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Treacher Collins syndrome (TCS, MIM #154500) is a severe congenital disorder implicated in particular dysplasia of the craniofacial bones, accompanied by downslanting palpebral fissures, lower eyelid colobomas, microtia, or other craniofacial malformations. However, the underlying pathogenic mutations in TCS are still unknown, and elucidating these is of primary importance for TCS researchers. We collected samples from a Chinese TCS family, including the proband and two parents. Sequencing, genotyping, and in silico analyses were employed to detect pathogenic mutations in the pedigree. In the proband, a de novo frameshift mutation of TCOF1 c.1562_1574del (p.A521fs) was identified as a pathogenic candidate, while the parents showed no mutations. The frameshift mutation results in TCOF1 truncation and damages the central repeat domain, which is the binding site for transcriptional factors. In conclusion, we identified a novel mutation TCOF1 c.1562_1574del, which is likely a pathogenic mutation for TCS, thereby expanding the mutation spectrum of TCS.

New targets and strategies are urgently needed for the identification and development of anabolic drugs for osteoporosis. Farnesoid X receptor (FXR) is a promising novel therapeutic target for bone metabolism diseases. Although used clinically, FXR agonists have obvious side effects; therefore, the development of new FXR agonists for the treatment of osteoporosis would be welcomed. Geniposidic acid (GPA) is a bioactive compound extracted from Eucommiae cortex, which is used for treating arthritis, osteoporotic fractures, and hypertension. However, the therapeutic effects of GPA against osteoporosis remain underexplored.This study aims to reveal the potential osteogenic effects of FXR and to explore the effect of GPA on bone formation, osteoporosis treatment, and FXR signaling.The role of FXR in promoting bone formation was evaluated in Fxr knockout (FxrWe found that FXR was highly expressed in bone tissues and enriched in osteoblasts. Notably, deletion of FXR significantly reduced the bone formation rate and bone mass of the FxrThis study demonstrated that FXR is a promising target for treating osteoporosis and that GPA promotes bone formation in OVX-induced osteoporosis by activating FXR signaling. These findings provide novel insight into the mechanism by which GPA promotes bone formation and more evidence for its application in the treatment of osteoporosis.

We investigated the serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels in a cohort of Chinese patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) in relation to clinical disease course and treatment. sNfL and sGFAP levels were determined by ultrasensitive single molecule array (Simoa) assay in patients with NMOSD (n = 102) and MS (n = 98) and healthy controls (HCs; n = 84). Notably, 13 patients with NMOSD and 27 patients with MS were enrolled in the 1-year follow-up cohort. Levels were compared with data such as clinical course, disease duration, Expanded Disability Status Scale (EDSS) score, and lesions on MRI. Higher levels of sNfL and sGFAP were found in subjects with NMOSD and MS than in HCs (sNfL, median 12.11, 17.5 vs. 8.88 pg/ml, p

Early reperfusion is increasingly prioritized in ischemic stroke care, but outcomes remain suboptimal. Therefore, there is an urgent need to find neuroprotective approaches that can be combined with reperfusion to maximize efficacy. Here, the neuroprotective mechanisms behind therapeutic hypothermia were evaluated in a monkey model of ischemic stroke. Focal ischemia was induced in adult rhesus monkeys by placing autologous clots in the middle cerebral artery. Monkeys were treated with tissue plasminogen activator (t-PA) alone or t-PA plus selective intra-arterial cooling (SI-AC). Serial MRI scans and functional deficit were evaluated after ischemia. Histopathology and immunohistochemistry analysis were performed after the final MRI scan. t-PA plus SI-AC treatment led to a higher rate of MRI tissue rescue, and significantly improved neurologic deficits and daily activity scores compared with t-PA alone. In peri-infarct areas, higher fractional anisotropy values and greater fiber numbers were observed in models receiving t-PA plus SI-AC. Histological findings indicated that myelin damage, spheroids, and spongiosis were significantly ameliorated in models receiving SI-AC treatment. White matter integrity was also improved by SI-AC based on immunochemical staining. Our study demonstrates that SI-AC can be effectively combined with t-PA to improve both structural and functional recovery in a monkey model of focal ischemia. These findings provide proof-of-concept that it may be feasible to add neuroprotective agents as adjunctive treatments to reperfusion therapy for stroke. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00895-6) contains supplementary material, which is available to authorized users.

Supplemental material, JCB903697 Supplemental Material for Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status by Di Wu, Jian Chen, Mohammed Hussain, Longfei Wu, Jingfei Shi, Chuanjie Wu, Yanhui Ma, Mo Zhang, Qi Yang, Yongjuan Fu, Yunxia Duan, Cui Ma, Feng Yan, Zixin Zhu, Xiaoduo He, Tianqi Yao, Ming Song, Xinglong Zhi, Chunxiu Wang, Lipeng Cai, Chuanhui Li, Shengli Li, Yongbiao Zhang, Yuchuan Ding and Xunming Ji in Journal of Cerebral Blood Flow & Metabolism

With the aim to improve the solubility and dissolution rate of tetrahydroberberine (THB) by forming hydrochloride salts, three salts of THB, [HTHB]Cl (1), [HTHB]Cl·CH3OH (2) and [HTHB]Cl·CH3COOH (3), have been synthesized and characterized. The solubility and dissolution rate suggest that the maximum solubility values for 1–3 are approximately 98, 47, and 43 times as large as that of THB, and the dissolution rates of the three compounds are also effectively improved relative to THB. Surprisingly, the hygroscopicity of 2 and 3 has been efficiently reduced compared to that of 1, which shows that the hygroscopicity of the formed hydrochloride salts could be successfully avoided by introducing solvents into the structures. Preliminary analyses of the relationship between structures and properties indicate that the ability of the chloride ion to absorb water molecules (mainly through hydrogen-bond interaction) was reduced due to the presence of solvents in 2 and 3. This successfully implemented work may provide an inspirational method for avoiding hygroscopicity without compromising the solubility of hygroscopic APIs. Additionally, the three compounds show advantages in terms of antibacterial properties in comparison to their corresponding parent compounds.

Long noncoding RNAs (lncRNAs) have emerged as integral regulators of physiology and disease, but specific roles of lncRNAs in bone disease remain largely unknown. Here, we show that lnc-ob1 regulates osteoblast activity and bone formation in mice by upregulating the osteogenic transcription factor Osterix. Expression of lnc-ob1 is enriched in osteoblasts and upregulated during osteoblastogenesis. We demonstrate that osteoblast-specific knock-in of lnc-ob1 enhances bone formation and increases bone mass. Pharmacological overexpression of lnc-ob1 specifically in osteoblasts confers resistance to ovariectomy-induced osteoporosis in mice. In humans, expression of the homologue, lnc-OB1, decreases with age in osteoblasts of patients with osteoporosis. Mechanistically, lnc-ob1 upregulates the expression of Osterix in mouse and human osteoblasts, probably via inhibition of H3K27me3 methylation. Our data indicate that lnc-OB1 regulates bone formation and might be a drug target for the treatment of osteoporosis.

Wavelength-tunable pulsed fiber lasers have many potential applications in sensing, communications, spectroscopy, and medicine. Pulsed fiber lasers based on two-dimensional (2D) materials are easier and simpler to integrate into the laser cavity than those based on traditional mode-locked techniques such as nonlinear polarization rotation and semiconductor saturable absorber mirror. In this review, we discuss the principles and report on the current progress of wavelength-tunable pulsed fiber lasers based on graphene, graphene oxide (GO), topological insulators (TIs), transition metal dichalcogenides (TMDs), and black phosphorus (BP). Then, we discuss the mechanisms to achieve wavelength-tunable pulsed operation. Finally, an outlook about the development of tunable pulsed fiber lasers is presented in the perspectives.

Terrapins and turtles are known to transmit Salmonella to humans. However, little was known about the occurrence of this pathogen in soft-shelled terrapin that is a popular delicacy in Chinese and other East Asian cuisines. We isolated and characterized 82 (24.4%) isolates of Salmonella from 336 fecal samples of soft-shelled terrapins (51 of 172; 29.7%) and pet turtles (31 of 164; 18.9%) in Shanghai. Salmonella Thompson was the most common serotype (17.1%) among others. Many isolates (84.1%) were resistant to multiple antimicrobials (≥3). Molecular analysis of Salmonella Thompson and Salmonella Typhimurium using pulsed-field gel electrophoresis unveiled a close genetic relationship between several human and terrapin isolates. Our results highlight the risk associated with the handling and consumption of turtles and their role in the spread of Salmonella in the human salmonellosis.

We aimed to observe the effects of cytochrome P450 epoxygenase 2J2 (CYP2J2) overexpression on right ventricular remodelling in monocrotaline-induced pulmonary hypertension in rats. Forty SD rats were randomly divided into normal control group (NC group), monocrotaline group (MCT group), pCB6

(This work was supported by grants 81500287 from National Nature Science Foundation Committee of China) The soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to their less active dihydroxy derivatives, dihydroxy epoxyeicosatrienoic acids (DHETs). The purpose of the study

Chronic Obstructive Pulmonary Disease (COPD) is a complex human disease which is driven not only by genetic factors, but also by various environmental variables, such as gender, age and smoking. Therefore, there is a demand for investigating the complexity among various risk factors involved in COPD. In this study, 44 tagging SNPs from EPHX1, GSTP1, SERPINE2 and TGFB1 were selected and genotyped in 310 COPD cases and 203 controls, all of which belong to the Han from North China. We integrated functional prediction algorithms of nonsynonymous SNPs (nsSNPs) into Bayesian network to explore the complex regulatory relationships among disease traits and various risk factors. The results showed that three basic variables (age, sex and smoking) were risk factors of COPD-related trait and phenotype. Besides these environmental risk factors, deleterious nsSNPs were found to perform better than those of significant synonymous SNPs when used as variables to make risk prediction of disease outcome. This study provides further evidences for detecting the complexity of COPD in Northern Chinese Han Population.

Chronic obstructive pulmonary disease (COPD) is a complex human disease influenced by multiple genes and environmental factors. The SERPINE2 gene has recently been demonstrated to be associated with COPD onset in a non-East Asian population. In this study, we genotyped 20 single nucleotide polymorphisms (SNPs) in SERPINE2 from 310 cases and 203 controls, all of which belong to the Han from North China. Genotype frequencies were compared between the cases and the controls and analyzed for statistical significance. Two SNPs (rs729631 and rs975278), which are in strong linkage disequilibrium (LD) and locate in block 1 on the LD map of our samples, showed significant association both with the risk of COPD and decline in baseline lung function after Bonferroni correction (P < 0.05). This study provides further evidences for SERPINE2 gene as a COPD susceptible gene, and block 1 of SERPINE2 appears to be the genetic variant region that affects the Han Chinese.