Analogs of α-conotoxin PnIC selectively inhibit α7ß2- over α7-only subtype nicotinic acetylcholine receptors via a novel allosteric mechanism.

This study was undertaken to identify and characterize the first ligands capable of selectively identifying nicotinic acetylcholine receptors containing α7 and ß2 subunits (α7ß2-nAChR subtype). Basal forebrain cholinergic neurons express α7ß2-nAChR. Here, they appear to mediate neuronal dysfunction induced by the elevated levels of oligomeric amyloid-ß associated with early Alzheimer's disease. Additional work indicates that α7ß2-nAChR are expressed across several further critically important cholinergic and GABAergic neuronal circuits within the central nervous system. Further studies, however, are significantly hindered by the inability of currently available ligands to distinguish heteromeric α7ß2-nAChR from the closely related and more widespread homomeric α7-only-nAChR subtype. Functional screening using two-electrode voltage-clamp electrophysiology identified a family of α7ß2-nAChR-selective analogs of α-conotoxin PnIC (α-CtxPnIC). A combined electrophysiology, functional kinetics, site-directed mutagenesis, and molecular dynamics approach was used to further characterize the α7ß2-nAChR selectivity and site of action of these α-CtxPnIC analogs. We determined that α7ß2-nAChR selectivity of α-CtxPnIC analogs arises from interactions at a site distinct from the orthosteric agonist-binding site shared between α7ß2- and α7-only-nAChR. As numerous previously identified α-Ctx ligands are competitive antagonists of orthosteric agonist-binding sites, this study profoundly expands the scope of use of α-Ctx ligands (which have already provided important nAChR research and translational breakthroughs). More immediately, analogs of α-CtxPnIC promise to enable, for the first time, both comprehensive mapping of the distribution of α7ß2-nAChR and detailed investigations of their physiological roles.

Binding of human ACE2 and RBD of Omicron enhanced by unique interaction patterns among SARS-CoV-2 variants of concern.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, has continued to mutate and spread worldwide despite global vaccination efforts. In particular, the Omicron variant, first identified in South Africa in late November 2021, has become the dominant strain worldwide. Compared to the original strain identified in Wuhan, Omicron features 50 genetic mutations, with 15 mutations in the receptor-binding domain (RBD) of the spike protein, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor for viral entry. However, it is not completely understood how these mutations alter the interaction and binding strength between the Omicron RBD and ACE2. In this study, we used a combined steered molecular dynamics (SMD) simulation and experimental microscale thermophoresis (MST) approach to quantify the interaction between Omicron RBD and ACE2. We report that the Omicron brings an enhanced RBD-ACE2 interface through N501Y, Q498R, and T478K mutations; the changes further lead to unique interaction patterns, reminiscing the features of previously dominated variants, Alpha (N501Y) and Delta (L452R and T478K). Among the Q493K and Q493R, we report that Q493R shows stronger binding to ACE2 than Q493K due to increased interactions. Our MST data confirmed that the Omicron mutations in RBD are associated with a five-fold higher binding affinity to ACE2 compared to the RBD of the original strain. In conclusion, our results could help explain the Omicron variant's prevalence in human populations, as higher interaction forces or affinity for ACE2 likely promote greater viral binding and internalization, leading to increased infectivity.

An efficient and cost-effective method for the purification of human basophils.

Human basophils are terminally differentiated granulocytes that are least abundant in the peripheral blood but play important roles in allergic diseases. Studies on human basophils are limited by the high cost on the isolation of human basophils by magnetic-activated cell sorting (MACS) for negative depletion of non-basophils, followed by CD123-based positive selection of basophils. Moreover, such CD123-based purification of basophils may be limited by blocking of the binding of IL-3/anti-CD123 to the surface CD123. Here we identified SSClow CD4- CD127- HLA-DR- CRTH2high as unique markers for the identification of human basophils through stringent flow cytometric analysis of leukocytes from buffy coat. We established an efficient and cost-effective method for isolating human basophils from buffy coat based on positive magnetic selection of CRTH2+ cells followed by flow cytometric sorting of SSClow CD4- CD127- HLA-DR- CRTH2high cells. Approximately 1 to 1.5 million basophils were isolated from one buffy coat with a purity of >97%. Basophils purified by this method were viable and efficiently responded to key regulators of basophils including IL-3 and anti-IgE. This method can be used for purifying human basophils for subsequent functional studies.

OsRAD51 Plays a Vital Role in Promoting Homologous Recombination in Rice Meiosis.

Meiotic recombination plays a pivotal role in achieving accurate chromosomal segregation and increasing genetic diversity. In the homologous recombination pathway, the detailed mechanisms of how OsRAD51 and OsDMC1 work in rice meiosis remain to be explored. Here, we obtained different types of mutants for Osrad51a1, Osrad51a2, Osdmc1a, and Osdmc1b through CRISPR/Cas9. Both Osrad51a1 and Osrad51a2 exhibited normal vegetative growth and fertility. Osrad51 (Osrad51a1 Osrad51a2) mutant plants show normal vegetative growth but exhibit complete sterility, indicating that OsRAD51A1 and OsRAD51A2 are functionally redundant in rice fertility. In contrast to the wild type, Osrad51 chromosomes are not paired perfectly at pachytene and synaptonemal complex (SC) formation is deficient. Moreover, univalents and multivalent associations were observed at metaphase I, chromosome fragments presented at anaphase I, and crossover formation is basically suppressed in Osrad51 pollen mother cells (PMCs). OsRAD51 foci emerge at leptotene and disappear from late pachytene and chromosome localization of OsRAD51 depends on the formation of double-strand breaks (DSBs). Most OsRAD51 foci can co-localize with OsDMC1 signals. OsRAD51 is essential for the loading of OsDMC1 onto chromosomes, and vice versa. In addition, both OsRAD51 and OsDMC1 can interact with OsFIGL1 and OsBRCA2, two important components in rice meiosis. Moreover, the Osrad51 Osdmc1 (Osrad51a1 Osrad51a2 Osdmc1a Osdmc1b) quadruple mutant PMCs exhibited similar defective phenotypes as Osrad51 in homologous pairing, synapsis, and DSB repair. Taken together, our results suggest that the recombinases DMC1 and RAD51 may functionally depend on each other and play important roles in meiotic recombination during meiosis in rice.

A systematic analysis of protein-carbohydrate interactions in the Protein Data Bank.

Protein-carbohydrate interactions underlie essential biological processes. Elucidating the mechanism of protein-carbohydrate recognition is a prerequisite for modeling and optimizing protein-carbohydrate interactions, which will help in discovery of carbohydrate-derived therapeutics. In this work, we present a survey of a curated database consisting of 6,402 protein-carbohydrate complexes in the Protein Data Bank (PDB). We performed an all-against-all comparison of a subset of nonredundant binding sites, and the result indicates that the interaction pattern similarity is not completely relevant to the binding site structural similarity. Investigation of both binding site and ligand promiscuities reveals that the geometry of chemical feature points is more important than local backbone structure in determining protein-carbohydrate interactions. A further analysis on the frequency and geometry of atomic interactions shows that carbohydrate functional groups are not equally involved in binding interactions. Finally, we discuss the usefulness of protein-carbohydrate complexes in the PDB with acknowledgement that the carbohydrates in many structures are incomplete.

GlyMDB: Glycan Microarray Database and analysis toolset.

MOTIVATION: Glycan microarrays are capable of illuminating the interactions of glycan-binding proteins (GBPs) against hundreds of defined glycan structures, and have revolutionized the investigations of protein-carbohydrate interactions underlying numerous critical biological activities. However, it is difficult to interpret microarray data and identify structural determinants promoting glycan binding to glycan-binding proteins due to the ambiguity in microarray fluorescence intensity and complexity in branched glycan structures. To facilitate analysis of glycan microarray data alongside protein structure, we have built the Glycan Microarray Database (GlyMDB), a web-based resource including a searchable database of glycan microarray samples and a toolset for data/structure analysis. RESULTS: The current GlyMDB provides data visualization and glycan-binding motif discovery for 5203 glycan microarray samples collected from the Consortium for Functional Glycomics. The unique feature of GlyMDB is to link microarray data to PDB structures. The GlyMDB provides different options for database query, and allows users to upload their microarray data for analysis. After search or upload is complete, users can choose the criterion for binder versus non-binder classification. They can view the signal intensity graph including the binder/non-binder threshold followed by a list of glycan-binding motifs. One can also compare the fluorescence intensity data from two different microarray samples. A protein sequence-based search is performed using BLAST to match microarray data with all available PDB structures containing glycans. The glycan ligand information is displayed, and links are provided for structural visualization and redirection to other modules in GlycanStructure.ORG for further investigation of glycan-binding sites and glycan structures. AVAILABILITY AND IMPLEMENTATION: http://www.glycanstructure.org/glymdb. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

CHARMM-GUI Ligand Designer for Template-Based Virtual Ligand Design in a Binding Site.

Rational drug design involves a task of finding ligands that would bind to a specific target protein. This work presents CHARMM-GUI Ligand Designer that is an intuitive and interactive web-based tool to design virtual ligands that match the shape and chemical features of a given protein binding site. Ligand Designer provides ligand modification capabilities with 3D visualization that allow researchers to modify and redesign virtual ligands while viewing how the protein-ligand interactions are affected. Virtual ligands can also be parameterized for further molecular dynamics (MD) simulations and free energy calculations. Using 8 targets from 8 different protein classes in the directory of useful decoys, enhanced (DUD-E) data set, we show that Ligand Designer can produce similar ligands to the known active ligands in the crystal structures. Ligand Designer also produces stable protein-ligand complex structures when tested using short MD simulations. We expect that Ligand Designer can be a useful and user-friendly tool to design small molecules in any given potential ligand binding site on a protein of interest.

Foxp2 regulates anatomical features that may be relevant for vocal behaviors and bipedal locomotion.

Fundamental human traits, such as language and bipedalism, are associated with a range of anatomical adaptations in craniofacial shaping and skeletal remodeling. However, it is unclear how such morphological features arose during hominin evolution. FOXP2 is a brain-expressed transcription factor implicated in a rare disorder involving speech apraxia and language impairments. Analysis of its evolutionary history suggests that this gene may have contributed to the emergence of proficient spoken language. In the present study, through analyses of skeleton-specific knockout mice, we identified roles of Foxp2 in skull shaping and bone remodeling. Selective ablation of Foxp2 in cartilage disrupted pup vocalizations in a similar way to that of global Foxp2 mutants, which may be due to pleiotropic effects on craniofacial morphogenesis. Our findings also indicate that Foxp2 helps to regulate strength and length of hind limbs and maintenance of joint cartilage and intervertebral discs, which are all anatomical features that are susceptible to adaptations for bipedal locomotion. In light of the known roles of Foxp2 in brain circuits that are important for motor skills and spoken language, we suggest that this gene may have been well placed to contribute to coevolution of neural and anatomical adaptations related to speech and bipedal locomotion.

[Prediction Method of Elastic Modulus of Trabecular Bone Based on SE-DenseVoxNet].

Osteoporosis is one of the common metabolic diseases, which can easily lead to osteoporotic fractures. Accurate prediction of bone biomechanical properties is of great significance for the early prevention and diagnosis of osteoporosis. Bone mineral density measurement is currently used clinically as the gold standard for assessing bone strength and diagnosing osteoporosis, but studies have shown that bone mineral density can only explain 60% to 70% of bone strength changes, and trabecular bone microstructure is an important factor affecting bone strength. In order to establish the connection between trabecular bone microstructure and bone strength, this paper proposes a prediction method of trabecular bone modulus based on SE-DenseVoxNet. This method takes three-dimensional binary images of trabecular bone as input and predicts its elastic modulus in the z-axis direction. Experiments show that the error and bias between the predicted value of the method and the true value of the sample are small and have good consistency.

OsRAD51D promotes homologous pairing and recombination by preventing nonhomologous interactions in rice meiosis.

Homologous recombination is carefully orchestrated to maintain genome integrity. RAD51D has been previously shown to be essential for double-strand break repair in mammalian somatic cells. However, the function of RAD51D during meiosis is largely unknown. Here, through detailed analyses of Osrad51d single and double mutants, we pinpoint the specific function of OsRAD51D in coordinating homologous pairing and recombination by preventing nonhomologous interactions during meiosis. OsRAD51D is associated with telomeres in both meiocytes and somatic cells. Loss of OsRAD51D leads to significant induction of nonhomologous pairing and chromosome entanglements, suggesting its role in suppressing nonhomologous interactions. The failed localization of OsRAD51 and OsDMC1 in Osrad51d, together with the genetic analysis of Osrad51d Osdmc1a Osdmc1b, indicates that OsRAD51D acts at a very early stage of homologous recombination. Observations from the Osrad51d pair1 and Osrad51d ku70 double mutants further demonstrate that nonhomologous interactions require double-strand break formation but do not depend on the KU70-mediated repair pathway. Moreover, the interplay between OsRAD51D and OsRAD51C indicates both conservation and divergence of their functions in meiosis. Altogether, this work reveals that OsRAD51D plays an essential role in the inhibition of nonhomologous connections, thus guaranteeing faithful pairing and recombination during meiosis.

The study of killing effect and inducing apoptosis of 630-nm laser on lung adenocarcinoma A549 cells mediated by hematoporphyrin derivatives in vitro.

To investigate the killing effect and inducing apoptosis of 630-nm laser mediated by hematoporphyrin derivatives (HPD) on human lung adenocarcinoma A549 cells. The human lung adenocarcinoma A549 cells were incubated at random with different concentrations of HPD (5, 10, 12, 15, 20 µg/ml) for 4 h and then illuminated by 630-nm laser with different energy densities (25, 50, 75, 100 mW/cm2). And, meanwhile, the simple photosensitizer group, laser irradiation group, and blank control group were established. Then, CCK8, Hoechst 33258 staining, RT-PCR, and Western blot were employed. HPD-PDT proved no killing effect on the lung adenocarcinoma A549 cells with photosensitizer or laser irradiation alone. With the combination, the killing effect was obvious. CCK8 showed that the A549 cell viability in 15 µg/ml and 20 µg/ml HPD group as well as 50 mW/cm2, 75 mW/cm2, and 100 mW/cm2 power density group decreased significantly compared with the control group. Hoechst 33258 staining showed that with the increase of HPD concentration, the cells presented chromatin fixation and hyperchromatic nuclei. The Annexin V-FITC/PI double staining was used to detect the apoptosis rate, and the difference was statistically significant. RT-PCR and Western blot showed that the expression of Caspase-3 and Bax were significantly up-regulated. However, the Bcl-2 and Survivin were significantly down-regulated in the HPD-PDT group, while those of the other three groups showed no significant changes. HPD-PDT has a significant effect on A549 cells. The mechanism of action may be related to the upregulation of the expression of Caspase-3, Bax, and downregulation of the expression of Bcl-2 and Survivin.

LncRNA ATB promotes proliferation and metastasis in A549 cells by down-regulation of microRNA-494.

Lung cancer is a commonly diagnosed disease with poor prognosis. Novel therapeutic targets and deep understanding of the regulatory mechanisms in lung cancer are of great importance. We aimed to figure out the functional roles of lncRNA-activated by transforming growth factor-ß (ATB) in A549 cells as well as the underlying molecular mechanisms. ATB was non-physiologically expressed in A549 cells after cell transfection. Then, cell proliferation, expressions of proteins related to proliferation and epithelial-mesenchymal transition (EMT), migration, and invasion were measured by BrdU incorporation assay, Western blot analysis, and Transwell assay, respectively. Afterwards, miR-494 expression in transfected A549 cells was determined by quantitative reverse transcription PCR. Meanwhile, effects of miR-494 overexpression on ATB-overexpressed cells were assessed. Finally, the phosphorylation levels of AKT and key kinases in the Janus-activated kinase (JAK)/signal transducer and activator of transcription-3 (STAT3) pathway were detected by Western blot analysis. ATB overexpression promoted proliferation, migration, and invasion of A549 cells. Meanwhile, EMT of A549 cells was also enhanced. ATB silence showed the opposite influence. Expression of miR-494 was negatively regulated by ATB. Following experiments showed ATB-induced alterations of proliferation, migration, invasion, and EMT were all reversed by miR-494 overexpression. Finally, we proved that ATB increased phosphorylated levels of AKT, JAK1, and STAT3, and those increases were all reversed by miR-494 overexpression. We interestingly figured out that ATB promoted proliferation, migration, invasion, and EMT through down-regulating miR-494 in A549 cells. Moreover, ATB might activate AKT and the JAK/STAT3 pathway via down-regulating miR-494.

[Three-Dimensional Facial Wrinkle Measurement and Quantification].

The three-dimensional facial wrinkle measurement and quantification have important applications in many fields, which are implemented by an entire system proposed in this paper. The system uses stereo vision method based on structured-light to achieve three-dimensional facial wrinkle measuring, where the system calibration, corresponding points matching and three-dimensional reverse method are implemented. Furthermore, the facial wrinkle is considered as the noise attached on smooth facial profi le so that the facial wrinkle is acquired quantitatively by three-dimensional noise acquisition and morphologic processing method. The experimental results show that this system can accomplish accurate facial wrinkle acquisition and objective quantifi cation. This system has comprehensive applications as it is non-contact and it has high precision.

Development and application of a multi-targeting reference plasmid as calibrator for analysis of five genetically modified soybean events.

Reference materials are important in accurate analysis of genetically modified organism (GMO) contents in food/feeds, and development of novel reference plasmid is a new trend in the research of GMO reference materials. Herein, we constructed a novel multi-targeting plasmid, pSOY, which contained seven event-specific sequences of five GM soybeans (MON89788-5', A2704-12-3', A5547-127-3', DP356043-5', DP305423-3', A2704-12-5', and A5547-127-5') and sequence of soybean endogenous reference gene Lectin. We evaluated the specificity, limit of detection and quantification, and applicability of pSOY in both qualitative and quantitative PCR analyses. The limit of detection (LOD) was as low as 20 copies in qualitative PCR, and the limit of quantification (LOQ) in quantitative PCR was 10 copies. In quantitative real-time PCR analysis, the PCR efficiencies of all event-specific and Lectin assays were higher than 90%, and the squared regression coefficients (R(2)) were more than 0.999. The quantification bias varied from 0.21% to 19.29%, and the relative standard deviations were from 1.08% to 9.84% in simulated samples analysis. All the results demonstrated that the developed multi-targeting plasmid, pSOY, was a credible substitute of matrix reference materials, and could be used as a reliable reference calibrator in the identification and quantification of multiple GM soybean events.

Sequence-dependent effects of hematoporphyrin derivatives (HPD) photodynamic therapy and cisplatin on lung adenocarcinoma cells.

BACKGROUND: Hematoporphyrin derivatives (HPD)-Photodynamic therapy (PDT) in combination with cisplatin (DDP) is an effective anticancer strategy. However, whether the order of combination affects efficacy has not been studied. METHODS: The human lung adenocarcinoma (LUAD) A549 cells were used as the study subjects. After A549 cells were treated with a single medication (PDT/DDP) or a sequential combination (PDT + DDP / DDP + PDT), the cell viability was assayed using the cell counting kit-8 method. Hoechst staining, Annexin-V/propidium iodide (PI) double staining, western blotting, and a real-time quantitative polymerase chain reaction (RT-qPCR) were performed to examine the mechanisms behind the combined effects. RESULTS: A synergistic impact between HPD-PDT and DDP was found. The cell viability in the PDT+DDP group was significantly lower than in the DDP+PDT group. A significant apoptotic profile and a high apoptotic rate were seen in the PDT + DDP group. The western blot showed that the expression levels of Bcl2-associated x(Bax) and cleaved-poly ADP-ribose polymerase (PARP) increased, and those of B-cell lymphoma-2 (Bcl-2) and Caspase-9 decreased in the PDT + DDP group. At the same time, the RT-qPCR revealed the upregulation of Bax and PARP mRNA and the downregulation of Bcl-2 and Caspase-9 mRNA. CONCLUSION: The order of the combination therapy (PDT + DDP / DDP + PDT) was important. The HPD-PDT followed by DDP significantly inhibited LUAD cell viability, which may be related to the mitochondrial apoptotic pathway.

Neuroprotective amyloid ß N-terminal peptides differentially alter human α7- and α7ß2-nicotinic acetylcholine (nACh) receptor single-channel properties.

BACKGROUND AND PURPOSE: Oligomeric amyloid ß 1-42 (oAß1-42) exhibits agonist-like action at human α7- and α7ß2-containing nicotinic receptors. The N-terminal amyloid ß1-15 fragment (N-Aß fragment) modulates presynaptic calcium and enhances hippocampal-based synaptic plasticity via α7-containing nicotinic receptors. Further, the N-Aß fragment and its core sequence, the N-amyloid-beta core hexapeptide (N-Aßcore), protect against oAß1-42-associated synapto- and neurotoxicity. Here, we investigated how oAß1-42, the N-Aß fragment, and the N-Aßcore regulate the single-channel properties of α7- and α7ß2-nicotinic receptors. EXPERIMENTAL APPROACH: Single-channel recordings measured the impact of acetylcholine, oAß1-42, the N-Aß fragment, and the N-Aßcore on the unitary properties of human α7- and α7ß2-containing nicotinic receptors expressed in nicotinic-null SH-EP1 cells. Molecular dynamics simulations identified potential sites of interaction between the N-Aß fragment and orthosteric α7+/α7- and α7+/ß2- nicotinic receptor binding interfaces. KEY RESULTS: The N-Aß fragment and N-Aßcore induced α7- and α7ß2-nicotinic receptor single-channel openings. Relative to acetylcholine, oAß1-42 preferentially enhanced α7ß2-nicotinic receptor single-channel open probability and open-dwell times. Co-application with the N-Aßcore neutralized these effects. Further, administration of the N-Aß fragment alone, or in combination with acetylcholine or oAß1-42, selectively enhanced α7-nicotinic receptor open probability and open-dwell times (compared to acetylcholine or oAß1-42). CONCLUSIONS AND IMPLICATIONS: Amyloid-beta peptides demonstrate functional diversity in regulating α7- and α7ß2-nicotinic receptor function, with implications for a wide range of nicotinic receptor-mediated functions in Alzheimer's disease. The effects of these peptides on α7- and/or α7ß2-nicotinic receptors revealed complex interactions with these subtypes, providing novel insights into the neuroprotective actions of amyloid ß-derived fragments against the toxic effects of oAß1-42.

Effect of a 630 nm light on vasculogenic mimicry in A549 lung adenocarcinoma cells in vitro.

OBJECTIVE: The objective of this study was to investigate the effect of photodynamic therapy (PDT) on the formation of vasculogenic mimicry (VM) in the human lung adenocarcinoma A549 cell line in vitro. METHODS: The participants were divided into a blank control group, a photosensitizer group, a light group, and a PDT group. Cells from each group were cultured in three dimensions using Matrigel, and vasculogenic mimicry generation was observed microscopically. Periodic Acid-Schiff (PAS) staining was used to verify the vasculogenic mimicry structure. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to detect the expression levels of cellular osteopontin (OPN) and vascular endothelial growth factor (VEGF) mRNA. Western blotting was used to detect the expression levels of cellular OPN and VEGF protein. RESULTS: A549 cells cultured on Matrigel for about six hours revealed VM on PAS staining, and the number of formations was significantly reduced in the PDT group compared with other groups (P < 0.05). The RT-PCR results showed that the PDT group downregulated OPN and VEGF mRNA expression compared with each control group (P < 0.05). Western blot results showed that OPN and VEGF protein expression was downregulated in the PDT group compared with each control group (P < 0.05). The results of RT-PCR showed that the expression of OPN and VEGF mRNA was downregulated in the PDT group compared with each control group (P < 0.05). The results of Western blotting showed that the expression of OPN and VEGF was downregulated in the protein PDT group compared with each control group (P < 0.001). CONCLUSION: Photodynamic therapy significantly inhibited the formation of vasculogenic mimicry in human lung adenocarcinoma A549 cells in vitro and downregulated the expression of OPN, VEGF mRNA, and protein levels.

A rare case of pulmonary artery embolism with choriocarcinoma: A case report and literature review.

Pulmonary embolism (PE) caused by malignant tumor is not uncommon, but pulmonary artery with choriocarcinoma is rare and difficult to timely diagnose and effectively treat. To the best of our knowledge, there are only 15 cases reported at present in the literature that present variable clinical characteristics and prognosis. In the current study reports a 21-year-old female with a history of chest pain and slight fever for 4 months who was treated as a case of pneumonia. Owing to the recurrence of the symptoms, a contrast-enhanced chest computer tomography scan was performed on the patient, which revealed complete occlusion of the right pulmonary artery. The patient was diagnosed to have pulmonary embolism (PE). However, no abnormalities were observed in D-dimer value, tumor antigen testing or ultrasonography. Positron emission tomography/computed tomography (PET/CT) was performed, which revealed the abnormal hypermetabolic lesion of the right pulmonary artery. Following the laboratory report of a significantly elevated human chorionic gonadotropin ß-subunit level combined with characteristic appearance of PET-CT, the diagnosis of primary pulmonary artery with choriocarcinoma was established based on guidelines of the European Society for Medical Oncology and the criteria formulated by the International Federation of Gynecology and Obstetrics. The patient underwent chemotherapy and responded well to the treatment. Although rare, choriocarcinoma should be considered for any fertile women who presents with a massive PE. These findings emphasize the importance of the early diagnosis and treatment of this disease.

Body composition and dietary intake in patients with head and neck cancer during radiotherapy: a longitudinal study.

OBJECTIVES: To investigate the body composition and dietary intake in the patients with head and neck cancer (HNC) during radiotherapy (RT), and explore the relationship between them. METHODS: This was a prospective, longitudinal observational study. Adult patients with HNC undergoing RT between March 2017 and August 2018 were recruited. Patients' body compositions were evaluated by bioelectrical impedance analysis, and dietary intake was recorded by 24-hour dietary recall at three time points, including baseline (T1), mid-treatment (T2) and post-treatment (T3). Patients were divided into low, middle and high energy intake groups based on the average daily energy intake (DEI). Changes in body weight (BW), fat mass (FM), fat-free mass (FFM) and skeletal muscle mass (SMM) among these three groups were compared. RESULTS: From T1 to T3, the median loss of patients' BW, FM, FFM and SMM was 4.60, 1.90, 2.60 and 1.50 kg, respectively. The loss of BW was more dramatic from T2 to T3 than that from T1 to T2. BW loss was mainly contributed by SMM loss from T1 to T2 and by FM loss from T2 to T3. Meanwhile, patients' dietary intake reduced during treatment. High DEI group had a significantly attenuated loss of patients' BW, FFM, SMM and FM compared with the low DEI group. CONCLUSION: Patients' BW, FM, FFM and SMM all significantly reduced, especially from T2 to T3, with decreased DEI during RT, which stresses the importance of nutrition intervention during the whole course of RT.

Binding of Human ACE2 and RBD of Omicron Enhanced by Unique Interaction Patterns Among SARS-CoV-2 Variants of Concern.

The 2019 coronavirus disease (COVID-19) pandemic has had devastating impacts on our global health. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, has continued to mutate and spread worldwide despite global vaccination efforts. In particular, the Omicron variant, first identified in South Africa in late November 2021, has now overtaken the Delta variant and become the dominant strain worldwide. Compared to the original strain identified in Wuhan, Omicron features 50 genetic mutations, with 15 mutations in the receptor-binding domain (RBD) of the spike protein, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor for viral entry. However, it is not completely understood how these mutations alter the interaction and binding strength between the Omicron RBD and ACE2. In this study, we used a combined steered molecular dynamics (SMD) simulation and experimental microscale thermophoresis (MST) approach to quantify the interaction between Omicron RBD and ACE2. We report that the Omicron brings an enhanced RBD-ACE2 interface through N501Y, Q493K/R, and T478K mutations; the changes further lead to unique interaction patterns, reminiscing the features of previously dominated variants, Alpha (N501Y) and Delta (L452R and T478K). Our MST data confirmed that the Omicron mutations in RBD are associated with a five-fold higher binding affinity to ACE2 compared to the RBD of the original strain. In conclusion, our result could help explain the Omicron variant’s prevalence in human populations, as higher interaction forces or affinity for ACE2 likely promote greater viral binding and internalization, leading to increased infectivity.