Effects of foetal size, sex and developmental stage on adaptive transcriptional responses of skeletal muscle to intrauterine growth restriction in pigs.

Intrauterine growth restriction (IUGR) occurs both in humans and domestic species. It has a particularly high incidence in pigs, and is a leading cause of neonatal morbidity and mortality as well as impaired postnatal growth. A key feature of IUGR is impaired muscle development, resulting in decreased meat quality. Understanding the developmental origins of IUGR, particularly at the molecular level, is important for developing effective strategies to mitigate its economic impact on the pig industry and animal welfare. The aim of this study was to characterise transcriptional profiles in the muscle of growth restricted pig foetuses at different gestational days (GD; gestational length ~ 115 days), focusing on selected genes (related to development, tissue injury and metabolism) that were previously identified as dysregulated in muscle of GD90 fetuses. Muscle samples were collected from the lightest foetus (L) and the sex-matched foetus with weight closest to the litter average (AW) from each of 22 Landrace x Large White litters corresponding to GD45 (n = 6), GD60 (n = 8) or GD90 (n = 8), followed by analyses, using RT-PCR and protein immunohistochemistry, of selected gene targets. Expression of the developmental genes, MYOD, RET and ACTN3 were markedly lower, whereas MSTN expression was higher, in the muscle of L relative to AW littermates beginning on GD45. Levels of all tissue injury-associated transcripts analysed (F5, PLG, KNG1, SELL, CCL16) were increased in L muscle on GD60 and, most prominently, on GD90. Among genes involved in metabolic regulation, KLB was expressed at higher levels in L than AW littermates beginning on GD60, whereas both IGFBP1 and AHSG were higher in L littermates on GD90 but only in males. Furthermore, the expression of genes specifically involved in lipid, hexose sugar or iron metabolism increased or, in the case of UCP3, decreased in L littermates on GD60 (UCP3, APOB, ALDOB) or GD90 (PNPLA3, TF), albeit in the case of ALDOB this only involved females. In conclusion, marked dysregulation of genes with critical roles in development in L foetuses can be observed from GD45, whereas for a majority of transcripts associated with tissue injury and metabolism differences between L and AW foetuses were apparent by GD60 or only at GD90, thus identifying different developmental windows for different types of adaptive responses to IUGR in the muscle of porcine foetuses.

Mechanisms Underlying a Quantum Superposition Microscope Based on THz-Driven Coherent Oscillations in a Two-Level Molecular Sensor.

We report pump-probe measurements of a hydrogen molecule (H_{2}) in the tunnel junction of a scanning tunneling microscope coupled to ultrashort terahertz (THz) pulses. The coherent oscillation of the THz-induced dc tunneling current at a frequency of ∼0.5 THz fingerprints the absorption by H_{2} as a two-level system (TLS). Two components of the oscillatory signal are observed and point to both photon and field aspects of the THz pulses. A few loosely bound states with similar energies for the upper state of the TLS are evidenced by the coherent revival of oscillatory signal. Furthermore, the comparison of spectroscopic features of H_{2} with different tips provides an understanding of the TLS for H_{2}.

Origin of photoinduced DC current and two-level population dynamics in a single molecule.

Studying the photoinduced changes of materials with atomic-scale spatial resolution can provide a fundamental understanding of light-matter interaction. A long-standing impediment has been the detrimental thermal effects on the stability of the tunneling gap from intensity-modulated laser irradiation of the scanning tunneling microscope junction. Photoinduced DC current transduces photons to an electric current and is widely applied in optoelectronics as switches and signal transmission. Our results revealed the origin of the light-induced DC current and related it to the two-level population dynamics and related nonlinearity in the conductance of a single molecule. Here, we compensated for the near-visible laser-induced thermal effects to demonstrate photoinduced DC current spectroscopy and microscopy and to observe the persistent photoconductivity of a two-level pyrrolidine molecule. The methodology can be generally applied to the coupling of light to scan probes to investigate light-matter interactions at the atomic scale.

Electrical Manipulation of Quantum Coherence in a Two-Level Molecular System.

We report the manipulation of ultrafast quantum coherence of a two-level single hydrogen molecular system by employing static electric field from the sample bias in a femtosecond terahertz scanning tunneling microscope. A H_{2} molecule adsorbed on the polar Cu_{2}N surface develops an electric dipole and exhibits a giant Stark effect. An avoided crossing of the quantum state energy levels is derived from the resonant frequency of the single H_{2} two levels in a double-well potential. The dephasing time of the initial wave packet can also be changed by applying the electric field. The electrical manipulation for different tunneling gaps in three dimensions allows quantification of the surface electrostatic fields at the atomic scale. Our work demonstrated the potential application of molecules as controllable two-level molecular systems.

Single-Molecule Continuous-Wave Terahertz Rectification Spectroscopy and Microscopy.

We report rectification spectroscopy (RS) for single molecules performed with continuous-wave terahertz (CW THz) radiation at the tunneling junction of a scanning tunneling microscope (STM) at 8 K. CW THz-RS serves as a new technique in single-molecule vibrational and magnetic excitation spectroscopy besides inelastic electron tunneling spectroscopy (IETS). By quantitatively studying IETS and THz RS, we show that CW THz induces a sinusoidal bias modulation with amplitude linearly dependent on the THz far-field amplitude. Such THz-induced bias modulation amplitude appears to be sensitive to the THz beam alignment but insensitive to variation in the tunneling gap far smaller than the THz wavelength.

Ganciclovir-induced mutations are present in a diverse spectrum of post-transplant malignancies.

BACKGROUND: Ganciclovir (GCV) is widely used in solid organ and haematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown. METHODS: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs. RESULTS: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCVsig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids. CONCLUSIONS: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.

Atomic-Scale Rectification and Inelastic Electron Tunneling Spectromicroscopy.

The phenomenon of rectification describes the emergence of a DC current from the application of an oscillating voltage. Although the origin of this effect has been associated with the nonlinearity in the current-voltage I(V) relation, a rigorous understanding of the microscopic mechanisms for this phenomenon remains challenging. Here, we show the close connection between rectification and inelastic electron tunneling spectroscopy and microscopy for single molecules with a scanning tunneling microscope. While both techniques are based on nonlinear features in the I(V) curve, comprehensive line shape analyses reveal notable differences that highlight the two complementary techniques of nonlinear conductivity spectromicroscopy for probing nanoscale systems.

Clinical presentation and in-hospital prognosis of lung cancer patients presenting with suspected and confirmed COVID-19.

We sought to compare the clinical presentation and prognosis of patients with lung cancer and confirmed COVID-19 infection to those with negative RT-PCR SARS-CoV-2 results. We included patients with confirmed lung cancer and suspected COVID-19 who presented to the emergency department. The primary outcome was in-hospital mortality and secondary outcomes included admission to intensive care unit (ICU) or mechanical ventilation. We analyzed the characteristics according to RT-PCR results and primary outcome. We constructed a logistic regression for each RT-PCR result group to find potential predictors of the primary outcome. Among 110 individuals with confirmed lung cancer (65±9 years, 51% male), 38 patients had positive RT-PCR and 72 patients had negative RT-PCR. There was no difference between groups for any clinical characteristic or comorbidities though individuals with confirmed COVID-19 had higher functionality in the ECOG scale. Leucocytes and lymphocytes were lower in individuals with positive tests. The primary outcome occurred in 58 (53%) individuals, 37 (34%) were admitted to the ICU, and 29 (26%) required mechanical ventilation. Although mortality was similar between the two groups, individuals with confirmed COVID-19 were significantly more likely to be admitted to the ICU or receive mechanical ventilation. Only lower lymphocytes and higher CRP were significantly associated with higher mortality. The clinical presentation of COVID-19 in lung cancer is not sufficient to identify higher or lower probability groups among symptomatic individuals, the overall mortality is high irrespective of RT-PCR results, and lymphopenia on admission was associated with the diagnosis and prognosis for COVID-19.

Confinement-Induced Catalytic Dissociation of Hydrogen Molecules in a Scanning Tunneling Microscope.

The catalytic scission of single chemical bonds has been induced by the nanoscale confinement in a scanning tunneling microscope (STM) junction. Individual hydrogen molecules sandwiched between the STM tip and a copper substrate can be dissociated solely by the reciprocating movement of the tip. The reaction rate depends sensitively on the local molecular environment, as exemplified by the effects of a nearby carbon monoxide molecule or a gold adatom. Detailed mechanisms and the nature of the transition states are revealed by density functional theory (DFT) calculations. This work provides insights into chemical reactions at the atomic scale induced by localized confinement applied by the STM tip. Furthermore, a single diatomic molecule can act as a molecular catalyst to enhance the reaction rate on a surface.

Moving beyond 90% Carbon Capture by Highly Selective Membrane Processes.

A membrane-based system with a retentate recycle process in tandem with an enriching cascade was studied for >90% carbon capture from coal flue gas. A highly CO2-selective facilitated transport membrane (FTM) was utilized particularly to enhance the CO2 separation efficiency from the CO2-lean gases for a high capture degree. A techno-economic analysis showed that the retentate recycle process was advantageous for ≤90% capture owing to the reduced parasitic energy consumption and membrane area. At >90% capture, the enriching cascade outperformed the retentate recycle process since a higher feed-to-permeate pressure ratio could be applied. An overall 99% capture degree could be achieved by combining the two processes, which yielded a low capture cost of USD47.2/tonne, whereas that would be USD 42.0/tonne for 90% capture. This FTM-based approach for deep carbon capture and storage can direct air capture for the mitigation of carbon emissions in the energy sector.

Atomic-scale quantum sensing based on the ultrafast coherence of an H2 molecule in an STM cavity.

A scanning tunneling microscope (STM) combined with a pump-probe femtosecond terahertz (THz) laser can enable coherence measurements of single molecules. We report THz pump-probe measurements that demonstrate quantum sensing based on a hydrogen (H2) molecule in the cavity created with an STM tip near a surface. Atomic-scale spatial and femtosecond temporal resolutions were obtained from this quantum coherence. The H2 acts as a two-level system, with its coherent superposition exhibiting extreme sensitivity to the applied electric field and the underlying atomic composition of the copper nitride (Cu2N) monolayer islands grown on a Cu(100) surface. We acquired time-resolved images of THz rectification of H2 over Cu2N islands for variable pump-probe delay times to visualize the heterogeneity of the chemical environment at sub-angstrom scale.

Effects of treatment processes on AOC removal and changes of bacterial diversity in a water treatment plant.

The effectiveness of different treatment processes on assimilable organic carbon (AOC) removal and bacterial diversity variations was evaluated in a water treatment plant. The van der Kooij technique was applied for AOC analysis and responses of bacterial communities were characterized by the metagenomics assay. Results show that the AOC concentrations were about 93, 148, 43, 51, 37, and 38 µg acetate-C/L in effluents of raw water basin, preozonation, rapid sand filtration (RSF), ozonation, biofiltration [biological activated carbon (BAC) filtration], and chlorination (clear water), respectively. Increased AOC concentrations were observed after preozonation, ozonation, and chlorination units due to the production of biodegradable organic matters after the oxidation processes. Results indicate that the oxidation processes were the main causes of AOC formation, which resulted in significant increases in AOC concentrations (18-59% increment). The AOC removal efficiencies were 47, 28, and 60% in the RSF, biofiltration, and the whole system, respectively. RSF and biofiltration were responsible for the AOC treatment and both processes played key roles in AOC removal. Thus, both RSF and biofiltration processes would contribute to AOC treatment after oxidation. Sediments from the raw water basin and filter samples from RSF and BAC units were collected and analyzed for bacterial communities. Results from scanning electron microscope analysis indicate that bacterial colonization was observed in filter materials. This indicates that the surfaces of the filter materials were beneficial to bacterial growth and AOC removal via the adsorption and biodegradation mechanisms. Next generation sequencing analyses demonstrate that water treatment processes resulted in the changes of bacterial diversity and community profiles in filters of RSF and BAC. According to the findings of bacterial composition and interactions, the dominant bacterial phyla were Proteobacteria (41% in RSF and 56% in BAC) followed by Planctomycetes and Acidobacteria in RSF and BAC systems, which might affect the AOC biodegradation efficiency. Results would be useful in developing AOC treatment and management processes in water treatment plants.

MiRNAs in milk can be used towards early prediction of mammary gland inflammation in cattle.

Considering the importance of early disease detection for reducing the huge financial and animal welfare impact of bovine mastitis globally, improved tools are urgently needed that can accurately detect early mammary inflammation. MiRNAs have demonstrated value as disease biomarkers, however, their potential for accurately detecting early mammary inflammation has not been examined in detail. To address this, we investigated the association between levels of four inflammation-associated miRNAs (bta-miR-26a, bta-miR-142-5p, bta-miR-146a and bta-miR-223) and CMT scores (0 to 3) obtained from a large number of individual quarter milk samples (n = 236) collected from dairy cows at different lactations (1 to 4). Initial analyses (n = 21 samples) confirmed that the levels of each of bta-miR-142-5p, bta-miR-146a and bta-miR-223 in whole milk were significantly correlated with mRNA levels of known inflammatory markers (HP, TNF, CXCL8 and IL1B) in milk cells (Rho ≥ 0.49, P < 0.005). Subsequent analyses (n = 215 samples) revealed a significant effect of CMT score on each of the four miRNAs analysed (P < 0.0001), characterised by a progressive increase in miRNA levels in milk as CMT score increase from 0 to > 1. Moreover, a significant effect of lactation number (P < 0.01) for bta-miR-26a, bta-miR-142-5p and bta-miR-146a was attributed to higher miRNA levels during lactation 1 than later lactations. Finally, by generating ROC curves we showed that bta-miR-223 and bta-miR-142-5p levels could identify early inflammatory changes in individual quarter milk samples (CMT1) with high accuracy (100% sensitivity, > 81% specificity). Our results provide novel proof of the value of miRNAs as early diagnostic biomarkers of bovine mastitis.

Total Neoadjuvant Therapy for High Risk Rectal Cancer in Western and Asian Populations - Current Evidence and Clinical Applications.

Recent data from several randomized controlled trials (RCTs) have shown that Total Neoadjuvant Therapy (TNT) can improve the treatment outcome of patients with high-risk rectal cancer from Western and East Asian populations. Systemic intensification with chemotherapy administered before (induction) or after (consolidation) neoadjuvant radiotherapy (RT) prior to total mesorectal excision (TME) surgery has been shown to improve disease-free survival (DFS), pathologic complete response (pCR) rate, treatment compliance and/or reduce the risk of disease-related treatment failure for high-risk rectal cancer. In this review we highlighted the key results of RCTs on different TNT approaches conducted in Western and Asian populations, and their impact on clinical practice and research direction. We discussed the salient issues and controversies arising from these studies such as the optimal duration of TNT, factors affecting patient selection and the feasibility of adopting a watch-and-wait approach in complete responders to TNT. There are considerable variations between treatment guidelines from Western and East Asian regions on adopting TNT in the management of high-risk rectal cancer, therefore reflecting regional differences in oncologist's preferences and feasibility in implementing TNT. The review concluded by providing an update on some of the key ongoing RCTs into a risk-adapted approach to incorporating TNT in clinical practice, and also translational research into predictive and prognostic biomarkers of response to TNT for high risk rectal cancer.

Clinical presentation and in-hospital prognosis of lung cancer patients presenting with suspected and confirmed COVID-19

We sought to compare the clinical presentation and prognosis of patients with lung cancer and confirmed COVID-19 infection to those with negative RT-PCR SARS-CoV-2 results. We included patients with confirmed lung cancer and suspected COVID-19 who presented to the emergency department. The primary outcome was in-hospital mortality and secondary outcomes included admission to intensive care unit (ICU) or mechanical ventilation. We analyzed the characteristics according to RT-PCR results and primary outcome. We constructed a logistic regression for each RT-PCR result group to find potential predictors of the primary outcome. Among 110 individuals with confirmed lung cancer (65±9 years, 51% male), 38 patients had positive RT-PCR and 72 patients had negative RT-PCR. There was no difference between groups for any clinical characteristic or comorbidities though individuals with confirmed COVID-19 had higher functionality in the ECOG scale. Leucocytes and lymphocytes were lower in individuals with positive tests. The primary outcome occurred in 58 (53%) individuals, 37 (34%) were admitted to the ICU, and 29 (26%) required mechanical ventilation. Although mortality was similar between the two groups, individuals with confirmed COVID-19 were significantly more likely to be admitted to the ICU or receive mechanical ventilation. Only lower lymphocytes and higher CRP were significantly associated with higher mortality. The clinical presentation of COVID-19 in lung cancer is not sufficient to identify higher or lower probability groups among symptomatic individuals, the overall mortality is high irrespective of RT-PCR results, and lymphopenia on admission was associated with the diagnosis and prognosis for COVID-19.

Discrete Time-Crystalline Order Enabled by Quantum Many-Body Scars: Entanglement Steering via Periodic Driving.

The control of many-body quantum dynamics in complex systems is a key challenge in the quest to reliably produce and manipulate large-scale quantum entangled states. Recently, quench experiments in Rydberg atom arrays [Bluvstein et al. Science 371, 1355 (2021)SCIEAS0036-807510.1126/science.abg2530] demonstrated that coherent revivals associated with quantum many-body scars can be stabilized by periodic driving, generating stable subharmonic responses over a wide parameter regime. We analyze a simple, related model where these phenomena originate from spatiotemporal ordering in an effective Floquet unitary, corresponding to discrete time-crystalline behavior in a prethermal regime. Unlike conventional discrete time crystals, the subharmonic response exists only for Néel-like initial states, associated with quantum scars. We predict robustness to perturbations and identify emergent timescales that could be observed in future experiments. Our results suggest a route to controlling entanglement in interacting quantum systems by combining periodic driving with many-body scars.

Controlling quantum many-body dynamics in driven Rydberg atom arrays.

The control of nonequilibrium quantum dynamics in many-body systems is challenging because interactions typically lead to thermalization and a chaotic spreading throughout Hilbert space. We investigate nonequilibrium dynamics after rapid quenches in a many-body system composed of 3 to 200 strongly interacting qubits in one and two spatial dimensions. Using a programmable quantum simulator based on Rydberg atom arrays, we show that coherent revivals associated with so-called quantum many-body scars can be stabilized by periodic driving, which generates a robust subharmonic response akin to discrete time-crystalline order. We map Hilbert space dynamics, geometry dependence, phase diagrams, and system-size dependence of this emergent phenomenon, demonstrating new ways to steer complex dynamics in many-body systems and enabling potential applications in quantum information science.

Recent Progress in the Engineering of Polymeric Membranes for CO2 Capture from Flue Gas.

CO2 capture from coal- or natural gas-derived flue gas has been widely considered as the next opportunity for the large-scale deployment of gas separation membranes. Despite the tremendous progress made in the synthesis of polymeric membranes with high CO2/N2 separation performance, only a few membrane technologies were advanced to the bench-scale study or above from a highly idealized laboratory setting. Therefore, the recent progress in polymeric membranes is reviewed in the perspectives of capture system energetics, process synthesis, membrane scale-up, modular fabrication, and field tests. These engineering considerations can provide a holistic approach to better guide membrane research and accelerate the commercialization of gas separation membranes for post-combustion carbon capture.