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Abstract Fungal diseases, such as powdery mildew and rusts, significantly affect the quality and yield of wheat. Pyramiding diverse types of resistance genes into cultivars represents the preferred strategy to combat these diseases. Moreover, achieving collaborative improvement between diseases resistance, abiotic stress, quality, and agronomic and yield traits is difficult in genetic breeding. In this study, the wheat cultivar, Guinong 29 (GN29), showed high resistance to powdery mildew and stripe rust at both seedling and adult plant stages, and was susceptible to leaf rust at the seedling stage but slow resistance at the adult-plant stage. Meanwhile, it has elite agronomic and yield traits, indicating promising coordination ability among multiple diseases resistance and other key breeding traits. To determine the genetic basis of these elite traits, GN29 was tested with 113 molecular markers for 98 genes associated with diseases resistance, stress tolerance, quality, and adaptability. The results indicated that two powdery mildew resistance (Pm) genes, Pm2 and Pm21, confirmed the outstanding resistance to powdery mildew through genetic analysis, marker detection, genomic in situ hybridization (GISH), non-denaturing fluorescence in situ hybridization (ND-FISH), and homology-based cloning; the stripe rust resistance (Yr) gene Yr26 and leaf rust resistance (Lr) genes Lr1 and Lr46 conferred the stripe rust and slow leaf rust resistance in GN29, respectively. Meanwhile, GN29 carries dwarfing genes Rht-B1b and Rht-D1a, vernalization genes vrn-A1, vrn-B1, vrn-D1, and vrn-B3, which were consistent with the phenotypic traits in dwarf characteristic and semi-winter property; carries genes Dreb1 and Ta-CRT for stress tolerance to drought, salinity, low temperature, and abscisic acid (ABA), suggesting that GN29 may also have elite stress-tolerance ability; and carries two low-molecular-weight glutenin subunit genes Glu-B3b and Glu-B3bef which contributed to high baking quality. This study not only elucidated the genetic basis of the elite traits in GN29 but also verified the capability for harmonious improvement in both multiple diseases resistance and other comprehensive traits, offering valuable information for breeding breakthrough-resistant cultivars.

IntroductionGluten quality is one of the most important traits of the common wheat (Triticum aestivum L.). In Chinese wheat production, Yannong series cultivars/derivative lines possess unique characteristics and play an important role in both yield and quality contribution.MethodsTo dissect their genetic basis of the gluten quality, in this study, allelic variations of high-molecular-weight glutenin subunit (HMW-GS) and low-molecular-weight glutenin subunit (LMW-GS) in 30 Yannong series wheat cultivars/derivative lines and three check cultivars were evaluated using the allele-specific molecular markers, and six crucial quality indexes were also further measured and analyzed.ResultsThe results demonstrated that the frequencies of HMW-GSs By8, Dx5+Dy10 and Dx5+Dy10+Dy12 in these 30 genotypes and three check cultivars accounted for 87.9%, 24.2% and 9.1%, respectively. For the allelic variations of LMW-GSs, Glu-A3a, Glu-A3b, Glu-A3c, Glu-A3f, and Glu-A3g were identified in 18, 9, 13, 11, and 2 genotypes, respectively; Glu-B3d, Glu-B3g and Glu-B3f were identified in 13, 23 and 4 genotypes, respectively. Notably, Yannong 999, containing By8 + Dx5 + Dy10, and Jinan 17 containing By8 + Dy12 both meet the national standard for high-quality wheat and belong to the category of first-class high-quality strong gluten wheat.DiscussionThese findings can provide reference for wheat quality improvement and popularization in the production.

IntroductionWheat awns are crucial determinants of wheat yield due to their capacity to photosynthesize and exchange gas. Understanding the genetic basis of awn length (AL) is essential for improving wheat yield in molecular breeding programs.MethodsIn this study, quantitative trait loci (QTLs) of AL were analyzed using recombinant inbred line (RIL) mapping population referred to as YY-RILs, which was derived from a cross between Yannong 15 (YN15) and Yannong 1212 (YN1212).Results and discussionSeven putative additive QTLs and 30 pairwise epistatic QTLs for AL were identified. Among them, five novel additive QTLs (except qAl-2A and qAl-5A.2) and 30 novel pairwise epistatic QTLs were identified. qAl-5A.1 was repeatedly identified in all five environment datasets, which was considered to be one novel stable QTL for AL with minor additive effects. eqAl-2B.2-2 significantly interacted with eight loci and could be of great importance in regulating awn development. The genes associated with the major stable QTL of qAl-5A.2 and the minor stable QTL of qAl-2A were B1 and WFZP-A, respectively. Awn lengths exhibited significant genetic correlations with kernel weight and kernels per spike, which could affect grain protein content to a lesser extent. This study enhances our understanding of the genetic basis of awn development and identifies novel genes as well as markers for future genetic improvement of wheat yield.

Abstract Background Viral infection elicits the type I interferon (IFN-I) response in host cells and subsequently inhibits viral infection through inducing hundreds of IFN-stimulated genes (ISGs) that counteract many steps in the virus life cycle. However, most of ISGs have unclear functions and mechanisms in viral infection. Thus, more work is required to elucidate the role and mechanisms of individual ISGs against different types of viruses. Results Herein, we demonstrate that poliovirus receptor-like protein4 (PVRL4) is an ISG strongly induced by IFN-I stimulation and various viral infections. Overexpression of PVRL4 protein broadly restricts growth of enveloped RNA and DNA viruses, including vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whereas deletion of PVRL4 in host cells increases viral infections. Mechanistically, it suppresses viral entry by blocking viral-cellular membrane fusion through inhibiting endosomal acidification. The vivo studies demonstrate that Pvrl4-deficient mice were more susceptible to the infection of VSV and IAV. Conclusion Overall, our studies not only identify PVRL4 as an intrinsic broad-spectrum antiviral ISG, but also provide a candidate host-directed target for antiviral therapy against various viruses including SARS-CoV-2 and its variants in the future.

Most of the existing virtual scenarios built for the digital protection of Chinese classical private gardens are too modern in expression style to show the aesthetic significance of their historical period. Considering the aesthetic commonality between traditional Chinese landscape paintings and classical private gardens and referring to image style transfer, here, a deep neural network was proposed to transfer the aesthetic style from landscape paintings to the virtual scenario of classical private gardens. The network consisted of two parts: style prediction and style transfer. The style prediction network was used to obtain style representation from style paintings, and the style transfer network was used to transfer style representation to the content scenario. The pre-trained network was then embedded into the scenario rendering pipeline and combined with the screen post-processing method to realise the stylised expression of the virtual scenario. To verify the feasibility of this methodology, a virtual scenario of the Humble Administrator’s Garden was used as the content scenario and five garden landscape paintings from different time periods and painting styles were selected for the case study. The results demonstrated that this methodology could effectively achieve the aesthetic style transfer of a virtual scenario.

Introduction Latin America is burdened by high levels of violence. Although boys and men often experience more violence and fatalities, girls and women face a greater risk of being killed by family members or intimate partners due to their gender, a phenomenon known as femicide. Our study estimates femicide rates in Latin America across age groups, examining city-level variations and temporal trends.Methods Utilising data from the Salud Urbana en America Latina project, we analysed mortality data from 343 cities in nine countries between 2000 and 2019. We calculate the variability between and within countries using data from 2015 to 2019. We then describe time trends using femicide counts by year and city and fitting a three-level negative binomial model with a random intercept for country, fixed effects for age categories, and city-level and country-level random slopes for time (scaled to decades). Finally, we assess longitudinal time trends by age by including an interaction term for age and time (scaled to decades).Results Our results highlight substantial heterogeneity in femicide rates within and between countries. Additionally, we find that women 15–29 and 30–44 years of age experience the highest femicide rates across all countries. While our findings suggest a slight decline in femicide rates per additional decade (RR 0.95, 95% CI: 0.74 to 1.24) between 2000 and 2019, the trends diverge in different countries, suggesting increasing rates in some countries like Mexico. Age-specific trends suggest the persistence of higher rates among women 15–29 and 30–44 years of age over time.Conclusion We underscore the need to consider gender dynamics in understanding and preventing femicides, focusing on city-level interventions to address the multifaceted causes of violence against girls and women in the region.

Abstract Introduction The HIV response has long recognized that certain “key populations” such as individuals in detention, adolescent girls and young women, sex workers, people who use drugs, LGBTQ individuals, migrants and others face higher barriers to access to, uptake of, and retention in HIV prevention and treatment services. One approach to addressing these barriers is the training of community paralegals to advocate for the rights of individuals and to address discrimination in health settings. Discussion Community paralegal programmes have been able to successfully address rights violations that impact access to health services and underlying determinants of health across a range of countries and populations, focusing upon issues such as discrimination and the denial of health services; unlawful detention of outreach workers, sex workers, persons who use drugs and men who have sex with men; and harmful traditional practices and gender‐based violence. In addition to resolving specific cases, evaluations of paralegal programmes have found that these programmes increased legal literacy among key populations at risk of HIV and increased understanding of human rights among healthcare providers, resulting in improved access to HIV services. Some evaluations have noted challenges related to the sustainability of paralegal programmes similar to those raised with community health worker programmes more broadly. Conclusions To achieve global HIV goals, funding for legal literacy and paralegal programmes should be increased and interventions should be rigorously evaluated. Efforts should target discrimination in access to HIV prevention and treatment and criminalization of key populations, two key barriers to ensuring access to HIV prevention and treatment services.

Abstract Background Recognition of viral invasion by innate antiviral immune system triggers activation of the type I interferon (IFN-I) and proinflammatory signaling pathways. Subsequently, IFN-I induction regulates expression of a group of genes known as IFN-I-stimulated genes (ISGs) to block viral infection. The tripartite motif containing 22 (TRIM22) is an ISG with strong antiviral functions. Results Here we have shown that the TRIM22 has been strongly upregulated both transcriptionally and translationally upon Zika virus (ZIKV) infection. ZIKV infection is associated with a wide range of clinical manifestations in human from mild to severe symptoms including abnormal fetal brain development. We found that the antiviral function of TRIM22 plays a crucial role in counterattacking ZIKV infection. Overexpression of TRIM22 protein inhibited ZIKV growth whereas deletion of TRIM22 in host cells increased ZIKV infectivity. Mechanistically, TRIM22, as a functional E3 ubiquitin ligase, promoted the ubiquitination and degradation of ZIKV nonstructural protein 1 (NS1) and nonstructural protein 3 (NS3). Further studies showed that the SPRY domain and Ring domain of TRIM22 played important roles in protein interaction and degradation, respectively. In addition, we found that TRIM22 also inhibited other flaviviruses infection including dengue virus (DENV) and yellow fever virus (YFV). Conclusion Thus, TRIM22 is an ISG with important role in host defense against flaviviruses through binding and degradation of the NS1 and NS3 proteins.

In China, although drug use is an administrative and not criminal offense, individuals detained by public security authorities are subject to coercive or compulsory “treatment,” which can include community-based detoxification and rehabilitation and two years of compulsory isolation. Individuals are also entered into a system called the Drug User Internet Dynamic Control and Early Warning System, or simply the Dynamic Control System. The Dynamic Control System, run by the Ministry of Public Security, acts as an extension of China’s drug control efforts by monitoring the movement of people in the system and alerting police when individuals, for example, use their identity documents when registering at a hotel, conducting business at a government office or bank, registering a mobile phone, applying for tertiary education, or traveling. This alert typically results in an interrogation and a drug test by police. This paper seeks to summarize, using published government reports, news articles, and academic papers, what is known about the Dynamic Control System, focusing on the procedures of (1) registration; (2) management; and (3) exit. At each step, people subject to the Dynamic Control System face human rights concerns, especially related to the right to privacy, rights to education and work, and right to health.

Summary: Upon sensing DNA double-strand breaks (DSBs), eukaryotic cells either die or repair DSBs via one of the two competing pathways, i.e., non-homologous end-joining (NHEJ) or homologous recombination (HR). We show that cell fate after DSBs hinges on GIV/Girdin, a guanine nucleotide-exchange modulator of heterotrimeric Giα•βγ protein. GIV suppresses HR by binding and sequestering BRCA1, a key coordinator of multiple steps within the HR pathway, away from DSBs; it does so using a C-terminal motif that binds BRCA1’s BRCT-modules via both phospho-dependent and -independent mechanisms. Using another non-overlapping C-terminal motif GIV binds and activates Gi and enhances the “free” Gβγ→PI-3-kinase→Akt pathway, which promotes survival and is known to suppress HR, favor NHEJ. Absence of GIV, or loss of either of its C-terminal motifs enhanced cell death upon genotoxic stress. Because GIV selectively binds other BRCT-containing proteins suggests that G-proteins may fine-tune sensing, repair, and survival after diverse types of DNA damage.

Fungal diseases, drought, pre-harvest sprouting (PHS) and other biotic and abiotic stresses have seriously affected the quality and yield in wheat production. Identifying related genes/loci in released cultivars/lines can provide reference information and theoretical basis for wheat improvement. Yannong series wheat cultivars/lines have distinctive characteristics in wheat cultivars and play an important role in genetic improvement and production of Chinese wheat production system. To dissect their genetic basis of the stress-resistant traits, in this study, 23 representative Yannong series wheat cultivars/lines were tested by 58 molecular markers for 40 genes related to adaptability, disease resistance and stress tolerance to clarify the genetic composition of the key loci. The results showed that most of the tested wheat accessions carried dwarfing genes RhtB1b/RhtD1b/Rht8 and recessive vernalization genes vrn-A1/vrn-B1/vrn-D1/vrn-B3. It was also consistent with the phenotypic traits of tested Yannong series wheat which were dwarf and winter or semi winter wheat. In addition, the overall level of seedling powdery mildew resistance in 23 Yannong wheat cultivars/lines was moderate or inadequate. Eleven accessions carried none of the tested Pm genes and twelve accessions carried Pm2, Pm6, Pm42 and Pm52 singly or in combination. Then, 23 wheat cultivars/lines were also tested by 17 diagnostic markers for 14 Yr genes. The results showed that 16 wheat cultivars/lines were likely to carry one or more of tested Yr genes, whereas Yannong 15, Yannong 17, Yannong 23, Yannong 24, Yannong 377, Yannong 572 and Yannong 999 carried none of the tested Yr genes. Moreover, in our study, nine markers for four genes related to drought tolerance and PHS were used to evaluate the stress tolerance of the 23 wheat cultivars/lines. The results indicated that all 23 wheat cultivars/lines carried drought resistance genes Ta-Dreb1/TaCRT-D, indicating that they had the drought resistance to the extent. Except for Yannong 30, Yannong 377, Yannong 390, Yannong 745 and Yannong 1766, other wheat cultivars/lines carried one to three elite PHS-resistant alleles Vp-1Bc/Vp-1Bf/TaAFP-1Bb.

Powdery mildew of wheat (Triticum aestivum), caused by Blumeria graminis f.sp. tritici (Bgt), is a destructive disease that seriously threatens the yield and quality of its host. Identifying resistance genes is the most attractive and effective strategy for developing disease-resistant cultivars and controlling this disease. In this study, a wheat breeding line Yannong 99102-06188 (YN99102), an elite derivative line from the same breeding process as the famous wheat cultivar Yannong 999, showed high resistance to powdery mildew at the whole growth stages. Genetic analysis was carried out using Bgt isolate E09 and a population of YN99102 crossed with a susceptible parent Jinhe 13–205 (JH13–205). The result indicated that a single recessive gene, tentatively designated pmYN99102, conferred seedling resistance to the Bgt isolate E09. Using bulked segregant exome capture sequencing (BSE-Seq), pmYN99102 was physically located to a ~33.7 Mb (691.0–724.7 Mb) interval on the chromosome arm 2BL, and this interval was further locked in a 1.5 cM genetic interval using molecular markers, which was aligned to a 9.0 Mb physical interval (699.2–708.2 Mb). Based on the analysis of physical location, origin, resistant spectrum, and inherited pattern, pmYN99102 differed from those of the reported powdery mildew (Pm) resistance genes on 2BL, suggesting pmYN99102 is most likely a new Pm gene/allele in the targeted interval. To transfer pmYN99102 to different genetic backgrounds using marker-assisted selection (MAS), 18 closely linked markers were tested for their availability in different genetic backgrounds for MAS, and all markers expect for YTU103-97 can be used in MAS for tracking pmYN99102 when it transferred into those susceptible cultivars.

Abstract Background Zika virus (ZIKV) infection and ZIKV epidemic have been continuously spreading silently throughout the world and its associated microcephaly and other serious congenital neurological complications poses a significant global threat to public health. Type I interferon response to ZIKV infection in host cells suppresses viral replication by inducing the expression of interferon-stimulated genes (ISGs). Methods The study aims to demonstrate the anti-ZIKV mechanism of PARP11. PARP11 knock out and overexpressing A549 cell lines were constructed to evaluate the anti-ZIKV function of PARP11. PARP11 −/− , PARP12 −/− and PARP11 −/− PARP12 −/− HEK293T cell lines were constructed to explain the synergistic effect of PARP11 and PARP12 on NS1 and NS3 protein degradation. Western blotting, immunofluorescence and immunoprecipitation assay were performed to illustrate the interaction between PARP11 and PARP12. Results Both mRNA and protein levels of PARP11 were induced in WT but not IFNAR1 −/− cells in response to IFNα or IFNβ stimulation and ZIKV infection. ZIKV replication was suppressed in cells expressed PARP11 but was enhanced in PARP11 −/− cells. PARP11 suppressed ZIKV independently on itself PARP enzyme activity. PARP11 interacted with PARP12 and promoted PARP12-mediated ZIKV NS1 and NS3 protein degradation. Conclusion We identified ADP-ribosyltransferase PARP11 as an anti-ZIKV ISG and found that it cooperated with PARP12 to enhance ZIKV NS1 and NS3 protein degradation. Our findings have broadened the understanding of the anti-viral function of ADP-ribosyltransferase family members, and provided potential therapeutic targets against viral ZIKV infection.

Objective: Hepatocyte nuclear factor 4α (HNF4A) has been demonstrated to be an oncogene in gastric cancer (GC). However, the roles of different HNF4A isoforms derived from the 2 different promoters (P1 and P2) and the underlying mechanisms remain obscure. Methods: The expression and prognostic values of P1- and P2-HNF4A were evaluated in The Cancer Genome Atlas (TCGA) databases and GC tissues. Then, functional assays of P1- and P2-HNF4A were conducted both in vivo and in vitro. High-throughput RNA-seq was employed to profile downstream pathways in P1- and P2-HNF4A-overexpressing GC cells. The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays. Results: HNF4A amplification was a key characteristic of GC in TCGA databases, especially for the intestinal type and early stage. Moreover, P1-HNF4A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues (P < 0.05), but no significant differences were found in P2-HNF4A expression (P > 0.05). High P1-HNF4A expression indicated poor prognoses in GC patients (P < 0.01). Furthermore, P1-HNF4A overexpression significantly promoted SGC7901 and BGC823 cell proliferation, invasion and migration in vitro (P < 0.01). Murine xenograft experiments showed that P1-HNF4A overexpression promoted tumor growth (P < 0.05). Mechanistically, RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4A-overexpressing GC cells. Finally, chemokine (C-C motif) ligand 15 was identified as a direct target of P1-HNF4A in GC tissues. Conclusions: P1-HNF4A was the main oncogene during GC progression. The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.

Background Non‐small cell lung cancer (NSCLC) accounts for 85% of lung cancer which is the most frequently diagnosed malignancy in China. Colon cancer associated transcript 1 (CCAT1) acts as an oncogene in enhancing tumor progression. However, the effects of CCAT1 in NSCLC remain unclear. The purpose of this study was to explore the role of CCAT1 in NSCLC. Methods Wound healing and transwell assays were performed to measure cell migration. RT‐qPCR was employed to calculate the mRNA level of CCAT1 and miR‐490. Results High expression of CCAT1 was observed in NSCLC tissues and cells, with low expression of miR‐490. CCAT1 promoted the proliferation and metastasis of H1299 and A549 cells, while miR‐490 had the opposite effect. CCAT1 could specifically bind to miR‐490 and regulate its expression. MiR‐490 partially reversed the inhibitory effect of CCAT1 on cell proliferation and metastasis. Conclusions The CCAT1/miR‐490 molecular axis has been shown to be important for the treatment of NSCLC.

Powdery mildew of wheat, caused by Blumeria graminis f. sp. tritici (Bgt), is a devastating disease that seriously reduces yield and quality worldwide. Utilization of plant resistance genes is an attractive and effective strategy for controlling this disease. Among the reported powdery mildew (Pm) resistance genes, Pm2 exhibits a diverse resistance spectrum among its multiple alleles. It has been widely used in China for resistance breeding for powdery mildew. To mine more Pm2 alleles and clarify their distribution, we screened 33 wheat cultivars/breeding lines carrying Pm2 alleles from 641 wheat genotypes using diagnostic and Pm2-linked markers. To further investigate the relationships within the Pm2 alleles, we compared their resistance spectra, polymorphism of marker alleles and gene sequences, and found that they have identical marker alleles and gene sequences but diverse resistance spectra. In addition, the diagnostic kompetitive allele-specific PCR (KASP) marker, YTU-KASP-Pm2, was developed and was shown to detect all the Pm2 alleles in the different genetic backgrounds. These findings provide valuable information for the distribution and rational use of Pm2 alleles, push forward their marker-assisted breeding (MAS), and hence improve the control of wheat powdery mildew.

Digital health technologies have been heralded as a critical solution to challenges and gaps in the delivery of quality health care and essential to achieving the Sustainable Development Goals. Yet they also present threats to privacy and confidentiality, which can lead to discrimination and violence, resulting in violations of the rights to health, housing, employment, freedom of assembly, expression, protection from arbitrary detention, bodily autonomy, and security. More broadly, without proper planning and safeguards, digital health technologies can contribute to expanding health inequity, widening the “digital divide” that separates those who can and cannot access such interventions. This article outlines key harms related to digital technologies for health, as well as ethical and human rights standards relevant to their use. It also presents several strategies for mitigating risks from digital health technologies and reviews mechanisms of accountability, including recent judicial rulings.

Abstract Background Intestinal metaplasia (IM) is a premalignant lesion associated with gastric cancer. Both animal and clinical studies have revealed that bile acid reflux and subsequent chronic inflammation are key causal factors of IM. Previous studies indicated that SOX2, the key transcription factor in gastric differentiation, was downregulated during IM development while CDX2, the pivotal intestine-specific transcription factor was upregulated significantly. However, it remains unclear whether the downregulation of SOX2 promotes gastric IM emergence or is merely a concomitant phenomenon. In addition, the underlying mechanisms of SOX2 downregulation during IM development are unclear. Methods Gastric cell lines were treated with deoxycholic acid (DCA) in a dose-dependent manner. The expression of CDX2 and miR-21 in gastric tissue microarray were detected by immunohistochemistry and in situ hybridization. Coimmunoprecipitation and immunofluorescence were performed to ascertain the interaction of SOX2 and CDX2. Luciferase reporter assays were used to detect the transcriptional activity of CDX2, and confirm miR-21 binding to SOX2 3′-UTR. The protein level of SOX2, CDX2 and downstream IM-specific genes were investigated using western blotting. mRNA level of miR-21, SOX2, CDX2 and downstream IM-specific genes were detected by qRT-PCR. Results Bile acid treatment could suppress SOX2 expression and simultaneously induce expression of CDX2 in gastric cell lines. Furthermore, we demonstrated that SOX2 overexpression could significantly inhibit bile acid- and exogenous CDX2-induced IM-specific gene expression, including KLF4, cadherin 17 and HNF4α expression. In contrast, SOX2 knockdown had the opposite effect. A dual-luciferase reporter assay demonstrated that SOX2 overexpression could significantly suppress CDX2 transcriptional activity in HEK293T cells. CDX2 and SOX2 could form protein complexes in the nucleus. In addition, bile acid induced the expression of miR-21. The inhibition of SOX2 in bile acid-treated gastric cell lines was rescued by miR-21 knockdown. Conclusions These findings suggested that SOX2 can interfere with the transcriptional activity of CDX2 in bile acid-induced IM and that miR-21 might play a key role in this process, which shed new lights in the prevention of gastric cancer.

Summary: Influenza A virus (IAV) infection stimulates a type I interferon (IFN-I) response in host cells that exerts antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). However, most ISGs are poorly studied for their roles in the infection of IAV. Herein, we demonstrate that SERTA domain containing 3 (SERTAD3) has a significant inhibitory effect on IAV replication in vitro. More importantly, Sertad3−/− mice develop more severe symptoms upon IAV infection. Mechanistically, we find SERTAD3 reduces IAV replication through interacting with viral polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), and polymerase acidic protein (PA) to disrupt the formation of the RNA-dependent RNA polymerase (RdRp) complex. We further identify an 8-amino-acid peptide of SERTAD3 as a minimum interacting motif that can disrupt RdRp complex formation and inhibit IAV replication. Thus, our studies not only identify SERTAD3 as an antiviral ISG, but also provide the mechanism of potential application of SERTAD3-derived peptide in suppressing influenza replication.

Solitary fibrous tumor of the pleura (SFTP) is a rare disease, and most published case reports are in patients over 40 years old. We report a case of SFTP in a 22-year-old woman. The imaging features were observed using contrast-enhanced computed tomography (CT), and histomorphological features were evaluated using pathology and immunohistochemistry. The CT showed a mass in the pleura inside the ninth rib on the left. Pathological results of percutaneous puncture in the chest suggested the possibility of solitary fibroma. The patient underwent surgical resection, and the tumor measured 2.5 × 1.5 × 1.5 cm with an intact capsule. Pathological examination revealed a spindle cell tumor, and immunohistochemistry showed strong positive staining for CD34 and STAT6, consistent with typical solitary fibroma. Although SFTP is rare in young patients, early diagnosis and intervention are needed to avoid the possibility of future complications.

Summary: Molecular imaging of metastatic “potential” is an unvanquished challenge. To engineer biosensors that can detect and measure the metastatic “potential” of single living cancer cells, we carried out a comprehensive analysis of the pan-cancer phosphoproteome to search for actin remodelers required for cell migration, which are enriched in cancers but excluded in normal cells. Only one phosphoprotein emerged, tyr-phosphorylated CCDC88A (GIV/Girdin), a bona fide metastasis-related protein across a variety of solid tumors. We designed multi-modular biosensors that are partly derived from GIV, and because GIV integrates prometastatic signaling by multiple oncogenic receptors, we named them “‘integrators of metastatic potential (IMP).” IMPs captured the heterogeneity of metastatic potential within primary lung and breast tumors at steady state, detected those few cells that have acquired the highest metastatic potential, and tracked their enrichment during metastasis. These findings provide proof of concept that IMPs can measure the diversity and plasticity of metastatic potential of tumor cells in a sensitive and unbiased way. : Optical Imaging; Protein Physics; Cancer Subject Areas: Optical Imaging, Protein Physics, Cancer

In this study, the physicochemical properties, pharmacokinetics properties, and drug-likeness of pigments from Monascus-fermented rice (Monascus pigments, MPs) were predicted in silico using SwissADME tool. In silico prediction of physicochemical properties showed that MPs had desirable lipophilic drug-like physicochemical properties including molecular weight (236 to 543), TPSA (44.76 to 179.77), lipophilicity (−0.81 to 4.14), and water solubility (−4.94 to −0.77). The pharmacokinetic properties of MPs (i.e., GIA, P-glycoprotein substrate, and CYP3A4 inhibitor) illustrated that most MPs had high intestinal absorption and bioavailability, but some MPs might cause pharmacokinetics-related drug–drug interactions. Following this, six main well-known MPs (monascin, ankaflavin, rubropunctatin, monascorubrin, rubropunctamine, monascorubramine) were selected for molecular docking with some enzyme receptors. The docking results were shown with the best molecular docking poses, and the interacting residues, number and distance of hydrogen bonds of the MPs and monacolin K (for docking with 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA reductase)), or MPs and oleic acid (for docking with lipase). Dissociation constants showed that MPs had lower inhibitory potential for HMGR (compared with Monacolin K), and higher inhibitory potential for lipase. Individual pigments from Monascus-fermented rice, therefore, have the potential to be developed as drug candidates for controlling hyperlipidemia.

For arts departments in many institutions, technology education entails prohibitive equipment costs, maintenance requirements and administrative demands. There are also inherent pedagogical challenges: for example, recording studio classes where, due to space and time constraints, only a few students in what might be a large class can properly observe and try out the procedures. These and other practical and pedagogical considerations when teaching using hardware may suggest that conventional studios may not provide the best learning environment. In this paper I suggest that desktop simulation may not only help to solve the aforementioned problems, but can contribute to the creation of a cooperative learning environment.

Abstract Background Studies indicate that brain clearance via the glymphatic system is impaired in idiopathic normal pressure hydrocephalus (INPH). This has been suggested to result from reduced cerebrospinal fluid (CSF) turnover, which could be caused by a reduced CSF formation rate. The aim of this study was to determine the formation rate of CSF in a cohort of patients investigated for INPH and compare this to a historical control cohort. Methods CSF formation rate was estimated in 135 (75 ± 6 years old, 64/71 men/women) patients undergoing investigation for INPH. A semiautomatic CSF infusion investigation (via lumbar puncture) was performed. CSF formation rate was assessed by downregulating and steadily maintaining CSF pressure at a zero level. During the last 10 min, the required outflow to maintain zero pressure, i.e., CSF formation rate, was continuously measured. The values were compared to those of a historical reference cohort from a study by Ekstedt in 1978. Results Mean CSF formation rate was 0.45 ± 0.15 ml/min (N = 135), equivalent to 27 ± 9 ml/hour. There was no difference in the mean (p = 0.362) or variance (p = 0.498) of CSF formation rate between the subjects that were diagnosed as INPH (N = 86) and those who were not (N = 43). The CSF formation rate in INPH was statistically higher than in the reference cohort (0.46 ± 0.15 vs. 0.40 ± 0.08 ml/min, p = 0.005), but the small difference was probably not physiologically relevant. There was no correlation between CSF formation rate and baseline CSF pressure (r = 0.136, p = 0.115, N = 135) or age (-0.02, p = 0.803, N = 135). Conclusions The average CSF formation rate in INPH was not decreased compared to the healthy reference cohort, which does not support reduced CSF turnover. This emphasizes the need to further investigate the source and routes of the flow in the glymphatic system and the cause of the suggested impaired glymphatic clearance in INPH.