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Background: Elevated blood pressure (BP) in childhood is associated with adult hypertension and arterial stiffness. However, the effect of long-term time in target range (TTR) for BP since childhood on the risk of arterial stiffness in midlife remains unclear. Objectives: The purpose of this study was to determine the independent association of TTR for systolic blood pressure (SBP) from childhood to midlife with arterial stiffness in adulthood. Methods: This study used data from the ongoing cohort of the Hanzhong Adolescent Hypertension Study. SBP-TTR was assessed over 36 years, with the target ranges of SBP defined as the 90th to 95th percentile of SBP for age, sex, and height in childhood, and 110 to 130 mm Hg in adulthood. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1,400 cm/s. Results: Of the total 1,959 participants, 55.5% (1,088 of 1,959) were men, and the mean age was 49 years. The risk of arterial stiffness exhibited a gradual decrease with increasing SBP-TTR over the 36-year follow-up. Compared with the participants in the lowest quartile of SBP-TTR from childhood to midlife, those in the highest quartile showed significantly reduced arterial stiffness risk in midlife. This association persisted even after adjusting for mean SBP and SBP variability. Furthermore, men in the highest quartile of SBP-TTR demonstrated a markedly lower arterial stiffness risk than those in the lowest quartile, whereas this effect was not observed in women. Conclusions: Higher long-term SBP-TTR from childhood to midlife is associated with a reduced risk of arterial stiffness in midlife, regardless of the mean SBP or SBP variability.

Abstract Background Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. Methods Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. Results A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88–0.95, P = 2.92 × 10−7) and Europe (OR = 0.92, 95%CI 0.88–0.95, P = 4.61 × 10−6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. Conclusion Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Abstract Background Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. Methods and results A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P

Abstract Background The aim of the study was to investigate whether the expression of CD27−CD38+ in interferon (IFN)-γ+CD4+ T cells stimulated by the specific antigen early secreted antigenic target-6 (ESAT-6)/culture filter protein-10 (CFP-10) could be a potential new therapeutic evaluation indicator for anti-tuberculosis (TB) treatment. Methods Newly diagnosed active pulmonary TB patients, latent TB infection (LTBI) and healthy controls were enrolled from January 2021 to December 2021. PTB patients were treated by standard anti-TB regimen 2HREZ/4HR (2 months of isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (Z) followed by 4 months of isoniazid (H) and rifampin (R)). The difference of CD27−CD38+ expression in IFN-γ+CD4+ T cells before treatment, 2 months after treatment, and 6 months after treatment were compared. Results Total 45 PTB patients, 38 LTBI cases and 43 healthy controls were enrolled. The expression of CD27−CD38+ decreased significantly after anti-TB treatment and was comparable with that in LTBI and healthy controls when the 6-month anti-TB treatment course was completed. The decline rate of CD27−CD38+ between 6 months after treatment and baseline was positively correlated with erythrocyte sedimentation rate (r = 0.766, P

Steel slag–peanut shell-based activated carbon was prepared using ultrafine steel slag powder and peanut shells through microwave processing. The response surface method was used to evaluate the effects of microwave power, impregnation ratio, steel slag content, and steel slag particle size on the rate of the adsorption of formaldehyde gas by the prepared activated carbon. Subsequently, optimum parameters were calculated for the preparation of activated carbon with the maximum rate of adsorption for formaldehyde gas adsorption. Finally, the activated carbon was characterized by an X-ray infrared spectrometer, field emission scanning electron microscope, and specific surface area and pore size analyzer. Results revealed that the activated carbon prepared using 530 W of microwave power, steel slag powder corresponding to a mesh size 1160, steel slag content equal to 10.8%, and impregnation ratio of 1.25 has the highest formaldehyde adsorption rate. According to the established regression model, the theoretical adsorption rate of formaldehyde gas will be 94.96% under the above optimal preparation conditions. Thus, the prepared activated carbon had a formaldehyde adsorption rate of 94.14%, which is within a 5% error range of the adsorption rate estimated by our regression model for the same conditions. We further demonstrated that our response curve model can predict the adsorption rate of the activated carbon prepared by this process efficiently and that it is feasible to optimize the preparation of activated carbon by the response surface method. Furthermore, the regression analysis further reveals that the degree of influence of the four factors related to this method of preparing activated carbon on the rate of formaldehyde gas adsorption is in the following order, from large to small: microwave power, steel slag content, impregnation ratio, and steel slag fineness. The mutual interaction of the four influencing factors on the formaldehyde gas adsorption rate can be intuitively observed through the three-dimensional response surface graph. Pore structure analysis of the activated carbon prepared using the optimal preparation conditions revealed that it has an H3-type hysteresis loop and a flat-panel slot-like structure. The pore size distribution is uneven, with predominant micropores and small-sized mesopores. Fourier-transform infrared spectroscopy analysis showed that after adding steel slag for modification, the activated carbon had more acidic functional groups, which is beneficial to the adsorption of formaldehyde. Morphological analysis reveals that the layered structure of the activated carbon is clear and that adding a small amount of steel slag is beneficial to improve the rate of pulverization.

Aim: A meta-analysis was conducted to assess the effectiveness of Chinese patent medicines when used in combination with Western medicines for the treatment of irritable bowel syndrome (IBS). Methods: CNKI, Wanfang Academic Journal Full Text Database, VIP, Pubmed, Embase, Web of Science, and Cochrane Library databases were searched for clinical studies on the treatment of IBS using Chinese patent medicines that were published from inception until March 15, 2023. The shortlisted data were strictly screened and the data were extracted and evaluated, followed by data analyses and collation using RevMan 5.4 and stata16 software. Results: The final 21 randomized controlled trials(RCT), which included 14 proprietary Chinese medicines that were all orally administered, were in a total population of 2007 patients. Meta-analysis revealed that the combination of Chinese patent medicines with Western medicines could improve the overall clinical effectiveness (OR = 3.81, 95 % CI [2.84–5.12], P < 0.00001); significantly improved the abdominal pain scores (MD = -0.66, 95 % CI [-0.93, -0.40], P < 0.00001); improved the stool trait scores (MD = -0.48, 95 % CI [-0.59, -0.37], P < 0.00001); improved the IBS symptom severity scale(IBS-SSS) scores (MD = -44.36, 95 % CI [-53.64, -35.08], P < 0.00001); improved IBS quality of life(IBS-QOL) -positive (MD = 10.27, 95 % CI [3.50, 17.04], P = 0.003 < 0.05) and -negative scores (MD = -7.91, 95 % CI[-15.62, -0.02], P = 0.04 < 0.05); and improved the Hamilton Anxiety Scale(HAMA) scores (MD = -3.37, 95 % CI [-6.49, -0.24], P = 0.03); albeit no statistical difference was noted in improving Hamilton Depression Scale(HAMD) scores (MD = -2.83, 95 % CI [-5.74, 0.08], P = 0.06 > 0.05). Conclusion: For treating irritable bowel syndrome, the effectiveness of combining Chinese patent medicine with Western medicine is better than that of using Western medicine alone both in terms of relieving gastrointestinal discomfort and regulating mood. However, as the sample size was limited, it is advisable to conduct large-scale, high-quality, and rigorous randomized controlled trials to enhance the clinical evidence.

Intrauterine adhesions (IUAs) often occurred after common obstetrical and gynecological procedures or infections in women of reproductive age. It was characterized by the formation of endometrial fibrosis and prevention of endometrial regeneration, usually with devastating fertility consequences and poor treatment outcomes so far. Telocytes (TCs), as a novel interstitial cell type, present in female uterus with in vitro therapeutic potential in decidualization-defective gynecologic diseases. This study aims to further investigate the role of TC-derived Wnt ligands carried by exosomes (Exo) in reversal of fibrosis and enhancement of regeneration repair in endometrium. IUA cellular and animal models were established from endometrial stromal cells (ESCs) and mice, followed with treatment of TC-conditioned medium (TCM) or TC-derived Exo. In cellular model, fibrosis markers (collagen type 1 alpha 1 [COL1A1], fibronectin [FN], and α-smooth muscle actin [α-SMA]), angiogenesis (vascular endothelial growth factor [VEGF]), and pathway protein (β-catenin) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting (WB), and immunofluorescence. Results showed that, TCs (either TCM or TC-derived Exo) provide a source of Wnts that inhibit cellular fibrosis, as evidenced by significantly elevated VEGF and β-catenin with decreased fibrotic markers, whereas TCs lost salvage on fibrosis after being blocked with Wnt/β-catenin inhibitors (XAV939 or ETC-159). Further in mouse model, regeneration repair (endometrial thickness, number of glands, and fibrosis area ratio), fibrosis markers (fibronectin [FN]), mesenchymal–epithelial transition (MET) (E-cadherin, N-cadherin), and angiogenesis (VEGF, microvessel density [MVD]) were studied by hematoxylin–eosin (HE), Masson staining, and immunohistochemistry. Results demonstrated that TC-Exo treatment effectively promotes regeneration repair of endometrium by relieving fibrosis, enhancing MET, and angiogenesis. These results confirmed new evidence for therapeutic perspective of TC-derived Exo in IUAs.

Abstract Background Active tuberculosis (ATB) originates from primary Mycobacterium tuberculosis (MTB) infection or reactivation of latent tuberculosis. Besides bacteriological examination, MTB-reactive immunocytes detection can be an alternative testing for discrimination of active tuberculosis. The purpose of this study is to investigate the accuracy of peripheral blood CD27−CD38+IFN-γ+CD4+T cells in ATB diagnosis. Methods This prospective diagnostic accuracy study was conducted at Shanghai Pulmonary Hospital between January 2019 and December 2021. Patients with ATB, non-tuberculosis mycobacterium infection (NTM), latent tuberculosis infection (LTBI), other respiratory diseases (OD), and healthy individuals (HC) were enrolled. The accuracy of CD27−CD38+IFN-γ+CD4+/CD4+ and other phenotypic markers for ATB diagnosis was assessed. Results A total of 376 patients (237 ATB, 38 LTBI, 8 NTM, 50 OD, and 43 HC) were enrolled. The ratios of CD4+IFN-γ+CD27− and CD4+IFN-γ+CD27−CD38+ profiles in CD4+IFN−γ+ cells and the ratios of CD4+IFN-γ+CD38+, CD4+IFN-γ+CD27−, and CD4+IFN-γ+CD38+CD27− profiles in CD4+ cells in the ATB group were significantly higher than in the other groups. The area under the curve (AUC) of CD27−CD38+IFN-γ+CD4+/CD4+ for the diagnosis of ATB was the highest, with a value of 0.890. With the optimal cutoff value of 1.34 × 10–4, the sensitivity and specificity of CD27−CD38+IFN-γ+CD4+/CD4+ for ATB diagnosis was 0.869 and 0.849, respectively. Conclusion CD27−CD38+IFN-γ+CD4+/CD4+ might be a potential biomarker for active tuberculosis diagnosis.

Traditional cloud computing is developed from a high-performance cluster. Every server in the high-performance cluster has its own resources, including a CPU, memory, a network, I/O (Input/Output), a power system, and a heat dissipation system. Using software virtualization technologies such as the kernel-based virtual machine (KVM), Xen, VMware, and Hyper-V, these exclusive resources can be shared among these servers to improve the utilization rate. Although these technologies provide a great improvement in the resource utilization rate, some overhead in the process of software virtualization is inevitable. Server architecture and virtualization technology are the two factors that mainly affect cloud computing efficiency. With the rapid development of internet services, big data, and cloud computing, the cloud server has become mainstream instead of the traditional server. On the other hand, hardware virtualization technology has gradually developed. Compared with the traditional cloud computing solutions based on virtual machines, the cloud server based on hardware virtualization can achieve much higher efficiency to better meet cloud computing requirements by removing the software overhead. The cloud server’s design concept of configuration on demand, distributed sharing of hardware resource architecture, and construction method of hardware resource virtualization are presented. A three-level interconnection architecture of the cloud server is designed. In Level-1, the computing pool and the memory pool are built, while Level-2 is for the network pool, and Level-3 is for all resource pools. Different applications in these levels can be realized in the cloud server: Level-1 for computing-intensive applications, Level-2 for transactional applications, and Level-3 for virtual applications. A prototype system of a 16-processor cloud server using hardware virtualization architecture is designed and implemented. In this system, there are sixteen physical nodes. Every physical node is composed of a CPU and two DIMMs (dual inline memory modules). Different types of CPUs may be used in these physical nodes. Every four physical nodes form a computing module. In every computing module, a field-programmable gate array (FPGA)-based interconnection fabric controller (IFC) integrated network, storage, and general I/O resources is designed to interconnect these processors. All IFCs are interlinked. All the processors in this prototype system can share the network, storage, and general I/O resources to realize hardware resource virtualization through these IFCs. For the prototyping system, evaluation experiments on network performance tests by the Netperf program and storage performance tests by the FIO program are performed. The test results show that the prototyping system not only keeps the traditional cloud server’s advantages but also provides better scalability and performance. The advantages of this cloud server are in providing a high-density, high performance-to-cost ratio, a high performance-to-Watt ratio, and high scalability compared with the existing traditional cloud server.

The CPU is the core part of all integrated circuits. Although some homemade CPUs of proprietary intellectual property rights are rapidly developed, few high-performance chipsets are available, especially in server domains, to match them. Thus, the total systems designed using these CPUs and low-performance chipsets do not have proper performance. The Loongson CPU faces the same problem. To seek better chipsets for it, certain architecture and some methods are designed and implemented to adapt different types of chipsets. In this architecture, a field-programmable gate array (FPGA) is linked between a CPU and these chipsets. An FPGA is divided into three domains: an HT (hyper transport) bus domain, a processing domain for important but temporarily indeterminate signals, and a CPLD (complex programmable logic device) function domain. In these adaption processes, HT bus signals, the temporarily indeterminate signals, and power signals in CPUs and chipsets are respectively linked into three domains in an FPGA and treated by a programming FPGA to perform all types of possible signal combinations. The power sequence between the CPU and chipsets is coordinated to the right order using an FPGA. The signal integrity difference between them is avoided and trimmed to the right state by amending their signals in the FPGA. In this system, the experimental results show that this architecture and these methods simultaneously make more chipsets work together to be adapted than before in a single motherboard. This combination avoids researching and developing many different motherboards for every type of possible chipset and greatly reduces costs. High-performance server chipsets can be found to properly match the Loongson CPU and have better specifications and higher performance than those currently used for the Loongson CPU. A prototype system composed of the Loongson CPU and five types of chipsets is designed and implemented. Using the above architecture and methods, a type of optimal server chipsets SR5690 + SP5100 has been found, and the matching principles or correct settings for the signal connection and power sequence have been concluded. The Loongson 3B4000 two-way SMP motherboard with SR5690 + SP5100 chipsets is also produced. On this motherboard, the results of evaluation experiments on computing performance tests by the SPEC CPU 2006 program, storage performance tests by the IO zone program, and network performance tests by the Netperf program are performed. Compared with the current Loongson 3B4000 server with a 7A1000 chipset, the test results show the performance on three items is improved by approximately 10%. The combination of the Loongson CPU and this type of server chipset provides wider applications in the server market and promotes the development of the Loongson CPU in its ecosystem.

This study investigates the pricing formula for European options when the underlying asset follows a fuzzy mixed weighted fractional Brownian motion within a jump environment. We construct a pricing model for European options driven by fuzzy mixed weighted fractional Brownian motion with jumps. By converting the partial differential equation (PDE) into a Cauchy problem, we derive explicit solutions for both European call options and European put options. The figures and tables demonstrating the effectiveness of the results highlight the suitability of the fuzzy mixed weighted fractional Brownian motion with jump model for option pricing.

Abstract The increasing incidence of hepatocellular carcinoma (HCC) is of great concern globally, but the molecular pathogenesis of these tumors remains unclear. Sorafenib is a first-line drug for the treatment of advanced HCC. However, the efficacy of sorafenib in improving patient survival is limited, and most patients inevitably develop resistance to this drug. Recent studies have demonstrated that the activation of the IRE1α–XBP1s pathway might play a protective role in the response to sorafenib and contribute to malignancy in HCC. Here, we found that RCN1, an endoplasmic reticulum resident protein, is significantly upregulated in sorafenib-resistant HCC cells and promotes tumor progression. Our analysis showed that RCN1 may be an independent predictor of tumor recurrence and overall survival. Mechanistically, RCN1 promotes the dissociation of GRP78 from IRE1α in sorafenib-resistant cells by interacting with GRP78 through its EFh1/2 domain. Subsequently, the IRE1α–XBP1s pathway, a branch of the unfolded protein response, is sustainably activated. Interestingly, IRE1α–XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in HCC. These results suggest that RCN1-targeted therapy might be a feasible strategy for the treatment of HCC.

Matrices have important applications of statistical analysis, circuits, mechanics, optics, and quantum physics. In this article, matrix explicit formulas of the exponentials for computing exp(αA), where A is a special n × n matrix and α is the order of fractional derivative, were obtained. The definitions of the fractional derivative respectively are the Caputo fractional derivative and Riemann-Liouville fractional derivative. Here, we need to point that the new results can be looked as an extended the previous work of the authors. The explicit formulas can help us better to explore deep connotations from natural science.

Abstract Cerebral ischemia–reperfusion (I/R) injury can induce the mitophagy of neurons in the ischemic brain. Long non‐coding RNAs (lncRNAs) play an important role in the pathogenesis of various injuries, especially in cerebral I/R injury. The purpose of this study is to investigate the molecular mechanism of lncRNA RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in cerebral I/R injury. The middle cerebral artery occlusion (MCAO) mouse model was established. Neurological deficit score, pathological structure, infarcted area, neuron number, cell apoptosis, and coagulation ability of MCAO mice were evaluated. The expressions of RMRP, microRNA (miR)‐613, and ATG3 in MCAO mice were detected. The binding relationships among miR‐613, RMRP, and ATG3 were predicted and verified. Neuro 2A (N2a) cells were treated with oxygen–glucose deprivation/reperfusion (OGD/R) to simulate I/R injury. Cell viability and apoptosis assays were performed. The effects of miR‐613, ATG3, and RMRP on I/R injury were verified by functional rescue experiments. JAK2/STAT3 phosphorylation level was detected. We found significantly upregulated RMRP and ATG3, and downregulated miR‐613 expressions in MCAO mice. RMRP could escalate ATG3 mRNA expression through miR‐613. RMRP knockdown promoted viability and inhibited apoptosis of OGD/R‐treated N2a cells, which could be reversed by miR‐613 inhibition or ATG3 overexpression. RMRP overexpression inhibited the activation of JAK2/STAT3 signaling pathway. We demonstrated that lncRNA RMRP competitively bound to miR‐613, leading to the increase of ATG3 expression and the inhibition the JAK2/STAT3 pathway, thus promoting cerebral I/R injury in mice.

Telocytes (TCs), a distinct type of interstitial (stromal) cells, have been discovered in many organs of human and mammal animals. TCs, which have unique morphological characteristics and abundant paracrine substance, construct a three-dimensional (3D) interstitial network within the stromal compartment by homocellular and heterocellular communications which are important for tissue homeostasis and normal development. Fibrosis-related diseases remain a common but challenging problem in the field of medicine with unclear pathogenesis and limited therapeutic options. Recently, increasing evidences suggest that where TCs are morphologically or numerically destructed, many diseases continuously develop, finally lead to irreversible interstitial fibrosis. It is not difficult to find that TCs are associated with chronic inflammation and fibrosis. This review mainly discusses relationship between TCs and the occurrence of fibrosis in various diseases. We analyzed in detail the potential roles and speculated mechanisms of TCs in onset and progression of systemic fibrosis diseases, as well as providing the most up-to-date research on the current therapeutic roles of TCs and involved related pathways. Only through continuous research and exploration in the future can we uncover its magic veil and provide strategies for treatment of fibrosis-related disease.

An analytical framework for the extension of solutions to fractional differential equations (FDEs) to the negative half-line is presented in this paper. The proposed technique is based on the construction of a special characteristic equation corresponding to the original FDE (when the characteristic equation does exist). This characteristic equation enables the construction analytic solutions to FDEs are expressed in the form of infinite fractional power series. Necessary and sufficient conditions for the existence of such an extension are discussed in detail. It is demonstrated that the extension of solutions to FDEs to the negative half-line is not a single-valued operation. Computational experiments are used to illustrate the efficacy of the proposed scheme.

Abstract Background China is a highly endemic area of chronic hepatitis B (CHB). The accuracy of existed noninvasive biomarkers including TE, APRI and FIB-4 for staging fibrosis is not high enough in Chinese cohort. Methods Using liver biopsy as a gold standard, a novel noninvasive indicator was developed using laboratory tests, ultrasound measurements and liver stiffness measurements with machine learning techniques to predict significant fibrosis and cirrhosis in CHB patients in north and east part of China. We retrospectively evaluated the diagnostic performance of the novel indicator named FibroBox, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) in CHB patients from Jilin and Huai’an (training sets) and also in Anhui and Beijing cohorts (validation sets). Results Of 1289 eligible HBV patients who had liver histological data, 63.2% had significant fibrosis and 22.5% had cirrhosis. In LASSO logistic regression and filter methods, fibroscan results, platelet count, alanine transaminase (ALT), prothrombin time (PT), type III procollagen aminoterminal peptide (PIIINP), type IV collagen, laminin, hyaluronic acid (HA) and diameter of spleen vein were finally selected as input variables in FibroBox. Consequently, FibroBox was developed of which the area under the receiver operating characteristic curve (AUROC) was significantly higher than that of TE, APRI and FIB-4 to predicting significant fibrosis and cirrhosis. In the Anhui and Beijing cohort, the AUROC of FibroBox was 0.88 (95% CI, 0.72–0.82) and 0.87 (95% CI, 0.83–0.91) for significant fibrosis and 0.87 (95% CI, 0.82–0.92) and 0.90 (95% CI, 0.85–0.94) for cirrhosis. In the validation cohorts, FibroBox accurately diagnosed 81% of significant fibrosis and 84% of cirrhosis. Conclusions FibroBox has a better performance in predicting liver fibrosis in Chinese cohorts with CHB, which may serve as a feasible alternative to liver biopsy.

Telocytes (TCs), which are a recently discovered interstitial cell type present in various organs and tissues, perform multiple biological functions and participate in extensive crosstalk with neighboring cells. Endometriosis (EMs) is a gynecological disease characterized by the presence of viable endometrial debris and impaired macrophage phagocytosis in the peritoneal environment. Here, CD34/vimentin-positive TCs were co-cultured with RAW264.7 cells in vitro . M1/M2 differentiation-related markers were detected; phagocytosis, energy metabolism, proliferation, apoptosis, and pathway mechanisms were studied; and the mitochondrial membrane potential (ΔΨm) was measured. Furthermore, in an EMs mouse model, the differentiation of macrophages in response to treatment with TC-conditioned medium (TCM) in vivo was studied. The results showed that upon in vitro co-culture with TCM, RAW264.7 cells differentiated more toward the M1 phenotype with enhancement of phagocytosis, increase in energy metabolism and proliferation owing to reduced the loss of ΔΨm, and suppression of dexamethasone-induced apoptosis. Further, along with the activation of NF-κB, Bcl-2 and Bcl-xl, the expression of Bax, cleaved-caspase9, and cleaved-caspase3 reduced in RAW264.7 cells. In addition, the M1 subtype was found to be the dominant phenotype among tissue and peritoneal macrophages in the EMs model subjected to in vivo TCM treatment. In conclusion, TCs enhanced M1 differentiation and phagocytosis while inhibiting apoptosis via the activation of NF-κB in macrophages, which potentially inhibited the onset of EMs. Our findings provide a potential research target and the scope for developing a promising therapeutic strategy for EMs.

Objective To determine if plasma exosomal microRNAs (miRNAs) can predict survival in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods The study enrolled patients with IPAH that underwent right heart catheterization. Plasma was collected and exosomal miRNAs were extracted. Exosomes were evaluated using transmission electron microscopy, Western blot analysis and particle size distribution analysis. MiRNAs were evaluated using a miRNA microarray and validated using real-time polymerase chain reaction. Results This study included 12 patients with IPAH in the study group and 48 patients with IPAH in the validation group. The mean ± SD follow-up duration was 60.3 ± 35.4 months in the overall cohort. The levels of miR-596 were higher in the nonsurvivors compared with the survivors. The levels of miR-596 significantly correlated with survival time, mean right atrial pressure, pulmonary vascular resistance (PVR) and cardiac index. High levels of miR-596 and PVR were significantly associated with poor overall survival. Multivariate analysis demonstrated that exosomal miR-596 (hazard ratio [HR] = 2.119; 95% confidence interval [CI] 1.402, 3.203) and PVR (HR = 1.146; 95% CI 1.010, 1.300) were independent predictors of survival. Conclusions High levels of plasma exosomal miR-596 were significantly associated with disease severity and poor prognosis of patients with IPAH.

Establishing effectively protected and managed ecosystems with high biodiversity is the broad aim of the Aichi initiative. Assessing the biodiversity of a specific ecosystem is the first step in estimating its conservation value. Most lakes on the Yunnan–Guizhou Plateau are formed by mountain faulting and are surrounded by human settlements. Lake ecosystems are fragile and frequently disturbed by pollution, agricultural activities, and tourism. The current lakeside wetland parks are intended to abate pollution and promote tourism. However, the composition of the monthly and yearly waterbird population and the impacts of the parks on waterbirds are unclear. Using direct observation and spot map census methods, we conducted 104 field surveys across 4 consecutive years at Lake Dianchi to fill the gaps in current knowledge. The results showed that Dianchi could provide habitats for more than 60,000 individual birds of 105 species, including residents, summer visitors, migrants, and winter visitors. The current oxidation ponds in wetland parks, created for water purification and tourism, were not suitable for most shorebirds. Consequently, we suggest that plans for the construction of artificial wetlands or wetland parks in this region should consider the habitat requirements of different waterbirds in different seasons. Particular attention should be given to protecting the marshlands and mudflats that wading birds require. We also suggest that increased waterbird monitoring in different seasons across different years is needed around Lake Dianchi and other wetlands on the Yunnan–Guizhou Plateau for effective conservation.

Abstract Background Telocytes (TCs), a recently discovered novel type of interstitial cells, were also found in a wide variety of human and mammalian reproductive organs/tissues, including uterus, oviduct and placenta. Previously, we demonstrated that TCs-conditioned media was capable of activating peritoneal macrophages (pMACs) through paracrine effects. This study investigates the hypothesis that direct interaction of TCs with pMACs will also play a significant role in immunoregulation of pMACs. Methods TCs and pMACs were derived from the uterus and intraperitoneal cavity of female BALB/c mice, respectively. TCs were identified by immunofluorescence and then co-cultured directly with pMACs for 24 h without added cytokines, to observe the in vitro biological behavior of pMACs. We used histochemical staining to study morphology and mitochondrial metabolism of pMACs, scanning electron microscopy to study heterocellular junctions, flow cytometry to investigate mitochondrial membrane potential (ΔΨm) and apoptosis, and transwell chambers to study invasion ability. Student-t test was used accordingly. Results Presently, TCs with typical structure and immunophenotype of double CD-34-positive/vimentin-positive were successfully isolated. pMACs co-cultured with TCs showed obviously morphological activation, with enhanced energy metabolism (P

Abstract In this article, an anomalous diffusion model via a new Liouville-Caputo general fractional operator with the Mittag-Leffler function of Wiman type is investigated for the first time. The convergence of the series solution for the problem is discussed with the aid of the Laplace transform. The anomalous diffusion processes are compared to the characteristics of the conventional diffusion graphically. The results show that the new Liouville-Caputo general fractional operator is effective in characterizing and solving the problems of the anomalous diffusion.

Abstract Background The glacial-interglacial cycles in the Pleistocene caused repeated range expansion and contraction of species in several regions in the world. However, it remains uncertain whether such climate oscillations had similar impact on East Asian biota, despite its widely recognized importance in global biodiversity. Here we use both molecular and ecological niche profiles on 11 East Asian avian species with various elevational ranges to reveal their response to the late Pleistocene climate changes. Results The ecological niche models (ENM) consistently showed that these avian species might substantially contract their ranges to the south during the Last Interglacial period (LIG) and expanded their northern range margins through the Last Glacial Maximum (LGM), leading to the LGM ranges observed for all 11 species. Consistently, coalescent simulations based on 25–30 nuclear genes retrieved signatures of significant population growth through the last glacial period across all species studied. Climate statistics suggested that high climatic variability during the LIG and a relatively mild climate at the LGM potentially explained the historical population dynamics of these birds. Conclusions This is the first study based on multiple species and both lines of ecological niche profiles and genetic data to characterize the unique response of East Asian biota to late Pleistocene climate. The present study highlights regional differences in the evolutionary consequence of climate change during the last glacial cycle and implies that global warming might pose a great risk to species in this region given potentially higher climatic variation in the future analogous to that during the LIG.

Background: Oral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis. Methods: Based on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated. Findings: Our results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema – patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89. Interpretation: Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy.

Objective: To explore the correlation between contents of serum transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) and acute radiation pneumonitis (RP) in patients with lung cancer. Methods: A total of 138 patients with non-small cell lung cancer receiving three-dimensional conformal radiation therapy in our hospital from May 2012 to October 2015 were selected as the research objects. According to the presence or absence of RP in the process of radiotherapy, those patients were divided into the RP group and non RP group to detect the contents of TGF-β1 and IL-6 in serum. Results: Before radiotherapy, there was no significant difference in the serum contents of TGF-β1 and IL-6 in the RP group and non RP group. At weeks 2, 4, 6, 8 and 10 after radiotherapy, the serum contents of TGF-β1 and IL-6 in patients of the RP group were all higher than those in the non RP group. Differences of the contents of TGF-β1 and IL-6 in each time point after radiotherapy between two groups had statistical significance (P

BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS) and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC) remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed to treat peritoneal carcinomatosis (PC). This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A) or recurrent EOC (group B) were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI) 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2) for group B (P = .68). The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5) for group B (P = .034). Better median OS correlated with peritoneal cancer index (PCI) < 20 (76.6 months for PCI ≤ 20 group vs 38.5 months for PCI > 20 group, P = .01), complete cyroreduction (residual disease ≤ 2.5 mm) [79.5 months for completeness of cytoreduction (CC) score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05). Serious adverse events occurred in five patients (10.0%). Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.

Fraxinellone (1) is a naturally occurring degraded limonoid isolated from Meliaceae and Rutaceae plants. As a potential natural-product-based insecticidal agent, fraxinellone has been structurally modified to improve its activity. Furan ring of fraxinellone is critical in exhibiting its insecticidal activity, but with few modifications. Herein, C-ring-modified cyclopropyl analogues were semi-synthesized by Rh(II)-catalyzed cyclopropanation. The structures of the target compounds were well characterized by NMR and HRMS. The precise three-dimensional structural information of 3a was established by X-ray crystallography. Their insecticidal activity was evaluated against Mythimna separata Walker by a leaf-dipping method. Compound 3c exhibited stronger insecticidal activity than 1 and toosendanin against M. separata with teratogenic symptoms during the different periods, implying that cyclopropanation of the furan ring could strengthen the insecticidal activity of fraxinellone.

Furan ring is a key pharmacophore for insecticidal activity of limoninoids. To develop natural-product-based insecticidal agents, a series of furan-site transformations (2, 3 and 3a–j) of obacunone were synthesized by selective bromination and following coupling reactions without altering other functional groups. Bioassays indicated that derivatives 3e, 3f and 3j displayed more potent insecticidal activity than obacunone and toosendanin against the instar larvae of Mythimna separate Walker. Besides, their structure–activity relationships were discussed.

In this article, the local fractional Homotopy perturbation method is utilized to solve the non-homogeneous heat conduction equations. The operator is considered in the sense of the local fractional differential operator. Comparative results between non-homogeneous and homogeneous heat conduction equations are presented. The obtained result shows the non-differentiable behavior of heat conduction of the fractal temperature field in homogeneous media.

This study aims to explore the changes and clinical significances of T helper 17 (Th17) cells in the peripheral blood of patients with acute cerebral hemorrhage. The percentage of Th17 cells were assessed by flow cytometry. The mRNA levels of retinoid-related orphan receptor γt (RORγt) were detected by real-time quantitative reverse transcriptase⁃polymerase chain reaction (RT-PCR). The serum levels of interleukin-17 (IL-17) were measured by enzyme-linked immunosorbent assay (ELISA). According to the examination results, the percentage of Th17 cells, the mRNA expression of RORγt and the serum levels of IL-17 at 24 h, 3 d and 7 d increased significantly in patients with acute cerebral hemorrhage than in normal controls (P = 0.000, for all). Although the patients with acute cerebral hemorrhage had no significant differences in the percentage of Th17 cells, the mRNA expression of ROR γ t comparable with normal controls (P = 0.058, 0.239), the serum levels of IL-17 in patients were statistically higher than those in normal controls at 14 d (P = 0.000). The percentage of Th17 cells and the serum levels of IL-17 increase in the peripheral blood of patients with acute cerebral hemorrhage, suggesting Th17 cells may participate in the occurrence and development of cerebral hemorrhage.

In this paper, an anomalous advection-dispersion model involving a new general Liouville–Caputo fractional-order derivative is addressed for the first time. The series solutions of the general fractional advection-dispersion equations are obtained with the aid of the Laplace transform. The results are given to demonstrate the efficiency of the proposed formulations to describe the anomalous advection dispersion processes.

We investigate a nonlinear wave phenomenon described by the perturbation K(n,m) Rosenau-Hyman equation within the concept of derivative with fractional order. We used the Caputo fractional derivative and we proposed an iteration method in order to find a particular solution of the extended perturbation equation. We proved the stability and the convergence of the suggested method for solving the extended equation without any restriction on (m,n) and also on the perturbations terms. Using the inner product we proved the uniqueness of the special solution. By choosing randomly the fractional orders and m, we presented the numerical solutions.

The fractal heat flow within local fractional derivative is investigated. The nonhomogeneous heat equations arising in fractal heat flow are discussed. The local fractional Fourier series solutions for one-dimensional nonhomogeneous heat equations are obtained. The nondifferentiable series solutions are given to show the efficiency and implementation of the present method.

BACKGROUND:Peritoneal carcinomatosis (PC) is a difficult clinical challenge in colorectal cancer (CRC) because conventional treatment modalities could not produce significant survival benefit, which highlights the acute need for new treatment strategies. Our previous case-control study demonstrated the potential survival advantage of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) over CRS alone. This phase II study was to further investigate the efficacy and adverse events of CRS+HIPEC for Chinese patients with CRC PC. METHODS:A total of 60 consecutive CRC PC patients underwent 63 procedures consisting of CRS+HIPEC and postoperative chemotherapy, all by a designated team focusing on this combined treatment modality. All the clinico-pathological information was systematically integrated into a prospective database. The primary end point was disease-specific overall survival (OS), and the secondary end points were perioperative safety profiles. RESULTS:By the most recent database update, the median follow-up was 29.9 (range 3.5-108.9) months. The peritoneal cancer index (PCI) ≤20 was in 47.0% of patients, complete cytoreductive surgery (CC0-1) was performed in 53.0% of patients. The median OS was 16.0 (95% confidence interval [CI] 12.2-19.8) months, and the 1-, 2-, 3-, and 5-year survival rates were 70.5%, 34.2%, 22.0% and 22.0%, respectively. Mortality and grades 3 to 5 morbidity rates in postoperative 30 days were 0.0% and 30.2%, respectively. Univariate analysis identified 3 parameters with significant effects on OS: PCI ≤20, CC0-1 and adjuvant chemotherapy over 6 cycles. On multivariate analysis, however, only CC0-1 and adjuvant chemotherapy ≥6 cycles were found to be independent factors for OS benefit. DISCUSSION:CRS+HIPEC at a specialized treatment center could improve OS for selected CRC PC patients from China, with acceptable perioperative safety.

A mathematical model of fractal waves on shallow water surfaces is developed by using the concepts of local fractional calculus. The derivations of linear and nonlinear local fractional versions of the Korteweg-de Vries equation describing fractal waves on shallow water surfaces are obtained.

Local fractional derivatives were investigated intensively during the last few years. The coupling method of Sumudu transform and local fractional calculus (called as the local fractional Sumudu transform) was suggested in this paper. The presented method is applied to find the nondifferentiable analytical solutions for initial value problems with local fractional derivative. The obtained results are given to show the advantages.

We suggest a new model of the scale conservation equation in the mathematical theory of vehicular traffic flow on the fractal network based on the local fractional calculus.

We investigate the local fractional linear transport equations arising in fractal porous media by using the local fractional variational iteration method. Their approximate solutions within the nondifferentiable functions are obtained and their graphs are also shown.

We perform a comparison between the fractional iteration and decomposition methods applied to the wave equation on Cantor set. The operators are taken in the local sense. The results illustrate the significant features of the two methods which are both very effective and straightforward for solving the differential equations with local fractional derivative.

The local fractional Laplace variational iteration method was applied to solve the linear local fractional partial differential equations. The local fractional Laplace variational iteration method is coupled by the local fractional variational iteration method and Laplace transform. The nondifferentiable approximate solutions are obtained and their graphs are also shown.

The local fractional Poisson equations in two independent variables that appear in mathematical physics involving the local fractional derivatives are investigated in this paper. The approximate solutions with the nondifferentiable functions are obtained by using the local fractional variational iteration method.

The local fractional decomposition method is applied to approximate the solutions for Fokker-Planck equations on Cantor sets with local fractional derivative. The obtained results give the present method that is very effective and simple for solving the differential equations on Cantor set.