing attention owing to its superior global search ability. However, there still lacks a simple and efficient software for drug developers to take advantage of evolutionary computation for feature selection. To remedy this issue, in this paper, a user-friendly and standalone software, named ECoFFeS, is developed. ECoFFeS is expected to lower the entry barrier for drug developers to deal with feature selection problems at hand by using evolutionary algorithms. To the best of our knowledge, it is the first software integrating a set of evolutionary algorithms (including two modified evolutionary algorithms proposed by the authors) with various evaluation combinations for feature selection. Specifically, ECoFFeS considers both single-objective and multi-objective evolutionary algorithms, and both regressionand classification-based models to meet different requirements. Five data sets in drug discovery are collected in ECoFFeS. In addition, to reduce the total analysis time, the parallel execution technique is incorporated into ECoFFeS. The source code of ECoFFeS can be available from https://github.com/JiaweiHuang/ECoFFeS/.

To solve the problem of security and efficiency of anonymous authentication in vehicular ad hoc network,a pairing-free certificateless batch anonymous authentication scheme was proposed.The public and private keys and pseudonyms were jointly generated by the trusted third party and vehicle,so the system security didn't depend on the tamper device.The scheme can realize authentication,anonymity,traceability,unforgeability,forward or backward security,and so on.Furthermore,under the random oracle model,the scheme can resist Type I and Type II attacks.Because there is no need to use certificates during authentication,the system storage load is effectively reduced.At the same time,the scheme realizes the batch message authentication on the basis of pairing-free operation,so the authentication efficiency is improved.Therefore,the scheme has important theoretical significance and application value in the resource-limited internet of things or embedded environment.

To solve the problem of efficiency of anonymous authentication in vehicular ad hoc network,a batch anonymous authentication scheme was proposed by using bilinear pairing on elliptic curves .The signature was generated by the roadside unit node (RSU) and the vehicle together.Thus,the burden of VANET certification center was reduced and the authentication efficiency was proved.Meanwhile,the difficulty of the attacker to extract the key was increased.Furthermore,security proofs were given to the scheme in the random oracle model.Analysis shows that the proposed scheme can meet the needs of many kinds of security requirements,the computational overhead is significantly reduced,and the authentication efficiency is improved effectively too.Therefore,the scheme has important theoretical significance and application value under computational capability constrained Internet of things (IoT) environment.

BACKGROUND: The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study is to evaluate the role of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal cancer susceptibility. We performed a meta-analysis on all the eligible studies that provided 5,817 cases and 6,544 controls for CYP1A2*F (from 13 studies), 9219 cases and 10406 controls for CYP1B1 Leu432Val (from 12 studies), 6840 cases and 7761 controls for CYP1B1 Asn453Ser (from 8 studies), and 4302 cases and 4791 controls for CYP1B1Arg48Gly (from 6 studies). Overall, no significant association was found between CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly and colorectal cancer risk when all the eligible studies were pooled into the meta-analysis. And in the subgroup by ethnicity and source of controls, no evidence of significant association was observed in any subgroup analysis. CONCLUSIONS/SIGNIFICANCE: In summary, this meta-analysis indicates that CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly polymorphisms do not support an association with colorectal cancer, and further studies are needed to investigate the association. In addition, our work also points out the importance of new studies for CYP1A2*F polymorphism in Asians, because high heterogeneity was found (dominant model: I(2) = 81.3%; heterozygote model: I(2) = 79.0).

Direct or ex vivo BMP9 adenoviral gene therapy can induce massive bone formation at the injection sites and clearly promote spinal fusion. A comprehensive analysis of the osteogenic activity indicated that BMP9 was one of the most potent inducers of osteogenic differentiation both in vitro and in vivo among 14 types of human BMPs. However, genetic variations and whether they correlated with OPLL were not considered. We have sequenced the complete BMP9 gene in 450 patients with OPLL and in 550 matched controls. Analyses were performed on single markers and haplotypes. Single marker tests identified 6 SNPs, among which the minor alleles of rs7923671 (T>C; P=0.0026; OR: 1.33, CI: 1.10-1.60), rs75024165 (C>T, Thr304Met; PC; P