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Early prevention of liver injury by controlling risk factors deserves concern because of the heavy liver disease burden. Helicobacter pylori (HP) infection affects half of the world’s population and the relationship between it and early liver damage is unclear. This study focuses on assessing the correlation between them in the general population to provide clues to prevent liver disease. A total of 12,931 individuals underwent liver function and imaging tests as well as 13C/14C-urea breath tests. Results showed that the detection rate of HP was 35.9%, and the HP-positive group had a higher rate of liver injury (47.0% versus 44.5%, P = 0.007). Specifically, Fibrosis-4 (FIB-4) and alpha-fetoprotein levels in the HP-positive group were higher whereas the serum albumin level was lower. HP infection would raise the percentage of elevated aspartate aminotransferase (AST; 2.5% versus 1.7%, P = 0.006), elevated FIB-4 (20.2% versus 17.9%, P = 0.002), and abnormal liver imaging (31.0% versus 29.3%, P = 0.048). Most of these results remained stable after covariate adjustment but, for liver injury and liver imaging, the conclusions only held in young people (ORliver injury, odds ratio of liver injury, 1.127, P = 0.040; ORAST, 1.33, P = 0.034; ORFIB-4, 1.145, P = 0.032; ORimaging, 1.149, P = 0.043). Overall, HP infection might be associated with early liver injury, particularly in youth, suggesting that people with early liver injury should pay more attention to HP infection to prevent the occurrence of severe liver diseases.

Phenotypic heterogeneity within or between families with a same deep-intronic splice-altering variant in the DMD gene has never been systematically analyzed. This study aimed to determine the phenotypic and genetic characteristics of patients with deep-intronic DMD variants.Of 1338 male patients with a suspected dystrophinopathy, 38 were confirmed to have atypical pathogenic DMD variants via our comprehensive genetic testing approach. Of the 38 patients, 30 patients from 22 unrelated families with deep-intronic DMD variants underwent a detailed clinical and imaging assessment.Nineteen different deep-intronic DMD variants were identified in the 30 patients, including 15 with Duchenne muscular dystrophy (DMD), 14 with Becker muscular dystrophy (BMD), and one with X-linked dilated cardiomyopathy. Of the 19 variants, 15 were single-nucleotide variants, 2 were structural variants (SVs), and 2 were pure-intronic large-scale SVs causing aberrant inclusion of other protein-coding genes sequences into the mature DMD transcripts. The trefoil with single fruit sign was observed in 18 patients and the concentric fatty infiltration pattern was observed in 2 patients. Remarkable phenotypic heterogeneity was observed not only in skeletal but also cardiac muscle involvement in 2 families harboring a same deep-intronic variant. Different skeletal muscle involvement between families with a same variant was observed in 4 families. High inter-individual phenotypic heterogeneity was observed within two BMD families and one DMD family.Our study first highlights the variable phenotypic expressivity of deep-intronic DMD variants and demonstrates a new class of deep-intronic DMD variants, i.e., pure-intronic SVs involving other protein-coding genes.

(1) Background: it is unclear whether serum vitamin B12 and circulating methylmalonic acid (MMA) are related with a poor prognosis among individuals with chronic kidney disease (CKD); (2) Methods: this prospective cohort study included 2589 individuals with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004, and from 2011 to 2014, respectively. Hazard ratios (HRs) and 95% Cis for the associations of MMA and vitamin B12 levels with the risk of all-cause and cardiovascular disease (CVD) mortality were calculated using multivariable Cox proportional hazards regression models. Restricted cubic spline analyses were used to examine the non-linear association of MMA levels with all-cause and CVD mortality. (3) Results: among the 2589 participants, we identified 1192 all-cause deaths and 446 CVD deaths, respectively, with a median follow-up of 7.7 years. Compared with participants with MMA < 123 nmol/L, those with MMA ≥ 240 nmol/L had an increased all-cause and CVD mortality in the multivariable-adjusted model [HR (95% CI), 2.01 (1.54–2.62) and 1.76 (1.18–2.63), respectively]; (4) Conclusions: higher circulating MMA levels were found to be strongly associated with an elevated all-cause and CVD mortality among individuals with CKD, while serum vitamin B12 levels were not associated.

Diabetes has been linked to an increased risk of epilepsy in observational studies. The antiglycemic drugs have been shown in animal studies to improve seizures. However, whether the associations between antiglycemic drugs and epilepsy in human is not known. In this study, we conducted a Mendelian randomization investigation to assess the potential causal role of antiglycemic drug targets in epilepsy.We used the International League Against Epilepsy Data as the discovery set and FinnGen Data as the replication set .Three antidiabetic drug target genes, including ETFDH, CYP21A2, and CYP2D6 were discovered to be involved in epilepsy. ETFDH predicted as a target gene in the discovery set (IVW, OR = 1.018, 95% CI, 1.004–1.033, p = 0.009), replication set (IVW, OR = 1.074, 95% CI, 1.034–1.114, p = 0.00016) and CYP21A2 gene in the discovery set (IVW, OR = 1.029, 95% CI, 1.005– 1.053, p = 0.016) and replication set (IVW, OR = 1.057, 95% CI, 1.001–1.116, p = 0.045) showed a causal association with an increased risk of epilepsy. In contrast, the CYP2D6 gene was found to be a protective factor for epilepsy in both the discovery set (IVW, OR = 0.0984, 95% CI, 0.969–0.998, p = 0.025) and the replication set (IVW, OR = 0.977, 95% CI, 0.955–1.000, p = 0.046). By searching the pharmacological effects of anti-glucose drug target gene related drugs and binding drugs in DrguBank, Metformin was found to be ETFDH gene inhibitor, showing a potential therapeutic effect on epilepsy.

Background: N7-methylguanosine (m7G) modification signature has been found recently in cancer and is now known as an essential regulator of tumor progression and treatment. As a result of the function of m7G methylation modification genes in tumorigenesis and progression, there isn't much information related to the genomic profile of lower-grade gliomas(LGGs). Methods: In this research, bioinformatics analysis methods were used to characterize m7G modifications in individuals with LGG from The Chinese Glioma Genome Atlas(CGGA) and The Cancer Genome Atlas(TCGA). Afterward, gene set enrichment analysis(GSEA), single sample GSEA(ssGSEA), CIBERSORT algorithm, ESTIMATE algorithm, R package "GSVA," and TIDE were used to evaluate the association between m7G modification patterns, TME cell infiltration properties as well as the correlation regarding immune infiltration markers. The m7G scoring scheme using principal component analysis(PCA) was employed to investigate the m7G modification patterns of individual tumors quantitatively. We examined the m7G modification hub genes' expression levels in normal samples, refractory epilepsy samples, and lower-grade glioma samples using immunohistochemistry, western-blotting, and QRT-PCR. Result: It was discovered that individuals with LGG were categorized into two groups in terms of m7G scores (high and low) as per the properties of m7G. After observing the anti-PD-1 cohort, it has been noted that individuals having a high m7G score had significant clinical benefit, along with considerably prolonged survival duration. Opposing this, individuals in the anti-PD-L1 cohort having low m7G scores had improved prognostic outcomes and were more likely to have CR(Complete Response) / PR(Partial Response). Different m7G subtypes have different TMB(Tumor Mutational Burden) and immune profiles and might have varied responses to immunotherapy. Moreover, five potential genetic markers were found that were highly correlated with the index of the m7G score signature. Conclusion: Conclusively, a thorough investigation of the features and classification associated with m7G methylation modifications may improve the clinical outcome of LGG.

Heteropanax fragrans (Roxb.) Seem is a common garden landscape tree in China. In December 2020, a leaf disease on H. fragrans was observed in a 2 ha field in Zhanjiang (20.85° N, 109.28° E), Guangdong province, China. Early symptoms were small yellow spots on leaves. Later, the spots gradually expanded and turned into necrotic tissues with a clear yellow halo and a white center. The disease incidence on plants was 100%. Twenty diseased leaves were collected from the field. The margin of the diseased tissues was cut into 2 mm × 2 mm pieces, surface disinfected with 75% ethanol and 2% sodium hypochlorite for 30 and 60 s, respectively, and rinsed thrice with sterile water before isolation. The tissues were plated onto potato dextrose agar (PDA) medium and incubated at 28 ℃. After 2-day incubation, grayish fungal colonies appeared on the PDA, then pure cultures were produced by transferring hyphal tips to new PDA plates. Single-spore isolation method was used to recover pure cultures for three isolates (HFA-1, HFA-2, and HFA-3). The colonies first produced a light-grayish aerial mycelia, which turned dark grayish upon maturity. Conidiophores were branched. Conidia numbered from two to four in chains, were dark brown, ovoid, or ellipsoid and mostly beakless; had 1–4 transverse and 0–3 longitudinal septa; measured within 7.2–17.8 (average = 10.2) × 2.5–7.5 (average = 4.3) µm (n = 30). Molecular identification was performed using the colony polymerase chain reaction method with MightyAmp DNA Polymerase (Takara-Bio, Dalian, China) (Lu et al. 2012) to amplify the large subunit (LSU), internal transcribed spacer (ITS) region, translation elongation factor (TEF) , and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with NL1/LR3, ITS1/ITS4, EF-1α-F/EF-1α-R, and GDF1/GDR1 (Walther et al. 2013;Woudenberg et al. 2015; Nishikawa and Nakashima. 2020). Amplicons of the isolates were sequenced and submitted to GenBank (LSU, ON088978-ON088980; ITS, MW629797, ON417005 and ON417006; TEF, MW654167, ON497264,and ON497265;GAPDH, MW654166, ON497262,and ON497263). The obtained sequences were 100% identical with those of Alternaria alternata strain CBS 102600 upon BLAST analysis . The sequences were also concatenated for phylogenetic analysis by maximum likelihood. The isolates clustered with A. alternata (CBS 102600, CBS 102598, CBS 118814, CBS 918.96,CBS 106.24, CBS 119543, CBS 916.96). The fungus associated with leaf yellow spot on H. fragrans was thus identified as A. alternata. Pathogenicity tests were conducted in a greenhouse at 24 ℃–30 ℃ with 80% relative humidity. Individual plants were grown in pots (n = 5, 1 month old). The unwounded leaflets were inoculated with 5 mm-diameter mycelial plugs of the isolates or agar plugs (as control). The test was performed thrice. Disease symptoms were found on the leaves after 7 days, whereas the controls remained healthy. The pathogen was re-isolated from infected leaves and phenotypically identical to the original isolates to fulfill Koch’s postulates. To our knowledge, this report is the first one on A. alternata causing leaf yellow spot on H. fragrans. Thus, this work provides an important reference for the control of this disease in the future.

Yingna Chen,1 Jieya Lu,2 Zhihao Xie,1 Jialing Tang,1 Xuejiao Lian,1 Xiuwen Li1 1School of Pharmacy, School of Medicine, Changzhou University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Nephrology, Yixing Hospital of Traditional Chinese Medicine, Yixing, Jiangsu, People’s Republic of ChinaCorrespondence: Yingna Chen, School of Pharmacy, School of Medicine, Changzhou University, No. 21, Lake Gehu Road, Wujin District, Changzhou, Jiangsu, People’s Republic of China, Tel +86-13813661630, Email chenyingna@cczu.edu.cn Jieya Lu, Department of Nephrology, Yixing Hospital of Traditional Chinese Medicine, 128 Yangquan East Road, Yicheng Street, Yixing, Jiangsu, People’s Republic of China, Tel +86-15906153777, Email ljy7011645@sina.comBackground: Tumor microenvironment has attracted more and more attention in oncology. Alisol B23 acetate (AB23A) inhibits the proliferation of tumor cells including non-small cell lung cancer (NSCLC) cells. However, whether AB23A plays a role in the tumor microenvironment of NSCLC still remains obscure.Methods: After THP-1 cells were polarized to M0 type by PMA, M0 macrophages were differentiated into M1 by LPS and IFNγ, and were differentiated into M2 by IL-4 and IL-13. The differentiation of THP-1 cells was detected by flow cytometry. After AB23A was given to macrophage RT-qPCR and ELISA detected the expressions of IL-6, IL-1β, IL-10 and TGF-β. Western blot and RT-qPCR detected the expressions of CD11b and CD18 at both mRNA and protein levels. Lung cancer cell A549 cells were induced by above related macrophage culture medium. Cell proliferation was detected by CCK-8. Tunel, wound healing and Transwell detected the apoptotic, migration and invasion capabilities. Next, M0 and M1-type macrophages were cultured in the cell culture medium of conventional A549 cells, to which AB23A was added. Subsequently, cell differentiation and inflammatory response were measured. Finally, the expression of CD18 in A549 cells was knocked down to construct NSCLC tumor-bearing mice and AB23A was applied for intragastric administration. Immunohistochemistry detected the polarization of macrophages in tumor tissues. Western blot detected the expressions of CD11b, CD18, invasion-, migration- and apoptosis-related proteins.Results: AB23A promoted the polarization of macrophages towards M1, thus promoting the apoptosis and inhibiting the invasion and migration of A549 cells. The tumor cell culture medium induced M0 macrophages to M2, while AB23A reversed this effect. AB23A targeted CD11b/CD18 and improved the polarization of macrophages, thereby affecting tumor invasion, migration and apoptosis.Conclusion: AB23A affected the polarization of tumor-associated macrophages through the targeted regulation of CD11b/CD18, thus inhibiting the development of lung cancer.Keywords: Alisol B23 acetate, lung cancer, CD11b/CD18, tumor microenvironment

Background: Lower WHO grade II and III gliomas (LGGs) are characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the heterogeneity of the DNA Damage Repair (DDR), its function in tumor biology, coupling with the transcriptome and tumor microenvironment (TM) and its possible impact for tumor development. Methods: In this study, we analyzed gene expression profiles downloaded from TCGA, CGGA, and GEO databases. The DNA damage repair (DDR) alterations among LGG have been studied via multi-omics data integration. For this, LGG patients have been grouped into distinct subtypes (DDR-activated and the DDR-suppressed subtype) based on different clinicalparameters and molecular characteristics. The differences in gene mutation, immune spectrum, and immune cell infiltration between the two DDR subtypes were compared. We generated DDR subtype features (DDR scores) to implement DDR classification in LGG and confirmed the results using a multi-layer data cohort. In addition, the characteristics of DDR subtypes predicted by immunotherapy responses and their roles in the tumor immune microenvironment (TIM) were explored. Result: The DDR activation subgroup was found to be associated with poorer overall survival based on molecular subtypes, and clinicopathological features of advanced-age and higher-grade were more common in the DDR-activated subgroup. DDR-suppressed subtypes also exhibited more frequent mutations in IDH1. We also found significant upregulation of activated immune cells in the DDR-activated subgroup, which indicates significant influence posed by infiltration of immune cells on tumor progression as well as immunotherapeutic responses. In addition, six DDR genes were selected to construct a DDR signature of LGG, dividing patients into low- and high-risk groups. Within the IMvigor210 cohort, there were fewer CR/PR groups in the high-score patients, as well as concomitant shorter survival times. CR/PR group had higher DDR characteristics scores compared to the SD/PD group. QRT-PCR results showed that the expression levels of CDK1, CDK2, TYMS, SMC4, and WEE1 were found to be considerably higher for LGG samples compared to normal brain tissue samples (p < 0.05). Conclusion: In conclusion, our work sheds light on the DDR heterogeneity of LGG and advances our knowledge of the molecular pathways in DDR that lead to LGG.

Rhododendron pulchrum Sweet is a famous ornamental flower in China. In December 2020, a leaf spot disease was observed on cv. Maojuan in Zhanjiang (21.17 N, 110.18 E), Guangdong, China. The spots were irregular and distributed on both sides of the main vein. They were dark to black, and their borders were obvious. The coalescence of the spots eventually led to leaf wilt. The disease incidence was 100% (n = 100, about 50 ha ). Thirty infected leaves were collected from the field, and the margin of the diseased tissues was cut into 2 mm × 2 mm pieces. Samples were surface disinfected with 75% ethanol and 2% sodium hypochlorite for 30 and 60 s, respectively. They were rinsed thrice with sterile water before isolation. The tissues were plated on potato dextrose agar (PDA) medium and incubated at 28 ℃. After 5 days, fungal colonies appeared on the PDA. Pure cultures were produced by transferring hyphal tips to new PDA plates. Three isolates (RSP-1, RSP-2, and RSP-3) were obtained and the colonies of isolates were preserved in glycerol (15%) at -80 °C deposited at the Museum of Guangdong Ocean University. The morphology of these three isolates was consistent, and their sequences showed 100% homology according to ITS, TEF1, and ACT analysis results. The colonies grew to approximately 5 cm in diameter after 10 days. They showed olive green with off-white aerial mycelia. Stromata and conidia were observed on leaf lesions. Stromata were olivaceous brown. Conidia were solitary, cylindrical to narrowly obclavate, mildly curved, obtuse to rounded at the apex, and 1- to 3-septate; they had dimensions of 20 to 60 × 2.0 to 3.0 μm (n = 30). These morphological characteristics were not different from the description of Pseudocercospora rhododendricola (J.M. Yen) Deighton (Liu et al. 1998). For molecular identification, the colony PCR method with MightyAmp DNA Polymerase (Takara-Bio, Dalian, China) (Lu et al. 2012) was used to amplify the internal transcribed spacer (ITS), translation elongation factor 1-α gene (TEF1), and actin (ACT) loci of the isolates using primer pairs ITS4/ITS5, EF1/EF2, and ACT-512F/ACT-783R, respectively (White et al., 1990; O'Donnell et al. 1997). The sequences of the isolate RSP-1 were deposited in the GenBank (ITS, MW629798; TEF1, MW654168; and ACT, MW654170). BLAST analysis showed that the sequences of P. rhododendricola were submitted to GenBank for the first time by the author of this paper. A phylogenetic tree was generated based on the concatenated data of ITS, TEF1, and ACT sequences from GenBank by the Maximum Likelihood method. The isolates were closest to Pseudocercospora sp. CPC 14711 (Crous et al., 2013). Phylogenetic and morphological analyses identified the isolates as P. rhododendricola. Pathogenicity tests were conducted in a greenhouse at 24 °C-30 ℃ with 80% relative humidity. Healthy cv. Maojuan were grown in pots. Unwounded leaflets were inoculated with 5 mm-diameter mycelial plugs of the isolates or agar plugs (as control) (5 leaflets per plant, 3 plants, 2-month-old plants). The test was performed thrice. Disease symptoms were found on the leaves after 2 weeks, whereas the control plants remained healthy. The fungus was re-isolated from the infected leaves and confirmed as the same isolates by morphological and ITS analyses. P. rhododendricola was the cause of leaf spot of Rhododendron sp. from Singapore (Liu et al., 1998). For the first time, this pathogen was identified by combining phylogenetic and morphological analyses. The sequences in this study would be used as the reference sequences for further studies.

Mechanical shoe properties impact running biomechanics, triggering subjective shoe perception. Regarding midsole hardness little is known about the minimal mechanical alteration needed to change ru...

Although phosphate rock has been considered as a potential new rare earth elements (REEs) resource, the recovery of REEs from phosphate rock is impeded by technical challenges and cost issues. This study investigated the effects of operation conditions on the leaching efficiencies of REEs and phosphorus from Zhijin phosphate ore, a large phosphate deposit in China. The leaching process overtime was also studied by chemical analysis, scanning electron microscope with energy dispersive spectroscopy (SEM-EDS), and X-ray diffraction (XRD). The results indicated that the REEs from Zhijin phosphate ore were mainly present in fluorapatite and dolomite, and REEs had similar trends of leaching efficiency to those of phosphorus and magnesium. Under the conditions of 25 wt% phosphoric acid concentration in the initial pulp, a weight ratio of liquid to solid of 12 mL/g, a temperature of 60°C, an agitation speed of 220 rpm, and leaching time of 120 min, REEs and phosphorus leaching efficiencies of 97.8% and 99.7% were obtained. Most parts of dissoluble substances were decomposed within 30 min. Chemical analysis, SEM-EDS, and XRD results indicated that leaching efficiencies of minerals in Zhijin phosphate ore increased following the order: quartz, aluminosilicate, pyrite, fluorapatite, dolomite, and calcite.

Chaihu-Shugan-San (CHSGS), a noted traditional Chinese medicine formula, has been used as a complementary and alternative therapy for liver fibrosis. However, the antifibrotic mechanisms of CHSGS still remain unclear. Thus, we used network pharmacology approach in combination with single cell and bulk transcriptomics to elucidate the antifibrotic mechanisms of CHSGS. We first screened out 134 bioactive ingredients of CHSGS through the defined criteria. Then, 1150 genes were predicted to be targets for CHSGS, while 625 liver fibrosis-associated genes were identified by single cell transcriptomics analysis. Next, 71 intersecting genes of CHSGS and liver fibrosis were defined as the therapeutic targets in CHSGS against liver fibrosis. Further, 21 core targets and 12 core ingredients of CHSGS against liver fibrosis were also identified. Meanwhile, enrichment analyses of core targets highlighted that the key mechanisms of CHSGS against liver fibrosis include modulation of inflammation responses, inhibition of angiogenesis, and regulation of ECM remodeling, of which the most important mechanism was the regulation of ECM remodeling. The molecular docking simulation validated strong binding affinity between the core targets and core ingredients. Furthermore, 62-gene signature may be used for determining the prognosis in cirrhotic patients based on the results of ssGSEA-Cox analysis. In conclusion, the present study revealed the multiple pharmacological targets and therapeutic mechanisms of CHSGS against liver fibrosis, which may thus serve as an effective antifibrotic therapy. Meanwhile, CHSGS may improve survival of patients with liver cirrhosis by the interaction of 62-gene signature.

To find out the effect on the biomechanical response of the eye in the setting of diabetes combined with glaucoma.Five finite element models of the human eyes with various iris-lens channel (ILC) distances (2 μm-20 μm) were constructed, respectively. The human eye model used for finite element analysis contain all the ocular contents and the optic nerve head. All these models with different ILC distances were used to simulate the effect of pupillary block and abnormal aqueous flow induced by diabetes. And those models were also used for the biomechanical properties study of ocular tissues under the elevated intraocular pressure (IOP), using unidirectional fluid-solid coupling numerical simulation method.For the most severe cases of pupil block (2 μm), a significant difference in chamber pressure caused the iris to move forward and had posterior adhesion to the lens. And the strain, stress, and displacement of the whole eyeball were significantly higher than those of the other four cases, while the Optic Nerve Head (ONH) region was the opposite. The promotion of IOP to biomechanical response at both global eye and ONH region was close to the normal eye conditions, or even ease for ILC = 2 μm. But in the cases of glaucoma with pupil block and high aqueous flow, the biomechanical properties of the whole eyeball were remarkably enhanced for all IOP conditions. Less influence was observed in the ONH region.The promotion of diabetes for glaucoma is not directly on the optic nerve, instead, it indirectly affects the optic nerve by affecting the global eye. Glaucoma combined with diabetes complications may increase the biomechanical damage of IOP to the whole eye.

Phosphate rock has been considered as one of the most significant secondary rare-earth resource, and the utilization of rare earth elements (REEs) in phosphate rock has attracted increasing attention. In this study, the leaching kinetics of REEs from a phosphate ore from China was studied with the variation of temperature and phosphoric acid concentration under the conditions: ratio of liquid to solid of 12 mL/g, stirring speed of 120 r/min, and phosphate particle size of −0.074 mm amounts 61.1%. The results suggest that there were two distinct stages in leaching process and kinetics of both stages followed shrinking core model. At fast reaction stage, the semi-empirical equation describing the kinetics was 1 − 3(1 − α)2/3 + 2(1 − α) = 1.885CH3PO40.89exp(−11220/8.31T)t. The semi-empirical equation for slow reaction stage was 1 − 3(1 − α)2/3 + 2(1 − α) = 0.299CH3PO42.50exp(−18720/8.31T)t. Using shrinking core model and time-to-a-given-fraction method, we found that leaching rate of fast reaction stage was controlled by solid product layer diffusion, and both solid product layer diffusion and chemical reaction determined slow reaction stage.

Previous studies reported cerebral hypoperfusion ocurred in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).1 2 As a cerebral small vessels disease, the reduction of blood flow velocity in cerebral small arteries may precede cerebral hypoperfusion and lesions formation. Due to the limitations of spatial resolution, conventional methods failed to detect the velocity of cerebral small vessels. Ultrahigh field MRI provided us a non-invasive way to investigate the velocity in lenticulostriate arteries (LSAs) of patients with CADASIL.3–5 Assessing blood flow velocity of small arteries can monitor the progress of the disease in long-term follow-up of patients. We enrolled 32 patients with CADASIL and 34 healthy controls from September 2019 to September 2020 at Peking University First Hospital. Details of subject selection, clinical assessment, MRI acquisition and analysis were described in online supplemental methods, online supplemental figure 1, online supplemental tables 1 and 2. The phase contrast magnetic resonance angiography (PC-MRA) was acquired at a 7 T MR scanner with high resolution (0.35×0.35×0.40 mm3) and low velocity-encoding (VENC) value (15.00 cm/s) was acquired to measure blood flow velocities of LSAs. The analysis pipeline of LSA velocities includes: (1) intensity bias corrections; (2) LSA region extraction on maximum intensity projection images; (3) threshold-based noise masking; (4) velocity components reconstruction from phase-difference data; (5) extracting dominant branches of the LSAs and calculating mean velocity. Test–retest experiments and Bland-Altman analysis were performed to validate the precision of the measurement method (online supplemental figure 2).5 ### Supplementary data [jnnp-2021-326258supp001.pdf] ### Demographic and clinical features One patient and three healthy controls were excluded for excessive head motion causing large artefacts and poor image quality. Ultimately, we included 31 patients from 24 pedigrees and 31 healthy controls in this study. The heterozygous mutations affecting the patients with CADASIL were listed in online supplemental table 3 …

The aim of this study was to examine prognostic differences between liver resection (LR) and percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC) based on preoperative predicted microvascular invasion (MVI) risk. Data on consecutive patients who underwent LR (n = 1344) or PRFA (n = 853) for hepatitis B virus-related HCC within the Milan criteria (MC) were analyzed. A preoperative nomogram was used to estimate MVI risk. Overall survival (OS), time to recurrence, and patterns of recurrence were compared using propensity score matching. The concordance indices of the nomogram to predict MVI were 0.813 and 0.781 among LR patients with HCC within the MC or ≤ 3 cm, respectively. LR and PRFA resulted in similar 5-year recurrence and OS for patients with nomogram-predicted low-risk of MVI. LR provided better 5-year recurrence and OS versus PRFA for patients with high-risk of MVI (71.6% vs. 80.7%, p = 0.013; 47.9% vs. 34.0%, p = 0.002, for HCC within the MC; 62.3% vs. 78.8%, p = 0.020; 63.6% vs. 38.3%, p = 0.015, for HCC ≤ 3 cm). Among high-risk patients, LR was associated with lower recurrence and improved OS compared with PRFA, on multivariate analysis [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63–0.97, and HR 0.68, 95% CI 0.52–0.88, for HCC within the MC; HR 0.51, 95% CI 0.32–0.81, and HR 0.47, 95% CI 0.26–0.84, for HCC ≤ 3 cm], and resulted in less early and local recurrence than PRFA (42.4% vs. 54.8%, p = 0.007, and 31.2% vs. 46.1%, p = 0.007, for HCC within the MC; 27.9% vs. 50.8%, p = 0.016, and 15.6% vs. 39.5%, p = 0.046, for HCC ≤ 3 cm). LR was oncologically superior over PRFA for early HCC patients with predicted high-risk of MVI. LR was associated with better local disease control than PRFA in these patients.

Pseudoexon (PE) inclusion has been implicated in various dystrophinopathies, however, its splicing characteristics have not been fully investigated. This study aims to analyze the splicing characteristics of dystrophin PEs and compare them with those of dystrophin canonical exons (CEs). Forty-two reported dystrophin PEs were divided into a splice site (ss) group and a splicing regulatory element (SRE) group. Five dystrophin PEs with characteristics of poison exons were identified and categorized as the possible poison exon group. The comparative analysis of each essential splicing signal among different groups of dystrophin PEs and dystrophin CEs revealed that the possible poison exon group had a stronger 3&prime, ss compared to any other group. As for auxiliary SREs, different groups of dystrophin PEs were found to have a smaller density of diverse types of exonic splicing enhancers and a higher density of several types of exonic splicing silencers compared to dystrophin CEs. In addition, the possible poison exon group had a smaller density of 3&prime, ss intronic splicing silencers compared to dystrophin CEs. To our knowledge, our findings indicate for the first time that poison exons might exist in DMD (the dystrophin gene) and present with different splicing characteristics than other dystrophin PEs and CEs.

This paper analyzed urban network and regions in China using a complex network model. Data of daily migration among 348 prefectural-level cities from the Baidu Map location-based service (LBS) Open Platform were used to calculate urban network metrics and to delineate boundaries of urban regions. Results show that urban network in China displays an obvious hierarchy in terms of attracting and distributing population and controlling regional interaction. Regional integration has become increasingly prominent, as administrative boundaries and natural barriers no longer have strong impacts on urban connections. Overall, 18 urban regions were identified according to urban connectivity, and the degree of urban connection is higher among cities in the same urban region. Due to geographical proximity and close interaction, several provincial capital cities form an urban region with cities from neighboring provinces instead of those from the same province. Identification of urban region boundaries is of significant importance for sustainable development and policymaking on the demarcation of urban economic zones, urban agglomerations, and future adjustment of provincial administrative boundaries in China.

Background The prevalence of myopia and associated risk factors among children in Chongqing has not yet been determined. This study investigated the prevalence of myopia and possible relationships between myopia and several related factors among school children in Chongqing. Methods This cross-sectional study assessed a sample of 997 children (7–13 years of age) attending primary school in Chongqing. Data were obtained from visual acuity and refractive error measurements and a structured questionnaire. Myopia was defined as visual acuity Results The overall prevalence of myopia was 33.9% [95% confidence interval (CI) = 31.0–36.8]; myopia prevalence significantly increased with age. Girls were at a higher risk of myopia than boys [odds ratio (OR) = 1.449, 95% CI = 1.060–1.979]. Children with paternal myopia (OR = 2.130, 95% CI = 1.376–3.297) or maternal myopia (OR = 1.861, 95% CI =1.153–3.002) had a higher risk of myopia than those without myopic parents. Children who spent more than 1 h daily outdoors were less likely to have myopia; meanwhile, children who did homework more than 3 h daily (OR = 2.237, 95% CI = 1.041–4.804), watched television more than 3 h daily (OR = 2.106, 95% CI = 1.200–3.697), or played electronics more than 1 h daily (OR = 2.983, 95% CI = 2.088–4.262) had a higher risk of myopia. Conclusions Myopia in school children is a serious public health problem in Chongqing. Myopia was significantly positively associated with higher age, female sex, parental myopia, and spending a long time indoors; notably, playing with electronics had the greatest influence on the risk of myopia.

Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.