The middle Heihe River Basin (MHRB) in arid areas in China faces the challenge of sustainability, but frequent over-irrigation deteriorated the situation. The water balance and energy budget have not been widely used for the quantifying evaluation of over-irrigation. Although some studies have measured the energy budget and water balance in cropland, the energy and water balance in pepper fields is still unclear. An experiment was conducted using an eddy covariance system, SmartView fluke and other measurements in MHRB. The leaf area index (LAI) for pepper increased in the first two months, then decreased thereafter. After Aug. 4, the daily evapotranspiration (ET) decreased during the maturation stage. The soil moisture was higher than the field capacity frequently, indicating that over-irrigation had occurred. Soil water content was relatively high at 100 cm depth, causing high percolation. The water inputs were 1.5 times ET, and the deep percolations accounted for 74% of the total irrigation inputs. Irrigation water could be conserved 301 mm, in case that percolation was avoided. Therefore, the irrigation amount (per time and total) should be reduced to achieve high water use efficiency (WUE). The latent heat flux (LE) consumed 80% of the net radiation (Rn). In July, the LE/Rn was the highest among all months, whereas H/Rn was the lowest due to the highest value of LAI in July. The net radiation had a significant positive linear correlation with the latent heat flux because of the high water supply. Our study showed that there was considerable room for water conservation in MHRB. Keywords: Sensible heat flux; Soil water content; Evapotranspiration; Latent heat flux; Leaf area index

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High-throughput DNA sequencing technologies make it possible now to sequence entire genomes relatively easily. Complete genomic information obtained by whole genome resequencing (WGS) can aid in identifying and delineating species even if they are extremely young, cryptic or morphologically difficult to discern and closely related. Yet for taxonomic or conservation biology purposes WGS can remain cost-prohibitive, too time-consuming, and often constitute a “data overkill”. Rapid and reliable identification of species (and populations) that is also cost-effective is possible based on species-specific markers that can be discovered by WGS. Based on WGS data we designed a PCR restriction fragment length polymorphism (PCR-RFLP) assay for 19 Neotropical Midas cichlid populations (Amphilophus cf. citrinellus), that includes all 13 described species of this species complex. Our work illustrates that identification of species and populations (i.e., fish from different lakes) can be greatly improved by designing genetic markers using available “high resolution” genomic information. Yet, our work also shows that even in the best-case scenario, when whole-genome resequencing information is available, unequivocal assignments remain challenging when species or populations diverged very recently, or gene flow persists. In summary, we provide a comprehensive workflow on how to design RFPL markers based on genome re-sequencing data, how to test and evaluate their reliability, and discuss the benefits and pitfalls of our approach.

The goal of the surgery is to eradicate the cancerous process without compromising patient's autonomy. Not leaving a residual tumour-spot that will offer a niche for local tumour recurrence is the surgeon's obsession. We highlight the mechanisms and risk factors to elaborate preventive and therapeutic means to combat this complication.

Coronary artery fistulas are rare congenital anomalies for which the ideal management strategies remain under study, with surgical repair being the mainstay of treatment in complex, aneurysmal fistulas.

The survival of animals under global warming strongly depends on their individual thermal niches, which result from the balance between energy loss and gain. Active movement is an important component of this energetic balance, as it affects not only energy gain via food intake but also energy loss via activity metabolism. Here, we develop a novel trait-based approach for how thermal niches arise from temperature-dependent movement. Therefore, we used image-based tracking to quantify the unimodal responses of the movement speed of carabid beetles to temperature. We used these empirical data to parameterize a mathematical model based on metabolic and predator-prey theory for net energy gain to derive a general mechanistic concept of thermal niches. This trait-based approach allows a relatively rapid and cost-effective assessment of climate change vulnerability for a wide range of animal taxa on broad geographic scales.

Crustaceans comprise an ecologically and morphologically diverse taxonomic group. They are typically considered resilient to many environmental perturbations found in marine and coastal environments, due to effective physiological regulation of ions and hemolymph pH, and a robust exoskeleton. Ocean acidification can affect the ability of marine calcifying organisms to build and maintain mineralized tissue and poses a threat for all marine calcifying taxa. Currently, there is no consensus on how ocean acidification will alter the ecologically-relevant exoskeletal properties of crustaceans. Here, we present a systematic review and meta-analysis on the effects of ocean acidification on the crustacean exoskeleton, assessing both exoskeletal ion content (calcium and magnesium) and functional properties (biomechanical resistance and cuticle thickness). Our results suggest that the effect of ocean acidification on crustacean exoskeletal properties varies based upon seawater pCO2 and species identity, with significant levels of heterogeneity for all analyses. Calcium and magnesium content were significantly lower in animals held at pCO2 levels of 1500-1999 μatm as compared to those under ambient pCO2. At lower pCO2 levels, however, statistically significant relationships between changes in calcium and magnesium content within the same experiment were observed: a negative relationship between calcium and magnesium content at pCO2 of 500-999 μatm and a positive relationship at 1000-1499 μatm. Exoskeleton biomechanics, such as resistance to deformation (microhardness) and shell strength, also significantly decreased under pCO2 regimes of 500-999 μatm and 1500-1999 μatm, indicating functional exoskeletal change coincident with decreases in calcification. Overall, these results suggest that the crustacean exoskeleton can be susceptible to ocean acidification at the biomechanical level, potentially predicated on changes in ion content, when exposed to high influxes of CO2. Future studies will need to accommodate the high variability of crustacean responses to ocean acidification, as well as ecologically-relevant ranges of pCO2 conditions, when designing experiments with conservation-level endpoints.

We illustrate a case of atrioventricular valve stenosis associated with insufficiency detected in fetal echocardiography performed in a pregnant woman (22 gestational weeks) of 3rd gravida. The early prenatal diagnosis demonstrated, isolated bilateral atrioventricular value stenosis and insufficiency in the absence of any other associated complex congenital heart diseases such as tricuspid atresia, hypoplastic left heart syndrome, endocardial cushion defect. However, the mother of the affected foetus was found to be normal with no risk factors. Thus, fetal echocardiography plays a pivotal role even in low risk pregnancies for early detection of prenatal cardiac anomalies that guide the obstetricians in determining the risk stratification, therapeutic strategies and prognosis.

Allergy related outcomes at 12 months in the CORAL Birth cohort of Irish children born during the first COVID 19 lockdown.Word count: 1248, References: 10

Fortification of Asian sea bass bone bio-calcium (ASBC) at different levels (0-10%) into mayonnaise was carried out. Firmness, consistency and cohesiveness of mayonnaise were augmented with increasing ASBC levels (P<0.05). ASBC raised lightness (L*) and total color difference (E*), but decreased a* and b*-values of mayonnaise in a dose dependent manner (P<0.05). Higher G’, G”, viscosity and shear stress value were observed in mayonnaise sample added with ASBC. However, lower acceptability was attained when mayonnaise was added with ASBC at level higher than 2.5% due to fishy odor and grittiness perceived by panelists. Ultrasonicated ASBC (U-ASBC) was prepared using pulse mode at 70% amplitude for different times (5, 10 and 15 min) in the presence of hexane. Based on acceptability, mayonnaise added with U-ASBC using ultrasonication time of 15 min was selected. Reduced particle size with lowered volatile compounds was attained in U-ASBC powder than that of ASBC. Mayonnaise added with 7.5% U-ASBC (M-UBC-7.5) had higher viscosity with lower creaming and thermal creaming index (P<0.05) compared to the control and that added with 2.5% ASBC (M-BC-2.5). Optical microscopic images showed that denser and smaller droplet size was observed for M-BC-2.5 and M-UBC-7.5 than control. The lowest moisture, fat and carbohydrate contents were attained for M-UBC-7.5 with the higher protein, ash and calcium content (P<0.05), compared to control and M-BC-2.5. Fortification of mayonnaise with ASBC at 2.5% or U-ASBC at 7.5% could increase calcium content by 54 or 174 times, respectively, without any sensorial changes.

Transient receptor potential vanilloid subfamily member 6 (TRPV6) is an epithelial Ca 2+ channel that regulates the initial step of the transcellular Ca 2+ transport pathway. TRPV6 is expressed in the kidney, intestine, placenta, and other tissues, and the dysregulation of the channel is implicated in several human cancers. It has been reported that phosphatidylinositol 4,5-bisphosphate (PIP 2) activates TRPV6 and its close homologue TRPV5; however, the underlying molecular mechanism is less clear. Recently, a structure of rabbit TRPV5 in complex with dioctanoyl (diC 8) PIP 2, a soluble form of PIP 2, was determined by cryo-electron microscopy. Based on this structure, the structural model of human TRPV6 with PIP 2 was set up, and then molecular dynamics simulations were performed for TRPV6 with and without PIP 2. Simulation results show that the positively charged residues responsible for TRPV5 binding of diC 8 PIP 2 are involved in the interactions between TRPV6 and PIP 2. The binding of PIP 2 to TRPV6 increases the distance between the diagonally opposed residues D542 in the selectivity filter and that between the diagonally opposed M578 residues in the lower gate of TRPV6. A secondary structural analysis reveals that residues of M578 in TRPV6 undergo structural and position changes during binding of PIP 2 with TRPV6. In addition, principal component analysis indicates that the binding of PIP 2 increases the dynamical motions of both the selectivity filter and the lower gate of TRPV6. These changes induced by PIP 2 favor the channel opening. Thus, this study provides a basis for understanding the mechanism underlying the PIP 2-induced TRPV6 channel activation.

Background and aim of the study Objective of this analysis was to use coronary computed tomography in patients with normal tricuspid aortic valves to perform detailed aortic root and aortic valve geometric analysis with focus on asymmetry of the three leaflets. Materials and methods We analyzed aortic valves in 70 anonymized coronary computed tomography angiograms. Mean patient age was 53 ± 11 years. All aortic valves were tricuspid, without calcifications and aortic roots were of normal dimensions. Asymmetry of the three leaflets in individual patients was assessed by calculating absolute and relative differences between the largest and the smallest of the three leaflets. Results Some degree of asymmetry was present in all analyzed valves. Absolute and relative differences for free margin length were 3.2 ± 1.4 mm and 9.3 ± 3.8%, respectively. The largest relative difference was noted in coaptation area (36.5 ± 16.5%) and the smallest in leaflet effective height (6.1 ± 4.8%). Using predefined cut-off criteria for absolute differences in leaflet dimensions, 86% of the valves were classified as asymmetric. Conclusions Equal free margin length of the three leaflets is not needed for normal tricuspid aortic valve function. Aligning the leaflet free margin length in standardized aortic valve repair may not be necessary in tricuspid aortic valve repair, whereas equalization of effective leaflet heights is.

The osteopontin released from mesenchymal stem cells (MSC) undergoing lineage differentiation can negatively influence the expansion of hematopoietic stem cells (HSCs) in co-culture systems developed for expanding HSCs. Therefore, minimising the amount of osteopontin in the co-culture system is important for the successful ex vivo expansion of HSCs. Towards this goal, a bioengineered 3D-microfibrous matrix that can maintain MSCs in less osteopontin releasing condition has been developed and its influence on the expansion of HSCs has been studied. The newly developed 3D-matrix significantly decreased the release of osteopontin, depending on the MSC culture conditions used during the priming period before HSC seeding. The culture system with the lowest amount of osteopontin facilitated more than 40-fold increase in HSC number in 1 weeks’ time period. Interestingly, the viability of expanded cells and the CD34+ pure population of HSCs found to be the highest in the low osteopontin containing system. Therefore, bioengineered microfibrous 3D-matrices seeded with MSCs, primed under suitable culture conditions can be an improved ex vivo expansion system for HSC culture.

Comment on: Burden of central nervous system complications in sickle cell disease: A systematic review and meta-analysis R. Grant Steen, PhD103 Van Doren PlaceChapel Hill, NC 27517G_Steen_MediCC@yahoo.comDear Editor;I read with interest a recent paper in Pediatric Blood & Cancer(1), about cognitive impairment in children with sickle cell disease (SCD). I’m always grateful to have my work cited, especially since our paper is almost 20 years old (2).However, it seems that Lee et al . have gone to great lengths to mischaracterize our work. They write (pg. 5) that, “SCI [silent cerebral infarct] and absence of SCI/CVA [cerebrovascular accident] were verified by review of brain MRIs in all studies except Ghafuri et al . and Steen et al . In these studies, absence of SCI/CVA was defined as no mention of cerebral infarcts in the subject’s medical records.” Also on pg. 5, they write that, “An alternative analysis was conducted excluding studies with insufficient definition of overt stroke and/or SCI based on clinical opinion (Ghafuriet al . and Steen et al .)”. I cannot speak for Ghafuriet al , but we did a careful review of MRI findings for every single patient in our study, as is necessary for a paper in theAmerican Journal of Neuroradiology . This should be pellucidly clear because the title of our paper is, “Cognitive Impairment in Children with Hemoglobin SS Sickle Cell Disease: Relationship to MR Imaging Findings and Hematocrit ”. All our SCD patients were evaluated by at least two neuroradiologists, and patients thought to be abnormal were evaluated by a third neuroradiologist blinded as to previous findings (2). One wonders what other errors may be present in Leeet al (1).Fortunately, this mischaracterization of our work did not lead to incorrect conclusions (1). A comparison of Table 1 to Supplementary Table 6, in which our paper and Ghafuri et al were deleted from analysis, shows that none of the major findings were changed much by deleting these papers (1). I agree with most conclusions in Lee et al .; in fact, I would go further. In uncited work from St. Jude Children’s Research Hospital, we found that children with SCD can suffer cognitive impairment even in the absence of MRI evidence of brain injury (3). We tested a hypothesis that children with SCD who are completely normal by MRI can still be cognitively impaired, as predicted by a model of diffuse brain injury. A total of 54 patients with hemoglobin SS (average age 10.9 years ± 2.9 years SD) were examined with the Wechsler Intelligence Scale for Children-III (WISC-III) and were randomly matched by age, race, and gender to healthy children from the Wechsler normative database. Patients were also imaged at 1.5 Tesla with standard imaging sequences. Among 30 patients judged normal by MRI, there were substantial deficits in Wechsler Full-Scale IQ, Verbal IQ, and Performance IQ (all P < 0.01), when compared to African-American controls. The patient Wechsler Full-Scale IQ was 12.9 points lower than that of matched controls and decreased as a function of age (P = 0.014). These findings strongly suggest that there is diffuse brain injury in SCD patients, perhaps associated with chronic hypoxia (3).

Background Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions. Objective: To evaluate the impact on gradual home introduction of foods containing cows milk after a supervised, single low dose exposure to whole milk at time of diagnosis. Methods Infants less than 12 months old, referred with suspected IgE-mediated cow’s milk allergy were recruited to an open-label randomised, controlled trial of intervention - a single dose of fresh cow’s milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED 05 – vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at Home. Parents completed food allergy quality of life and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post randomisation. Results: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p=0.048). By 6 months 11/37 (30%) intervention subjects had reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). Twelve months post randomisation 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p=0.03). Maternal STAIs were significantly associated with their infants’ progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion This study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows milk allergy in a very young cohort. A supervised single dose of milk at the ED 05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards completion of the milk ladder, but pre-existing high levels of maternal anxiety are associated with poorer progress.

Successful Extubation in Preterm InfantsTo the Editor,I read with great interest the article by O’Connor et al1 describing factors that lower the likelihood of successful extubation by day 14 in mechanically ventilated neonates with or at risk of developing bronchopulmonary dysplasia (BPD), born at <30week gestational age (GA). These factors were younger GA at birth, and at the time of commencing steroids had higher MAPs and had higher oxygen requirements. They studied 287 neonates and noted that each additional week of GA at birth led to a 1.53 increase in the odds of successful extubation. Higher average fraction of inspired oxygen (FiO2) requirements in the preceding 24 h resulted in a 0.94 decrease in the odds of successful extubation and higher mean airway pressure (MAP) resulted in 0.76 decrease in odds of successful extubation.I have been using the probability of successful extubation calculator (http://extubation.net/), which incorporates the same factors as described by Connor et al 1. The calculator was described earlier by Gupta et al 2. They incorporated GA, MAP and FiO2 in the calculation, same as Connor et al 1. The only difference was the inclusion of the respiratory severity score (RSS), which is nothing but a product of MAP and FiO2 [(RSS= mean airway pressure (cm H2O) x FiO2 (0.21-1.00)].Although, we have a probability score model for successful extubation among preterm infants, as described by Gupta et al 2, I do agree with Connor et al 1 that we need to develop prognostic scoring model for intubated preterm infants.References:O’Connor K, Hurst C, Llewellyn S, Davies M. Factors associated with successful extubation following the first course of systemic dexamethasone in ventilator-dependent preterm infants with or at risk of developing bronchopulmonary dysplasia [published online ahead of print, 2022 Jan 7]. Pediatr Pulmonol . 2022;10.1002/ppul.25821. doi:10.1002/ppul.25821Gupta D, Greenberg RG, Sharma A, et al. A predictive model for extubation readiness in extremely preterm infants. J Perinatol . 2019;39(12):1663-1669. doi:10.1038/s41372-019-0475-xAuthor:Shabih Manzar, MDLouisiana State University Health Sciences CenterDepartment of Pediatrics1501 Kings HighwayShreveport, LA 71103Phone: 318-626-1623Fax: 318-675-6059Email: shabih.manzar@lsuhs.eduAuthor contribution: Dr. Manzar wrote the draft.Funding and financial support: NoneConflict of interest: None

anterior mini‐thoracotomy in multivessel coronary revascularization by Cyn I read with interest the article, routine minimally invasive approach via left ak and colleagues1. The main problem of mini anterior thoracotomy coronary revascularization is the limited or even bad exposure to the right coronary and posterior obtuse marginal branches which may affect the quality of the distal anastomosis. This is the most important technical point of a successful revascularization.

This article is devoted to the study of existence of a mass conserving global solution for the collision-induced nonlinear fragmentation model which arises in particulate processes, with the following type of collision kernel: \[C(x,y)~\le~k_1 \frac{(1 + x)^\nu (1 + y)^\nu}{\left(xy\right)^\sigma},\] for all ~$x, y \in (0,\infty)$, where $k_1$ is a positive constant, $\sigma \in \left[0,\tfrac{1}{2}\right]$ and $\nu \in [0, 1]$. The above-mentioned form includes many practical oriented kernels of both \emph{singular} and \emph{non-singular} types. The singularity of the unbounded collision kernel at coordinate axes extends the previous existence result of Paul and Kumar [Mathematical Methods in the Applied Sciences 41 (7) (2018) 2715–2732 (\href{https://doi.org/10.1002/mma.4775}{doi:10.1002/mma.4775})] and also exhibits at most quadratic growth at infinity. Finally, uniqueness of solution is also investigated for pure singular collision rate, i.e., for ~ $\nu=0$.

Myeloid cell leukemia-1 (MCL1), an anti-apoptotic BCL-2 family protein plays a major role in the control of apoptosis as the regulator of mitochondrial permeability which is deregulated in various solid and hematological malignancies. Interaction of the executioner proteins Bak/Bax with anti-apoptotic MCL1 and its cellular composition determines the apoptotic or survival pathway. This study highlighted the deleterious MCL1-Bax stabilizing effect of the mutation V220F on MCL1 structure through computational protein-protein interaction predictions and molecular dynamics simulations. The single point mutation at V220F was selected as it is residing at the hydrophobic core region of BH3 conserved domain, the site of Bax binding. The molecular dynamics simulation studies showed increase in stability of the mutated MCL1 before and after Bax binding comparable with the native MCL1. The clusters from free energy landscape found out structural variation in folding pattern with additional helix near the BH3 domain in the mutated structure. This loop to helix structural change in the mutated complex favored stable interaction of the complex and also induced Bax conformational change. Moreover, molecular mechanics based binding free energy calculations confirmed increased affinity of Bax towards mutated MCL1. Residue-wise interaction network analysis showed the individual residues in Bax binding responsible for the change in stability and interaction due to the protein mutation. In conclusion, the overall findings from the study reveal that the presence of V220F mutation on MCL1 is responsible for the structural confirmational change leading to disruption of its biological functions which might be responsible for tumorigenesis. The mutation could possibly be used as future diagnostic markers in treating cancers.

Growth suppression and defense signaling are simultaneous strategies that plants invoke to respond to abiotic stress. Here, we show that the drought stress response of poplar trees ( Populus trichocarpa) is initiated by a suppression in cell wall derived methanol (meOH) emissions and activation of acetic acid (AA) fermentation defenses. Temperature sensitive emissions dominated by meOH (AA/meOH < 30%) were observed from physiologically active branches, detached stems, leaf cell wall isolations, and whole ecosystems. In contrast, drought treatment resulted in a suppression of meOH emissions and strong enhancement in AA emissions together with fermentation volatiles acetaldehyde, ethanol, and acetone. These drought-induced changes coincided with a reduction in stomatal conductance, photosynthesis, transpiration, and leaf water potential. The strong enhancement in AA/meOH emission ratios during drought (400-3,500%) was associated with an increase in acetate content of whole leaf cell walls, which became significantly 13C 1,2-labeled following the delivery of 13C 1,2-acetate via the transpiration stream. The results are consistent with central roles of acetate fermentation in regulating plant defense and metabolic responses to drought, and suggest that cell wall O-acetylation may be reversible allowing plants to rapidly respond to drought stresses by down-regulating methyl ester hydrolysis and growth processes while enhancing O-acetylation. We suggest that AA/meOH emission ratios could be used as a highly sensitive non-destructive sensor to discriminate between thresholds of rapid plant growth and drought stress responses.

Sanghuangporus baumii is a traditional medicinal fungus that produces pharmacological terpenoids, but natural resources are insufficient for applications, and growth and development mechanisms are poorly understood. Combining metabolomic and transcriptomic analyses, we identified four terpenoid hormones and a central gene isopentenyl diphosphate isomerase (IDI) involved in growth and development. The importance of the four terpenoid hormones was further confirmed by exogenous hormones addition, we found that Cis-Zeatin (CZ) plays a major role in the mycelia stage, Trans-Zeatin (TZ) and Gibberellin A4 (GA4) are important in the primordia stage, GA4 is crucial for the fruiting bodies stage, and Abscisic Acid (ABA) may be a marker of maturity. Later, hormone content determination and qRT-PCR were used to verify the growth and development mechanism, and finally it was confirmed that IDI gene affects the content of terpenoid hormones content by regulating the transcript level of terpenoid biosynthesis genes, thus affecting the morphological changes of S. baumii. Our results illuminate the growth and development mechanisms of S. baumii, and may promote the breeding and utilisation of high-quality varieties.

In this paper, we present a new operational matrix of derivative of Jacobi wavelets. Shifted Jacobi polynomials and their properties are employed for deriving a procedure to forme this matrix. Then Jacobi wavelets expansions along with this operational matrix are applied for solving ordinary differentiel equations with non analytic solution. It is shown that Jacobi wavelets are very efficient and suitable for solving this kind of problem. Several numerical examples are given to illustrate the efficiency and performane of the presented method.

Host cell proteins (HCPs) are a significant class of process-related impurities commonly associated with the manufacturing of biopharmaceuticals. However, due to the increased use of crude enzymes as biocatalysts for modern organic synthesis, HCPs can also be introduced as a new class of impurities in chemical drugs. In both cases, residual HCPs need to be adequately removed to ensure product purity, quality, and patient safety. Although a lot of attentions have been focused on defining a universally acceptable limit for such impurities, the risks associated with residual HCPs on product quality, safety, and efficacy often need to be determined on a case-by-case basis taken into consideration of residual HCP profile in the product, the dose, dosage form, and administration route etc. Here we describe the unique challenges for residual HCP control presented by the biocatalytic synthesis of a Merck investigational stimulator of interferon genes protein (STING) agonist, MK-1454, which is a cyclic dinucleotide synthesized using E. coli cell lysate overexpressing cyclic GMP-AMP synthase (cGAS) as a biocatalyst. In this study, a holistic characterization of residual protein impurities using a variety of analytical tools, together with in silico immunogenicity prediction of identified proteins, facilitated risk assessment and guided process development to achieve adequate removal of residual protein impurities in MK-1454 API.

Retinal arterial macroaneurysm shows rapid vision loss when rupture occurs; therefore, preventive photocoagulation should be considered, if necessary.