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Adaptive metabolic responses and innate metabolites hold promising therapeutic potential for stroke, while targeted interventions require a thorough understanding of underlying mechanisms. Adiposity is a noted modifiable metabolic risk factor for stroke, and recent research suggests that it benefits neurological rehabilitation. During the early phase of experimental stroke, the lipidomic results showed that fat depots underwent pronounced lipolysis and released fatty acids (FAs) that feed into consequent hepatic FA oxidation and ketogenesis. Systemic supplementation with the predominant ketone beta‐hydroxybutyrate (BHB) is found to exert discernible effects on preserving blood‐brain barrier (BBB) integrity and facilitating neuroinflammation resolution. Meanwhile, blocking FAO‐ketogenesis processes by administration of CPT1α antagonist or shRNA targeting HMGCS2 exacerbated endothelial damage and aggravated stroke severity, whereas BHB supplementation blunted these injuries. Mechanistically, it is unveiled that BHB infusion is taken up by monocarboxylic acid transporter 1 (MCT1) specifically expressed in cerebral endothelium and upregulated the expression of tight junction protein ZO‐1 by enhancing local β‐hydroxybutyrylation of H3K9 at the promoter of TJP1 gene. Conclusively, an adaptive metabolic mechanism is elucidated by which acute lipolysis stimulates FAO‐ketogenesis processes to restore BBB integrity after stroke. Ketogenesis functions as an early metabolic responder to restrain stroke progression, providing novel prospectives for clinical translation. [ABSTRACT FROM AUTHOR]

The stable Pepsin@covalent organic framework (Pepsin@COF) were constructed base on matching COF pore diameter to pepsin dimension. It exhibits excellent chiral recognition capabilities (e. e. % up to 62.63 %) and potential for enantioseparation. Furthermore, a positive correlation between the immobilized enzyme activity and chiral recognition was revealed, offering insights for the design of biocatalytic nanosystems in chiral separation. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most serious and deadly cancers in women worldwide, with distant metastases being the leading cause of death. Tn antigen, a tumor‐associated carbohydrate antigen, was frequently detected in breast cancer, but its exact role in breast cancer metastasis has not been well elucidated. Here we investigated the impact of Tn antigen expression on breast cancer metastasis and its underlying mechanisms. The expression of Tn antigen was induced in two breast cancer cell lines by deleting T‐synthase or Cosmc, both of which are required for normal O‐glycosylation. It showed that Tn‐expressing cancer cells promoted epithelial–mesenchymal transition (EMT) and metastatic features as compared to Tn(−) control cells both in vitro and in vivo. Mechanistically, we found that cancer susceptibility candidate 4 (CASC4), a heavily O‐glycosylated protein, was significantly downregulated in both Tn(+) cells. Overexpression of CASC4 suppressed Tn‐induced activation of EMT and cancer metastasis via inhibition of Cdc42 signaling. Furthermore, we confirmed that O‐glycosylation is essential for the functional role of CASC4 because defective O‐glycosylated CASC4 (mutant CASC4, which lacks nine O‐glycosylation sites) exerted marginal metastatic‐suppressing effects in comparison with WT CASC4. Collectively, these data suggest that Tn‐mediated aberrant O‐glycosylation contributes to breast cancer metastasis via impairment of CASC4 expression and function. [ABSTRACT FROM AUTHOR]

Background: The enlarged vestibular aqueduct (EVA) is the commonest malformation of inner ear accompanied by sensorineural hearing loss in children. Three genes SLC26A4, FOXI1, and KCNJ10 have been associated with EVA, among them SLC26A4 being the most common. Yet, hotspot mutation screening can only diagnose a small number of patients. Methods: Thus, in this study, we designed a new molecular diagnosis panel for EVA based on multiplex PCR enrichment and next‐generation sequencing of the exon and flanking regions of SLC26A4. A total of 112 hearing loss families with EVA were enrolled and the pathogenicity of the rare variants detected was interpreted according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Our results showed that 107/112 (95.54%) families carried SLC26A4 biallelic mutations, 4/112 (3.57%) carried monoallelic variants, and 1/112 (0.89%) had none variant, resulting in a diagnostic rate of 95.54%. A total of 49 different variants were detected in those patients and we classified 30 rare variants as pathogenic/likely pathogenic, of which 13 were not included in the Clinvar database. Conclusion: Our diagnostic panel has an increased diagnostic yield with less cost, and the curated list of pathogenic variants in the SLC26A4 gene can be directly used to aid the genetic counseling to patients. [ABSTRACT FROM AUTHOR]

Background: Treacher Collins syndrome‐1 (TCS1; OMIM# 154500) is a rare autosomal dominant disease that is defined by congenital craniofacial dysplasia. Here, we report four sporadic and one familial case of TCS1 in Chinese patients with clinical features presenting as hypoplasia of the zygomatic complex and mandible, downslanting palpebral fissures, coloboma of the lower eyelids, and conductive hearing loss. Materials and Methods: Audiological, radiological, and physical examinations were performed. Targeted next‐generation sequencing (NGS) was performed to examine the genetics of this disease in five probands, and Sanger sequencing was used to confirm the identified variants. A literature review discusses the pathogenesis, treatment, and prevention of TCS1. Results: We identified a novel insertion of c.939_940insA (p.Gly314Argfs*35; NM_001135243.1), a novel deletion of c.1766delC (p.Pro589Leufs*7), two previously reported insertions of c.1999_2000insC (p.Arg667Profs*31) and c.4218_4219insG (p.Ser1407Valfs*23), and one previously reported deletion of c.4369_4373delAAGAA (p.Lys1457Glufs*12) in the TCOF1 gene. All five cases exhibited a degree of interfamilial and intrafamilial phenotypic variability. A review of the literature revealed no clear evidence of a genotype–phenotype correlation in TCS1. Conclusion: Our results expand the variant spectrum of TCOF1 and highlight that NGS is essential for the diagnosis of TCS and that genetic counseling is beneficial for guiding prevention. [ABSTRACT FROM AUTHOR]

Background: Perrault syndrome (PRLTS4; OMIM# 615300) is a rare autosomal recessive disorder and only a few cases have been reported worldwide. We report a Chinese female characterized by sensorineural hearing loss and premature ovarian insufficiency. Methods: We evaluated audiological, endocrine, and ultrasound examinations and examined the genetic causes using whole‐exome sequencing. We reviewed the literature to discuss the pathogenesis, genotype–phenotype correlation, treatment, and prevention of PRLTS4. Results: Bioinformatic analysis revealed compound heterozygous mutations in the LARS2 gene, c.880G>A (p.Glu294Lys), and c.2108T>C (p.Ile703Thr) which is a novel missense mutation, co‐segregated in this family. Taken together, the patient was clinically diagnosed as PRLTS4. The literature review showed that the phenotype for PRLTS4 varies widely, but the sensorineural hearing loss, increased gonadotropin levels, and amenorrhea occurred frequently. All reported mutations are highly conserved in mammals based on conservation analysis, and there is a mutation hotspot for PRLTS4. Conclusion: This study expanded the mutation spectrum of LARS2 and is the first report of PRLTS4 in a Chinese family. Genetic testing plays an important role in early diagnosis of syndromic deafness and clinical genetic evaluation is essential to guide prevention. [ABSTRACT FROM AUTHOR]

The aim of the study was to research the biological functions of circRNA (hsa_circ_0079662) and its underlying mechanism in colorectal cancer. Drug‐resistant cell lines (HT29‐LOHP, HCT116‐LOHP, HCT8‐LOHP) were separately dealt with oxaliplatin concentration gradient (0.1‐10 μmol/L). Real‐time PCR, Western blotting, dual‐luciferase assay, miRNA pull‐down assay, coimmunoprecipitation and ELASA were performed to explore the mechanism of chemotherapy drug oxaliplatin resistance in CRC. The results showed that the expression of hsa_circ_0079662 was increased in drug‐resistant cell lines by RT‐PCR. The expression of HOXA9, TRIP6, Vcam‐1, VEGFC, MMP3, MMP9 and MMP14 was higher by Western blotting. Interaction between HOXA9 and TRIP6 in CO‐IP detection. Additionally, the cytokines TNF‐α, IL‐1 and IL‐6 were also found. In conclusion, hsa_circ_0079662, as a ceRNA binding with hsa‐mir‐324‐5p, can regulate target gene HOXA9 and induced the mechanism of chemotherapy drug oxaliplatin resistance in CRC through the TNF‐α pathway in human colon cancer. [ABSTRACT FROM AUTHOR]

Background and Aim: Whether routine screening for the JAK2V617F mutation should be performed in Chinese patients with Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) is unclear. Therefore, we aimed to evaluate the prevalence of the JAK2V617F mutation in such patients and to explore the risk factors associated with the mutation. Methods: All consecutive patients with BCS and PVT diagnosed between September 2009 and May 2011 were prospectively enrolled in the observational study and underwent the JAK2V617F mutation detection. Results: Prevalence of the JAK2V617F mutation was 4.3% (4/92) in patients with primary BCS, 26.6% (17/64) in non-malignant and non-cirrhotic patients with PVT, and 1.4% (1/71) in cirrhotic patients with PVT. All BCS patients with the JAK2V617F mutation had both platelet count (PLT) of above 100 × 109/L (range, 107-188 × 109/L) and splenomegaly. In non-malignant and non-cirrhotic patients with PVT, higher PLT and older ages were the independent predictors of the JAK2V617F mutation. Further, the difference in PLT between the patients with and without the mutation displayed greater significance in the subgroup of patients with splenomegaly ( P < 0.0001), but the statistical significance disappeared in the subgroup of patients with splenectomy ( P = 0.1312). Conclusions: The low prevalence of the JAK2V617F mutation in patients with BCS suggests that myeloproliferative neoplasm should be an uncommon etiological factor of BCS in China. Routine screening for the JAK2V617F mutation might be recommended in non-malignant and non-cirrhotic patients with PVT, but not in cirrhotic patients with PVT. The coexistence of higher PLT and splenomegaly might be closely associated with the JAK2V617F mutation. [ABSTRACT FROM AUTHOR]

The authors numerically studied the irreversibility temperature (Tirr) of a spin glass (SG) and how to use a SG to stabilize a ferromagnet. The rate of Tirr/SG‐anisotropic‐field increment can reach ≈121 K T−1. In ferromagnet/SG bilayers, exchange bias (EB) may be enhanced fivefold at 10 K with increasing interfacial coupling (JIF), whereas the EB blocking temperature (TBEB) does not change. However, decreases in SG exchange coupling (JSG) can twofold enhance TBEB with maintaining a table‐like EB. On the contrary, small JIF and large JSG are both destructive to coercivity. Nevertheless, EB field and coercivity are switchable, opening an opportunity to design temperature‐controlled write‐to‐read switches. [ABSTRACT FROM AUTHOR]