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We analyze the performance of an active terahertz (THz)-frequency signal detector based on an antiferromagnetic tunnel junction (ATJ) Pt/Ir ${}_{0.2}$ Mn ${}_{0.8}$ /MgO/Pt in a wide temperature range $T = 4.2$ –300 K. Assuming that the geometric parameters of the ATJ depend on temperature due to the standard thermal expansion, and using usual thermal dependencies for the ATJ resistance-area product and tunneling anisotropic magnetoresistance (TAMR) ratio, we show that the output dc voltage of the detector operating in the frequency range of 0.1–1 THz increases by 50%–70% as the temperature decreases from 300 to 4.2 K. In addition, the cooling of the detector results in a substantial reduction of the low-frequency Johnson-Nyquist noise, and a corresponding increase of the detector signal-to-noise ratio (SNR) (up to 20), as well as in the reduction of the minimum detectable power of the detector (to 1 pW or less). The detector characteristics reach their optimal values near the temperature of $T \simeq 10$ K and frequency of $f \approx 0.15$ THz due to the interplay between the inertial properties of the detector, and its impedance-matching conditions. The developed formalism can be used for the optimization of practical parameters of ATJ-based spintronic devices.

Protein oligomerization regulates many critical physiological processes, and its dysregulation can contribute to dysfunction and diseases. Elucidating the assembly pathways and quantifying their underlying thermodynamic and kinetic parameters are crucial for a comprehensive understanding of biological processes and for advancing therapeutics targeting abnormal protein oligomerization. Established binding assays, with limited mass precision, often rely on simplified models for data interpretation. In contrast, high-resolution native mass spectrometry (nMS) can directly determine the stoichiometry of biomolecular complexes in vitro. However, quantification is hindered by the fact that the relative abundances of gas-phase ions generally do not reflect solution concentrations due to nonuniform response factors. Recently, slow mixing mode (SLOMO)-nMS, which can quantify the relative response factors of interacting species, has been demonstrated to reliably measure the affinity (Kd) of binary biomolecular complexes. Here, we introduce an extended form of SLOMO-nMS that enables simultaneous quantification of the thermodynamics in multistep association reactions. Application of this method to homo-oligomerization of concanavalin A and insulin confirmed the reliability of the assay and uncovered details about the assembly processes that had previously resisted elucidation. Results acquired using SLOMO-nMS implemented with charge detection shed new light on the binding of recombinant human angiotensin-converting enzyme 2 and the SARS-CoV-2 spike protein. Importantly, new assembly pathways were uncovered, and the affinities of these interactions, which regulate host cell infection, were quantified. Together, these findings highlight the tremendous potential of SLOMO-nMS to accelerate the characterization of protein assembly pathways and thermodynamics and, in so doing, enhance fundamental biological understanding and facilitate therapeutic development. https://orcid.org/0000-0002-3389-7112

One-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimers (IAJDs) were discovered in our laboratories in 2021 to represent a new class of synthetic vectors for the targeted delivery of messenger RNA (mRNA). They coassemble with mRNA by simple injection of their ethanol solution into a pH 4 acetate buffer containing the nucleic acid into monodisperse dendrimersome nanoparticles (DNPs) with predictable dimensions. DNPs are competitive with 4-component lipid nanoparticles (LNPs), which are used in commercial COVID-19 vaccines, except that IAJDs are prepared in fewer reaction steps than each individual component of the LNPs. This simple methodology for the synthesis of IAJDs and their coassembly with mRNA into DNPs, together with the precise placement of their individual components and indefinite stability at room temperature in air, make them attractive candidates for the development of nanomedicine-based targeted mRNA delivery. Access to the large-scale synthesis of IAJDs without the need for sophisticated technologies, instrumentation, and synthetic skills is expected to open numerous new opportunities worldwide in nanomedicine. The goal of this publication is to report an accelerated ten-gram-scale synthesis of IAJD97 from inexpensive food additives obtained from renewable plant phenolic acid starting materials by methodologies accessible to any laboratory. This accelerated synthesis can be accomplished in 4 days. We expect that the work reported here will impact the field of nanomedicine in both developed and less developed countries.

Hyperthermia plays a significant role in cancer treatment by inducing cell damage through temperature elevation, often used alongside other treatment modalities. During hyperthermia therapy, temperature control is crucial. Here, we report on a simple synthesis route of hybrid plasmonic nanodiamonds either completely wrapped with an Au shell (NV@Au) or densely covered with Au NPs (NV@SiO2@Au). Such integration of nanodiamonds with Au NPs is advantageous both for heating and precise thermometry at nanoscale. After structural and optical investigations, heating abilities of the obtained plasmonic nanodiamonds were thoroughly inspected on glass, in association with living cells, and in tissue slices ex vivo, revealing their effective heat generation under excitation with light using a single excitation source. The developed hybrid plasmonic nanodiamonds were finally applied for local photothermal therapy of melanoma in vivo, demonstrating their efficacy in eradicating cancer cells and monitoring temperature during the process.

The formation of calcium phosphate under the control of water-soluble polymers is important for understanding bone growth in living organisms. These experiments also have spin-offs in the creation of composite materials, including for regenerative medicine applications. The formation of calcium phosphate (hydroxyapatite) from calcium chloride and diammonium phosphate was studied in the presence of polymers containing carboxyl, amine, and imidazole groups. Depending on the polymer composition, solid products and stable dispersions of positively or negatively charged nanoparticles were obtained. Oppositely charged nanoparticles can interact with each other to form a macroporous composite material, which holds promise as a filler for bone defects. The formation of a calcium phosphate layer around a living cell (dinoflagellate Gymnodinium corollariumA. M. Sundström, Kremp et Daugbjerg) using positive composite nanoparticles is a one-step approach to cell mineralization.

Recent advances in mRNA technology and its delivery have enabled mRNA-based therapeutics to enter a new era in medicine. The rapid, potent, and transient nature of mRNA-encoded proteins, without the need to enter the nucleus or the risk of genomic integration, makes them desirable tools for treatment of a range of diseases, from infectious diseases to cancer and monogenic disorders. The rapid pace and ease of mass-scale manufacturability of mRNA-based therapeutics supported the global response to the COVID-19 pandemic. Nonetheless, challenges remain with regards to mRNA stability, duration of expression, delivery efficiency, and targetability, to broaden the applicability of mRNA therapeutics beyond COVID-19 vaccines. By learning from the rapidly expanding preclinical and clinical studies, we can optimise the mRNA platform to meet the clinical needs of each disease. Here, we will summarise the recent advances in mRNA technology; its use in vaccines, immunotherapeutics, protein replacement therapy, and genomic editing; and its delivery to desired specific cell types and organs for development of a new generation of targeted mRNA-based therapeutics.

Constitutional isomerism has been previously demonstrated by one of our laboratories to represent a powerful design strategy for the elaboration of complex functional self-organizations. Here we report the design, synthesis, and characterization of 14 positional, skeletal, and functional constitutional isomeric one-component, multifunctional, sequence-defined, amphiphilic ionizable Janus dendrimers (IAJDs). Their coassembly by simple injection with luciferase mRNA (Luc-mRNA) to form dendrimersome nanoparticles (DNPs) was studied. Subsequently, the resulting DNPs were employed to investigate, with screening experiments, the delivery of Luc-mRNA in vivo. Constitutional isomerism was shown to produce changes of up to two orders of magnitude of the total-body luciferase activity and targeted luciferase activity to the spleen and liver, of up to three orders of magnitude difference in targeted luciferase activity to the lungs and up to six orders of magnitude to lymph nodes. These results indicate that constitutional isomerism may represent not only a simple but also an important synthetic strategy that most probably may impact the activity of all components of synthetic vectors used in RNA-based nanomedicine, including in mRNA vaccines and therapeutics.

Seasonal cycles in climatic factors affect drivers of child growth and contribute to seasonal fluctuations in undernutrition. Current growth seasonality models are limited by categorical definitions of seasons that rely on assumptions about their timing and fail to consider their magnitude.

Reduction of wasting, or low weight-for-height, is a critical target for the Zero Hunger Sustainable Development Goal, yet robust evidence establishing continuous seasonal patterns of wasting is presently lacking. The current consensus of greatest hunger during the preharvest period is based on survey designs and analytical methods, which discretize time frame into preharvest/postharvest, dry/wet, or lean/plenty seasons. We present a spatiotemporally nuanced study of acute malnutrition seasonality in African drylands using a 15-year data set of Standardized Monitoring and Assessment of Relief and Transition surveys (n = 412,370). Climatological similarity was ensured by selecting subnational survey regions with 1 rainy season and by spatially matching each survey to aridity and livelihood zones. Harmonic logit regression models indicate 2 peaks of wasting during the calendar year. Greatest wasting prevalence is estimated in April to May, coincident with the primary peak of temperature. A secondary peak of wasting is observed in August to October, coinciding with the primary peak of rainfall and secondary peak of temperature. This pattern is retained across aridity and livelihood zones and is sensitive to temperature, precipitation, and vegetation. Improved subnational estimation of acute malnutrition seasonality can thus assist decision makers and practitioners in data-sparse settings and facilitate global progress toward Zero Hunger.

Background: Understanding seasonal patterns in nutritional status is critical for achieving and tracking global nutrition goals. However, the majority of nutrition seasonality research design draws on 2 or 3 within-year time points based on existing assumptions of seasonality, missing a more nuanced pattern.Objective: We aimed to identify the intra-year variability of childhood wasting, severe wasting, and weight-for-height z-scores (WHZ) in a dryland single wet-season context and illustrate an analytical approach for improving analysis of the seasonality of nutritional status.Methods: To quantify the intra-year variability in nutritional status, we use data from a 23-month panel study (May 2018 to March 2020) following 231 children (6-59 months of age) in eastern Chad. We apply a mixed-effects harmonic regression with child- and village-level fixed effects on the odds of being wasted, severely wasted, and on WHZ, testing for multiple and nonsymmetrical seasonal peaks, adjusted for child sex and age. We triangulate our findings using climate data on temperature, vegetation, and precipitation.Results: We identify 2 annual peaks of wasting and severe wasting. Wasting peaks at 14.7% (confidence interval [CI], 11.8-18.2) at the end of the dry season, while the smaller peak corresponds to the start of the harvest period at 13.4% (CI, 10.7-16.6). The odds of being wasted decline during the rainy season to 11.8% (CI, 9.4-14.7), with the lowest prevalence of 8.8% (CI, 6.9-11.1) occurring during the start of the dry season. In addition, a 1°C monthly increase in temperature is significantly associated with a 5% (CI, 1.4-8.7) and 12% (CI, 3.0-20.3) increase in the odds that a child is wasted and severely wasted, respectively.Conclusions: Intra-year variability of child wasting is far more complex and nuanced than identified by the literature, with 2 peaks, as opposed to 1, likely corresponding to different seasonal drivers, such as food insecurity, disease, water contamination, and care practices at different times of year. Better seasonality analysis can go a long way in improving the timing and content of programming with the goal of reducing child wasting.

Electron beam irradiation is of great interest to researchers as it opens up new opportunities for meaningful interdisciplinary collaboration between scientists from fields such as chemistry, physics, ecology, engineering, biology, nanotechnology, and materials science. The interaction of electrons with matter ensures the formation of highly efficient reactive particles. A setup for studying the interaction of an electron beam with a liquid is presented. The efficiency of transformation of dissolved organic compounds under the action of electron beam irradiation was evaluated using pulsed cathodoluminescence. The novelty of the study lies in the fact that the irradiation of solutions and the excitation of luminescence, which is used for diagnostics, are carried out simultaneously by the same electron beam. This setup is a tool for studying the physicochemical utilization of toxic dissolved compounds. The decay process, stimulated by pulsed electron beams from 50 to 3200 pulses, proceeded intensively in aqueous solutions with the addition of crystal violet or bisphenol A. Some of the transformation products were emitted into the air, changing the composition and intensity of its luminescence. The conversion of the studied compounds was carried out using electron absorption spectroscopy and stationary fluorescence.

Application of the prostate-specific antigen (PSA) test, which measures PSA levels in blood, is standard in prostate cancer (PCa) screening. However, because PSA levels may be elevated for reasons other than PCa, it leads to high rates of misdiagnosis and overtreatment. Recently, alteration in the N-glycan sialylation of PSA, specifically increased levels of α2-3-linked N-acetylneuraminic acid (α2-3-Neu5Ac or α2-3-sialic acid), was identified as a potential biomarker for clinically significant PCa. Here, we introduce a robust top-down native mass spectrometry (MS) approach, performed using a combination of α2-3-Neu5Ac-specific and nonspecific neuraminidases and employing center-of-mass monitoring (CoMMon), for quantifying the levels of α2-3-Neu5Ac as a fraction of total N-linked Neu5Ac present on PSA extracted from blood serum. To illustrate the potential of the assay for clinical diagnosis and disease staging of PCa, the percentages of α2-3-Neu5Ac on PSA (%α23PSA) in the serum of low-grade (International Society of Urological Pathology Grade Group/GG1), intermediate-grade (GG2), and high-grade (GG3,4,5) PCa individuals were measured. We observed a high sensitivity (85.5%) and specificity (84.6%) for discrimination of GG1 from clinically significant GG2–5 patients when using a %α23PSA test cut-off of 28.0%. Our results establish that the %α23PSA in blood serum PSA, which can be precisely measured in a non-invasive manner with our dual neuraminidase native MS/CoMMon assay, can discriminate between clinically significant PCa (GG2–5) and low-grade PCa (GG1). Such discrimination has not been previously achieved and represents an important clinical need. This assay could greatly improve the standard PSA test and serve as a valuable PCa diagnostic tool.

Native mass spectrometry (nMS) screening of natural glycan libraries against glycan-binding proteins (GBPs) is a powerful tool for ligand discovery. However, as the glycan concentrations are unknown, affinities cannot be measured directly from natural libraries. Here, we introduce Concentration-Independent (COIN)-nMS, which enables quantitative screening of natural glycan libraries by exploiting slow mixing of solutions inside a nanoflow electrospray ionization emitter. The affinities (Kd) of detected GBP–glycan interactions are determined, simultaneously, from nMS analysis of their time-dependent relative abundance changes. We establish the reliability of COIN-nMS using interactions between purified glycans and GBPs with known Kdvalues. We also demonstrate the implementation of COIN-nMS using the catch-and-release (CaR)-nMS assay for glycosylated GBPs. The COIN-CaR-nMS results obtained for plant, fungal, viral, and human lectins with natural libraries containing hundreds of N-glycans and glycopeptides highlight the assay’s versatility for discovering new ligands, precisely measuring their affinities, and uncovering “fine” specificities. Notably, the COIN-CaR-nMS results clarify the sialoglycan binding properties of the SARS-CoV-2 receptor binding domain and establish the recognition of monosialylated hybrid and biantennary N-glycans. Moreover, pharmacological depletion of host complex N-glycans reduces both pseudotyped virions and SARS-CoV-2 cell entry, suggesting that complex N-glycans may serve as attachment factors.

Background Three-dimensional (3-D) modelling can be a useful technical aid and we used it to reconstruct a homicide scene to corroborate the statement of an eyewitness. 3-D modelling of the bloodstain was conducted by Micro Smith Poser 11 and Autodesk 3-Ds Max software. The technique was found to be easily understandable by the police and judiciary in the interpretation of the sequence of the events of the crime. It refuted the eye-witness's account of the actions of the accused who was charged with murder and allowed collection, storage and retrieval of the patho-anatomic information about the deceased.Conclusion The checks on the accuracy of statements given by eye-witnesses that can be provided by 3-D modelling may change the outcome of criminal investigations in future.

Studies have demonstrated that visual-spatial skills correlate with student performance and success in science, technology, engineering, and math (STEM). The ability to reason with spatial information is essential for conceptual subjects like chemistry, a deep understanding of which requires dealing with the invisible world of atoms and molecules and linking microscopic properties to macroscopic observables. The link between spatial ability and chemistry achievement is well-studied and documented. The extent to which various teaching tools can help students visualize abstract physicochemical concepts is an active area of research. Virtual reality (VR) can leverage the proximity effect and create immersive learning experiences for students struggling with spatial imagery. For this reason, many VR resources have been developed to teach chemistry, yet the number of studies exploring the potential of VR to enhance spatial ability and chemistry achievement has so far been limited. Here, we report on an exploratory study conducted at a large public institution to evaluate the effect of virtual reality on learning in chemistry students with low visual-spatial skills. Spatial ability was assessed using a visual-spatial pretest. Those students who failed the test were randomized into the VR intervention and control groups. While no statistically significant difference in class performance between these two groups was observed, our data showed some improvement in the median scores in the VR intervention group compared to the control. Future studies enrolling a higher number of participants would help to make more definitive conclusions about the effect of VR on students with low visual-spatial skills.

Introduction: Rosa webbiana(RW) Wall Ex. Royle is used in traditional medicine in Pakistan for the treatment of several diseases including jaundice. To date, only neuroprotective potential of the plant has been evaluated.Objective: The current study was designed to isolate bioactive compound(s) and investigate its possible radical scavenging, anti-inflammatory and hepatoprotective activities.Methods: Column chromatography was done to isolate compounds from the chloroform fraction of RW. The compound was characterized by mass spectrometry, 1H-NMR, and 2D-NMR spectroscopy. Radical scavenging activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) assays, while anti-inflammatory potential was evaluated viaxylene-induced ear edema and carrageenan-induced paw edema models. For hepatoprotection, CCl4-induced model in mice was used.Results: A triterpene compound (3α, 21β-dihydroxy-olean-12-ene) was isolated from RW fruits (ARW1). The compound exhibited DPPH and H2O2scavenging activities 61 ± 1.31% and 66 ± 0.48% respectively at 500 µg/ml. ARW1 (at 50 mg/kg) exhibited 62.9 ± 0.15% inhibition of xylene-induced ear edema and 66.6 ± 0.17% carrageenan-induced paw edema in mice. In CCl4-induced hepatotoxic mice, ARW1 significantly countered elevation in alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (T.B), and reduction in total protein (T.P) levels. Liver histomorphological study supported the serum biochemical profile for hepatoprotection. Moreover, ARW1 significantly attenuated the toxic changes in body and liver weight induced by CCl4.Conclusion: The compound ARW1 exhibited anti-radical, anti-inflammatory and hepatoprotective effects. The anti-inflammatory and hepatoprotective activities may be attributed to anti-oxidant potential of the compound.

ABSTRACTSome studies have shown that the betel nut Areca catechu Land “binahong” leaves Anredera cordifolia (Ten) Steenishave anti-parasite and wound healing properties. This study evaluated the effect of A. catechunut and A. cordifolialeaves powder supplementation on faecal parasite number and type, histopathology of the intestine, caecum, associated organs, some serum biochemistry, and egg production of laying hens. Twenty-four 54-week-old ISA-brown laying hens from local layer farmers were assigned randomly into 4-treatment groups: 1) without supplementation (T0), 2) supplemented with 0.25% (T0.25%), 3) 0.5% (T0.5%), 4) 1.0% (T1.0%). We carried out the supplementation for 18 days by administering A. catechunut powder for 3-days, and subsequently, A. cordifolialeaves powder for another 3-days for 3-rounds to control the parasite larvae. Faecal parasite count and type were enumerated at the beginning and end of treatment. Egg production was recorded daily during the 18 days experiment. Blood was sampled at the end of the experiment to determine serum albumin, globulin, and transaminases. The intestinal tract, liver, and spleen samples were collected at the end of the study for histopathological examination. Faecal Ascaridia galliin control hens increased by 87.5% after 18 days of the experiment, while A. catechunut and A. cordifolialeaves powder supplementation prevented such an increase. Supplemented hens have a better reduction of Railentina cesticilluscompared to control birds. Supplementation improved intestinal and other tissue histopathology, especially in the caecum (free of erosion), improving serum albumin and transaminases without affecting egg production.

Much attention has been paid to experimental investigation of the thermodynamic properties of aromatic and heteroaromatic compounds since the beginning of the 20th century. The available data on thioxanthone (THX), sulfur-containing heterocycle, is in a significant scatter. The phase transition enthalpies of THX were reconciled by combining conventional measurements and empiric approaches recently developed in our laboratory. The heat capacities in the crystal and liquid states were determined by adiabatic calorimetry and power-compensated differential scanning calorimetry. The fusion enthalpy at the melting temperature was measured and adjusted to 298.15 K according to Kirchhoff’s law of thermochemistry. The value at 298.15 K was found using solution calorimetry. From these data, the temperature dependence of the sublimation enthalpy was evaluated. Ideal gas-phase heat capacities were calculated applying rigid rotor–harmonic oscillator approximation and then used to independently derive the temperature dependence of the sublimation enthalpy.