Lysine malonylation of DgnsLIPID TRANSFER PROTEIN1 at the K81 site improves cold resistance in chrysanthemum.

Lysine malonylation (Kmal) is a recently discovered posttranslational modification, and its role in the response to abiotic stress has not been reported in plants. In this study, we isolated a nonspecific lipid transfer protein, DgnsLTP1, from chrysanthemum (Dendranthema grandiflorum var. Jinba). Overexpression and CRISPR-Cas9-mediated gene editing of DgnsLTP1 demonstrated that the protein endows chrysanthemum with cold tolerance. Yeast 2-hybrid, bimolecular fluorescence complementation, luciferase complementation imaging, and coimmunoprecipitation experimental results showed that DgnsLTP1 interacts with a plasma membrane intrinsic protein (PIP) DgPIP. Overexpressing DgPIP boosted the expression of DgGPX (glutathione peroxidase), increased the activity of GPX, and decreased the accumulation of reactive oxygen species (ROS), thereby enhancing the low-temperature stress tolerance of chrysanthemum, while the CRISPR-Cas9-mediated mutant dgpip inhibited this process. Transgenic analyses in chrysanthemum showed that DgnsLTP1 improves the cold resistance of chrysanthemum in a DgPIP-dependent manner. Moreover, Kmal of DgnsLTP1 at the K81 site prevented the degradation of DgPIP in Nicotiana benthamiana and chrysanthemum, further promoted DgGPX expression, enhanced GPX activity, and scavenged excess ROS produced by cold stress, thereby further enhancing the cold resistance of chrysanthemum.

Beliefs about social mobility in young American children.

Although actual experiences of upward social mobility are historically low, many adolescents and adults express a belief in social mobility (e.g., that social status can change). Although a belief in upward mobility (e.g., that status can improve) can be helpful for economically disadvantaged adolescents and adults, a belief in upward social mobility in adults is also associated with greater acceptance of societal inequality. While this belief might have similar benefits or consequences in children, no previous work has examined whether children are even capable of reasoning about social mobility. This is surprising, given that elementary-aged children exhibit sophisticated reasoning about both social status, as well as about the fixedness or malleability of properties and group membership. Across an economically advantaged group of 5- to 12-year-old American children (N = 151, Mage = 8.91, 63% racial majority, 25% racially marginalized; Mhousehold income = $133,064), we found evidence that children can reason about social mobility for their own families and for others. Similar to research in adults, children believe that others are more likely to experience upward than downward mobility. However, in contrast to adult's typical beliefs-but in line with economic realities-between 7- and 9-years-old, children become less likely to expect upward mobility for economically disadvantaged, versus advantaged, families. In sum, children are capable of reasoning about social mobility in nuanced ways; future work should explore the implications of these beliefs. RESEARCH HIGHLIGHTS: Despite harsh economic realities, a belief in upward social mobility and the American Dream is alive and well. Between 7 and 9 years of age, economically advantaged, American children begin to expect economically disadvantaged families to experience less upward mobility than economically advantaged families. Children's beliefs about social mobility better accord with reality than adults' do.

Remembering the good and bad and the self and others in a culturally modulated self-memory system.

Wang and Conway (2006, Autobiographical memory, self, and culture. In L.-G. Nilsson, & N. Ohta (Eds.), Memory and society: Psychological perspectives (pp. 9-27). Psychology Press) posit that remembering takes place in a culturally modulated self-memory system in which working self-goals are shaped by society and, in turn, influence the encoding and construction of memories in a culturally canonical fashion. The current research examined the self-goal of competence, which manifests through self-enhancement versus self-improvement motivations, in influencing remembering in different cultural contexts. We conducted two cross-cultural studies to examine memories for personal successes and failures (Study 1) and autobiographical and vicarious experiences (Study 2) in connection with individuals' positive self-views. European Americans recalled a greater number of success than failure memories (Study 1) and US participants recalled a greater number of autobiographical than vicarious memories (Study 2), which was further associated with positive self-views at the individual level. In contrast, Asian (Study 1) and Chinese participants (Study 2) recalled even-handedly the different types of memories, and the memory retrieval was unrelated to individuals' self-views. We discuss the findings in light of the different manifestations of the competence goal in shaping memory in the culturally modulated self-memory system.

Quantum Sensing for Real-Time Monitoring of Drug Efficacy in Synovial Fluid from Arthritis Patients.

Diamond-based T1 relaxometry is a new technique that allows nanoscale magnetic resonance measurements. Here we present its first application in patient samples. More specifically, we demonstrate that relaxometry can determine the free radical load in samples from arthritis patients. We found that we can clearly differentiate between osteoarthritis and rheumatoid arthritis patients in both the synovial fluid itself and cells derived from it. Furthermore, we tested how synovial fluid and its cells respond to piroxicam, a common nonsteroidal anti-inflammatory drug (NSAID). It is known that this drug leads to a reduction in reactive oxygen species production in fibroblast-like synoviocytes (FLS). Here, we investigated the formation of free radicals specifically. While FLS from osteoarthritis patients showed a drastic decrease in the free radical load, cells from rheumatoid arthritis retained a similar radical load after treatment. This offers a possible explanation for why piroxicam is more beneficial for patients with osteoarthritis than those with rheumatoid arthritis.

A natural antisense RNA improves chrysanthemum cold tolerance by regulating the transcription factor DgTCP1.

Long noncoding RNAs (lncRNAs) are widely involved in the regulation of plant growth and development, but their mechanism of action in response to cold stress in plants remains unclear. Here, we found an lncRNA transcribed from the antisense strand of DgTCP1 (class I Teosinte branched1/Cycloidea/Proliferating [TCP] transcription factor) of chrysanthemum (Chrysanthemum morifolium Ramat.), named DglncTCP1. During the response of chrysanthemum to cold stress, overexpression of DgTCP1 improved the cold tolerance of chrysanthemum, while the DgTCP1 editing line (dgtcp1) showed decreased tolerance to cold stress. Overexpression of DglncTCP1 also increased the cold tolerance of chrysanthemum, while the DglncTCP1 amiRNA lines (DglncTCP1 amiR-18/38) also showed decreased tolerance to cold stress. Additionally, the overexpression of DglncTCP1 upregulated the expression of DgTCP1. This indicated that DglncTCP1 may play a cis-regulatory role in the regulatory process of DgTCP1 in cold tolerance. DglncTCP1 acts as a scaffold to recruit the histone modification protein DgATX (ARABIDOPSIS TRITHORAX from chrysanthemum) to DgTCP1 to enhance H3K4me3 levels, thereby activating DgTCP1 expression. Moreover, DgTCP1 can directly target DgPOD (peroxidase gene from chrysanthemum) to promote its expression and reduce reactive oxygen species accumulation, thereby improving the cold tolerance of chrysanthemum. In conclusion, these results suggest that natural antisense lncRNA plays a key role in improving the cold tolerance of chrysanthemum.

Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma.

Recent studies have demonstrated the close relationship between parathyroid adenoma (PA) and thyroid follicular adenoma (FTA). However, the underlying pathogenesis remains unknown. This study focused on exploring common pathogenic genes, as well as the pathogenesis of these two diseases, through bioinformatics methods. This work obtained PA and FTA datasets from the Integrated Gene Expression Database to identify the common differentially expressed genes (DEGs) of two diseases. The functions of the genes were investigated by GO and KEGG enrichment. The program CytoHubba was used to select the hub genes, while receiver operating characteristic curves were plotted to evaluate the predictive significance of the hub genes. The DGIbd database was used to identify gene-targeted drugs. This work detected a total of 77 DEGs. Enrichment analysis demonstrated that DEGs had activities of 3',5'-cyclic AMP, and nucleotide phosphodiesterases and were associated with cell proliferation. NOS1, VWF, TGFBR2, CAV1, and MAPK1 were identified as hub genes after verification. The area under the curve of PA and FTA was>0.7, and the hub genes participated in the Relaxin Signaling Pathway, focal adhesion, and other pathways. The construction of the mRNA-miRNA interaction network yielded 11 important miRNAs, while gene-targeting drug prediction identified four targeted drugs with possible effects. This bioinformatics study demonstrated that cell proliferation and tumor suppression and the hub genes co-occurring in PA and FTA, have important effects on the occurrence and progression of two diseases, which make them potential diagnostic biomarkers and therapeutic targets.

Do American children automatically encode cues to wealth?

As adults, we readily notice markers of social status and wealth and draw conclusions about individuals based on these cues. Do children do the same? Using a "Who Said What?" task across 5- to 9-year-old American children (n = 159; Mage = 7.44 years; 51.6% female, 47.2% male, 1.2% nonconforming or not provided; 59.1% White, 23.3% racial-ethnic minority, 17.6% not provided) and adults (n = 182; 84.1% female, 13.7% male, 2.2% nonconforming or not provided; 54.9% White, 44.5% racial-ethnic minority, 0.6% not provided), we found that both children and adults automatically encode (i.e., spontaneously notice and remember) occupational cues (i.e., work attire) and quantitative cues (i.e., amount of money) to wealth but that only adults automatically encode qualitative cues to wealth (i.e., car quality), suggesting developmental changes in which types of cues to wealth are most salient. Furthermore, automatic encoding in children was sensitive to contextual factors; children from communities with less affluence and higher rates of unemployment were more likely to encode some wealth cues than their peers from more affluent and employed communities. Finally, from 5 to 7 years of age, children began to draw connections between wealth cues, using occupational cues to make inferences about the quantity and quality of others' possessions. This research highlights the changing salience of wealth cues across development and suggests that even young children are likely to notice economic inequality and thus to be ready for conversations about inequality, as well as the origins of inequality, at an earlier age than previously supposed.

Early onset preeclampsia in a model for human placental trophoblast.

We describe a model for early onset preeclampsia (EOPE) that uses induced pluripotent stem cells (iPSCs) generated from umbilical cords of EOPE and control (CTL) pregnancies. These iPSCs were then converted to placental trophoblast (TB) representative of early pregnancy. Marker gene analysis indicated that both sets of cells differentiated at comparable rates. The cells were tested for parameters disturbed in EOPE, including invasive potential. Under 5% O2, CTL TB and EOPE TB lines did not differ, but, under hyperoxia (20% O2), invasiveness of EOPE TB was reduced. RNA sequencing analysis disclosed no consistent differences in expression of individual genes between EOPE TB and CTL TB under 20% O2, but, a weighted correlation network analysis revealed two gene modules (CTL4 and CTL9) that, in CTL TB, were significantly linked to extent of TB invasion. CTL9, which was positively correlated with 20% O2 (P = 0.02) and negatively correlated with invasion (P = 0.03), was enriched for gene ontology terms relating to cell adhesion and migration, angiogenesis, preeclampsia, and stress. Two EOPE TB modules, EOPE1 and EOPE2, also correlated positively and negatively, respectively, with 20% O2 conditions, but only weakly with invasion; they largely contained the same sets of genes present in modules CTL4 and CTL9. Our experiments suggest that, in EOPE, the initial step precipitating disease is a reduced capacity of placental TB to invade caused by a dysregulation of O2 response mechanisms and that EOPE is a syndrome, in which unbalanced expression of various combinations of genes affecting TB invasion provoke disease onset.

Short-term exposure to nitrogen dioxide and ischemic stroke incidence in Shenzhen, China: Modification effects by season and temperature.

BACKGROUND AND OBJECTIVES: China has experienced a serious public health burden because of the increased incidence of ischemic stroke. Evidence describing the association between short-term exposure to nitrogen dioxide (NO2) and ischemic stroke morbidity is limited, and few studies have focused on the effects of season and temperature. This study aimed to evaluate the acute effects of NO2 on ischemic stroke incidence in Shenzhen, a southeastern city of China, considering the modified effects of season and temperature. METHODS: A time-stratified case-crossover study was conducted between 2003 and 2014 among 98,482 ischemic stroke hospitalizations. Conditional quasi-Poisson regression was used to estimate the percentage changes in ischemic stroke admissions in relation to each 10 µg/m3 increment in NO2. RESULTS: NO2 was positively associated with ischemic stroke onset over the full year, as well as in the cold season (November through April) and on cold days (ambient temperature≤median temperature), with significant single-day effects within 3 days after the exposure, and significant cumulative effects within the delayed five days. The maximum percentage changes were obtained at lag0-5, with 1.81% (95% confidence interval (CI) was 0.86-2.76%) over the full year, 2.75% (1.48-4.03%) in the cold season, and 3.04% (1.74-4.35%) on cold days. Additionally, the effects of exposure were found to be greater in males and people with higher education, and were lasting longer in subgroups of older individuals. CONCLUSIONS: Our findings provide evidence that reductions in NO2 levels might decrease ischemic stroke morbidity, and enhance the understanding of ischemic stroke occurrence associated with NO2 modified by season and temperature.

Lysine decrotonylation of glutathione peroxidase at lysine 220 site increases glutathione peroxidase activity to resist cold stress in chrysanthemum.

Lysine crotonylation is a protein post-translational modification that has been newly discovered in recent years. There are few studies on the lysine crotonylation of proteins in plants, and their functions in response to cold stress are still unclear. In this study, the chrysanthemum (Chrysanthemum morifolium Ramat.) glutathione peroxidase (GPX) gene was selected and named DgGPX1, and was found to be responsive to low temperature. Overexpression of DgGPX1 improved the cold resistance of transgenic chrysanthemum by increasing GPX activity to reduce the accumulation of reactive oxygen species (ROS) under low-temperature conditions. Furthermore, the level of DgGPX1 lysine crotonylation at lysine (K) 220 decreased under low temperature in chrysanthemum. Lysine decrotonylation of DgGPX1 at K220 further increased GPX activity to reduce ROS accumulation under cold stress, and thereby enhanced the cold resistance of chrysanthemum. The above results show that lysine decrotonylation of DgGPX1 at K220 increases GPX activity to resist cold stress in chrysanthemum.

Modification effects of seasonal and temperature variation on the association between exposure to nitrogen dioxide and ischemic stroke onset in Shenzhen, China.

The independent associations of extreme temperature and ambient air pollutant with the admission to hospital and mortality of ischemic stroke have been widely investigated. However, knowledge about the modification effects of variation in season and temperature on the association between exposure to nitrogen dioxide (NO2) and ischemic stroke onset is still limited. This study purposed to explore the effect of NO2 on daily ischemic stroke onset modified by season and ambient temperature, and identify the potential population that susceptible to ischemic stroke onset connected with NO2 and ambient temperature. Data on daily ischemic stroke counts, weather conditions, and ambient air pollutant concentrations in Shenzhen were collected between January 1, 2008, and December 31, 2014. The seasonal effect on the NO2-associated onset was measured by a distributed-lag linear model. Furthermore, a generalized additive model that incorporated with stratification analyses was used to calculate the interactive effects between NO2 and ambient temperature. During the winter, the average percentage increase in daily ischemic stroke onset for each 10 µg/m3 increment in NO2 concentration on lagged 2 days was 3.05% (95% CI: 1.31-4.82%), while there was no statistically significant effect of NO2 during summer. And the low-temperature days ([Formula: see text] mean temperature), with a 2.23% increase in incidence (95% CI: 1.18-3.29%) for the same concentration increase in NO2, were significant higher than high temperature days ([Formula: see text] mean temperature). The modification effects of temperature on the study association were more pronounced in individuals aged 65 years or more and in males. The adverse health effects of NO2 on ischemic stroke are more pronounced during winter or low temperature periods. Elderly adults or males presented higher risks with these exposures.

Is SARS-CoV-2 Infection a Risk Factor for Early Pregnancy Loss? ACE2 and TMPRSS2 Coexpression and Persistent Replicative Infection in Primitive Trophoblast.

BACKGROUND: SARS-CoV-2 infection in term placenta is rare. However, growing evidence suggests that susceptibility of the human placenta to infection may vary by gestational age and pathogen. For several viral infections, susceptibility appears to be greatest during early gestation. Peri-implantation placental infections that result in pre-clinical pregnancy loss would typically go undetected. Little is known about the effects of SARS-CoV-2 on the peri-implantation human placenta since this time in pregnancy can only be modeled in vitro. METHODS: We used a human embryonic stem cell (hESC)-derived model of peri-implantation placental development to assess patterns of ACE2 and TMPRSS2 transcription and protein expression in primitive trophoblast. We then infected the same trophoblast cell model with a clinical isolate of SARS-CoV-2 and documented infection dynamics. RESULTS: ACE2 and TMPRSS2 were transcribed and translated in hESC-derived trophoblast, with preferential expression in syncytialized cells. These same cells supported replicative and persistent infection by SARS-CoV-2, while non-syncytialized trophoblast cells in the same cultures did not. CONCLUSIONS: Co-expression of ACE2 and TMPRSS2 in hESC-derived trophoblast and the robust and replicative infection limited to syncytiotrophoblast equivalents support the hypothesis that increased viral susceptibility may be a defining characteristic of primitive trophoblast.

Nuclear exclusion of YAP exacerbates podocyte apoptosis and disease progression in Adriamycin-induced focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a chronic glomerular disease with poor clinical outcomes. Podocyte loss via apoptosis is one important mechanism underlying the pathogenesis of FSGS. Recently, Yes-associated-protein (YAP), a key downstream protein in the Hippo pathway, was identified as an activator for multiple gene transcriptional factors in the nucleus to control cell proliferation and apoptosis. To investigate the potential role of YAP in the progression of FSGS, we examined kidney samples from patients with minimal change disease or FSGS and found that increases in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in human FSGS. Utilizing an established mT/mG transgenic mouse model and primary cultured podocytes, we found that YAP was distributed uniformly in nucleus and cytoplasm in the podocytes of control animals. Adriamycin treatment induced gradual nuclear exclusion of YAP with enhanced phospho-YAP/YAP ratio, accompanied by the induction of podocyte apoptosis both in vivo and in vitro. Moreover, we used verteporfin to treat an Adriamycin-induced FSGS mouse model, and found YAP inhibition by verteporfin induced nuclear exclusion of YAP, thus increasing podocyte apoptosis and accelerating disease progression. Therefore, our findings suggest that YAP nuclear distribution and activation in podocytes is an important endogenous anti-apoptotic mechanism during the progression of FSGS.

Polymeric RNAi Constructs Tailored with Appreciable Transcellular Trafficking Functions for Potential Suppression of Parathyroid Hormone Production.

Polymeric small interfering RNA (siRNA) conjugate was elaborated to sequentially circumvent the predefined biological barriers encountered in the journey of transcellular delivery of siRNA into cytosol. Herein, classic ring-opening polymerization was employed for synthesis of well-defined poly(amino acid) derivatives possessing an array of carboxyl groups in an attempt to resemble the structural characteristics of hyaluronan. Furthermore, the hyaluronan-like synthetic was conjugated with a multiple of siRNA through a glutathione (GSH)-responsive disulfide linkage. The siRNA conjugate appeared to utilize the hyaluronan-specific receptors of CD44 for cell internalization, indicating similar functionalities to our hyaluronan-mimicking synthetic. Furthermore, the carboxyl groups of hyaluronan-like synthetics were designed to be selectively detached in subcellular acidic endosomes/lysosomes and transform into the cytomembrane-disruptive flanking ethylenediamine moieties, which appeared to be crucial in facilitating translocation of siRNA payloads from entrapment and degradation in lysosomes toward the cytosol. Eventually, active siRNA could be smoothly released from the synthetic due to the GSH cleavage disulfide linkage (disulfide), consequently accounting for potent RNA knockdown activities (>90%) toward cancerous cells. In addition, appreciable knockdown of parathyroid hormone was also achieved from our proposed siRNA conjugates in parathyroid cells. Hence, the elaborated siRNA conjugate showed tremendous potential in treatment of hyperparathyroidism, and could be developed further for systemic RNA interference (RNAi) therapeutics. Moreover, this study could also be the first example of a synthetic mimic to hyaluronan acquiring its functionalities, which could have important implications for further development of biomimic materials in pursuit of biomedical applications.

Effect of ambient temperature on stroke onset: a time-series analysis between 2003 and 2014 in Shenzhen, China.

OBJECTIVE: Evidence on the relationship between ambient temperature and morbidity of different stroke subtypes in China is limited. This study aimed to assess the influence of ambient temperature on stroke risk in Shenzhen, China. METHODS: From 1 January 2003 to 31 December 2014, 114 552 stroke cases in Shenzhen were collected. A generalised additive model with quasi-Poisson regression combined with a distributed lag non-linear model was applied to evaluate the temperature effects on stroke subtypes. Furthermore, this study explored the variability of the effects across sex, age and education. RESULTS: The immediate heat effects on ischaemic stroke (IS) and the persistent effects of ambient temperature on intracerebral haemorrhage (ICH) were significant. Overall, the cold-related relative risks (RRs) of IS, ICH and subarachnoid haemorrhage (SAH) were 1.02 (0.97-1.07), 1.16 (1.04-1.30) and 1.12 (0.61-2.04), whereas the heat-related RRs were 1.00 (0.97-1.04), 0.80 (0.73-0.88) and 1.05 (0.63-1.78), respectively. For IS, a weakly beneficial cold effect was found among men while a detrimental heat effect among both men and women, the elderly and higher-educated population at lag0. However, regarding ICH, the temperature effects in men, the young and higher-educated population are stronger at lag0-4, lag0-7 as cold reveals threat and heat reveals protection. CONCLUSION: Responses of diverse stroke subtypes to ambient temperature varied. Effective measures should be taken to increase public awareness about the effects of ambient temperature on stroke attack and to educate the public about self-protection.

Estimation of the Outbreak Severity and Evaluation of Epidemic Prevention Ability of COVID-19 by Province in China.

Objectives. To compare the epidemic prevention ability of COVID-19 of each province in China and to evaluate the existing prevention and control capacity of each province.Methods. We established a quasi-Poisson linear mixed-effects model using the case data in cities outside Wuhan in Hubei Province, China. We adapted this model to estimate the number of potential cases in Wuhan and obtained epidemiological parameters. We estimated the initial number of cases in each province by using passenger flowrate data and constructed the extended susceptible-exposed-infectious-recovered model to predict the future disease transmission trends.Results. The estimated potential cases in Wuhan were about 3 times the reported cases. The basic reproductive number was 3.30 during the initial outbreak. Provinces with more estimated imported cases than reported cases were those in the surrounding provinces of Hubei, including Henan and Shaanxi. The regions where the number of reported cases was closer to the predicted value were most the developed areas, including Beijing and Shanghai.Conclusions. The number of confirmed cases in Wuhan was underestimated in the initial period of the outbreak. Provincial surveillance and emergency response capabilities vary across the country.

Quadrupling efficiency in production of genetically modified pigs through improved oocyte maturation.

Assisted reproductive technologies in all mammals are critically dependent on the quality of the oocytes used to produce embryos. For reasons not fully clear, oocytes matured in vitro tend to be much less competent to become fertilized, advance to the blastocyst stage, and give rise to live young than their in vivo-produced counterparts, particularly if they are derived from immature females. Here we show that a chemically defined maturation medium supplemented with three cytokines (FGF2, LIF, and IGF1) in combination, so-called "FLI medium," improves nuclear maturation of oocytes in cumulus-oocyte complexes derived from immature pig ovaries and provides a twofold increase in the efficiency of blastocyst production after in vitro fertilization. Transfer of such blastocysts to recipient females doubles mean litter size to about nine piglets per litter. Maturation of oocytes in FLI medium, therefore, effectively provides a fourfold increase in piglets born per oocyte collected. As they progress in culture, the FLI-matured cumulus-oocyte complexes display distinctly different kinetics of MAPK activation in the cumulus cells, much increased cumulus cell expansion, and an accelerated severance of cytoplasmic projections between the cumulus cells outside the zona pellucida and the oocyte within. These events likely underpin the improvement in oocyte quality achieved by using the FLI medium.

Generation of mastitis resistance in cows by targeting human lysozyme gene to ß-casein locus using zinc-finger nucleases.

Mastitis costs the dairy industry billions of dollars annually and is the most consequential disease of dairy cattle. Transgenic cows secreting an antimicrobial peptide demonstrated resistance to mastitis. The combination of somatic cell gene targeting and nuclear transfer provides a powerful method to produce transgenic animals. Recent studies found that a precisely placed double-strand break induced by engineered zinc-finger nucleases (ZFNs) stimulated the integration of exogenous DNA stretches into a pre-determined genomic location, resulting in high-efficiency site-specific gene addition. Here, we used ZFNs to target human lysozyme (hLYZ) gene to bovine ß-casein locus, resulting in hLYZ knock-in of approximately 1% of ZFN-treated bovine fetal fibroblasts (BFFs). Gene-targeted fibroblast cell clones were screened by junction PCR amplification and Southern blot analysis. Gene-targeted BFFs were used in somatic cell nuclear transfer. In vitro assays demonstrated that the milk secreted by transgenic cows had the ability to kill Staphylococcus aureus. We report the production of cloned cows carrying human lysozyme gene knock-in ß-casein locus using ZFNs. Our findings open a unique avenue for the creation of transgenic cows from genetic engineering by providing a viable tool for enhancing resistance to disease and improving the health and welfare of livestock.

Optical biomarker analysis for renal cell carcinoma obtained from preoperative and postoperative patients using ATR-FTIR spectroscopy.

Renal cell carcinoma (RCC) is the most common malignant tumor in the urinary system, accounting for 80 % to 90 % for all renal malignancies. Traditional diagnostic methods like magnetic resonance imaging (MRI) and computed tomography (CT) lack the sensitivity and specificity as they lack specific biomarkers. These limitations impede effective monitoring of tumor recurrence. This study aims to employ Attenuated Total Reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy, an optical technology sensitive to molecular groups, to analyze the potential optical biomarkers in urine and plasma samples from RCC patients pre- and post-surgery. The results reveal distinctive spectral information from both plasma and urine samples. Post-surgery urine spectra exhibit complexity compared to plasma, showing reduced content at 1072 cm-1, 1347 cm-1 and 1654 cm-1 bands, while increased content at 1112 cm-1, 1143 cm-1, 1447 cm-1, 3334 cm-1 and 3420 cm-1 bands. Utilizing machine learning models such as eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), partial least squares (PLS), and artificial neural network (ANN), the study evaluated plasma and urine samples pre- and post-surgery. Remarkably, the XGBoost method excelled in distinguishing between tumor conditions and recovery, achieving an impressive AUC value of 0.99. These results underscore the potential of ATR-FTIR technology in identifying RCC optical biomarkers, with XGBoost showing promise as a valuable screening tool for RCC recurrence diagnosis.