Material assembly from collective action of shape-changing polymers.

Some animals form transient, responsive and solid-like ensembles through dynamic structural interactions. These ensembles demonstrate emergent responses such as spontaneous self-assembly, which are difficult to achieve in synthetic soft matter. Here we use shape-morphing units comprising responsive polymers to create solids that self-assemble, modulate their volume and disassemble on demand. The ensemble is composed of a responsive hydrogel, liquid crystal elastomer or semicrystalline polymer ribbons that reversibly bend or twist. The dispersions of these ribbons mechanically interlock, inducing reversible aggregation. The aggregated liquid crystal elastomer ribbons have a 12-fold increase in the yield stress compared with cooled dispersion and contract by 34% on heating. Ribbon type, concentration and shape dictate the aggregation and govern the global mechanical properties of the solid that forms. Coating liquid crystal elastomer ribbons with a liquid metal begets photoresponsive and electrically conductive aggregates, whereas seeding cells on hydrogel ribbons enables self-assembling three-dimensional scaffolds, providing a versatile platform for the design of dynamic materials.

Cross species/genera transferability of simple sequence repeat markers, genetic diversity and population structure analysis in gladiolus (Gladiolus × grandiflorus L.) genotypes.

Background: Genetic analysis of gladiolus germplasm using simple sequence repeat (SSR) markers is largely missing due to scarce genomic information. Hence, microsatellites identified for related genera or species may be utilized to understand the genetic diversity and assess genetic relationships among cultivated gladiolus varieties. Methods: In the present investigation, we screened 26 genomic SSRs (Gladiolus palustris, Crocus sativus, Herbertia zebrina, Sysirinchium micranthum), 14 chloroplast SSRs (Gladiolus spp., chloroplast DNA regions) and 25 Iris Expressed Sequence Tags (ESTs) derived SSRs across the 84 gladiolus (Gladiolus × grandiflorus L.) genotypes. Polymorphic markers detected from amplified SSRs were used to calculate genetic diversity estimates, analyze population structure, cluster analysis and principal coordinate analysis (PCoA). Results: A total of 41 SSRs showed reproducible amplification pattern among the selected gladiolus cultivars. Among these, 17 highly polymorphic SSRs revealed a total of 58 polymorphic alleles ranging from two to six with an average of 3.41 alleles per marker. Polymorphic information content (PIC) values ranged from 0.11 to 0.71 with an average value of 0.48. A total of 4 SSRs were selectively neutral based on the Ewens-Watterson test. Hence, 66.66% of Gladiolus palustris, 48% of Iris spp. EST, 71.42% of Crocus sativus SSRs showed cross-transferability among the gladiolus genotypes. Analysis of genetic structure of 84 gladiolus genotypes revealed two subpopulations; 35 genotypes were assigned to subpopulation 1, 37 to subpopulation 2 and the remaining 12 genotypes could not be attributed to either subpopulation. Analysis of molecular variance indicated maximum variance (53.59%) among individuals within subpopulations, whereas 36.55% of variation among individuals within the total population. The least variation (9.86%) was noticed between two subpopulations. Moderate (FST = 0.10) genetic differentiation between two subpopulations was observed. The grouping pattern of population structure was consistent with the unweighted pair group method with arithmetic mean (UPGMA) dendrogram based on simple matching dissimilarity coefficient and PCoA. Conclusion: SSR markers from the present study can be utilized for cultivar identification, conservation and sustainable utilization of gladiolus genotypes for crop improvement. Genetic relationships assessed among the genotypes of respective clusters may assist the breeders in selecting desirable parents for crossing.

Retinal vascular occlusion following SARS-CoV-2 vaccination: A VAERS database analysis.

Purpose: To evaluate the cases of retinal vessel occlusion following COVID-19 vaccination and evaluate the onset interval and clinical presentations in patients diagnosed with vaccine associated retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Design: Retrospective study of the cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) between December 11, 2020 and July 1, 2022. Participants: Patients diagnosed with retinal vessel occlusion following vaccination with BNT162b2, mRNA-1273, and Ad26.COV2.S globally. Methods: We performed a descriptive analysis of the patient demographics and clinical presentation in patients with retinal vessel occlusion. The correlation between the vaccines and continuous and categorical variables were assessed. We performed the post-hoc analysis to evaluated the association between RAO and RVO onset post-vaccination, and vaccine and dosage. Finally, a 30-day reverse analysis for RAO and RVO onset following administration of vaccine. A major limitation in the methods of this study is the lack of control group for assessing the risk of retinal vessel occlusive disease in patients who received the vaccine compared to the patients who were unvaccinated. Main Outcome Measures: The crude reporting rate of retinal vessel occlusion following SARS-CoV-2 vaccine. The ocular and systemic presentations, onset duration and short term risk of RAO and RVO following vaccination. Results: During the study period, 1351 retinal vessel occlusion cases were reported globally. The crude reporting rates of retinal vessel occlusion for BNT162b2, mRNA-1273, and Ad26.COV2.S were 0.36, 0.41, and 0.69, respectively. The majority of the retinal vessel occlusion cases were reported following BNT162b2 (n=606, 74.17%). The mean age of patients with RVO and RAO was 58.54 ± 16.06 years and 64.63 ± 16.16 years, respectively. In the cohort, 817 and 433 patients were diagnosed with RVO and RAO, respectively. Most cases of RVO (41.12%) and RAO (48.27%) were reported within the first week post-vaccination. We observed that the mean onset interval for RVO was significantly longer in patients who received Ad26.Cov2.S (54.07 ± 88.98 days) compared to BNT162b2 (18.07 ± 28.66 days) and mRNA-1273 (22.85 ± 38.13 days) vaccines (p<0.0001). This was further confirmed by post-hoc analysis, which revealed a significantly longer onset duration for the Ad26.Cov2.S compared to BNT162b2 and mRNA 1273 vaccines (p<0.0001). The reverse Kaplan Meier 30-day risk analysis showed a significant a higher risk of RVO onset following BNT162b2 compared to other vaccines(p<0.0001). Conclusions: The low crude reporting rate highlights a low safety concern for retinal vessel occlusion following SARS-CoV-2 vaccination. This study provides insights into possible temporal association between reported retinal vessel occlusion events with SARS-CoV-2 vaccines, however further insights are needed to understand the underlying immunopathological mechanisms that promote thrombosis of retinal vasculature on vaccine administration.

A standardized quantitative analysis strategy for stable isotope probing metagenomics.

Stable isotope probing (SIP) facilitates culture-independent identification of active microbial populations within complex ecosystems through isotopic enrichment of nucleic acids. Many DNA-SIP studies rely on 16S rRNA gene sequences to identify active taxa, but connecting these sequences to specific bacterial genomes is often challenging. Here, we describe a standardized laboratory and analysis framework to quantify isotopic enrichment on a per-genome basis using shotgun metagenomics instead of 16S rRNA gene sequencing. To develop this framework, we explored various sample processing and analysis approaches using a designed microbiome where the identity of labeled genomes and their level of isotopic enrichment were experimentally controlled. With this ground truth dataset, we empirically assessed the accuracy of different analytical models for identifying active taxa and examined how sequencing depth impacts the detection of isotopically labeled genomes. We also demonstrate that using synthetic DNA internal standards to measure absolute genome abundances in SIP density fractions improves estimates of isotopic enrichment. In addition, our study illustrates the utility of internal standards to reveal anomalies in sample handling that could negatively impact SIP metagenomic analyses if left undetected. Finally, we present SIPmg, an R package to facilitate the estimation of absolute abundances and perform statistical analyses for identifying labeled genomes within SIP metagenomic data. This experimentally validated analysis framework strengthens the foundation of DNA-SIP metagenomics as a tool for accurately measuring the in situ activity of environmental microbial populations and assessing their genomic potential. IMPORTANCE Answering the questions, "who is eating what?" and "who is active?" within complex microbial communities is paramount for our ability to model, predict, and modulate microbiomes for improved human and planetary health. These questions can be pursued using stable isotope probing to track the incorporation of labeled compounds into cellular DNA during microbial growth. However, with traditional stable isotope methods, it is challenging to establish links between an active microorganism's taxonomic identity and genome composition while providing quantitative estimates of the microorganism's isotope incorporation rate. Here, we report an experimental and analytical workflow that lays the foundation for improved detection of metabolically active microorganisms and better quantitative estimates of genome-resolved isotope incorporation, which can be used to further refine ecosystem-scale models for carbon and nutrient fluxes within microbiomes.

Dynamically crosslinked thermoresponsive granular hydrogels.

Granular hydrogels are a promising biomaterial for a wide range of biomedical applications, including tissue regeneration, drug/cell delivery, and 3D printing. These granular hydrogels are created by assembling microgels through the jamming process. However, current methods for interconnecting the microgels often limit their use due to the reliance on postprocessing for crosslinking through photoinitiated reactions or enzymatic catalysis. To address this limitation, we incorporated a thiol-functionalized thermo-responsive polymer into oxidized hyaluronic acid microgel assemblies. The rapid exchange rate of thiol-aldehyde dynamic covalent bonds allows the microgel assembly to be shear-thinning and self-healing, with the phase transition behavior of the thermo-responsive polymer serving as secondary crosslinking to stabilize the granular hydrogels network at body temperature. This two-stage crosslinking system provides excellent injectability and shape stability, while maintaining mechanical integrity. In addition, the aldehyde groups of the microgels act as covalent binding sites for sustained drug release. These granular hydrogels can be used as scaffolds for cell delivery and encapsulation, and can be 3D printed without the need for post-printing processing to maintain mechanical stability. Overall, our work introduces thermo-responsive granular hydrogels with promising potential for various biomedical applications.

Silicone-containing thermoresponsive membranes to form an optical glucose biosensor.

Glucose biosensors that could be subcutaneously injected and interrogated without a physically connected electrode and transmitter affixed to skin would represent a major advancement in reducing the user burden of continuous glucose monitors (CGMs). Towards this goal, an optical glucose biosensor was formed by strategically tailoring a thermoresponsive double network (DN) membrane to house a phosphorescence lifetime-based glucose sensing assay. This membrane was selected based on its potential to exhibit reduced biofouling via 'self-cleaning' due to cyclical deswelling/reswelling in vivo. The membrane was strategically tailored to incorporate oxygen-sensitive metalloporphyrin phosphor, Pd meso-tetra(sulfophenyl)-tetrabenzoporphyrin ([PdPh4(SO3Na)4TBP]3) (HULK) and glucose oxidase (GOx). Specifically, electrostatic interactions and colvalent bonds were used to stabilize HULK and GOx within the membrane, respectively. Enhancing the oxygen permeability of the membrane was necessary to achieve sensitivity of HULK/GOx to physiological glucose levels. Thus, silicone microparticles were incorporated at two concentrations. Key properties of SiHy-0.25 and SiHy-0.5 microparticle-containing compositions were compared to a control having no microparticles (SiHy-0). The discrete nature of the silicone microparticles maintained the desired thermosensitivity profile and did not impact water content. While the modulus decreased with silicone microparticle content, membranes were more mechanically robust versus a conventional hydrogel. SiHy-0.25, owing to apparent phase separation, displayed greater glucose diffusion and oxygen permeability versus SiHy-0.5. Furthermore, SiHy-0.25 biosensors exhibited the greatest glucose sensitivity range of 100 to 300 mg dL-1versus only 100 to 150 mg dL-1 for both SiHy-0 and SiHy-0.5 biosensors.

Nano-bio interactions of 2D molybdenum disulfide.

Two-dimensional (2D) molybdenum disulfide (MoS2) is an ultrathin nanomaterial with a high degree of anisotropy, surface-to-volume ratio, chemical functionality and mechanical strength. These properties together enable MoS2 to emerge as a potent nanomaterial for diverse biomedical applications including drug delivery, regenerative medicine, biosensing and bioelectronics. Thus, understanding the interactions of MoS2 with its biological interface becomes indispensable. These interactions, referred to as "nano-bio" interactions, play a key role in determining the biocompatibility and the pathways through which the nanomaterial influences molecular, cellular and biological function. Herein, we provide a critical overview of the nano-bio interactions of MoS2 and emphasize on how these interactions dictate its biomedical applications including intracellular trafficking, biodistribution and biodegradation. Also, a critical evaluation of the interactions of MoS2 with proteins and specific cell types such as immune cells and progenitor/stem cells is illustrated which governs the short-term and long-term compatibility of MoS2-based biomedical devices.

2D Covalent Organic Framework Direct Osteogenic Differentiation of Stem Cells.

2D covalent organic frameworks (COFs) are an emerging class of crystalline porous organic polymers with a wide-range of potential applications. However, poor processability, aqueous instability, and low water dispersibility greatly limit their practical biomedical implementation. Herein, a new class of hydrolytically stable 2D COFs for sustained delivery of drugs to direct stem cell fate is reported. Specifically, a boronate-based COF (COF-5) is stabilized using amphiphilic polymer Pluronic F127 (PLU) to produce COF-PLU nanoparticles with thickness of ≈25 nm and diameter ≈200 nm. These nanoparticles are internalized via clathrin-mediated endocytosis and have high cytocompatibility (half-inhibitory concentration ≈1 mg mL-1 ). Interestingly, the 2D COFs induce osteogenic differentiation in human mesenchymal stem cells, which is unique. In addition, an osteogenic agent-dexamethasone-is able to be loaded within the porous structure of COFs for sustained delivery which further enhances the osteoinductive ability. These results demonstrate for the first time the fabrication of hydrolytically stable 2D COFs for sustained delivery of dexamethasone and demonstrate its osteoinductive characteristics.

Production of Haploids and Doubled Haploids in Marigold (Tagetes spp.) Using Anther Culture.

Homozygous parental lines are indispensable for commercial hybrid seed production in many ornamental and vegetable crops. The in vitro induction of haploids and doubled haploids (DHs) through gametic embryogenesis is an effective approach for single-step development of complete homozygous lines from heterozygous donor plants. Anther culture is one of the most popular and widely employed techniques for development of haploids. Here we describe the detailed protocol for rapid and successful induction of haploids in Tagetes spp. using in vitro androgenesis approach. In this protocol, we have provided the comprehensive details of various steps of anther culture in marigold right from the growing of donor plants, selection of buds, pretreatment, embryogenesis and regeneration to ploidy analysis, and chromosome doubling for development of DHs.

Ocular Manifestations of Neuronal Ceroid Lipofuscinoses.

Neuronal ceroid lipofuscinoses (NCLs) are a group of rare neurodegenerative storage disorders associated with devastating visual prognosis, with an incidence of 1/1,000,000 in the United States and comparatively higher incidence in European countries. The pathophysiological mechanisms causing NCLs occur due to enzymatic or transmembrane defects in various sub-cellular organelles including lysosomes, endoplasmic reticulum, and cytoplasmic vesicles. NCLs are categorized into different types depending upon the underlying cause i.e., soluble lysosomal enzyme deficiencies or non-enzymatic deficiencies (functions of identified proteins), which are sub-divided based on an axial classification system. In this review, we have evaluated the current evidence in the literature and reported the incidence rates, underlying mechanisms and currently available management protocols for these rare set of neuroophthalmological disorders. Additionally, we also highlighted the potential therapies under development that can expand the treatment of these rare disorders beyond symptomatic relief.

Light-Triggered In Situ Gelation of Hydrogels using 2D Molybdenum Disulfide (MoS2 ) Nanoassemblies as Crosslink Epicenter.

Light-responsive biomaterials are an emerging class of materials used for developing noninvasive, noncontact, precise, and controllable biomedical devices. Long-wavelength near-infrared (NIR) radiation is an attractive light source for in situ gelation due to its higher penetration depth and minimum side effects. The conventional approach to obtain crosslinked biomaterials relies heavily on the use of a photoinitiator by generating reactive species when exposed to short-wavelength radiation, which is detrimental to surrounding cells and tissue. Here, a new class of NIR-triggered in situ gelation system based on defect-rich 2D molybdenum disulfide (MoS2 ) nanoassemblies and thiol-functionalized thermoresponsive polymer in the absence of a photoinitiator is introduced. Exposure to NIR radiation activates the dynamic polymer-nanomaterials interactions by leveraging the photothermal characteristics of MoS2 and intrinsic phase transition ability of the thermoresponsive polymer. Specifically, upon NIR exposure, MoS2 acts as a crosslink epicenter by connecting with multiple polymeric chains via defect-driven click chemistry. As a proof-of-concept, the utility of NIR-triggered in situ gelation is demonstrated in vitro and in vivo. Additionally, the crosslinked gel exhibits the potential for NIR light-responsive release of encapsulated therapeutics. These light-responsive biomaterials have strong potential for a range of biomedical applications, including artificial muscle, smart actuators, 3D/4D printing, regenerative medicine, and therapeutic delivery.

Small cell carcinoma of the lung in a patient with previously treated synchronous adenocarcinoma and squamous cell carcinoma.

A 66-year-old Caucasian female with a 40-pack-year history of smoking and chronic obstructive pulmonary disease presented for follow-up of synchronous multiple primary lung cancers: Stage IB left upper lobe adenocarcinoma and Stage IA right middle lobe (RML) squamous cell carcinoma. The patient was treated with left upper lobectomy and RML pulmonary wedge resection 5 years prior. Surveillance chest computed tomography showed an increase in the size of the subcarinal lymph node and right lymph node conglomerate encasing the right upper lobe pulmonary artery, consistent with metastasis. Fine-needle aspiration of level 4R lymph nodes was performed. Histology and immunohistochemical staining confirmed the diagnosis of small cell carcinoma. Consequently, the patient was placed on cisplatin/etoposide combination chemotherapy.

Improvement in molecular detection of phytoplasma associated with rose by selection of suitable primers and development of a multiplex PCR assay.

Sensitive and effective phytoplasma DNA amplification in symptomatic rose cultivars is a long unresolved problem. In the present study, improvement in standardization for PCR assay for phytoplasma detection was established with rose samples by selection of various combinations of nested primer pairs of 16S ribosomal gene and secA gene. CTAB DNA extraction method was slightly modified by adding 2% polyvinyl pyrrolidone and increased the isopropanol volume which yielded better quality DNA. Best amplification results were achieved in nested PCR assay employing P1/P7, R16mF2/R16mR2 and R16F2n/R16R2, P1/P7 and R16mF2/R16mR2, and R16mF2/R16mR2 and fU5/rU3 primer pairs. Besides, a multiplex PCR assay was also developed and optimized for consistent identification of phytoplasma in rose samples by employing primer pairs of 16S rRNA and secA genes together in a single PCR reaction by optimizing annealing temperature at 55 °C.

"Equality", the "Capability Approach" and the Ethical Health Care Paradigm: The Interface.

As a means of abating the crises of society, the idea of equality has long been a progressive, universal, moral and legal principle to seek justice. However, equality is open to a broad spectrum of meanings and practical applications, mainly due to its endorsement of different interpretations and concepts that give rise to complementary and competing interests. Likewise, the "capability approach", which is proposed as an alternative to the "ideal of equality", is not only contentious but also insufficient to build the theoretical basis of an ethical health care paradigm. This article aims to expand the discussion on the ambiguity around the concept of equality, particularly how it interacts with the diversities in human capabilities in a given context.

Ocular complications of perioperative anesthesia: a review.

Ocular complications associated with anesthesia in ocular and non-ocular surgeries are rare adverse events which may present with clinical presentations vacillating between easily treatable corneal abrasions to more serious complication such as irreversible bilateral vision loss. In this review, we outline the different techniques of anesthetic delivery in ocular surgeries and highlight the incidence and etiologies of associated injuries. The changes in vision in non-ocular surgeries are mistaken for residual sedation or anesthetics, therefore require high clinical suspicion on part of the treating ophthalmologists, to ensure early diagnosis, adequate and swift management especially in surgeries such as cardiac, spine, head and neck, and some orthopedic procedures, that have a comparatively higher incidence of ocular complications. In this article, we review the literature for reports on the clinical incidence of different ocular complications associated with anesthesia in non-ocular surgeries and outline the current understanding of pathophysiological processes associated with these adverse events.

Polymer-Coated Extracellular Vesicles for Selective Codelivery of Chemotherapeutics and siRNA to Cancer Cells.

Combination therapies involving small-interfering RNA (siRNA)-mediated gene silencing and small-molecule drugs are of high interest for cancer treatment. Among the current gene delivery carriers, cell-derived extracellular vesicles (EVs) are particularly promising candidates due to their high biocompatibility, low immunogenicity, in vivo stability, and inherent targeting ability. Here, we developed a multifunctional EV platform capable of selective codelivery of siRNA and doxorubicin (DOX) to cancer cells. siRNA was first loaded into engineered lipid-hybridized EVs (eEVs) to serve as a core. Subsequently, DOX was incorporated into a polyelectrolyte shell surrounding eEVs, which was deposited by layer-by-layer (LbL) assembly. This approach resulted in the production of a stable EV-polymer complex (LbL-eEV) with a diameter of 140.2 ± 9.0 nm and zeta potential of +22.1 ± 0.5 mV. Experiments were performed to assess cellular uptake, cytotoxicity, and gene silencing efficacy in lung adenocarcinoma cells (A549), with noncancerous fibroblast cells (CCL-210) used as a control. The results demonstrated that the LbL-eEV complex can traffic through cells and release siRNA in the cytoplasm, while delivered DOX enters nuclei to induce programmed cell death. Moreover, the inherent selectivity of the particles for cancer cells resulted in effective gene silencing and cancer killing efficiency with reduced cytotoxicity to normal cells. Synchronous delivery of siRNA and DOX was also verified by flow cytometry analysis of single cells. In summary, these data provide a proof of concept for engineering EVs to deliver multiple therapeutics and suggest that LbL-eEVs are a promising drug delivery platform for targeting cancer.

The influence of dysbiosis on kidney stones that risk up renal cell carcinoma (RCC).

Kidney stone is a common urological condition, the prevalence and incidence of which has escalated in the last few years due to dietary habits and other related medical conditions such as obesity and diabetes mellitus. It is a chronic disease which leads to loss of kidney function(s) and nephrectomy. Chronic kidney stone disease has been shown to be associated with transitional cell carcinoma (TCC) or renal cell carcinoma (RCC) and kidney tumors have been found to be more frequent among patients with kidney stones. Although hyperoxaluria is mainly responsible for kidney stone formation, dysbiosis of the gut and urinary tract microbiome may in part contribute to kidney stone disease. Dysbiosis of the gut and urinary tract microbiome have been linked to kidney stone diseases with both gain and loss of function. The review provides a detailed study of how the variations in the microbiome of the human gut and urinary tract result in the chronic kidney stone diseases which are associated with increased papillary RCC risks.

Challenges faced in establishing a dedicated 250 bed COVID-19 intensive care unit in a temporary structure.

An Intensive Care Unit (ICU) is an organized system for the provision of care to critically ill patients that provides intensive and specialized medical and nursing care, an enhanced capacity for monitoring, and multiple modalities of physiologic organ support to sustain life during a period of life-threatening organ system insufficiency. While this availability of trained manpower and specialized equipment makes it possible to care for critically ill patients, it also presents singular challenges in the form of man and material management, design concerns, budgetary concerns, and protocolization of treatment. Consequently, the establishment of an ICU requires rigorous design and planning, a process that can take months to years. However, the Coronavirus disease-19 (COVID-19) epidemic has required the significant capacity building to accommodate the increased number of critically ill patients. At the peak of the pandemic, many countries were forced to resort to the building of temporary structures to house critically ill patients, to help tide over the crisis. This narrative review describes the challenges and lessons learned while establishing a 250 bedded ICU in a temporary structure and achieving functionality within a period of a fortnight.

Photothermal modulation of human stem cells using light-responsive 2D nanomaterials.

Two-dimensional (2D) molybdenum disulfide (MoS2) nanomaterials are an emerging class of biomaterials that are photoresponsive at near-infrared wavelengths (NIR). Here, we demonstrate the ability of 2D MoS2 to modulate cellular functions of human stem cells through photothermal mechanisms. The interaction of MoS2 and NIR stimulation of MoS2 with human stem cells is investigated using whole-transcriptome sequencing (RNA-seq). Global gene expression profile of stem cells reveals significant influence of MoS2 and NIR stimulation of MoS2 on integrins, cellular migration, and wound healing. The combination of MoS2 and NIR light may provide new approaches to regulate and direct these cellular functions for the purposes of regenerative medicine as well as cancer therapy.