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Abstract Background This retrospective study aimed to analyze the evolution of primary indications and surgical techniques for corneal transplantation in Southern China from 2012 to 2021. Methods The medical charts of all patients who underwent keratoplasty between January 2012 and December 2021 at Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangzhou, Southern China were reviewed. We collected and analyzed the primary indications for corneal transplantation and the surgical methods used in each keratoplasty. Results The total number of corneal transplantations was 7,286 during this decade, increasing from 210 cases in 2012 to 1054 cases in 2021. The primary indications for keratoplasty included acquired nontraumatic corneal diseases (56.2%), congenital corneal abnormalities (16.4%), acquired traumatic corneal diseases (14.0%), and regraft (13.4%). Infectious keratitis was the leading indication among all keratoplasties (18.5%), followed by regraft (13.4%). Over the decade, the proportion of infectious keratitis gradually decreased (P = 0.013), while the proportion of regraft increased (P = 0.019). The predominant surgical technique was penetrating keratoplasty (PKP), accounting for 56.7%. However, the number of deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK) significantly increased from 2012 to 2021 (P = 0.007 and P = 0.002). Conclusions The annual number of corneal transplants significantly increased from 2012 to 2021. In the past decade, infectious keratitis and regraft have become the leading primary indications for corneal transplantation. Although the use of customized lamellar techniques has dramatically increased, PKP remains the predominant surgical technique for keratoplasty.

Abstract Two-dimensional topological semimetals are typically characterized by the vorticity of gapless points, and can be classified according to the band representations. However, the topological properties involving the distribution of the Berry curvature in the entire Brillouin zone are often overlooked. In this study, we investigate a two-band two-dimensional topological semimetal protected by C 4z T magnetic symmetry, exhibiting a two-fold band degeneracy at the Γ(0, 0) and M(π, π) points. Due to the presence of C 4z T symmetry, the Brillouin zone is divided into two patches characterized by half-quantized Berry curvature fluxes with opposite signs. In multi-band case, the half-quantization deviates, indicating the fragile nature. The semimetal presents counter-propagating half-edge channels, accompanied by power-law decaying and oscillating edge currents. The band topology leads to unconventional Landau levels featuring anisotropic edge modes. Each massless Dirac cone, associated with the half-quantized Berry curvature flux, exhibits an integer quantum Hall conductance. Additionally, we calculate the local orbital magnetization with open boundary conditions in both the x and y directions. This reveals isolated magnetization islands, highlighting an experimentally observable magnetic phenomenon in this topological semimetal.

Abstract Objectives Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty infiltration of atrial and ventricular myocardium resulting in adverse cardiac events. Atrial function has been increasingly recognized as prognostically important for cardiovascular disease. As the right atrial (RA) strain is a sensitive parameter to describe RA function, we aimed to analyze the prognostic value of the RA strain in ARVC. Methods RA strain parameters were derived from cardiac magnetic resonance (CMR) images of 105 participants with definite ARVC. The endpoint was defined as a combination of sudden cardiac death, survival cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. Cox regression and Kaplan–Meier survival analyses were performed to evaluate the association between RA strain parameters and endpoint. Concordance index (C index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the incremental value of RA strain in predicting the endpoint. Results After a median follow-up of 5 years, 36 (34.3%) reaching the endpoint displayed significantly reduced RA strain parameters. At Kaplan–Meier analysis, impaired RA reservoir (RARS) and booster strains (RABS) were associated with an increased risk of the endpoint. After adjusting for conventional risk factors, RARS (hazard ratio [HR], 0.956; p = 0.005) and RABS (HR, 0.906; p = 0.002) resulted as independent predictors for endpoint at Cox regression analyses. In addition, RARS and RABS improved prognostic value to clinical risk factors and CMR morphological and functional predictors (all p

Background Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral‐cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke‐induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. Methods and Results In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3‐deficient mice in combination with Smart‐seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke‐induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte‐derived macrophages into the heart. Subsequently, we identified that cardiac monocyte‐derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3‐deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte‐derived macrophages and subsequent cardiac dysfunction. Conclusions Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve–monocyte‐derived macrophage axis.

Abstract Background Although the adiponectin signalling exerts exercise‐mimicking effects, whether this pathway contributes to the anti‐ageing benefits of physical exercise has not been established yet. Methods Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross‐sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA‐Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy‐ and senescence‐related markers. Results The C. elegans adiponectin receptor PAQR‐1/AdipoR1, but not PAQR‐2/AdipoR2, was activated (3.55‐fold and 3.48‐fold increases in p‐AMPK on Days 1 and 6, respectively, P

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a−/−, Angptl4−/−, and Il17a−/−Angptl4−/− mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K–AKT–NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5–CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K–AKT–NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.

Abstract Disruption of gamma‐amino butyric acid type A receptors (GABAARs) synaptic clustering and a decrease in the number of GABAARs in the plasma membrane are thought to contribute to alteration of the balance between excitatory and inhibitory neurotransmission, which promotes seizure induction and propagation. The multipass transmembrane protein cleft lip and palate transmembrane protein 1 (Clptm1) controls the forward trafficking of GABAAR, thus decaying miniature inhibitory postsynaptic current (mIPSC) of inhibitory synapses. In this study, using a pentylenetetrazol (PTZ)‐induced epilepsy rat model, we found that Clptm1 regulates epileptic seizures by modulating GABAAR‐mediated inhibitory synaptic transmission. First, we showed that Clptm1 expression was elevated in the PTZ‐induced epileptic rats. Subsequently, we found that downregulation of Clptm1 expression protected against PTZ‐induced seizures, which was attributed to an increase in the number of GABAARγ2s in the plasma membrane and the amplitude of mIPSC. Taken together, our findings identify a new anti‐seizure target that provides a theoretical basis for the development of novel strategies for the prevention and treatment of epilepsy.

Abstract It is challenging to insulate sound transmission in low frequency-bands without blocking the air flow in a pipe. In this work, a small and light membrane-based cubic sound insulator is created to block acoustic waves in multiple low frequency-bands from 200 to 800 Hz in pipes. Due to distinct vibration modes of the membrane-type faces of the insulator and co-action of acoustic waves transmitting along different paths, large sound attenuation is achieved in multiple frequency-bands, and the maximum transmission loss reaches 25 dB. Furthermore, because the sound insulator with a deep subwavelength size is smaller than the cross-sectional area of the pipe, it does not block ventilation along the pipe.

Abstract The topological states of matter and topological materials have been attracting extensive interests as one of the frontier topics in condensed matter physics and materials science since the discovery of quantum Hall effect in 1980s. So far all the topological phases such as integer quantum Hall effect and topological insulators are characterized by integer topological invariants. None is a half integer or fractional. Here we propose a type of semimetals which hosts a single cone of Wilson fermions. The Wilson fermions possess linear dispersion near the Dirac point, but break the chiral or parity symmetry such that an unpaired Dirac cone can be realized on a lattice. In order to avoid the fermion doubling problem, the chiral symmetry or parity symmetry must be broken explicitly if the hermiticity, locality and translational invariance all hold. We find that the system can be classified by the relative homotopy group, and a half-integer topological invariant. We term the nontrivial quantum phase as quantum anomalous semimetal. The work opens the door towards exploring novel states of matter with fractional topological charge.

Hydrocolloids as Additives have been used for improving the quality of frozen dough for a long time. In this work, the effects of sodium carboxymethyl cellulose (CMC) on quality changes of frozen dough in storage were studied. The water loss rate of the dough and water holding capacity were measured. Rheological and texture properties of the frozen dough were measured by a rheometer and a texture analyzer, respectively. Scanning electron microscopy (SEM) was used to characterize surface network structure and protein structure changes of the frozen dough. Our results reveal that the addition of CMC can inhibit the formation of ice crystals and recrystallization, thus effectively stabilizing the molecular structure of starch, and resulting in more uniform moisture distribution in the frozen dough. When 3% addition of CMC, the water holding capacity of the two kinds of dough reached the best, and the water loss rate of corn dough reached the lowest. The cohesion of the two kinds of dough reaches the maximum with 3 wt% addition of CMC, while the hardness and chewiness of wheat and corn multigrain dough reaches the maximum with 3 wt% and 4 wt% addition of CMC, respectively. The results show proper CMC addition (3 wt% and 4 wt%) finally improves the stability and qualities of the frozen dough. The research concerning the effects of CMC on quality of frozen dough provides better understanding for the frozen food industry.

As a core component in intelligent edge computing, deep neural networks (DNNs) will increasingly play a critically important role in addressing the intelligence-related issues in the industry domain, like smart factories and autonomous driving. Due to the requirement for a large amount of storage space and computing resources, DNNs are unfavorable for resource-constrained edge computing devices, especially for mobile terminals with scarce energy supply. Binarization of DNN has become a promising technology to achieve a high performance with low resource consumption in edge computing. Field-programmable gate array (FPGA)-based acceleration can further improve the computation efficiency to several times higher compared with the central processing unit (CPU) and graphics processing unit (GPU). This paper gives a brief overview of binary neural networks (BNNs) and the corresponding hardware accelerator designs on edge computing environments, and analyzes some significant studies in detail. The performances of some methods are evaluated through the experiment results, and the latest binarization technologies and hardware acceleration methods are tracked. We first give the background of designing BNNs and present the typical types of BNNs. The FPGA implementation technologies of BNNs are then reviewed. Detailed comparison with experimental evaluation on typical BNNs and their FPGA implementation is further conducted. Finally, certain interesting directions are also illustrated as future work.

ABSTRACT Sulfate-reducing bacteria (SRB) are essential functional microbial taxa for degrading organic matter (OM) in anoxic marine environments. However, there are little experimental data regarding how SRB regulates microbial communities. Here, we applied a top-down microbial community management approach by inhibiting SRB to elucidate their contributions to the microbial community during OM degradation. Based on the highly replicated microcosms (n = 20) of five different incubation stages, we found that many microbial community properties were influenced after inhibiting SRB, including the composition, structure, network, and community assembly processes. We also found a strong coexistence pattern between SRB and other abundant phylogenetic lineages via positive frequency-dependent selection. The relative abundances of the families Synergistaceae, Peptostreptococcaceae, Dethiosulfatibacteraceae, Prolixibacteraceae, Marinilabiliaceae, and Marinifilaceae were simultaneously suppressed after inhibiting SRB during OM degradation. A close association between SRB and the order Marinilabiliales among coexisting taxa was most prominent. They contributed to preserved modules during network successions, were keystone nodes mediating the networked community, and contributed to homogeneous ecological selection. The molybdate tolerance test of the isolated strains of Marinilabiliales showed that inhibited SRB (not the inhibitor of SRB itself) triggered a decrease in the relative abundance of Marinilabiliales. We also found that inhibiting SRB resulted in reduced pH, which is unsuitable for the growth of most Marinilabiliales strains, while the addition of pH buffer (HEPES) in SRB-inhibited treatment microcosms restored the pH and the relative abundances of these bacteria. These data supported that SRB could modify niches to affect species coexistence. IMPORTANCE Our model offers insight into the ecological properties of SRB and identifies a previously undocumented dimension of OM degradation. This targeted inhibition approach could provide a novel framework for illustrating how functional microbial taxa associate the composition and structure of the microbial community, molecular ecological network, and community assembly processes. These findings emphasize the importance of SRB during OM degradation. Our results proved the feasibility of the proposed study framework, inhibiting functional taxa at the community level, for illustrating when and to what extent functional taxa can contribute to ecosystem services.

Abstract Background To explore possible associations between glucose transporter 4 (GLUT4) genetic polymorphisms in the patients with coronary heart disease (CHD) in Han and Uygur Chinese populations in Xinjiang, China. Methods Two GLUT4 polymorphisms (rs5418 and rs5435) were genotyped in 1262 Han (628 CHD patients and 634 healthy controls) and 896 Uyghur (397 CHD patients and 499 healthy controls) Chinese populations. Results In the Han Chinese population, there were no significant differences in allelic or genotypic distribution of rs5418 and rs5435 between the CHD and control groups (all P > 0.05). However, in the Uygur population, there were significant differences in genotype and allele distributions for rs5418 between CHD and the control group (all P

Abstract Background Coronary artery disease (CAD) remains one of the major causes of death in humans. Genetic testing may allow early detection and prevention of this disease. This study aimed to investigate the association between the macrophage migration inhibitory factor (MIF) -173G/C (rs755622) polymorphism and susceptibility to CAD based on a meta-analysis. Methods We searched several databases to identify observational case-control studies investigating the association between the MIF -173G > C (rs755622) polymorphism and CAD risk published before July 30, 2019. Data were analyzed using the STATA software. Results Six studies, comprising a total of 1172 CAD cases and 1564 controls evaluated for MIF polymorphisms, were included. The occurrence of CAD was found to be associated with the C allele of the MIF rs755622 SNP in the total population (C/G, OR = 1.489, 95% CI = 1.223–1.813). Further, MIF –173G/C polymorphism was significantly associated with CAD under the allelic model in the Asian (C/G, OR = 1.775, 95% CI = 1.365–2.309) and Caucasian (C/G, OR = 1.288, 95% CI 1.003–1.654) subgroups. The data showed that the risk of CAD was higher in the population carrying the C allele. Conclusions We found evidence of associations between MIF -173C/G and CAD susceptibility in the Asian and Caucasian populations.

Abstract Neutrophils constitute abundant cellular components in human gastric cancer (GC) tissues, but their protumorigenic subset in pathogenesis of GC progression is unclear. Here, it is found that patients with GC show significantly higher neutrophil infiltration in tumors that is regulated by CXCL12‐CXCR4 chemotaxis. These tumor‐infiltrating neutrophils express high level immunosuppressive molecules FasL and PD‐L2, and this FasL+PD‐L2+ neutrophil subset with a unique phenotype constitutes at least 20% of all neutrophils in advanced GC and predicts poor patient survival. Tumor induces neutrophils to express FasL and PD‐L2 proteins with similar phenotype to those in GC tumors in both time‐dependent and dose‐dependent manners. Mechanistically, Th17 cell‐derived IL‐17A and tumor cell‐derived G‐CSF can significantly induce neutrophil FasL and PD‐L2 expression via activating ERK‐NF‐κB and JAK‐STAT3 signaling pathway, respectively. Importantly, upon over‐expressing FasL and PD‐L2, neutrophils acquire immunosuppressive functions on tumor‐specific CD8+ T‐cells and promote the growth and progression of human GC tumors in vitro and in vivo, which can be reversed by blocking FasL and PD‐L2 on these neutrophils. Thus, the work identifies a novel protumorigenic FasL+PD‐L2+ neutrophil subset in GC and provides new insights for human cancer immunosuppression and anti‐cancer therapies targeting these pathogenic cells.

The effects of twelve different pre-drying and drying methods on the chemical composition in the pericarp and kernel of Amomum tsao-ko were studied. The volatile components were isolated from the samples by simultaneous distillation and extraction and analyzed by gas chromatography-mass spectrometry (GC-MS). Sixty and thirty-eight compounds were identified from pericarp and kernel, respectively, and the main constituents were oxygenated monoterpenes. These compounds were not only significantly affected by pre-drying and drying methods but also varied in content due to different tissue locations. The total volatile content of pericarp varied from 0.70 to 1.55%, with the highest obtained by microwave-dried samples (150 W) and the lowest in freeze-dried samples. The total volatile content of the kernel varied from 6.11 to 10.69%, with the highest content obtained during sun drying (SD) and the lowest content in samples treated with boiling water for 2 min. Oxygenated monoterpenes were the highest compounds in pericarp and kernel, which were also the most affected by drying methods. The highest content of oxygenated monoterpenes in the pericarp (0.77%) could be obtained by boiling water treatment for 5 min, and the highest content of oxygenated monoterpenes in the kernel (7.48%) could be obtained by SD. Additionally, the main components such as 1,8-cineole, 2-carene, (Z)-citral, nerolidol, (Z)-2-decenal, (E)-2-dodecenal, citral, (E)-2-octenal, 4-propylbenzaldehyde, and phthalan showed remarkable variations in pre-drying and drying methods.

Genetic variation of macrophage migration inhibitory factor (MIF) gene has been linked to coronary artery disease. We investigated an association between the polymorphism of MIF gene rs2070766 and acute coronary syndromes (ACS) and the predictive value of MIF gene variation in clinical outcomes. This study involved in 963 ACS patients and 932 control subjects from a Chinese population. All participants were genotyped for the single nucleotide polymorphism (SNP) of MIF gene rs2070766 using SNPscan™. A nomogram model using MIF genetic variation and clinical variables was established to predict risk of ACS. Major adverse cardiovascular events (MACE) were monitored during a follow-up period. The frequency of rs2070766 GG genotype was higher in ACS patients than in control subjects (6.2 vs 3.8%, p = 0.034). Multivariate logistic regression analysis revealed that individuals with mutant GG genotype had a 1.7-fold higher risk of ACS compared with individuals with CC or CG genotypes. Using MIF rs2070766 genotypes and clinical factors, we developed a nomogram model to predict risk of ACS. The nomogram model had a good discrimination with an area under the curve of 0.781 (95% CI: 0.759–0.804), concordance index of 0.784 (95% CI: 0.762–0.806) and well-fitted calibration. During the follow-up period of 25 months, Kaplan-Meier curves demonstrated that ACS patients carrying GG phenotype developed more MACE compared to CC or CG carriers (p < 0.05). GG genotype of MIF gene rs2070766 was associated with a higher risk of ACS in a Chinese population. The GG genotype carriers in ACS patients had worse clinical outcomes compared with those carrying CC or CG genotype. Together with rs2070766 genetic variant of MIF gene, we established a novel nomogram model that can provide individualized prediction for ACS.

Cerebral-cardiac syndrome (CCS) refers to cardiac dysfunction following varying brain injuries. Ischemic stroke is strongly evidenced to induce CCS characterizing as arrhythmia, myocardial damage, and heart failure. CCS is attributed to be the second leading cause of death in the post-stroke stage; however, the responsible mechanisms are obscure. Studies indicated the possible mechanisms including insular cortex injury, autonomic imbalance, catecholamine surge, immune response, and systemic inflammation. Of note, the characteristics of the stroke population reveal a common comorbidity with diabetes. The close and causative correlation of diabetes and stroke directs the involvement of diabetes in CCS. Nevertheless, the role of diabetes and its corresponding molecular mechanisms in CCS have not been clarified. Here we conclude the features of CCS and the potential role of diabetes in CCS. Diabetes drives establish a “primed” inflammatory microenvironment and further induces severe systemic inflammation after stroke. The boosted inflammation is suspected to provoke cardiac pathological changes and hence exacerbate CCS. Importantly, as the key element of inflammation, NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is indicated to play an important role in diabetes, stroke, and the sequential CCS. Overall, we characterize the corresponding role of diabetes in CCS and speculate a link of NLRP3 inflammasome between them.

Ischemic stroke remains a devastating disease which is the leading cause of death worldwide. Visual impairment after stroke is a common complication which may lead to vision loss, greatly impacting life quality of patients. While ischemic stroke is traditionally characterized by a blockage of blood flow to the brain, this may coincide with reduced blood flow to the eye, resulting in retinal ischemia and leading to visual impairment. Diabetes increases the risk of ischemic stroke and induces diabetic retinopathy; the latter may be more sensitive to the ischemic retinal injury. In diabetic status, the underlying mechanism in stroke-induced retinal injury has not been fully clarified. The NLR pyrin domain containing 3 (NLRP3) inflammasome is an important activator of inflammation, which may play a critical role in catalyzing and forming certain pro-inflammatory cytokines in both cerebral and retinal ischemia. Isoflurane has been demonstrated to inhibit the activation of the NLRP3 inflammasome and show neuroprotective effects. In this study, we established a diabetic mouse model and performed the middle cerebral artery occlusion procedure to induce ischemic stroke. Our results revealed that cerebral ischemia-induced retinal injury in the diabetic model. Isoflurane pretreatment alleviated the cerebral and retinal injury after ischemic stroke. Of note, isoflurane pretreatment inhibited the NLRP3 inflammasome activation in the retina, indicating that isoflurane pretreatment may provide substantial retinal protection in stroke-induced retinal injury in diabetes.

Objective To assess the awareness, attitude and barriers of colorectal cancer screening among high-risk populations in China.Design A cross-sectional study was employed.Setting This study was conducted in nine hospitals in Hunan province, China.Participants Individuals with a high-risk for colorectal cancer were interviewed using a pretested structured questionnaire.Primary and secondary outcome measures Knowledge, attitude towards colorectal cancer screening, sociodemographic factors associated with screening knowledge and behaviour and barriers of colorectal cancer screening.Results This study included 684 participants. The mean knowledge score was 11.86/24 (SD 4.84). But over 70% of them held a positive attitude towards screening. Only 13.3% had undergone colorectal cancer screening. Independent factors related to knowledge were education level of college or above, working as a white collar, higher income, having health insurance, having seen a doctor in the past year and with a high perceived risk (p

Abstract Rationale Neutrophils constitute massive cellular constituents in inflammatory human gastric cancer (GC) tissues, but their roles in pathogenesis of inflammatory T helper (Th) subsets are still unknown. Methods Flow cytometry analysis and immunohistochemistry were used to analyze the responses and phenotypes of neutrophils in different samples from 51 patients with GC. Kaplan‐Meier plots and Multivariate analysis for the survival of patients were used by log‐rank tests and Cox proportional hazards models. Neutrophils and CD4+ T cells were purified and cultured for ex vivo, in vitro and in vivo regulation and function assays. Results GC patients exhibited increased tumoral neutrophil infiltration with GC progression and poor patient prognosis. Intratumoral neutrophils accumulated in GC tumors via CXCL6/CXCL8‐CXCR1‐mediated chemotaxis, and expressed activated molecule CD54 and co‐signaling molecule B7‐H2. Neutrophils induced by tumors strongly expressed CD54 and B7‐H2 in both dose‐ and time‐dependent manners, and a close correlation was obtained between the expressions of CD54 and B7‐H2 on intratumoral neutrophils. Tumor‐derived tumor necrosis factor‐α (TNF‐α) promoted neutrophil activation and neutrophil B7‐H2 expression through ERK‐NF‐κB pathway, and a significant correlation was found between the levels of TNF‐α and CD54+ or B7‐H2+ neutrophils in tumor tissues. Tumor‐infiltrating and tumor‐conditioned neutrophils effectively induced IL‐17A‐producing Th subset polarization through a B7‐H2‐dependent manner ex vivo and these polarized IL‐17A‐producing Th cells exerted protumorigenic roles by promoting GC tumor cell proliferation via inflammatory molecule IL‐17A in vitro, which promoted the progression of human GC in vivo; these effects could be reversed when IL‐17A is blocked. Moreover, increased B7‐H2+ neutrophils and IL‐17A in tumors were closely related to advanced GC progression and predicted poor patient survival. Conclusion We illuminate novel underlying mechanisms that TNF‐α‐activated neutrophils link B7‐H2 to protumorigenic IL‐17A‐producing Th subset polarization in human GC. Blocking this pathological TNF‐α‐B7‐H2‐IL‐17A pathway may be useful therapeutic strategies for treating GC.

In vitro interaction of osthol (Ost) and fluconazole (FLC) was investigated against 11 fluconazole-resistant clinical isolates of Candida albicans. Synergistic activities were determined using the checkerboard microdilution assay. The results of agar diffusion test confirmed the synergistic interaction. We used an enteric material Eudragit S100 for preparation of Ost nanoparticle (Ost-NP) to improve the oral bioavailability, biological activity of Ost. The physicochemical characteristics of Ost-S100-NP revealed Ost-S100-NP with mean particle size of 55.4±0.4 nm, encapsulation efficiency of 98.95±0.06%, drug loading efficiency of 23.89±0.25%, yield of 98.5±0.1% and a polydispersity index (PDI) of 0.165. As the Ost concentration-time curve showed, Ost-S100-NP can increase the plasma concentration and relative bioavailability of Ost compared with Ost-suspension by oral administration. In vivo, Ost-S100-NP enhanced the therapeutic efficacy of Ost against FLC-resistant C. albicans in immunosuppressed candidiasis mice model. The available information strongly suggests that Ost-S100-NP may be used as a promising compound against drug-resistant fungi.

ObjectiveThe objective of this study was to investigate family history (FH) of upper gastrointestinal (UGI) cancer and risk of esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric non-cardia carcinoma (GNCC) in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. Methods: This prospective analysis was conducted using the Linxian NIT cohort data. Subjects with FH of UGI cancer was treated as an exposed group while the remainders were considered as a comparison group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between FH of UGI cancer and risk of UGI cancer incidence and mortality were estimated using Cox proportional hazards models.ResultsThere were 5,680 newly diagnosed UGI cancer cases during the follow-up period, with a total of 4,573 UGI cancer deaths occurred, including 2,603 ESCC, 1,410 GCC, and 560 GNCC deaths. A positive FH of UGI cancer was associated with a significantly increased risk of ESCC and GCC (Incidence: HRESCC = 1.45, 95%CI: 1.35–1.56; HRGCC = 1.27, 95%CI: 1.15–1.40; Mortality: HRESCC = 1.40, 95%CI: 1.30–1.52; HRGCC = 1.27, 95%CI: 1.14–1.42) after adjusting for age at baseline, gender, smoking status, alcohol drinking, education level, and frequency of fresh fruit and vegetable consumption. Subjects with FH in both parents had the highest risk of ESCC and GCC incidence (HRESCC = 1.65, 95%CI: 1.40–1.95; HRGCC = 1.42, 95%CI: 1.12–1.81) and deaths (HRESCC = 1.65, 95%CI: 1.38–1.97; HRGCC = 1.42, 95%CI: 1.09–1.85). Spouse diagnosed with UGI cancer did not increase the risk of any UGI cancers of the subjects. In subgroup analysis, FH of UGI cancer was shown to significantly increase the risk of GCC in non-drinkers (Incidence: HR = 1.31, 95%CI: 1.17–1.47; Mortality: HR = 1.33, 95%CI: 1.17–1.50). No associations were observed for risk of GNCC. Sensitivity analysis by excluding subjects who were followed up less than three years did not materially alter our results.ConclusionOur data point to the role of the FH of UGI cancer to the risk of ESCC and GCC incidence and mortality. The influence of family history on the risk of UGI cancer varies from different types of family members.

Objective To identify Parkinson’s disease (PD)-associated deregulated pathways and genes, to further elucidate the pathogenesis of PD. Methods Dataset GSE100054 was downloaded from the Gene Expression Omnibus, and differentially expressed genes (DEGs) in PD samples were identified. Functional enrichment analyses were conducted for the DEGs. The top 10 hub genes in the protein–protein interaction (PPI) network were screened out and used to construct a support vector machine (SVM) model. The expression of the top 10 genes was then validated in another dataset, GSE46129, and a clinical patient cohort. Results A total of 333 DEGs were identified. The DEGs were clustered into two gene sets that were significantly enriched in 12 pathways, of which 8 were significantly deregulated in PD, including cytokine–cytokine receptor interaction, gap junction, and actin cytoskeleton regulation. The signature of the top 10 hub genes in the PPI network was used to construct the SVM model, which had high performance for predicting PD. Of the 10 genes, GP1BA , GP6 , ITGB5 , and P2RY12 were independent risk factors of PD. Conclusion Genes such as GP1BA , GP6 , P2RY12, and ITGB5 play critical roles in PD pathology through pathways including cytokine−cytokine receptor interaction, gap junctions, and actin cytoskeleton regulation.

The continuous miniaturization of modern electromechanical systems calls for a comprehensive understanding of the mechanical properties of metallic materials specific to micrometer and sub-micrometer scales. At these scales, the nature of dislocation-mediated plasticity changes radically: sub-micrometer metallic samples exhibit high yield strengths, however accompanied by detrimental intermittent strain fluctuations endangering structural stability. In this paper, we studied the effects of plate-like θ′-Al2Cu precipitates on the strength and plastic fluctuations of Al-Cu alloys from micro-pillar compression testing. The particularity of our samples is that the plate-like precipitates have diameters commensurate with the external size of the Al-Cu micro-pillars. Our results show that these plate-like precipitates can strengthen the materials through the Orowan mechanism at large sample size. However, the breakdown of the mean-field pinning landscape weakens its suppression effect on plastic intermittency. On the other hand, the plastic intermittency can be inhibited efficiently at small sample size by using the plate-like θ′-Al2Cu precipitates penetrating the entire micro-pillar, in association with the presence of {100}-slip traces along the coherent precipitate/Al matrix interface and enhanced strain isotropy. Besides these experimental observations, we also aim to extract the laws common in different Al alloys, and address the specific plastic mechanisms for Al-Cu micro-crystals. Keywords: Dislocation dynamics, Size effects, Plastic fluctuations

A kind of novel anti-wear Ni-TiC composite coatings was deposited successfully on 42CrMo steel by pulsed electrodeposition method with various TiC particles concentration. The effect of TiC concentration on morphologies and properties of Ni-TiC composite coatings were investigated and the optimum concentration of TiC particle was obtained. Results demonstrate that TiC particles were distributed uniformly in the Ni-based coatings and Ni-TiC composite coatings consisted of refined nickel nanocrystalline size. When the TiC particles concentration was 32 g/L, the highest volume percentage of TiC particles with 23.9 Vol.% and maximum micro-indentation hardness of the Ni-TiC composite coatings with 475 HV were achieved. Ni-TiC composite coatings show significant improvement in wear resistance in comparison with TiC free Ni-P coating.

The pituitary gland, an important endocrine organ, can secrete a variety of reproductive hormones under the action of hypothalamus-secreted gonadotropin-releasing hormone (GnRH) and plays important roles in animal reproduction. Circular RNAs (circRNAs) are a class of RNA molecules with stable covalently closed circular structures. CircRNAs are equipped with miRNA response elements (MREs), which can regulate the expression of target genes by competitively binding miRNAs. However, whether the expression levels of circRNAs in the pituitary gland change under the action of GnRH and whether such changes can further affect the secretion of reproductive hormones are still unclear. In this study, we performed RNA sequencing (RNA-Seq) of GnRH-treated rats to identify differentially expressed circRNAs. The results revealed 1433 related circRNAs, 14 of which were differentially expressed. In addition, we randomly selected five differentially expressed circRNAs and tested their relative expression levels by RT-qPCR, the results of which were consistent with the RNA sequencing results. Finally, we predicted targeted relationships between the differentially expressed circRNAs and FSHb-LHb-associated miRNAs. In all, a total of 14 circRNAs were identified that may act on the secretion and regulation of reproductive hormones in GnRH-treated rats. Our expression profiles of circRNAs in the anterior pituitaries of rats treated with GnRH can provide insights into the roles of circRNAs in mammalian development and reproduction.

Growth hormone (GH) is an important hormone released by the pituitary gland that plays a key role in the growth and development of organisms. In our study, TargetScan analysis and the dual luciferase reporter assays were used to predict and screen for miRNAs that might act on the rat Gh1 gene, and we identified miR-543-5p. Then, the GH3 cell line and the primary rat pituitary cells were transfected with miRNA mimic, inhibitor, and siRNA. We detected the Gh1 gene expression and the GH secretion by real-time PCR and ELISAs, respectively, to verify the regulatory effect of miR-543-5p on GH secretion. The results showed that miR-543-5p can inhibit Gh1 mRNA expression and reduce GH secretion. MiR-543-5p inhibitor upregulated Gh1 mRNA expression and increased GH secretion compared with the negative control. In summary, miR-543-5p downregulates Gh1 expression, resulting in a decrease in GH synthesis and secretion, which demonstrates the important role of miRNAs in regulating GH and animal growth and development.

The potential contributions of CD8+ memory stem T cells to anti-tumor immunity and immunotherapy responses in gastric cancer has not been demonstrated. We found that CD8+ memory stem T cell frequencies were increased in the peripheral blood of gastric cancer patients compared to healthy donors and declined in frequency with disease progression. Despite minimal in vitro cytotoxic activity, the adoptive transfer of CD8+ memory stem T cells into Rag1−/− tumor bearing mice enhanced tumor regression compared to CD8+ central or effector memory T cell counterparts. This effect was associated with an increase in splenic, draining lymph node and tumor infiltrating CD8+ T cell numbers and the development of an altered CD8+ T cell phenotype not seen during homeostasis. GSK-3β inhibition is known to promote memory stem T cell accumulation by arresting effector T cell differentiation in vivo. Surprisingly however, GSK-3β inhibition conversely increased the cytotoxic capacity of CD8+ memory stem T cells in vitro, and this was associated with the induction of effector T cell-associated effector proteins including FasL. Finally, FasL neutralization following GSK-3β inhibition directly attenuated the anti-tumoral capacity of CD8+ memory stem T cells both in vitro and in vivo. Altogether, our findings identify the therapeutic potential of modulating CD8+ memory stem T cells for improved anti-tumoral responses against gastric cancer.

Natural killer (NK) cell activity is influenced by a complex integration of signaling pathways activated downstream of both activating and inhibitory surface receptors. The tumor microenvironment can suppress NK cell activity, and there is a great clinical interest in understanding whether modulating tumor-mediated NK cell suppression and/or boosting preexisting NK cell numbers in cancer patients is therapeutically viable. To this light, we characterized the surface receptor phenotypes of peripheral blood NK cells and examined their clinical relevance to human gastric cancer (GC). We found that the proportion of peripheral blood NK cells which expressed the activating receptors NKp30, NKp46, NKG2D, and DNAM-1 was significantly decreased in GC patients compared to healthy donors, and that this decrease was positively associated with tumor progression. At the same time, plasma TGF-β1 concentrations were significantly increased in GC patients and negatively correlated with the proportion of NKp30, NKp46, NKG2D, and DNAM-1 expressing NK cells. Furthermore, TGF-β1 significantly downregulated the expression of NKp30, NKp46, NKG2D, and DNAM-1 on NK cells in vitro, and the addition of galunisertib, an inhibitor of the TGF-β receptor subunit I, reversed this downregulation. Altogether, our data suggest that the decreased expression of activating receptors NKp30, NKp46, NKG2D, and DNAM-1 on peripheral blood NK cells is positively associated with GC progression, and that TGF-β1-mediated NK cell suppression may be a therapeutically targetable characteristic of GC.

Mice with spontaneous coat mutations are ideal animal models for studying skin development and tumorigenesis. In this study, skin hair growth cycle abnormalities were examined in NIH hairless mice 42 days after birth (P42) by using hematoxylin-eosin (H&E) staining. To examine the gene expression patterns in the skin of mutant mice, the dorsal skin of P42 female NIH mice and NIH hairless mice was sequenced by RNA-Seq, and 5,068 differentially expressed genes (DEGs) were identified (false discovery rate [FDR] ≥ 2, P < 0.05). A pathway analysis showed that basal cell carcinoma, the cell cycle and the Hippo, Hedgehog and Wnt signaling pathways were up-regulated in NIH hairless mice. Previous studies have shown that these pathways are closely associated with cell proliferation, cell cycle, organ size and cancer development. In contrast, signal transduction, bacterial and parasitic infection, and receptor-mediated pathways, including calcium signaling, were down-regulated in NIH hairless mice. A gene interaction network analysis was performed to identify genes related to hair follicle development. To verify the reliability of the RNA-Seq results, we used q-PCR to analyze 12 key genes identified from the gene interaction network analysis, including eight down-regulated and four up-regulated genes, and the results confirmed the reliability of the RNA-Seq results. Finally, we constructed the differential gene expression profiles of mutant mice by RNA-Seq. NIH hairless mice exhibited abnormalities in hair development and immune-related pathways. Pik3r1 and Pik3r3 were identified as key genes, laying the foundation for additional in-depth studies of hairless mice.

We describe a case of generalized cutis laxa (CL) in a 7-year-old female child. At 2 months of age, she was found to have a hoarse voice, and at 3 years, she was much smaller than her peers. Her aging face and short stature caught our attention, and the treatment of the patient was accepted by our hospital. She underwent a thorough examination. X-ray of the wrist bone showed a markedly delayed bone age, and thyroid function tests revealed significantly elevated free triiodothyronine 3 and free thyroxine 4 levels, but thyrotropin was within the normal range. Thyroid dysfunction and CL can be associated with lagged growth and development. Whether her abnormal development was due to thyroid dysfunction or CL could not be ascertained. CL is possibly more complex than it has been supposed so far, and is therefore worth to be further studied.

The aim of this study was to synthesize novel amide derivatives of bergapten and evaluate their lipid-lowering and triglyceride-lowering activities in mice. Amide derivatives of bergapten were synthesized by using lactone ring opening strategy in DMSO using NaOH as base followed by alkylation in presence of methyl iodide. The compounds were subjected to preliminary in vivo screening. Fenofibrate (30 mg/kg/day) was used as positive controls in this assay. The lipid lowering activity was evaluated using in vivo Triton model and Triton WR-1339 was used as positive control. Most of the synthesized analogs displayed remarkable plasma triglyceride-lowering activity. Compound 5 showed the best activity with (41%) triglyceride lowering activity. This compound also exhibited the most potent lipid lowering activity displaying 33%, 32% and 29% lowering in total cholesterol, phospholipids, and triglycerides, respectively. The other derivatives showed almost comparable activity with that of the parent molecule.

This paper has proposed a new thermal wave image sequence compression algorithm by combining double exponential decay fitting model and differential evolution algorithm. This study benchmarked fitting compression results and precision of the proposed method was benchmarked to that of the traditional methods via experiment; it investigated the fitting compression performance under the long time series and improved model and validated the algorithm by practical thermal image sequence compression and reconstruction. The results show that the proposed algorithm is a fast and highly precise infrared image data processing method.

Background: Aggressive embryo and receptive endometrium are necessary for successful implantation. On this time endometrium transformates to receptive state, which permits embryonic implantation. Studies about embryonic implantation and endometrial receptivity are always a hot spot in the field of reproductive medicine., Objective: To investigate the expression pattern of Meis1 during peri-implantation in mice endometrium., Materials and Methods: Mice for experiment were raised in SPF environment. The mice were mated with a female/male ratio of 2:1. The female mice with detected plugs were regarded as pregnant day 1 (pd1). Endometrial tissues were collected respectively on pd1, pd2, pd4, pd5 and pd6. Immunohistochemistry was used to detect the location of Meis1 in mice endometrium. The expression level of mRNA and protein of Meis1 were further detected using Quantitative PCR and Western blotting, respectively., Results: We found that Meis1 is located in the cytoplasm and membrane of endometrial glandual epithelium cells and the nucleus of endometrial stromal and decidual cells. Both Quantitative RT-PCR and western blotting showed that Meis1 expressed regularly in mice endometrium. Meis1 mRNA expressed weakly on pd1, then significantly increased on pd4 (p=0.018), and achieved to a peak on pd5 (p=0.0012), it showed a decrease trend on pd6. Meis1 protein expressed weakly on pd1 and pd2, then significantly increased on pd4 and pd5 (p=0.0019), it showed a decrease trend on pd6 CONCLUSION: Meis1 is dynamically expressed in mice endometrium during peri-implantation. The time that Meis1 expression reaches its peak value is coincident with the implantation window, which implied that Meis1 is closely related with embryonic implantation.

The contents of three components in compound acetylsalicylic acid tablets were determined by dual-wavelength ratio spectrometry. According to the feature of the spectra, 213, 227, 245 and 265 nm were chosen as the determining wavelengths. It is shown that for the three components good linear correlations exist for acetylsalicylic acid (5-20 microg x mL(-1)), phenacetin (2-10 microg x mL(-1)), and caffeine (2-20 microg x mL(-1)). The average recoveries were 100.03%, 100.23% and 99.96% respectively. The results were consistent with those obtained by the standard method of Health Ministry(P > 0.05). The method is simple and practical with fewer determination wavelengths and powerful spectral resolution, and can be performed on a lower level instrument, as well as be easily spreaded for application.