Patient-Derived Xenograft Models for Ovarian Cancer.

Patient-derived xenograft (PDX) models play a crucial role for in vivo research. They maintain the original molecular characteristics of the human tumor and provide a more accurate tumor microenvironment, which cannot be replicated by in vitro models. This chapter describes four different transplantation methods, namely, intra-bursal, intrarenal capsule, intraperitoneal, and subcutaneous, to develop PDX models for ovarian cancer research.

The OPI•AID Zone Tool as a composite outcome for postoperative pain management quality-A protocol for an observational pilot study.

BACKGROUND: Managing postoperative pain while minimizing opioid-related adverse drug events (ORADEs) remains a significant challenge. The OPI•AID Zone Tool is proposed as a novel clinical decision support tool that - both graphically and in a scoring-system - represents the relationship between pain management and the occurrence of ORADEs, aiming to enhance patient outcomes in postoperative care. The OPI•AID Zone Tool places pain score on the x-axis and an ORADE score on the y-axis, and stratifies patients into five zones to reflect the composite impact of pain severity and ORADEs on the quality of postoperative patient care. The study will have two key aims: (1) to explore whether the OPI•AID Zone Tool can function as a composite outcome measure for postoperative pain and ORADEs, and (2) to evaluate the use of the OPI•AID Zone Tool in visual presentations and for evaluation of patients' postoperative pain management quality. METHODS: This prospective observational cohort study will include 200 adults undergoing various surgical procedures in general anesthesia with a subsequent stay in the post-anesthesia care unit (PACU) at Bispebjerg Hospital, Denmark. Substudy 1 primary outcome: To assess whether a zone score in the OPI•AID Zone Tool is associated with patient-perceived health (EQ VAS), quality of recovery (QoR-PACU), and time to discharge readiness in PACU, and if the zone score has a stronger association than pain and ORADE score in themselves. Substudy 2 primary outcome: To assess how the use of intraoperative non-opioid analgesics impact where patients are placed in the OPI•AID Zone Tool's XY scatterplot right after surgery. To assess if patients who receive more comprehensive non-opioid analgesic basic regimens, generally fall into lower zones. CONCLUSION: The OPI•AID Zone Tool could potentially be a valuable clinical decision-making tool for optimizing postoperative care by simultaneously addressing pain management and the risk of ORADEs. By computing a composite measure of these two critical outcomes, the tool could guide more nuanced and patient-centered analgesic regimens, potentially improving patient satisfaction and operational efficiency in postoperative settings. The tool's applicability will be explored in this observational pilot and followed up in a planned series of studies (opiaid.dk).

Robot-assisted biopsy sampling for online Raman spectroscopy cancer confirmation in the operating room.

PURPOSE: Cancer confirmation in the operating room (OR) is crucial to improve local control in cancer therapies. Histopathological analysis remains the gold standard, but there is a lack of real-time in situ cancer confirmation to support margin confirmation or remnant tissue. Raman spectroscopy (RS), as a label-free optical technique, has proven its power in cancer detection and, when integrated into a robotic assistance system, can positively impact the efficiency of procedures and the quality of life of patients, avoiding potential recurrence. METHODS: A workflow is proposed where a 6-DOF robotic system (optical camera + MECA500 robotic arm) assists the characterization of fresh tissue samples using RS. Three calibration methods are compared for the robot, and the temporal efficiency is compared with standard hand-held analysis. For healthy/cancerous tissue discrimination, a 1D-convolutional neural network is proposed and tested on three ex vivo datasets (brain, breast, and prostate) containing processed RS and histopathology ground truth. RESULTS: The robot achieves a minimum error of 0.20 mm (0.12) on a set of 30 test landmarks and demonstrates significant time reduction in 4 of the 5 proposed tasks. The proposed classification model can identify brain, breast, and prostate cancer with an accuracy of 0.83 (0.02), 0.93 (0.01), and 0.71 (0.01), respectively. CONCLUSION: Automated RS analysis with deep learning demonstrates promising classification performance compared to commonly used support vector machines. Robotic assistance in tissue characterization can contribute to highly accurate, rapid, and robust biopsy analysis in the OR. These two elements are an important step toward real-time cancer confirmation using RS and OR integration.

The therapeutic landscape for COVID-19 and post-COVID-19 medications from genetic profiling of the Vietnamese population and a predictive model of drug-drug interaction for comorbid COVID-19 patients.

Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.

Spin-labeling Insights into How Chemical Fixation Impacts Glycan Organization on Cells.

As new methods to interrogate glycan organization on cells develop, it is important to have a molecular level understanding of how chemical fixation can impact results and interpretations. Site-directed spin labeling technologies are well suited to study how the spin label mobility is impacted by local environmental conditions, such as those imposed by cross-linking effects of paraformaldehyde cell fixation methods. Here, we utilize three different azide-containing sugars for metabolic glycan engineering with HeLa cells to incorporate azido glycans that are modified with a DBCO-based nitroxide moiety via click reaction. Continuous wave X-band electron paramagnetic resonance spectroscopy is employed to characterize how the chronological sequence of chemical fixation and spin labeling impacts the local mobility and accessibility of the nitroxide-labeled glycans in the glycocalyx of HeLa cells. Results demonstrate that chemical fixation with paraformaldehyde can alter local glycan mobility and care should be taken in the analysis of data in any study where chemical fixation and cellular labeling occur.

Natural Polymorphisms D60E and I62V Stabilize a Closed Conformation in HIV-1 Protease in the Absence of an Inhibitor or Substrate.

HIV infection remains a global health issue plagued by drug resistance and virological failure. Natural polymorphisms (NPs) contained within several African and Brazilian protease (PR) variants have been shown to induce a conformational landscape of more closed conformations compared to the sequence of subtype B prevalent in North America and Western Europe. Here we demonstrate through experimental pulsed EPR distance measurements and molecular dynamic (MD) simulations that the two common NPs D60E and I62V found within subtypes F and H can induce a closed conformation when introduced into HIV-1PR subtype B. Specifically, D60E alters the conformation in subtype B through the formation of a salt bridge with residue K43 contained within the nexus between the flap and hinge region of the HIV-1 PR fold. On the other hand, I62V modulates the packing of the hydrophobic cluster of the cantilever and fulcrum, also resulting in a more closed conformation.

Sociodemographic, biological, and timing characteristics of dental caries and fluorosis using mixed-type cluster analysis on 12-year-olds in Ho Chi Minh city, 1989-2019.

Objectives: In 1990, Ho Chi Minh City started Community water fluoridation (CWF) at 0.7 ppm F, and in 2000, it was adjusted to 0.5 ppm F. Here, we analyzed dental caries and fluorosis data in Ho Chi Minh City to explore commonalities associated with CWF among 12-year-old children. Methods: Dental caries and fluorosis data were collected in 1989, 2003, 2012, and 2019 (N = 4773). Trained dentists scored dental caries using the WHO detection criteria and fluorosis using Dean's Fluorosis Index. We used these data and the k-prototypes method by the R package to identify clusters of participants with shared clinical and water fluoride levels. Results: We used datasets 1 (4773 participants) and 2 (4194 participants, missing fluorosis data in 1989). K-prototypes analysis identified three clusters in each dataset. Cluster 1, with 80 % of the sample at 0.5 ppm F area characterized by low caries and fluorosis scores. Cluster 2 with 60 % of the sample non-fluoridated area had high caries and low fluorosis scores. Cluster 3, with 75 % of the sample in 0.7 ppm area, had low caries but borderline high fluorosis scores. Conclusion: Identifying three clusters based on clinical and environmental scores supports the decision to fluoridate the water to prevent caries (0-0.7 ppm) and the shift from 0.7 to 0.5 ppm to keep the caries preventive effect while reducing the risk of fluorosis. Clinical significance: Our results support the effectiveness of CWF in preventing dental caries and the appropriateness of changing the F concentration to reduce the risk of fluorosis while maintaining its effectiveness.

A simple and precise alignment calibration method for cone-beam computed tomography with the verifications.

Cone-beam Computed Tomography (CBCT) is widely used in dental imaging, small animal imaging, radiotherapy, and non-destructive industrial inspection. The quality of CBCT images depends on the precise knowledge of the CBCT system's alignment. We introduce a distinct procedure, "precision alignment loop (PAL)", to calibrate any CBCT system with a circular trajectory. We describe the calibration procedure by using a line-beads phantom, and how PAL determines the misalignments from a CBCT system. PAL also yields the uncertainties in the simulated calibration to give an estimate of the errors in the misalignments. From the analytical simulations, PAL can precisely obtain the source-to-rotation axis distance (SRD), and the geometric center G, "the point in z-axis meets the detector", where the z-axis is coincident with the line from the X-ray source that intersects the axis of the rotation (AOR) orthogonally. The uncertainties of three misalignment angles of the detector are within ±0.05°, which is close to ±0.04° for the results of Yang et al. [18], but our method is easy and simple to implement. Our distinct procedure, on the other hand, yields the calibration of a micro-CT system and an example of reconstructed images, showing our calibration method for the CBCT system to be simple, precise, and accurate.

Probing polypharmacy, ageing and sex effects on physical function using different tests.

BACKGROUND: Ageing, sex and polypharmacy affect physical function. OBJECTIVES: This mouse study investigates how ageing, sex and polypharmacy interact and affect grip strength, balance beam and wire hang, correlating and comparing the different test results between and within subgroups. METHODS: Young (2.5 months) and old (21.5 months) C57BL/6 J male and female mice (n = 10-6/group) were assessed for physical function at baseline on grip strength, balance beam and wire hang with three trials of 60 s (WH60s) and one trial of 300 s (WH300s). Mice were randomised to control or diet containing a high Drug Burden Index (DBI, total anticholinergic and sedative drug exposure) polypharmacy regimen (metoprolol, simvastatin, citalopram, oxycodone and oxybutynin at therapeutic oral doses). Following 6-8 weeks of treatment, mice were reassessed. RESULTS: High DBI polypharmacy and control mice both showed age group differences on all tests (p < 0.05). Only control mice showed sex differences, with females outperforming males on the WH60s and balance beam for old mice, WH300s for young mice (p < 0.05). Polypharmacy reduced grip strength in all subgroups (p < 0.05) and only in old females reduced wire hang time and cumulative behaviour and balance beam time and %walked (p < 0.05). Physical function assessments were all correlated with each other, with differences between subgroups (p < 0.05), and mice within subgroups showed interindividual variability in performance. CONCLUSION: Age, sex and polypharmacy have variable effects on different tests, and behavioural measures are useful adjuvants to assessing performance. There was considerable within-group variability in change in measures over time. These findings can inform design and sample size of future studies.

Analysis of p-Type Doping in Graphene Induced by Monolayer-Oxidized TMDs.

Doping is one of the most difficult technological challenges for realizing reliable two-dimensional (2D) material-based semiconductor devices, arising from their ultrathinness. Here, we systematically investigate the impact of different types of nonstoichiometric solid MOx (M are W or Mo) dopants obtained by oxidizing transition metal dichalcogenides (TMDs: WSe2 or MoS2) formed on graphene FETs, which results in p-type doping along with disorders. From the results obtained in this study, we were able to suggest an analytical technique to optimize the optimal UV-ozone (UVO) treatment to achieve high p-type doping concentration in graphene FETs (∼2.5 × 1013 cm-2 in this study) without generating defects, mainly by analyzing the time dependency of D and D' peaks measured by Raman spectroscopy. Furthermore, an analysis of the structure of graphene sheets using TEM indicates that WOx plays a better protective role in graphene, compared to MoOx, suggesting that WOx is more effective for preventing the degradation of graphene during UVO treatment. To enhance the practical application aspect of our work, we have fabricated a graphene photodetector by selectively doping the graphene through oxidized TMDs, creating a p-n junction, which resulted in improved photoresponsivity compared to the intrinsic graphene device. Our results offer a practical guideline for the utilization of surface charge transfer doping of graphene toward CMOS applications.

Protective Role of MAVS Signaling for Murine Lipopolysaccharide-Induced Acute Kidney Injury.

Despite treatment advances, acute kidney injury (AKI)-related mortality rates are still high in hospitalized adults, often due to sepsis. Sepsis and AKI could synergistically worsen the outcomes of critically ill patients. TLR4 signaling and mitochondrial antiviral signaling protein (MAVS) signaling are innate immune responses essential in kidney diseases, but their involvement in sepsis-associated AKI (SA-AKI) remains unclear. We studied the role of MAVS in kidney injury related to the TLR4 signaling pathway using a murine LPS-induced AKI model in wild-type and MAVS-knockout mice. We confirmed the importance of M1 macrophage in SA-AKI through in vivo assessment of inflammatory responses. The TLR4 signaling pathway was upregulated in activated bone marrow-derived macrophages, in which MAVS helped maintain the LPS-suppressed TLR4 mRNA level. MAVS regulated redox homeostasis via NADPH oxidase Nox2 and mitochondrial reverse electron transport in macrophages to alleviate the TLR4 signaling response to LPS. Hypoxia-inducible factor 1α (HIF-1α) and AP-1 were key regulators of TLR4 transcription and connected MAVS-dependent reactive oxygen species signaling with the TLR4 pathway. Inhibition of succinate dehydrogenase could partly reduce inflammation in LPS-treated bone marrow-derived macrophages without MAVS. These findings highlight the renoprotective role of MAVS in LPS-induced AKI by regulating reactive oxygen species generation-related genes and maintaining redox balance. Controlling redox homeostasis through MAVS signaling may be a promising therapy for SA-AKI.

Improving the prediction of wildfire susceptibility on Hawai'i Island, Hawai'i, using explainable hybrid machine learning models.

This study presents a comparative analysis of four Machine Learning (ML) models used to map wildfire susceptibility on Hawai'i Island, Hawai'i. Extreme Gradient Boosting (XGBoost) combined with three meta-heuristic algorithms - Whale Optimization (WOA), Black Widow Optimization (BWO), and Butterfly Optimization (BOA) - were employed to map areas susceptible to wildfire. To generate a wildfire inventory, 1408 wildfire points were identified within the study area from 2004 to 2022. The four ML models (XGBoost, WOA-XGBoost, BWO-XGBoost, and BOA-XGBoost) were run using 14 wildfire-conditioning factors categorized into four main groups: topographical, meteorological, vegetation, and anthropogenic. Six performance metrics - sensitivity, specificity, positive predictive values, negative predictive values, the Area Under the receiver operating characteristic Curve (AUC), and the average precision (AP) of Precision-Recall Curves (PRCs) - were used to compare the predictive performance of the ML models. The SHapley Additive exPlanations (SHAP) framework was also used to interpret the importance values of the 14 influential variables for the modeling of wildfire on Hawai'i Island using the four models. The results of the wildfire modeling indicated that all four models performed well, with the BWO-XGBoost model exhibiting a slightly higher prediction performance (AUC = 0.9269), followed by WOA-XGBoost (AUC = 0.9253), BOA-XGBoost (AUC = 0.9232), and XGBoost (AUC = 0.9164). SHAP analysis revealed that the distance from a road, annual temperature, and elevation were the most influential factors. The wildfire susceptibility maps generated in this study can be used by local authorities for wildfire management and fire suppression activity.

Structural conservation in the glutathione binding in Sphingomonas sp. glutaredoxin Grx3 and variations for cold adaptation.

Glutaredoxin 3 (Grx3), a redox protein with a thioredoxin-fold structure, maintains structural integrity and glutathione (GSH) binding capabilities across varying habitat temperatures. The cis-Pro loop, essential for GSH binding, relies on the Arg-Asp salt bridge (α2-α3) and Gln-His hydrogen bond (ß3-ß4) for its conformation. In some psychrophilic Grx3 variants, Arg in α2 is replaced with Tyr, and His in ß4 is replaced with Phe. This study examines the roles of these bonds in Grx3's structure, function, and cold adaptation, using SpGrx3 from the Arctic bacterium Sphingomonas sp. Despite its cold habitat, SpGrx3 maintains the Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond. The R51Y substitution disrupts the α2-α3 salt bridge, while the H63F and H63Y substitutions hinder the salt bridge through cation-π interactions with Arg51, involving Phe63/Tyr63, thereby enhancing flexibility. Conversely, mutations that disrupt the hydrogen bond (Q56A, H63A, and H63F) reduce thermal stability. In the psychrophilic Grx3 configuration A48T/R51Y/H63F, a Thr48-Gln56 hydrogen bond stabilizes the cis-Pro loop, enhancing flexibility by disrupting both bonds. Furthermore, all mutants exhibit reduced α-helical content and catalytic efficiency. In summary, the highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the cis-Pro loop and catalytic activity in SpGrx3. His63 is favored as it avoids cation-π interactions with Arg51, unlike Phe63/Tyr63. Psychrophilic Grx3 variants have adapted to cold environments by reducing GSH binding and increasing structural flexibility. These findings deepen our understanding of the structural conservation in Grx3 for GSH binding and the critical alterations required for cold adaptation.

Synergetic Enhancement of Quantum Yield and Exciton Lifetime of Monolayer WS2 by Proximal Metal Plate and Negative Electric Bias.

The efficiency of light emission is a critical performance factor for monolayer transition metal dichalcogenides (1L-TMDs) for photonic applications. While various methods have been studied to compensate for lattice defects to improve the quantum yield (QY) of 1L-TMDs, exciton-exciton annihilation (EEA) is still a major nonradiative decay channel for excitons at high exciton densities. Here, we demonstrate that the combined use of a proximal Au plate and a negative electric gate bias (NEGB) for 1L-WS2 provides a dramatic enhancement of the exciton lifetime at high exciton densities with the corresponding QY enhanced by 30 times and the EEA rate constant decreased by 80 times. The suppression of EEA by NEGB is attributed to the reduction of the defect-assisted EEA process, which we also explain with our theoretical model. Our results provide a synergetic solution to cope with EEA to realize high-intensity 2D light emitters using TMDs.

Beyond compliance: public voluntary standards and their effect on state institutional capacity in Vietnam.

Public certification standards have received limited scholarly attention, especially the institutional capacity of public authorities that develop and implement these standards to address complex challenges, such as the promotion of industrial ecology and industrial symbiosis for enhancing resource use efficiency. This research uses an institutional capacity assessment framework to examine the ways in which a voluntary public standard for certifying eco-industrial parks affected the Vietnamese state's capacity to coordinate and implement industrial ecology. The article draws upon the interviews and a review of official documentation to show that the benefits of public standards extend beyond compliance to the enhancement of state capacities to coordinate complex policy domains such as industrial ecology. The findings contribute to providing a basis to redesign standard-setting processes to move beyond end-user compliance and provide insights into how public actors can more effectively address 'systemic' sustainability challenges - from circular economy ambitions to the Sustainable Development Goals.

Molecular subtypes of Adenovirus-associated acute respiratory infection outbreak in children in Northern Vietnam and risk factors of more severe cases.

BACKGROUND: Under the pressure of Human Adenovirus (HAdV)-associated acute respiratory infection (ARI) outbreak in children in Northern Vietnam in the end of 2022, this study was initiated to identify the HAdV subtype(s) and examine the associated clinical features and risk factors of more severe cases. METHODS: This study evaluated pediatric patients with ARI which had tested positive for HAdV between October and November 2022 using a multiplex real-time PCR panel. Nasopharyngeal aspirates or nasal swab samples were used for sequencing to identify HAdV subtypes. Clinical data were collected retrospectively. RESULTS: Among 97 successfully sequenced samples, the predominant subtypes were HAdV-B3 (83%), HAdV-B7 (16%) and HAdV-C2 (1%). Lower respiratory manifestations were found in 25% of the patients of which 5% were diagnosed with severe pneumonia. There was no significant association between HAdV subtype and clinical features except higher white blood cell and neutrophil counts in those detected with HAdV-B3 (p<0.001). Co-detection of HAdV with ≥1 other respiratory viruses was found in 13/24(54%) of those with lower respiratory manifestations and 4/5(80%) of those with severe pneumonia (odds ratio (95% confidence interval) vs. those without = 10.74 (2.83, 48.17) and 19.44 (2.12, 492.73) respectively after adjusting for age, sex, birth delivery method, day of disease). CONCLUSION: HAdV-B3 and HAdV-B7 were predominant in the outbreak. Co-detection of HAdV together with other respiratory viruses was a strong risk factor for lower respiratory tract illnesses and severe pneumonia. The findings advocate the advantages of multi-factor microbial panels for the diagnosis and prognosis of ARI in children.

Influence of titanium dioxide and composite on the accuracy of an intraoral scanner for bilateral upper posterior edentulous jaw (Kennedy class I) scanning: An in vitro study.

OBJECTIVES: The accuracy of 3-dimensional images produced by the intraoral scanner (IOS) is affected by scanning-aid materials. This in vitro study aimed to elucidate the influence of scanning-aid materials on the accuracy (trueness and precision) of digital scanning on the bilateral upper posterior edentulous jaw (Kennedy class I). METHODS: The asymmetrical bilateral upper posterior edentulous model (reference model) was generated using a 3D printer with three groups (application of TiO2 powder - composite and no-treatment control). The experimental scans were executed (n = 10 per group) using TRIOS3 (3shape), while one reference scan was obtained by an industrial scanner (Solutionix - C500). Values of trueness and precision were evaluated using the 3D superimposition method on mean deviation values. The accuracy was assessed using mean deviation values following the 3D superimposition method. RESULTS: IOS had high trueness (20.6 µm), and significant differences were found between the no-treatment and TiO2 groups. Considering the cut-off value of deviations as 300 µm for clinical acceptability, the analysis clarified the most variations in the control group. There was a significant difference between the no-treatment group and others in the maxillary tuberosity area relating to long-span edentulous. The composite group had the best precision values (1.1 µm). Significant differences were found between composite and TiO2 groups (2.7 µm). CONCLUSIONS: The bilateral upper posterior edentulous jaw digital impressions obtained using IOS were accurate. However, the digital images in the palate and maxillary tuberosity area related to long-span edentulous differed significantly. TiO2-containing powder and composite landmarks affected the accuracy and stability of the IOS. CLINICAL SIGNIFICANCE: Scanning aid materials can increase the accuracy of the bilateral upper posterior edentulous jaw scanning with IOS.

Subsecond lung cancer detection within a heterogeneous background of normal and benign tissue using single-point Raman spectroscopy.

Significance: Lung cancer is the most frequently diagnosed cancer overall and the deadliest cancer in North America. Early diagnosis through current bronchoscopy techniques is limited by poor diagnostic yield and low specificity, especially for lesions located in peripheral pulmonary locations. Even with the emergence of robotic-assisted platforms, bronchoscopy diagnostic yields remain below 80%. Aim: The aim of this study was to determine whether in situ single-point fingerprint (800 to 1700 cm-1) Raman spectroscopy coupled with machine learning could detect lung cancer within an otherwise heterogenous background composed of normal tissue and tissue associated with benign conditions, including emphysema and bronchiolitis. Approach: A Raman spectroscopy probe was used to measure the spectral fingerprint of normal, benign, and cancer lung tissue in 10 patients. Each interrogated specimen was characterized by histology to determine cancer type, i.e., small cell carcinoma or non-small cell carcinoma (adenocarcinoma and squamous cell carcinoma). Biomolecular information was extracted from the fingerprint spectra to identify biomolecular features that can be used for cancer detection. Results: Supervised machine learning models were trained using leave-one-patient-out cross-validation, showing lung cancer could be detected with a sensitivity of 94% and a specificity of 80%. Conclusions: This proof of concept demonstrates fingerprint Raman spectroscopy is a promising tool for the detection of lung cancer during diagnostic procedures and can capture biomolecular changes associated with the presence of cancer among a complex heterogeneous background within less than 1 s.

Interspecies comparison of the early transcriptomic changes associated with hepatitis B virus exposure in human and macaque immune cell populations.

Background and aims: Hepatitis B virus (HBV) infection affects 300 million individuals worldwide, representing a major factor for the development of hepatic complications. Although existing antivirals are effective in suppressing replication, eradication of HBV is not achieved. Therefore, a multi-faceted approach involving antivirals and immunomodulatory agents is required. Non-human primates are widely used in pre-clinical studies due to their close evolutionary relationship to humans. Nonetheless, it is fundamental to identify the differences in immune response between humans and these models. Thus, we performed a transcriptomic characterization and interspecies comparison of the early immune responses to HBV in human and cynomolgus macaques. Methods: We characterized early transcriptomic changes in human and cynomolgus B cells, T cells, myeloid and plasmacytoid dendritic cells (pDC) exposed to HBV ex vivo for 2 hours. Differentially-expressed genes were further compared to the profiles of HBV-infected patients using publicly-available single-cell data. Results: HBV induced a wide variety of transcriptional changes in all cell types, with common genes between species representing only a small proportion. In particular, interferon gamma signaling was repressed in human pDCs. At the gene level, interferon gamma inducible protein 16 (IFI16) was upregulated in macaque pDCs, while downregulated in humans. Moreover, IFI16 expression in pDCs from chronic HBV-infected patients anti-paralleled serum HBsAg levels. Conclusion: Our characterization of early transcriptomic changes induced by HBV in humans and cynomolgus macaques represents a useful resource for the identification of shared and divergent host responses, as well as potential immune targets against HBV.

Unraveling the roles of aromatic cluster side-chain interactions on the structural stability and functional significance of psychrophilic Sphingomonas sp. glutaredoxin 3.

This study investigates the impact of aromatic cluster side-chain interactions in Grx3 (SpGrx3) from the psychrophilic Arctic bacterium Sphingomonas sp. Grx3 is a class I oxidoreductase with a unique parallel arrangement of aromatic residues in its aromatic cluster, unlike the tetrahedral geometry observed in Trxs. Hydrophilic-to-hydrophobic substitutions were made in the aromatic cluster, in ß1 (E5V and Y7F), adjacent ß2 (Y32F and Y32L), both ß1 and ß2 (E5V/Y32L), and short α2 (R47F). The hydrophobic substitutions, particularly those at or near Tyr7 (E5V, Y7F, Y32F, and R47F), increased melting temperatures and conformational stability, whereas disrupting ß1-ß2 interactions (Y32L and E5V/Y32L) led to structural instability of SpGrx3. However, excessive hydrophobic interactions (Y7F and E5V/Y32L) caused protein aggregation at elevated temperatures. All mutations resulted in a reduction in α-helical content and an increase in ß-strand content. The R47F mutant, which formed dimers and exhibited the highest ß-strand content, showed increased conformational flexibility and a significant decrease in catalytic rate due to the disturbance of ß1-α2 interactions. In summary, the configuration of the aromatic cluster, especially Tyr7 in the buried ß1 and Arg47 in the short α2, played crucial roles in maintaining the active conformation of SpGrx3 and preventing its protein aggregation. These modifications, reducing hydrophobicity in the central ß-sheet, distinguish Grx3 from other Trx-fold proteins, highlighting evolutionary divergence within the Trx-fold superfamily and its functional versatility.