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Alternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3 untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3 untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.

In order to explore the influence of different heating temperatures on the composition of aroma substances and the sensory attribute intensity of Xinjiang spicy chicken seasoning sauce, descriptive sensory evaluation and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) were used to analyze the volatile components of the seasoning sauces without heating and heated at 100 and 150 ℃, and their sensory attribute intensities were quantitatively compared. In addition, orthogonal partial least squares-discriminant analysis (OPLS-DA) and variable importance in projection (VIP) values were used to select and verify the key differential substances among the sauces with different heat treatments. The results showed that different heating temperatures significantly affected the sensory characteristics of Xinjiang spicy chicken seasoning sauce. By GC-MS, 6 volatile substances including hydrocarbons, aldehydes, esters, alcohols, ketones and others were detected, and 16 key differential flavor substances which were significantly affected by heating temperature were selected by OPLS-DA, including terpenes (eucalyptol, terpinolene and α-pinacol), aldehydes and alcohols. With the increase in heating temperature, the contents of terpenes (such as limonene and basil) increased first and then decreased, which were positively correlated with the fresh aroma and tongue-numbing taste of Xinjiang spicy chicken seasoning sauce. However, the contents of aldehydes such as hexanal and (E)-2-octenal significantly increased, resulting in unpleasant off-flavors such as fatty and metallic odors. The above results show that temperature is one of the key factors in the directional control of flavor quality in the industrial processing of Xinjiang spicy chicken seasoning sauce. The findings of the present study provide a basic theoretical basis for the directional optimization of flavor quality and process improvement in the production of Xinjiang spicy chicken seasoning sauce.

Viruses are among the main pathogens causing diarrhoea in calves. The current study found that bovine norovirus (BNoV) is one of the principal viruses causing diarrhoea in calves in Xinjiang, China.

Bovine coronavirus (BCoV) is a causative agent of enteric and respiratory disease in cattle. BCoV has been reported to cause a variety of animal diseases and is closely related to human coronaviruses; moreover, it has attracted extensive attention from both cattle farmers and researchers. With the rise of BCoV, a vaccine that is prophylactic and immunotherapeutic has to be utilized for a preemptive and adroit therapeutic approach. The aim of this study was to develop a novel multiepitope‐based BCoV vaccine that can induce an immune response using a silicon reverse vaccinology approach. In this study, an immunoinformatics approach was employed to identify potential vaccine targets against BCoV, and four candidate antigen proteins were selected to predict B‐cell and T‐cell epitopes. To identify dominant epitopes, we employed a variety of bioinformatics techniques, including antigenicity prediction, immunogenicity assessment, allergenicity analysis, conservative analysis, and toxicity assessment. Finally, six multiepitope vaccines were developed using dominant epitopes, suitable adjuvants, Pan HLADR—binding epitope (PADRE), and linkers. Then based on the antigenicity score, solubility analysis, allergenicity evaluation, physicochemical property assessment, and tertiary structure verification score, construct 6 was selected as the best candidate vaccine; it was named CY. Molecular modeling and structural validation ensured the high‐quality 3D structure of construct CY. The immunogenicity and complex stability of the vaccine were evaluated by molecular docking and kinetic simulation. In silicon clones, the BCoV vaccine had high levels of gene expression in the insect expression system. These results may contribute to the development of experimental BCoV vaccines with higher potency and safety. [ABSTRACT FROM AUTHOR]

Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines. [ABSTRACT FROM AUTHOR]

Alternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3′ untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3′ untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers. Alternative polyadenylation (APA) can play a key role in cancer initiation and progression. Here, the authors conducted a comprehensive pan-cancer APA TWAS analysis and discovered a distinct class of APA-mediated cancer susceptibility genes across 22 cancer types. [ABSTRACT FROM AUTHOR]

Background: Severe coronary artery calcification is associated with low success rate of interventional operation, perioperative adverse cardiac events, and poor prognosis, which is a major problem faced by operators. The existing therapy methods all have inherent limitations, such as unsatisfactory balloon crossability, inadequate balloon dilation, and so on. The emergence of intravascular lithotripsy (IVL) has brought the dawn of the treatment of calcified lesions by using unfocused acoustic pressure waves to fracture calcification in situ. And IVL is the only technology capable of targeting deep calcification. Hypothesis: IVL may have great clinical application values and potential prospects. Method: Based on the existing clinical evidence of IVL and traditional treatment ways, this review discusses the safety and efficacy of IVL. Combined with clinical practice, the precautions and coping strategies of IVL are analyzed. And the review improves the management algorithm of coronary calcification. Results: IVL has extremely high safety and effectiveness for severe coronary calcification compared with other ways, and structural improvements of IVL will further expand its value. Conclusions: The emergence of IVL could set off a revolution in the treatment of coronary artery calcification. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified thousands of disease-associated non-coding variants, posing urgent needs for functional interpretation. Molecular Quantitative Trait Loci (xQTLs) such as eQTLs serve as an essential intermediate link between these non-coding variants and disease phenotypes and have been widely used to discover disease-risk genes from many population-scale studies. However, mining and analyzing the xQTLs data presents several significant bioinformatics challenges, particularly when it comes to integration with GWAS data. Here, we developed xQTLbiolinks as the first comprehensive and scalable tool for bulk and single-cell xQTLs data retrieval, quality control and pre-processing from public repositories and our integrated resource. In addition, xQTLbiolinks provided a robust colocalization module through integration with GWAS summary statistics. The result generated by xQTLbiolinks can be flexibly visualized or stored in standard R objects that can easily be integrated with other R packages and custom pipelines. We applied xQTLbiolinks to cancer GWAS summary statistics as case studies and demonstrated its robust utility and reproducibility. xQTLbiolinks will profoundly accelerate the interpretation of disease-associated variants, thus promoting a better understanding of disease etiologies. xQTLbiolinks is available at https://github.com/lilab-bioinfo/xQTLbiolinks. [ABSTRACT FROM AUTHOR]

As an oxidant, deodorant and bleaching agent, the hypochlorous acid (HClO) and hypochlorite (ClO−) are widely used in corrosion inhibitors, textile dyes, pharmaceutical intermediates and in our daily lives. However, excess usage or aberrant accumulation of ClO− leads to tissue damage or some diseases and even cancer. Therefore, it is necessary to develop a fluorescent probe that specifically identifies ClO−. In this article, we synthesized a deep‐red xanthene‐based fluorescent probe (XA‐CN). The strong electron deficient group dicyano endows the probe XA‐CN deep‐red fluorescent emission with high solubility, selectivity and sensitivity for ClO− detection. Studies showed that the probe demonstrated turn‐off fluorescence (643 nm) at the presence of ClO− in dimethylsulfoxide/phosphate‐buffered saline 1:1 (pH 9) solution with a limit of detection of 1.64 μM. Detection mechanism investigation revealed that the electron deficient group ‐CN and the hydroxyl group was oxidized into aldehyde or carbonyl groups at the presence of ClO−, resulting ultraviolet‐visible absorption of the probe blue shifted and turned‐off fluorescence. Furthermore, XA‐CN was successfully used for the detection of ClO− in tap water samples. [ABSTRACT FROM AUTHOR]

Tail fat deposition of Altay sheep not only increased the cost of feeding but also reduced the economic value of meat. Currently, because artificial tail removal and gene modification methods cannot solve this problem, it is maybe to consider reducing tail fat deposition from the path of intestinal microbiota and metabolite. We measured body weight and tail fat weight, collected the serum for hormone detection by enzyme-linked immunosorbent assay, and collected colon contents to 16S rRNA sequence and liquid chromotography with mass spectrometry detection to obtain colon microbiota and metabolite information, from 12 3-month-old and 6-month-old Altay sheep. Subsequently, we analyzed the correlation between colon microbiota and tail fat weight, hormones, and metabolites, respectively. We identified that the tail fat deposition of Altay sheep increased significantly with the increase of age and body weight, and the main microbiota that changed were Verrucomicrobia, Cyanobacteria, Akkermansia , Bacteroides , Phocaeicola , Escherichia-Shigella , and Clostridium_sensu_stricto_1 . The results indicated that the diversities of metabolites in the colon contents of 3-months old and 6-months old were mainly reflected in phosphocholine (PC) and phosphatidylethanolamine (PE) in the lipid metabolism pathway. The correlations analyzed showed that Verrucomicrobia, Chlamydiae, Akkermansia , Ruminococcaceae_UCG-005 , Bacteroides , and Phocaeicola were negatively correlated with tail fat deposition. Verrucomicrobia, Akkermansia , and Bacteroides were negatively correlated with growth hormone (GH). Verrucomicrobia was positively correlated with L-a-lysophosphatidylserine and PE(18:1(9Z)/0:0). Our results showed that tail fat deposition of Altay sheep was probably correlated with the abundance of Verrucomicrobia, Akkermansia , Bacteroides of colon microbiota, PC, PE of metabolites, and GH of serum., Importance: Excessive tail fat deposition of Altay sheep caused great economic losses, and the current research results could not solve this problem well. Now, our research speculates that the tail fat deposition of Aletay sheep may be related to the abundance of Verrucomicrobia, Akkermansia, Bacteroides, metabolites phosphocholine, phosphatidylethanolamine, and growth hormone of serum. Further investigation of the interaction mechanism between these microbiota or metabolites and tail fat deposition is helpful in reducing tail fat deposition of Altay sheep and increasing the economic benefits of breeding farms., Competing Interests: The authors declare no conflict of interest.

As an oxidant, deodorant and bleaching agent, the hypochlorous acid (HClO) and hypochlorite (ClO - ) are widely used in corrosion inhibitors, textile dyes, pharmaceutical intermediates and in our daily lives. However, excess usage or aberrant accumulation of ClO - leads to tissue damage or some diseases and even cancer. Therefore, it is necessary to develop a fluorescent probe that specifically identifies ClO - . In this article, we synthesized a deep-red xanthene-based fluorescent probe (XA-CN). The strong electron deficient group dicyano endows the probe XA-CN deep-red fluorescent emission with high solubility, selectivity and sensitivity for ClO - detection. Studies showed that the probe demonstrated turn-off fluorescence (643 nm) at the presence of ClO - in dimethylsulfoxide/phosphate-buffered saline 1:1 (pH 9) solution with a limit of detection of 1.64 μM. Detection mechanism investigation revealed that the electron deficient group -CN and the hydroxyl group was oxidized into aldehyde or carbonyl groups at the presence of ClO - , resulting ultraviolet-visible absorption of the probe blue shifted and turned-off fluorescence. Furthermore, XA-CN was successfully used for the detection of ClO - in tap water samples., (© 2024 John Wiley & Sons Ltd.)