The role of angiotensin-converting enzyme 2 (ACE2) in silicosis remains unknown, although previous studies have suggested that ACE2 may be beneficial. We, therefore, investigated the effect of ACE2 on silicosis, particularly with regard to its role in regulating the epithelial-mesenchymal transition (EMT) induced by silica, with the aim to uncover a new potential target for the treatment of pulmonary fibrosis.

The purpose of this study was to determine the effects of Kinesin family member 3A (KIF3A) on primary cilia and myofibroblast differentiation during silicosis by regulating Sonic hedgehog (SHH) signalling. Methods: Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO2. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation. Results: Primary cilia (marked by ARL13B and Ac-α-Tub) and ciliary-related proteins (IFT 88 and KIF3A) were increased initially and then decreased as silicosis progressed. Loss and shedding of primary cilia were also found during silicosis. Treatment of MRC-5 fibroblasts with silica and then transfection of KIF3A-siRNA blocked activation of SHH signalling, but increased GLI2FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3R on ACTA2. Conclusion: Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO2.

Sleep deprivation is reported to cause oxidative stress and is hypothesized to induce subsequent aging-related diseases including chronic inflammation, Alzheimer's disease, and cardiovascular disease. However, how sleep deprivation contributes to the pathogenesis of sleep deficiency disorder remains incompletely defined. Accordingly, more effective treatment methods for sleep deficiency disorder are needed. Thus, to better understand the detailed mechanism of sleep deficiency disorder, a sleep deprivation mouse model was established by the multiple platform method in our study. The accumulation of free radicals and senescence-associated secretory phenotype (SASP) was observed in the sleep-deprived mice. Moreover, our mouse and human population-based study both demonstrated that telomere shortening and the formation of telomere-specific DNA damage are dramatically increased in individuals suffering from sleeplessness. To our surprise, the secretion of senescence-associated cytokines and telomere damage are greatly improved by folic acid supplementation in mice. Individuals with high serum baseline folic acid levels have increased resistance to telomere shortening, which is induced by insomnia. Thus, we conclude that folic acid supplementation could be used to effectively counteract sleep deprivation-induced telomere dysfunction and the associated aging phenotype, which may potentially improve the prognosis of sleeplessness disorder patients.

We report 301 dengue virus infections among cross-border travelers entering Yunnan Province, China, from Myanmar during 2017. Phylogenetic analysis of 99 strains found all 4 serotypes co-circulating; genetic characteristics have also changed. This finding highlights the urgent need for monitoring dengue virus cross-border transmission as early warning of severe dengue fever.

Basal/human epidermal growth factor receptor (HER)2-positive (HER2+) breast cancer is resistant to monoclonal antibody (herceptin) treatment. There are currently only three basal/HER2+ breast cancer cell lines available, but they are not from Chinese populations.

In this study, we synthesized a thermosensitive composite of Gel-SOR-LUF-SeNPs to achieve the localized synergistic chemoradiotherapy of hepatocellular carcinoma (HCC). Sorafenib (SOR) is one of the important clinical drugs for unresectable and advanced HCC. However, the uncontrollable release of SOR induced drug resistance and severe side effects. Recently, thermosensitive hydrogels have emerged as promising drug-delivery carriers, due to their superior advantages including biodegradability, low-toxicity, high drug loading, site-specificity, sustained and controlled drug release behavior. We synthesized the thermosensitive hydrogel nanosystem (Gel-SOR-LUF-SeNPs) as an effective drug release depot with the combination of radiotherapy for the localized and sustained treatment of HCC. The results showed that SOR was released continuously from Gel-SOR-LUF-SeNPs with the degradation of the hydrogel for a prolonged period (over 15 days). The combination of localized and chemoradiotherapy accelerated the apoptosis of HepG2 cells through reducing the expression of Ki67 and CD34, and activating caspase-3 signaling pathway. Further studies demonstrated that this nanosystem showed site-specific and long-term anticancer effects in mice up to 21 days after single subcutaneous injection, and no obvious side effects of mice were found. Taken together, this study presents a local and long-term treatment for HCC, which may shed light on unresectable HCC therapy in the future.

Maize ears and tassels are two separate types of inflorescence which are initiated by similar developmental processes but gradually develop distinct architectures. However, coordinated trans and cis regulation of differentially expressed genes determining ear and tassel architecture within the 3D genome context is largely unknown.

Early childhood caries (ECC) is one of the most prevalent chronic diseases affecting children worldwide, and thus its etiology, diagnosis, and prognosis are of particular clinical significance. This study aims to test the ability of salivary microbiome and electrolytes in diagnosing ECC, and their interplays within the same population. We here simultaneously profiled salivary microbiome and biochemical components of 331 children (166 caries-free (H group) and 165 caries-active children (C group)) aged 4-6 years. We identified both salivary microbial and biochemical dysbiosis associated with ECC. Remarkably, K+, Cl-, NH4 +, Na+, SO4 2-, Ca2+, Mg2+, and Br- were enriched while pH and NO3 - were depleted in ECC. Moreover, the dmft index (ECC severity) positively correlated with Cl-, NH4 +, Ca2+, Mg2+, Br-, while negatively with pH and NO3 -. Furthermore, machine-learning classification models were constructed based on these biomarkers from saliva microbiota, or electrolytes (and pH). Unexpectedly, the electrolyte-based classifier (AUROC = 0.94) outperformed microbiome-based (AUROC = 0.70) one and the composite-based one (with both microbial and biochemical data; AUC = 0.89) in predicting ECC. Collectively, these findings indicate ECC-associated alterations and interplays in the oral microbiota, electrolytes and pH, underscoring the necessity of developing diagnostic models with predictors from salivary electrolytes.

Differentiation and homeostasis of Foxp3+ regulatory T cells (Tregs) are tightly controlled by the interleukin-2 receptor (IL-2R) signaling, yet the mechanisms governing these processes are incompletely understood. Here, we report that transcription factor Bach2 attenuates IL-2R signaling to coordinate Treg differentiation and homeostasis. Bach2 is required for the quiescence, survival, and maintenance of resting Treg cells (rTregs). Unexpectedly, Bach2 directly represses CD25 (IL-2Rα) and subsequently attenuates IL-2R signaling in Tregs. Upregulated CD25/IL-2R signaling in Bach2-deficient rTregs acts as a parallel pathway to partially counteract their poor survival and maintenance. Furthermore, Bach2 suppresses CD25/IL-2R signaling in T follicular regulatory (Tfr) cells. Bach2 deficiency in Tregs prevents the formation of highly differentiated Tfr cells, associated with aberrant GC response. Finally, a mild and late onset of autoimmune disease is observed in mice with Bach2-deficient Tregs. Thus, Bach2 balances IL-2R signaling to orchestrate development and homeostasis of various Treg subsets.

Holmes tremor (HT) is a rare symptomatic movement disorder characterized by a combination of resting, postural, and action tremors. HT is usually caused by lesions in the brain stem, thalamus, and cerebellum, and the pathogenesis is believed to be related to the nigrostriatal pathway and/or the cerebello-thalamo-cortical pathway. Many medications have been used to treat HT with various degrees of effectiveness. We herein present a case involving an elderly woman who developed atypical HT 23 months after cerebral hemorrhage. The atypical HT manifested as a tremor of the right limb with involuntary flexion of the distal five fingers of the right upper limb. Imaging findings suggested the existence of an old hemorrhage in the left thalamus. Specifically, diffusion tensor imaging data of the whole brain and multimodal three-dimensional medical imaging revealed significant white matter microstructural changes in the centromedian nucleus of the left thalamus. Treatment with high-dose oral levodopa was not efficient, but the symptoms gradually decreased in severity and disappeared 1 month after switching to oral clonazepam treatment.

Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease (IBD) and Parkinson's disease (PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched PubMed, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle-Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population (adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15-1.34, P < 0.001). A meta-analysis of the temporal relationship revealed that the incidence of IBD was significantly increased before (adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18-1.35, P < 0.001) and after (adjusted RR = 1.40, 95% CI: 1.20-1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis (adjusted HR = 1.25, 95% CI: 1.13-1.38, P < 0.001) or Crohn's disease (adjusted HR = 1.33, 95% CI: 1.21-1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men (adjusted HR = 1.23, 95% CI: 1.10-1.39) and women (adjusted HR = 1.26, 95% CI: 1.10-1.43); however, older (> 65 years old) IBD patients (adjusted HR = 1.32, 95% CI: 1.17-1.48) may have a higher risk than younger (≤ 65 years old) patients (adjusted HR = 1.24, 95% CI: 1.08-1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk (adjusted HR = 1.6, 95% CI: 1.2-2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.

The therapeutic precision and clinical applicability of drug-eluting coatings can be substantially improved by facilitating tunable drug delivery. However, the design of coatings which allows for precise control over drug release kinetics is still a major challenge. Here, a double-layered silk fibroin (SF) coating system was constructed by sequential electrophoretic deposition. A mixture of dissolved Bombyx mori SF (bmSF) molecules and pre-made bmSF nanospheres at different ratios was deposited as under-layer. Subsequently, this underlayer was covered by a top-layer comprising Antheraea pernyi SF (apSF) molecules (rich in arginylglycylaspartic acid, RGD) to improve the cellular response of the resulting double-layered coatings. Additionally, model drug doxycycline was either pre-mixed with dissolved bmSF molecules or pre-loaded into pre-made bmSF nanospheres at the same amount before their mixing and deposition. The thickness and nanosphere content of the under-layer architecture were proportional to the deposition time and nanosphere concentration in precursor mixtures, respectively. The surface topography, wettability, degradation rate and adhesion strength were comparable within the double-layered coating system. As expected, RGD-rich apSF top-layer improved cell adhesion, spreading and proliferation compared with bmSF top-layer. Furthermore, the amount and duration of drug release increased linearly with increasing nanosphere concentration at fixed deposition time, whereas drug release amount increased linearly with increasing deposition time. These results indicate that the dosage and kinetics of loaded drugs can be quantitatively tailored by altering nanosphere concentration and deposition time as main processing parameters. Overall, this study illustrates the strong potential of pre-defining coating architecture to facilitate control over drug delivery.

Cryptosporidiosis is a significant cause of diarrhea in sheep and goats. Among the over 40 established species of Cryptosporidium, Cryptosporidium xiaoi is one of the dominant species infecting ovine and caprine animals. The lack of subtyping tools makes it impossible to examine the transmission of this pathogen. In the present study, we identified and characterized the 60-kDa glycoprotein (gp60) gene by sequencing the genome of C. xiaoi. The GP60 protein of C. xiaoi had a signal peptide, a furin cleavage site of RSRR, a glycosylphosphatidylinositol anchor, and over 100 O-glycosylation sites. Based on the gp60 sequence, a subtyping tool was developed and used in characterizing C. xiaoi in 355 positive samples from sheep and goats in China. A high sequence heterogeneity was observed in the gp60 gene, with 94 sequence types in 12 subtype families, namely XXIIIa to XXIIIl. Co-infections with multiple subtypes were common in these animals, suggesting that genetic recombination might be responsible for the high diversity within C. xiaoi. This was supported by the mosaic sequence patterns among the subtype families. In addition, a potential host adaptation was identified within this species, reflected by the exclusive occurrence of XXIIIa, XXIIIc, XXIIIg, and XXIIIj in goats. This subtyping tool should be useful in studies of the genetic diversity and transmission dynamics of C. xiaoi.

DNAzymes exhibit high potential as gene silencing agents for therapeutic applications. Such purposes, however, are significantly challenged by the targeted and successful delivery of unmodified DNAzymes into cells with minimal side effects. Here, we set out to formulate and demonstrate a new stimuli-responsive and constrained aptamer/DNAzyme (Apt/Dz) catenane nanostructure for highly specific gene silencing. The rational design of the Apt/Dz catenane nanostructure with the respective integration of the aptamer sequence and the completely closed catenane format enables both the targeted capability and significantly improved nuclease resistance, facilitating the stable and targeted delivery of unmodified Dz into cancer cells. Moreover, the Dz enzymatic activity in the constrained structure can only be conditionally regulated by the specific intracellular mRNA sequences to silence the target gene with highly reduced side effects. Results show that the Apt/Dz catenane nanostructure can effectively inhibit the expression of the target gene and the proliferation of cancer cells with high specificity.

Fenton-like system formed in a natural soil environment deemed to be significant in the aging process of biochar. Aged biochars have distinct physico-chemical and surface properties compared to non-aged biochar. The aged biochar proved to be useful soil amendment due to its improved elements contents and surface properties. The biochar aging process resulted in increased surface area and pore volume, as well as carbon and oxygen-containing functional groups (such as C=O, -COOH, O-C=O etc.) on its surface, which were also associated with the adsorption behavior of 2,4,6-trichlorophenol (2,4,6-TCP). The biochar aging increased the adsorption capacity of 2,4,6-TCP, which was maximum at pH 3.0. The 2,4,6-TCP adsorption capacity of aged-bush biochar (ABB) and aged-peanut shell biochar (APB) was increased by 1.0-11.0% and 7.4-38.8%, respectively compared with bush biochar (BB) and peanut shell biochar (PB) at the same initial concentration of 2,4,6-TCP. All biochars had similar 2,4,6-TCP desorption rates ranging from 33.2 to 73.3% at different sorption temperatures and times. The desorbed components were mainly 2,4,6-TCP and other degraded components, which were low in concentration with small molecule substance. The results indicated that the aged-biochar could be effective for the long-term remediation of naturally organic polluted soils.

The thalassemia of Hemoglobin H-Constant Spring disease (HbH-CS) is the most common type of Thalassemia in non-transfusion thalassemia. Interestingly, the clinical manifestations of the same genotype of thalassemia can be vastly different, likely due to epigenetic regulation. Here, we used microarray technology to reveal the epigenetic regulation of m6A in modifiable diseases and demonstrated a role of BCL2A1 in disease regulation. In this study, we revealed that methylating enzyme writers including METTL16, WTAP, CBLL1, RBM15B, and ZC3H13 displayed low expression and the demethylating enzyme ALKBH5, along with reader proteins including IGF2BP2 and YTHDF3 exhibited high expression. In addition, BCL2A1 was hypo-methylated and showed low expression. We also revealed that the BCL2A1 methylation level and IGF2BP2 expression were negatively correlated. Additionally, the mRNAs expression between ALKBH5 and IGF2BP2 were positively correlated. In HbH-CS, most genes were hypo-methylated. This included BCL2A1, which may play an important role in the process of red blood cell differentiation and development of HbH-CS. Moreover, the mRNA-M6A methylation status may be regulated by the demethylating enzyme ALKBH5 via IGF2BP2.

Gut microbiota plays an important role in the pathogenesis of immune-mediated diseases. However, the complex pathogenesis of Henoch-Schonlein Purpura (HSP) remains elusive. This study aimed to characterize the gut microbiota in HSP patients and explore the potential association between gut microbiota composition and phenotypic changes in HSP.

BCL7B plays a potential role in the progression of various cancers, while its role in sarcomas is unknown. We aimed to evaluate BCL7B's diagnostic and prognostic value, and potential BCL7B-related mechanisms in sarcomas based on The Cancer Genome Atlas (TCGA) database. We collected patients with sarcoma from TCGA. Wilcoxon rank sum test was used to compare the expression of BCL7B in sarcoma samples with different clinical-pathologic features. Univariate Cox regression analysis and multivariate Cox regression analysis were used to evaluate prognosis factors for sarcoma. Gene set enrichment analysis (GSEA) was conducted to elucidate the significant functions and pathways associated with BCL7B. BCL7B was a potential biomarker for distinguishing normal and tumor tissues with the analysis of ROC curve (AUC = 0.588). Low BCL7B expression was significantly correlated with tumor multifocal (OR = 0.39 for yes vs no), larger residual tumor (OR = 0.40 for R1,R2 vs RO), male gender (OR = 0.48 for male vs female) and White race (OR = 0.29 for White vs Asian, Black or African American). High BCL7B expression was correlated with leiomyosarcoma histological type (OR = 6.08 for leiomyosarcoma vs dedifferentiated liposarcoma, pleomorphic sarcoma). Univariate and multivariate Cox regression analysis showed that low BCL7B expression was independently associated with poor overall survival (P = .008). GSEA showed that GPCR (G protein-coupled receptors) ligand binding, secreted factors, class A1 rhodopsin-like receptors, extracellular matrix organization, core matrisome, Fc epsilon receptor I mediated NF-κB activation, and WNT signaling pathway were differentially enriched in BCL7B low expression phenotype (|NES| > 1, adjusted P value <.05, and FDR value <0.25). BCL7B may play an important role in sarcoma progression and may be a potential biomarker for prognosis and diagnosis in sarcomas.

It is often tricky to differentiate cystic pituitary adenoma from Rathke cleft cyst with visual inspection because of similar MRI presentations between them. We aimed to design an MR-based radiomics model for improving differential diagnosis between them.

Penile cancer is a rare male neoplasm with a wide variation in its global incidence. In this study, the prognostic value of lymph node ratio (LNR) was compared to that of positive lymph node count (PLNC) in penile squamous cell carcinoma.