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Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease that accounts for 10%-15% childhood cholestasis and could lead to infant disability or death. There are three well-established types of PFIC (1-3), caused by mutations in the ATP8B1, ABCB11, and ABCB4 genes. Biallelic pathogenic variants in the tight junction protein 2 gene (TJP2) were newly reported as a cause for PFIC type 4; however, only a limited number of patients and undisputable variants have been reported for TJP2, and the underlying mechanism for PFIC 4 remains poorly understood. To explore the diagnostic yield of TJP2 analysis in suspected PFIC patients negative for the PFIC1-3 mutation, we designed a multiplex polymerase chain reaction-based next-generation sequencing method to analyze TJP2 gene variants in 267 PFIC patients and identified biallelic rare variants in three patients, including three known pathogenic variants and two novel variants in three patients. By using CRISPR-cas9 technology, we demonstrated that TJP2 c.1202A > G was pathogenic at least partially by increasing the expression and nuclear localization of TJP2 protein. With the minigene assay, we showed that TJP2 c.2668-11A > G was a new pathogenic variant by inducing abnormal splicing of TJP2 gene and translation of prematurely truncated TJP2 protein. Furthermore, knockdown of TJP2 protein by siRNA technology led to inhibition of cell proliferation, induction of apoptosis, dispersed F-actin, and disordered microfilaments in LO2 and HepG2celles. Global gene expression profiling of TJP2 knockdown LO2 cells and HepG2 cells identified the dysregulated genes involved in the regulation of actin cytoskeleton. Microtubule cytoskeleton genes were significantly downregulated in TJP2 knockdown cells. The results of this study demonstrate that TJP2 c.1202A > G and TJP2 c.2668-11A > G are two novel pathogenic variants and the cytoskeleton-related functions and pathways might be potential molecular pathogenesis for PFIC.Fat deposition in yaks plays an important part in survival, multiplication, and meat quality. In this work, the characteristic of fat deposition in male yaks (MYs) and female yaks (FYs) and the regulations of gender to yak fat deposition were explored by mRNA-Seq and non-targeted metabolomics analyses. FYs possessed a higher body fat rate (BFR) of visceral fat, fat content in longissimus dorsi (LD) and liver, and subcutaneous fat thickness (p less then 0.05). The fat and cholesterol synthesis in liver and the fat transport in FY blood increased. The fat metabolism in yaks is the combined effect of carbohydrate, fatty acid, and amino acid metabolism by tricarboxylic acid (TCA) cycle, and an increase of triglyceride (TG) synthesis was accompanied by an increase of steroid synthesis. The high levels of myo-inositol and cortisol (COR) (p less then 0.01) activated the calcium signaling in FY subcutaneous fat, followed by the increase of adipocyte secretion, and resulted in more leptin (LEP) secretion (p less then 0.01). Then peroxisome proliferator-activated receptor (PPAR) signaling was activated by the focal adhesions and ECM-receptor interaction. Finally, the TG and steroid synthesis increased by the expression regulation of ME1, SCD, ELOVL6, DGAT2, DBI, LPL, CPT1, PLIN1, LIPA, DHCR24, and SQLE gene. The above genes can be considered as the candidate genes for yak with higher fat amount in molecular breeding in the future. This study can provide a theoretical basis for improving the meat quality and breeding of yaks.The clinical outcomes of triple-negative breast cancer (TNBC) chemotherapy are unsatisfactory. Water solubility and biosafety of chemo drugs are also major barriers for achieving satisfactory treatment effect. In this study, we have reported a combinational strategy by self-assembly engineering nanodrugs PC NDs, which were composed of paclitaxel (PTX) and curcumin (Cur), for effective and safe TNBC chemotherapy. PC NDs were prepared through reprecipitation method without using any additional carriers. The PC NDs were preferentially taken up by TNBC cells and we also observed pH-related drug release. Compared with free PTX and simple PTX/Cur mixture, PC NDs have shown higher therapeutic efficiency and better prognosis while the metastasis rate was significantly lower than that of either PTX or PTX/Cur mix group. Therefore, the self-assembly engineered PC NDs might be a promising nanodrugs for efficient and safe TNBC chemotherapy.Nanozymes own striking merits, including high enzyme-mimicking activity, good stability, and low cost. Due to the powerful and distinguished functions, nanozymes exhibit widespread applications in the field of biosensing and immunoassay, attracting researchers in various fields to design and engineer nanozymes. Recently, nanozymes have been innovatively used to bridge nanotechnology with analytical techniques to achieve the high sensitivity, specificity, and reproducibility. However, the applications of nanozymes in food applications are seldom reviewed. In this review, we summarize several typical nanozymes and provide a comprehensive description of the history, principles, designs, and applications of nanozyme-based analytical techniques in food contaminants detection. Based on engineering and modification of nanozymes, the food contaminants are classified and then discussed in detail via discriminating the roles of nanozymes in various analytical methods, including fluorescence, colorimetric and electrochemical assay, surface-enhanced Raman scattering, magnetic relaxing sensing, and electrochemiluminescence. Further, representative examples of nanozymes-based methods are highlighted for contaminants analysis and inhibition. Finally, the current challenges and prospects of nanozymes are discussed.Recent research on organic semiconductors has revealed that the composition of the constituent organic material, as well as the subtle changes in its structure (the stacking order of molecules), can noticeably affect its bulk properties. One of the reasons for this is that the charge transport in conjugated materials is strongly affected by their structure. Further, the charge mobility increases significantly when the conjugated materials exhibit self-assembly, resulting in the formation of ordered structures. However, well-organized nanostructures are difficult to obtain using classical solution processing methods, owing to their disordered state. A simple strategy for obtaining well-ordered material films involves synthesizing new conjugated materials that can self-organize. Adenosine Cyclophosphate Introducing hydrogen bonding in the materials to yield hydrogen-bonded material superstructures can be a suitable method to fulfill these critical requirements. The formed hydrogen bonds will facilitate the assembly of the molecules into a highly ordered structure and bridge the distance between the adjacent molecules, thus enhancing the intermolecular charge transfer. In this minireview, hydrogen-bonded small molecules and polymers as well as the relationship between their chemical structures and performances in organic field-effect transistors are discussed.We present two iridium complexes 1H + and 2H + that contain cationic ligands to extend the knowledge of charge-assisted hydrogen bonding (CAHB), which counts among the strongest non-covalent bonding interactions. Upon protonation, both complexes were converted into new hydrogen-bonding arrays with various selectivity for respective H-bonding partners. This study compares the association strengths of four hydrogen-bonding co-systems, emphasizing the roles of CAHB in supramolecular systems. We determined that the cationic charge in these systems contributed up to 2.7 kJ mol-1 in the H-bonding complexation processes.The biodistribution of medical imaging probes depends on the chemical nature of the probe and the preferred metabolization and excretion routes. Especially targeted probes, which have to reach a certain (sub)cellular destination, have to be guided to the tissue of interest. Therefore, small molecular probes need to exhibit a well-balanced polarity and lipophilicity to maintain an advantageous bioavailability. Labelled antibodies circulate for several days due to their size. To alter the biodistribution behavior of probes, different strategies have been pursued, including utilizing serum albumin as an inherent transport mechanism for small molecules. We describe here the modification of an existing fluorescent RGD mimetic probe targeted to integrin αvβ3 with three different albumin binding moieties (ABMs) a diphenylcyclohexyl (DPCH) group, a p-iodophenyl butyric acid (IPBA) and a fatty acid (FA) group with the purpose to identify an optimal ABM for molecular imaging applications. All three modifications resultdistribution and offers potential for future clinical applications.Botulism is typically described as a rapidly progressing, severe neuroparalytic disease. Foodborne botulism is transmitted through consuming food or drink that has been contaminated with botulinum toxin. During a botulism outbreak linked to illicitly brewed alcohol (also known as "hooch" or "pruno") in a prison, 11 (35%) of 31 inmates that consumed contaminated hooch had mild illnesses. This includes 2 inmates with laboratory confirmed botulism. The most frequently reported signs and symptoms among the 11 patients with mild illness included dry mouth (91%), hoarse voice (91%), difficulty swallowing (82%), fatigue (82%), and abdominal pain (82%). Foodborne botulism is likely underdiagnosed and underreported in patients with mild illness. Botulism should be considered on the differential diagnosis for patients with cranial nerve palsies.Typically, schools implement health promotion programs that focus on a single behavioral domain. Multiple related health topics may be addressed using separate interventions, potentially producing overlap in program content. However, integrative approaches in health promotion have the potential to produce interventions capable of improving multiple health behaviors. In particular, more research is needed to identify the conditions and the factors that can promote the transfer of learning to broaden the target outcomes of health promotion programs. The present study aims to identify the characteristics of an evidence-based life skills education program that can facilitate the transfer of learning to different health behaviors not initially targeted by the program, and the strategies for achieving successful transfer. A two round Delphi method was used with a diverse group of 21 experts in health promotion, life skills education, and methods of pedagogy for early adolescent students. Questionnaires with open and closed-ended questions were administered on-line. Content qualitative analysis was run, integrating codes, subcategories, and categories of the two rounds of the study. Results showed strong consensus among experts about the potential for promoting the transfer of skills from one health domain to another. Many elements were identified as important factors that facilitate the transfer of learning. Strategies for successful transfer were related to teaching methods, educational approaches, and consistency with the broader school curriculum. Findings suggest that the successful transfer of learning to a new health domain requires that educators recognize its importance and explicitly designate it as an educational aim.