Crosslinking albumin for drug release from spray dried particles.

In space, astronauts are exposed to a large doses of ionizing radiation which can cause various health problems. The drug delivery of antioxidants and anti-inflammatory substances is a promising countermeasure for the harmful cellular effects of radiation exposure. Curcumin is a polyphenol derived from the rhizome of the turmeric plant that has strong antioxidant capabilities. The therapeutic potential of this radical scavenging drug is limited by poor uptake in the body due to its insolubility in water, rapid metabolism by the intestinal mucosa and liver, and quick excretion. Drug delivery vehicles can be used to enhance the bioavailability of curcumin. Albumin, a biodegradable and non-immunogenic plasma protein, can be utilized as a drug delivery vehicle. Curcumin binds to albumin’s hydrophobic pockets, which increases its solubility and decreases its rate of degradation in physiological conditions. Curcumin was solubilized with 0.5% (w/v) fatty acid free human serum albumin (FAF HSA) and spray dried to form a dry powder of particles. To produce particles with a smooth and spherical morphology, 0.05% (v/v) Tween® 20 was included in the solution. Curcumin release from these particles followed a first-order release profile (Ct/Cinf = 1 - ekt, t = time in min) with k = 0.065 ± 0.003. To alter the release of curcumin from the spray dried particles, 0.5% FAF HSA was crosslinked using 0.01M 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and 5 mM Nhydroxysulfosuccinimide. This crosslinking method was confirmed by native polyacrylamide gel electrophoresis (PAGE) and differential scanning calorimetry (DSC). For the native PAGE results, multiple protein bands at high molecular weights were observed for the crosslinked FAF HSA and a single protein band for the uncrosslinked FAF HSA. This suggested that multiple FAF HSA molecules had been crosslinked to each other. DSC results reported a significant increase in melting point from 53.60 ± 1.35 °C to 63.82 ± 2.34 °C of spray dried FAF HSA particles, further confirming the crosslinking method. Curcumin was bound to the crosslinked FAF HSA in the presence of 0.05% Tween® 20 and spray dried. The resulting particles showed a less uniform morphology and curcumin release followed a first-order profile with a significantly lower k = 0.049 ± 0.004. Future work to improve the morphology of the crosslinked FAF HSA particles and increase the level of crosslinking to further slow curcumin release will enhance the applicability of these particles in mitigating radiation-induced cell damage

Application of Actinobacteria in Agriculture, Nanotechnology, and Bioremediation

“Actinobacteria” are of significant economic value to mankind since agriculture and forestry depend on their soil system contribution. The organic stuff of deceased creatures is broken down into soil, and plants are able to take the molecule up again. Actinobacteria can be used for sustainable agriculture as biofertilizers for the improvement of plant growth or soil health by promoting different plant growth attributes, such as phosphorus and potassium solubilization, production of iron-chelating compounds, phytohormones, and biological nitrogen attachment even under the circumstances of natural and abiotic stress. Nanotechnology has received considerable interest in recent years due to its predicted impacts on several key fields such as health, energy, electronics, and the space industries. Actinobacterial biosynthesis of nanoparticles is a dependable, environmentally benign, and significant element toward green chemistry, which links together microbial biotechnology and nanobiology. Actinobacterial-produced antibiotics are common in nearly all of the medical treatments, and they are also recognized to aid in the biosynthesis of excellent surface and size properties of nanoparticles. Bioremediation using microorganisms is relatively safe and more efficient. Actinobacteria use carbon toxins to synthesize economically viable antibiotics, enzymes, and proteins as well. These bacteria are the leading microbial phyla that are beneficial for deterioration and transformation of organic and metal substrates

tRNA Anticodon Cleavage by Target-Activated CRISPR-Cas13a Effector

Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA–guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Leptotrichia shahii Cas13a expressed in Escherichia coli cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus providing defense from the phages. In addition, Cas13a-mediated tRNA cleavage indirectly activates the RNases of bacterial toxin-antitoxin modules cleaving messenger RNA, which could provide a backup defense. The mechanism of Cas13a-induced antiphage defense resembles that of bacterial anticodon nucleases, which is compatible with the hypothesis that type VI effectors evolved from an abortive infection module encompassing an anticodon nuclease

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill & Melinda Gates Foundation

Impact of spin-orbit density dependent potential in heavy ion reactions forming Se nuclei

The Skyrme energy density formalism is employed to explore the effect of spin-orbit interaction potential by considering a two nucleon transfer process via various entrance channels such as 23Na + 49V , 25Mg + 47Ti , 27Al + 45Sc , 29Si + 43Ca and 31P + 41K , all forming the same compound system 72Se $^{\ast}$ , using both spherical as well as quadrupole deformed ( $\beta_{2}$ nuclei. For spherical nuclei, the spin-orbit density part $V_{J}$ of nuclear potential remains unaffected with the transfer of two nucleons from the target to the projectile, however, show notable variation in magnitude after inclusion of deformation effects. Likewise, deformations play an important role in the spin-orbit density independent part $V_{P}$ , as the fusion pocket start appears, which otherwise diminish for the spherical nuclei. Further, the effect of an increase in the N/Z ratio of Se is explored on $V_{J}$ as well as $V_{P}$ and results are compared with transfer channels. In addition to this, the role of double spin-orbit parameters ( $W_{0}$ and $W'_{0}$ with relative contribution of the isoscalar and isovector parts of spin-orbit strength is explored in view of SkI2, SkI3 and SkI4 Skyrme forces. Beside this, the decay path of 72Se $^{\ast}$ nucleus formed in 27Al + 45Sc reaction is investigated within the framework of dynamical cluster decay model (DCM), where the nuclear proximity potential is obtained by both Skyrme energy density formalism (SEDF) and proximity pocket formula. The fusion hindrance in the 27Al + 45Sc reaction is also addressed via the barrier lowering parameter $\Delta V_{B}$ . Finally, the contribution of spin-orbit density dependent interaction potential is estimated for the 27Al + 45Sc reaction using single ( $W_{0}$ or $W_{0}'$ and double spin-orbit parameters ( $W_{0}$ and $W_{0}'$

A Review on Biomechanics of Anterior Cruciate Ligament and Materials for Reconstruction

The anterior cruciate ligament is one of the six ligaments in the human knee joint that provides stability during articulations. It is relatively prone to acute and chronic injuries as compared to other ligaments. Repair and self-healing of an injured anterior cruciate ligament are time-consuming processes. For personnel resuming an active sports life, surgical repair or replacement is essential. Untreated anterior cruciate ligament tear results frequently in osteoarthritis. Therefore, understanding of the biomechanics of injury and properties of the native ligament is crucial. An abridged summary of the prominent literature with a focus on key topics on kinematics and kinetics of the knee joint and various loads acting on the anterior cruciate ligament as a function of flexion angle is presented here with an emphasis on the gaps. Briefly, we also review mechanical characterization composition and anatomy of the anterior cruciate ligament as well as graft materials used for replacement/reconstruction surgeries. The key conclusions of this review are as follows: (a) the highest shear forces on the anterior cruciate ligament occur during hyperextension/low flexion angles of the knee joint; (b) the characterization of the anterior cruciate ligament at variable strain rates is critical to model a viscoelastic behavior; however, studies on human anterior cruciate ligament on variable strain rates are yet to be reported; (c) a significant disparity on maximum stress/strain pattern of the anterior cruciate ligament was observed in the earlier works; (d) nearly all synthetic grafts have been recalled from the market; and (e) bridge-enhanced repair developed by Murray is a promising technique for anterior cruciate ligament reconstruction, currently in clinical trials. It is important to note that full extension of the knee is not feasible in the case of most animals and hence the loading pattern of human ACL is different from animal models. Many of the published reviews on the ACL focus largely on animal ACL than human ACL. Further, this review article summarizes the issues with autografts and synthetic grafts used so far. Autografts (patellar tendon and hamstring tendon) remains the gold standard as nearly all synthetic grafts introduced for clinical use have been withdrawn from the market. The mechanical strength during the ligamentization of autografts is also highlighted in this work

Higher order gaps in the renormalized band structure of doubly aligned hBN/bilayer graphene moiré superlattice

Abstract This paper presents our findings on the recursive band gap engineering of chiral fermions in bilayer graphene doubly aligned with hBN. Using two interfering moiré potentials, we generate a supermoiré pattern that renormalizes the electronic bands of the pristine bilayer graphene, resulting in higher order fractal gaps even at very low energies. These Bragg gaps can be mapped using a unique linear combination of periodic areas within the system. To validate our findings, we use electronic transport measurements to identify the position of these gaps as a function of the carrier density. We establish their agreement with the predicted carrier densities and corresponding quantum numbers obtained using the continuum model. Our study provides strong evidence of the quantization of the momentum-space area of quasi-Brillouin zones in a minimally incommensurate lattice. It fills important gaps in the understanding of band structure engineering of Dirac fermions with a doubly periodic superlattice spinor potential

Defining the seed sequence of the Cas12b CRISPR-Cas effector complex

<p>Target binding by CRISPR-Cas ribonucleoprotein effectors is initiated by the recognition of double-stranded PAM motifs by the Cas protein moiety followed by destabilization, localized melting, and interrogation of the target by the guide part of CRISPR RNA moiety. The latter process depends on seed sequences, parts of the target that must be strictly complementary to CRISPR RNA guide. Mismatches between the target and CRISPR RNA guide outside the seed have minor effects on target binding, thus contributing to off-target activity of CRISPR-Cas effectors. Here, we define the seed sequence of the Type V Cas12b effector from <i>Bacillus thermoamylovorans</i>. While the Cas12b seed is just five bases long, in contrast to all other effectors characterized to date, the nucleotide base at the site of target cleavage makes a very strong contribution to target binding. The generality of this additional requirement was confirmed during analysis of target recognition by Cas12b effector from <i>Alicyclobacillus acidoterrestris</i>. Thus, while the short seed may contribute to Cas12b promiscuity, the additional specificity determinant at the site of cleavage may have a compensatory effect making Cas12b suitable for specialized genome editing applications.</p