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Background The cell envelope of Staphylococcus aureus contains 2 major secondary cell wall glycopolymers: capsular polysaccharide (CP) and wall teichoic acid (WTA). Both CP and WTA are attached to the cell wall and play distinct roles in S. aureus colonization, pathogenesis, and bacterial evasion of host immune defenses. We aimed to investigate whether CP interferes with WTA-mediated properties. Methods Strains with natural heterogeneous expression of CP, strains with homogeneous high CP expression, and CP-deficient strains were compared regarding WTA-dependent phage binding, cell adhesion, IgG deposition, and virulence in vivo. Results WTA-mediated phage adsorption, specific antibody deposition, and cell adhesion were negatively correlated with CP expression. WTA, but not CP, enhanced the bacterial burden in a mouse abscess model, while CP overexpression resulted in intermediate virulence in vivo. Conclusions CP protects the bacteria from WTA-dependent opsonization and phage binding. This protection comes at the cost of diminished adhesion to host cells. The highly complex regulation and mostly heterogeneous expression of CP has probably evolved to ensure the survival and optimal physiological adaptation of the bacterial population as a whole. [ABSTRACT FROM AUTHOR]

Sodium alginate (AlgNa) is often used to prepare oral drug capsules, offering the advantages of facile carrier formation and pH sensitivity. However, these capsules suffer from high porosity, large pore size, and mechanical and physiological instabilities. Although the performance of AlgNa in oral drug carriers can be enhanced through hybridization with other substances, this results in increased complexity and additional preparation steps. To address this problem, organic–inorganic hybrid capsules are herein prepared via the one‐step incorporation of aminosilanes (3‐aminopropyltriethoxysilane and 3‐(2‐aminoethylamino)propyltrimethoxysilane) into AlgNa and evaluated as delivery vehicles for the sustained release of a model drug, diclofenac sodium. The hybrid capsules show elevated drug encapsulation efficiencies (up to 92.7%) and pH responsiveness and outperform pure alginate capsules, exhibiting contraction and low release rates (<10%) in a simulated stomach environment (pH 1.2) and swelling and sustained release (10 h) in a simulated intestinal environment (pH 7.4). The formation of siloxane bonds between the aminosilane molecules results in stronger and more compact capsule membranes contributing to sustained drug release. Thus, our results demonstrate the potential of the proposed capsules, fabricated using a simple ecofriendly method, as carriers for sustained drug release. [ABSTRACT FROM AUTHOR]

Hypervirulent K. pneumoniae (hvKp) have emerged as clinically important pathogens, posing a serious threat to human health. RfaH, a transcriptional elongation factor, has been regarded as implicated in facilitating the transcription of long virulence operons in certain bacterial species. In K. pneumoniae, RfaH plays a vital role in promoting CPS synthesis and hypermucoviscosity, as well as mediating bacterial fitness during lung infection. In this study, we aim to conduct a systematic investigation of the roles of rfaH in the survival, dissemination, and colonization of hvKp through in vitro and in vivo assays. We found that bacterial cells and colonies displayed capsule -deficient phenotypes subsequent to the deletion of rfaH in K. pneumoniae NTUH-K2044. We confirmed that rfaH is required for the synthesis of capsule and lipopolysaccharide (LPS) by positively regulating the expression of CPS and LPS gene clusters. We found that the ΔrfaH mutant led to a significantly decreased mortality of K. pneumoniae in a mouse intraperitoneal infection model. We further demonstrated that the absence of rfaH was associated with slower bacterial growth under conditions of low nutrition or iron limitation. ΔrfaH displayed reduced survival rates in the presence of human serum. Besides, the engulfment of the ΔrfaH mutant was significantly higher than that of NTUH-K2044 by macrophages in vivo, indicating an indispensable role of RfaH in the phagocytosis resistance of hvKp in mice. Both mouse intranasal and intraperitoneal infection models revealed a higher bacterial clearance rate of ΔrfaH in lungs, livers, and spleens of mice compared to its wild type, suggesting an important role of RfaH in the bacterial survival, dissemination, and colonization of hvKp in vivo. Histopathological results supported that RfaH contributes to the pathogenicity of hvKp in mice. In conclusion, our study demonstrates crucial roles of RfaH in the survival, colonization and full virulence of hvKp, which provides several implications for the development of RfaH as an antibacterial target. [ABSTRACT FROM AUTHOR]

Glaesserella parasuis (GPS) is an important bacterial pathogen of swine. Serotype identification has presented a bottleneck in GPS research since it was first identified as the pathogen causing Glässer's disease in pigs in 1910. This paper presents a systematic review of the history of the development and application of gel immunodiffusion (GID), indirect hemagglutination assay (IHA), and polymerase chain reaction (PCR) typing methods for GPS, and the discovery of their shared antigenic basis. It provides a systematic theoretical overview of the immunology and principles underlying the three typing methods and offers new ideas for research into the prevention and control of Glässer's disease. In 1992, GPS was first classified into serotypes 1–15 using GID based on GPS heat-stable antigens, but about 25% of the strains were found to be non-typeable, and the composition of their antigens for serotyping was unclear. In 2003, the IHA method was established based on saline-extracted antigens of GPS, whose sensitivity and typing rate were higher than for GID, although about 15% of strains were still found to be non-typeable. The results of IHA and GID typing are roughly consistent, since they share the same GPS surface polysaccharide serotyping antigens, although whether these are capsular polysaccharides, lipopolysaccharides, or other polysaccharides, remains to be determined. In 2013, the Capsular polysaccharide (CPS) synthetic gene clusters from GPS serotypes 1–15 were successfully analyzed, confirming that CPS is essential for the formation of antigens for serotyping. In 2015, primers were designed based on the specific target genes of GPS capsules to establish a PCR typing method (H-PCR) for GPS, which, however, could not identify serotypes 5 and 12. In 2017, a new PCR typing method (J-PCR) was established based on the specific target genes of GPS capsules, which could identify serotypes 5 and 12. A combination of the two PCR typing methods enables the typing of almost all GPS strains, and the consistency with GID and IHA was verified using molecular biological methods. The antigenic basis of the three typing methods was shown to involve the GPS capsule. PCR typing methods are characterized by simple operation, fast speed, and low cost, and can successfully solve many problems in GID and IHA serotyping, and so have become widely adopted. [ABSTRACT FROM AUTHOR]

Let R be any real closed field expanded by some o-minimal structure. Let f : A → Rd be a definable and continuous mapping defined on a definable, closed, bounded subset A of Rn. Let E be a finite family of definable subsets of Rn contained in A. Let p be any positive integer. We prove that then there exists a finite simplicial complex T in Rn and a definable homeomorphism h :|T| → A, where |T| := υT, such that for each simplex Δ ∈ T, the restriction of h to its relative interior ... is a Cp-embedding of ... into Rn and moreover both h and f o h are of class Cp in the sense that they have definable Cp-extensions defined on an open definable neighborhood of |T| in Rn. We then call a pair (T, h) a strict Cp-triangulation of A. In addition, this triangulation can be made compatible with E in the sense that for each E ∈ E, h-1(E) is a union of some ... where Δ ∈ T. We also give an application to approximation theory. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response. [ABSTRACT FROM AUTHOR]

Isolated volar distal radioulnar joint (DRUJ) dislocation is a rare condition with only a few cases reported in the literature. Its diagnosis is often overlooked in the acute phase, and there is no consensus in its management. We present the case of a 20-year-old male patient with an isolated volar radioulnar dislocation, together with a review of the literature. The aim is to present and summarize the acute management of this condition and propose a therapeutic algorithm. [ABSTRACT FROM AUTHOR]

3D food printers facilitate novel customization of the physicochemical properties of food. This study aimed to investigate the impact of storage conditions on the inactivation of the human norovirus surrogate, Tulane virus (TuV), within 3D printed foods. TuV-inoculated protein cookie food ink (∽ 4 log PFU/g) was distributed into 18 3D food printer capsules (50 g each); half immediately underwent extrusion. Storage of the capsules and printed food products at 20 °C (0, 6, 12, and 24 h), 4 °C (0, 1, 3, and 5d), and − 18 °C (0, 1, 3, and 5d) was completed before analysis for TuV via plaque assays in addition to aerobic plate count, yeast and mold counts, and pH and water activity (aw) measurements. A significant 3-way interaction effect was observed between time, temperature, and storage method (capsule/print) (p = 0.006). Significant findings include: (1) A greater reduction in virions was observed in capsules after 24 h at 20 °C and (2) a substantial reduction in virions at 4 °C from day 0 to day 1 was observed, independent of storage method. Microbial indicators remained steady across temperatures, with storage temperature significantly impacting pH and aw. A significant two-way interaction effect (p = 0.006) was found between microorganism type (yeast/aerobic counts) and temperature. This research seeks to provide insights for the food industry and regulatory bodies in crafting guidelines for the safe storage and handling of 3D printed foods and inks. [ABSTRACT FROM AUTHOR]

Abstract Glaesserella parasuis (GPS) is an important bacterial pathogen of swine. Serotype identification has presented a bottleneck in GPS research since it was first identified as the pathogen causing Glässer’s disease in pigs in 1910. This paper presents a systematic review of the history of the development and application of gel immunodiffusion (GID), indirect hemagglutination assay (IHA), and polymerase chain reaction (PCR) typing methods for GPS, and the discovery of their shared antigenic basis. It provides a systematic theoretical overview of the immunology and principles underlying the three typing methods and offers new ideas for research into the prevention and control of Glässer’s disease. In 1992, GPS was first classified into serotypes 1–15 using GID based on GPS heat-stable antigens, but about 25% of the strains were found to be non-typeable, and the composition of their antigens for serotyping was unclear. In 2003, the IHA method was established based on saline-extracted antigens of GPS, whose sensitivity and typing rate were higher than for GID, although about 15% of strains were still found to be non-typeable. The results of IHA and GID typing are roughly consistent, since they share the same GPS surface polysaccharide serotyping antigens, although whether these are capsular polysaccharides, lipopolysaccharides, or other polysaccharides, remains to be determined. In 2013, the Capsular polysaccharide (CPS) synthetic gene clusters from GPS serotypes 1–15 were successfully analyzed, confirming that CPS is essential for the formation of antigens for serotyping. In 2015, primers were designed based on the specific target genes of GPS capsules to establish a PCR typing method (H-PCR) for GPS, which, however, could not identify serotypes 5 and 12. In 2017, a new PCR typing method (J-PCR) was established based on the specific target genes of GPS capsules, which could identify serotypes 5 and 12. A combination of the two PCR typing methods enables the typing of almost all GPS strains, and the consistency with GID and IHA was verified using molecular biological methods. The antigenic basis of the three typing methods was shown to involve the GPS capsule. PCR typing methods are characterized by simple operation, fast speed, and low cost, and can successfully solve many problems in GID and IHA serotyping, and so have become widely adopted.

Background: Tuberculosis (TB), a global infectious threat, has seen a concerning rise in aminoglycoside-resistant Mycobacterium tuberculosis (M.tb) strains. The potential role of capsule proteins remains largely unexplored. This layer acts as the primary barrier for tubercle bacilli, attempting to infiltrate host cells and subsequent disease development. Methods: The study aims to bridge this gap by investigating the differentially expressed capsule proteins in aminoglycoside-resistant M.tb clinical isolates compared with drug-sensitive isolates employing two-dimensional gel electrophoresis, mass spectrometry, and bioinformatic approaches. Results: We identified eight proteins that exhibited significant upregulation in aminoglycoside-resistant isolates. Protein Rv3029c and Rv2110c were associated with intermediary metabolism and respiration; Rv2462c with cell wall and cell processes; Rv3804c with lipid metabolism; Rv2416c and Rv2623 with virulence and detoxification/adaptation; Rv0020c with regulatory functions; and Rv0639 with information pathways. Notably, the Group-based Prediction System for Prokaryotic Ubiquitin-like Protein (GPS-PUP) algorithm identified potential pupylation sites within all proteins except Rv3804c. Interactome analysis using the STRING 12.0 database revealed potential interactive partners for these proteins, suggesting their involvement in aminoglycoside resistance. Molecular docking studies revealed suitable binding between amikacin and kanamycin drugs with Rv2462c, Rv3804c, and Rv2623 proteins. Conclusion: As a result, our findings illustrate the multifaceted nature of aminoglycoside resistance in M.tb and the importance of understanding how capsule proteins play a role in counteracting drug efficacy. Identifying the role of these proteins in drug resistance is crucial for developing more effective treatments and diagnostics for TB.

Background Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage. Methods The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015–2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children. Results Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing. Conclusions A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines. [ABSTRACT FROM AUTHOR]

Background Klebsiella pneumoniae carbapenemase–producing K pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection. Methods We tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct enzyme-linked immunosorbent assay, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model. Results We found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In 5 genetically related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsonophagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice. Conclusions Loss of function in wcaJ led to increased complement resistance, complement binding, and opsonophagocytosis, which may promote KPC-Kp persistence by enabling coexistence of increased bloodstream fitness and reduced tissue virulence. [ABSTRACT FROM AUTHOR]

Introduction: Clostridioides difficile infections (CDI) continue to pose a challenge for clinicians. Fecal microbiota transplantation (FMT) is an effective treatment option in CDI. Furthermore, recent and ongoing studies suggest potential benefits of FMT in other diseases as well. Methods: We would like to present a novel protocol for encapsulation of lyophilized fecal material. Our method provides with better compliance as well as improved flexibility, storage and safety. Results: FMT was conducted in 28 patients with an overall success rate of 82,14% using apsules containing lyophilized stool. 16 of patients were given capsules with lessened bacteria counts. The success rate in this group was 93,75%. Discussion: The results highlight the still unanswered questions about the mechanism of action and contribute to a wider use of FMT in the clinical praxis and in research. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is a pathogenic bacterium that has been linked to several illnesses acquired in both the community and hospitals. This study aimed to determine the prevalence of the clbA, K1, and K2 genes in K. pneumoniae and their relationship with antibiotic resistance. In this research, 130 clinical samples from patients in hospitals were collected from blood, urine, wounds, burns, and sputum, and only 61 of those samples were positively identified as K. pneumoniae using biochemical tests, selective media, and Vitek II. The method of disc diffusion was utilized to evaluate the 61 isolates' susceptibility to 10 antibiotics, including Imipenem, Meropenem, Cefixime, Ceftazidime, Amoxicillin-clavulanate, Gentamicin, Aztreonam, Azithromycin, Levofloxacin, and Trimethoprim-sulfamethoxazole. The results showed that the highest resistance was towards amoxicillin-clavulanate (98.36%) and the lowest towards meropenem (13.11%), and that 95.08% of the isolates were multidrug resistant (MDR). The clbA, K1, and K2 genes were detected using conventional PCR; the results showed that out of 61 isolates, only 3 were positive for K1, 52 were positive for K2, and none of the isolates were clbA+. (2/3) of the K1 and (51/52) of the K2 isolates were MDR. The finding shows a substantial association between the K1 and K2 genes and resistance to antibiotics, as the capsule is the main virulence factor in this bacteria. [ABSTRACT FROM AUTHOR]

The objective of this investigation was to formulate an ideal nanostructured lipid carrier (NLC) for glib-enclamide in oral capsules. Employing factorial design, the NLC formulation was achieved through high-pressure homogenization using Design-Expert® software, optimized using a 32-factor experimental design and response surface analysis. Comprehensive analyses were conducted to characterize NLCs and determine the optimal formulation. Rigorous evaluations, including drug content, in vitro diffusion and stability studies, were performed. Safety assessments, efficacy studies and optimization led to the identification of an optimal NLC formulation with specific lipid and surfactant percentages, resulting in a desirable particle size (nm) and a robust zeta potential indicative of strong physical stability. [ABSTRACT FROM AUTHOR]

In rain-fed crop, after the first monsoon rain, the farmers plow their lands and sow seeds. Because of the lack of moisture in the soil, sown seeds fail to germinate and are eventually destroyed. As a result, the farmers suffer economic losses. To address this issue, seed encapsulation with seaweed powder was performed. Micro (Spirulina plantensis and Chlorella vulgaris) and macroalgae (Sargassum, Halimeda macrolaba, and Gracilaria) were collected from the southeast coast of India. The seaweeds were dried, powdered, and weighed about 1 g of each and were filled in a gelatin capsule. Soil profile (pH, EC, water percolation rate, moisture content, water holding capacity, capillary action, N, P, K, Zn, Fe, Cu, and Mn) was characterized before cropping. Abelmoschus esculentus, Raphanus sativus, Helianthus annuus, and Capsicum annum cultivation were done. The plant growth and yield were analyzed. The texture was clay loamy soil with micro and macronutrients present in it. In Abelmoschus esculentus, the number of leaves, plant height, and branches were increased as compared to control. Sargassum treatment shows highest yield (285.6 g) of A. esculentus. The nutritional quality was enriched in Sargassum treatment followed by C. vulgaris and S. platensis. In Raphanussativus L. cultivation, the estimated yield is as follows: in Sargassum (5.95 kg), C. vulgaris (5.10 kg), S. platensis (3.95 kg), and control (3.15 kg). The yield of Helianthus annuus L. cultivation showed increased in Sargassum treatment of about 200.5-g total seed weight. The yield was higher in Sargassum treatment as compared to C. vulgaris and Gracilaria in Capsicum annum cultivation. Sown seeds in novel seed encapsulation remain undamaged in soil until favorable rainfall occurs. Another benefit is that a marine source biofertilizer enriched with macro/micronutrients and hormones was encapsulated around the seeds, promoting plant growth and yield. The application of fertilizer to a large area is both costly and time consuming. In contrast, applying to specific roots around the plant is both effective and cost effective in terms of plant growth. This novel seed encapsulation with marine source biofertilizer has two advantages: (i) it protects the seed from damage and (ii) it supplements plant nutrition. As a result, farmers lose less and profit more by using less biofertilizer. (a) Powder of micro and macroalgae. (b) Seeds. (c) Encapsulation of seed with micro and macroalgae powder. (d) Encapsulated with macroalgae. (e) Encapsulated with microalgae. (f) Encapsulated with micro and macroalgae. (g) Dissolving of gelatin in soil. (h) Experimental field. (i) Capsule placing inside the soil. (j) Capsule in soil. (k) Seed germination. (l) Plant growth. (m) Ladies finger yield. (n) Sunflower yield. (o) Radish yield [ABSTRACT FROM AUTHOR]

A new, sensitive, and rapid isocratic reversed phase chromatographic method (RP-HPLC–UV) was developed for simultaneous separation of two newly co-formulated antiulcer mixtures; Amoxicillin, Vonoprazan and Clarithromycin [Mixture (I)], and Amoxicillin, Lansoprazole and Clarithromycin [Mixture (II)]. Analytical separation was performed using a Promosil C18 column and ultraviolet detection at 210 nm. The separation was achieved within only 8 min. For both mixtures, an aqueous solution, composed of (Acetonitrile: Methanol: 0. 2 M phosphoric acid) within ratio of (30: 30: 40) adjusted to final pH 3.0, was the mobile phase. This method was validated as per the International Conference on Harmonization guidelines. The linearity ranges of these proposed method of the (Mixture (I)) were 25.0–400.0 µg/mL Amoxicillin, 0.5–8.0 µg/mL Vonoprazan, and 12.5–200.0 µg/mL Clarithromycin. And the linearity ranges of the (Mixture (II)) were 10.0–300.0 µg/mL Amoxicillin, 0.3–9.0 µg/mL Lansoprazole and 5.0–150.0 µg/mL Clarithromycin. This method was firstly applied for effective separation of Amoxicillin, Vonoprazan and Clarithromycin [Mixture (I)]. It fulfilled good repeatability, sensitivity, and accuracy (R.S.D. < 2.0%). The mean recoveries of the analytes in their Tri-Pak formulations were acceptable. The greenness of the developed chromatographic methods was assessed using an Eco-scale method and it was applied for content uniformity testing as per the United States Pharmacopoeia (USP) and the acceptance value of Amoxicillin, in Mixture (I) was 2.88, the acceptance values for Amoxicillin, Lansoprazole in Mixture (II) were 2.592, 2.424, respectively. [ABSTRACT FROM AUTHOR]

Introduction: A distinct strain of Klebsiella pneumoniae (K. pneumoniae) referred to as hypervirulent (hvKp) is associated with invasive infections such as pyogenic liver abscess in young and healthy individuals. In South Africa, limited information about the prevalence and virulence of this hvKp strain is available. The aim of this study was to determine the prevalence of hvKp and virulence-associated factors in K. pneumoniae isolates from one of the largest tertiary hospitals in a South African province. Methods: A total of 74 K. pneumoniae isolates were received from Pelonomi Tertiary Hospital National Health Laboratory Service (NHLS), Bloemfontein. Virulence-associated genes (rmpA, capsule serotype K1/K2, iroB and irp2) were screened using Polymerase Chain Reaction (PCR). The iutA (aerobactin transporter) gene was used as a primary biomarker of hvKp. The extracted DNAs were sequenced using the next-generation sequencing pipeline and the curated sequences were used for phylogeny analyses using appropriate bioinformatic tools. The virulence of hvKp vs. classical Klebsiella pneumoniae (cKp) was investigated using the Caenorhabditis elegans nematode model. Results: Nine (12.2%) isolates were identified as hvKp. Moreover, hvKp was significantly (p < 0.05) more virulent in vivo in Caenorhabditis elegans relative to cKp. The virulence-associated genes [rmpA, iroB, hypermucoviscous phenotype (hmv) phenotype and capsule K1/K2] were significantly (p < 0.05) associated with hvKp. A homology search of the curated sequences revealed a high percentage of identity between 99.8 and 100% with other homologous iutA gene sequences of other hvKp in the GenBank. Conclusion: Findings from this study confirm the presence of hvKp in a large tertiary hospital in central South Africa. However, the low prevalence and mild to moderate clinical presentation of infected patients suggest a marginal threat to public health. Further studies in different settings are required to establish the true potential impact of hvKp in developing countries. [ABSTRACT FROM AUTHOR]

Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for Cryptococcus neoformans and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated phases of infection. In the pulmonary infection model, TPS1- deleted (tps1D) Cryptococci are rapidly cleared by mouse lungs whereas TPS1- sufficent WT (H99) and revertant (tps1D:TPS1) strains expand in the lungs and disseminate, causing 100%mortality. Rapid pulmonary clearance of tps1Dmutant is T-cell independent and relies on its susceptibility to lung resident factors and innate immune factors, exemplified by tps1D but not H99 inhibition in a coculture with dispersed lung cells and its rapid clearance coinciding with innate leukocyte infiltration. In the disseminated model of infection, which bypasses initial lung-- fungus interactions, tps1D strain remains highly attenuated. Specifically, tps1D mutant is unable to colonize the lungs from the bloodstream or expand in spleens but is capable of crossing into the brain, where it remains controlled even in the absence of T cells. In contrast, strains H99 and tps1D:TPS1 rapidly expand in all studied organs, leading to rapid death of the infected mice. Since the rapid pulmonary clearance of tps1D mutant resembles a response to acapsular strains, the effect of tps1 deletion on capsule formation in vitro and in vivo was examined. Tps1D cryptococci form capsules but with a substantially reduced size. In conclusion, TPS1 is an important virulence factor, allowing C. neoformans evasion of resident pulmonary and innate defense mechanisms, most likely via its role in cryptococcal capsule formation. [ABSTRACT FROM AUTHOR]

This study aims to evaluate and determine the correlation between in vitro release and in vivo pharmacokinetics of two extended-release dosage forms of Cilostazol. In vitro release profiles for two dosage forms, tablet and capsule, were analyzed under physiologically mimicked medium conditions using the paddle and basket USP release apparatus. A single-dose, two-period crossover study design in beagle dogs was applied for the pharmacokinetic study. The fed and fast effects were considered for evaluation. Pseudo gastric release medium transfer setup study from pH 1.2 to pH 6.8 (+0.5% SLS) and pH 1.2 to pH 6.8 (+1.0% SLS) demonstrated that Pletaal® SR 200 mg capsules have higher drug release rates than Cilostan® CR 200 mg tablets. Similarly, in vivo study showed Cilostazol concentration in plasma and AUC was lower under the fast state than the fed state. The ratio of least squared geometric mean values, Cmax, AUC0-t, and AUC0-inf of Cilostazol were 2.53-fold, 2.89-fold, and 2.87-fold higher for Pletaal® SR 200 mg capsules compared with Cilostan® CR 200 mg tablets, respectively. Correlation of in vitro/in vivo data indicated that Pletal® SR 200 mg capsules have better release and pharmacodynamic effect than Cilostan® CR 200 mg tablets. [ABSTRACT FROM AUTHOR]

Background: Many recent studies have shown that patients who undergo capsular repair after hip arthroscopy achieve superior clinical outcomes compared with those who do not. However, patients with dysplasia or generalized ligamentous laxity (GLL) were not excluded from most of these studies, which may have affected the outcomes. Purpose: To determine whether capsular repair influences the outcomes of hip arthroscopy for patients without dysplasia or GLL. Study Design: Systematic review; Level of evidence, 1. Methods: Under the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, randomized controlled trials comparing the outcomes of capsulotomy with versus without repair were included, but studies that included patients with dysplasia or GLL were excluded. The study outcomes were patient-reported outcome measures (PROMs) at 6 months and 2 years postoperatively—including the modified Harris Hip Score (mHHS), Hip Outcome Score–Activities of Daily Living (HOS-ADL), and Hip Outcome Score–Sport-Specific Subscale (HOS-SSS)— and were compared between the repair and no-repair groups. A narrative analysis and meta-analysis were performed to integrate and compare the results of the 2 groups. In the meta-analysis of the outcome measures, studies with significant differences in the preoperative scores between the repair and no-repair groups were excluded because previous studies have shown that these can affect the outcomes. Results: A total of 761 studies were initially identified, of which 3 were included. Of the 322 included patients, 136 underwent capsular repair, and 186 underwent capsulotomy with no repair. The meta-analysis showed that capsular repair was associated with significantly higher postoperative PROMs: the mHHS at 2 years (P =.03), the HOS-ADL at 6 months (P =.02) and 2 years (P <.0001), and the HOS-SSS at 6 months (P =.02) and 2 years (P =.001). Conclusion: Capsular repair after hip arthroscopy was associated with superior clinical outcomes when compared with no capsular repair in patients without dysplasia or GLL. [ABSTRACT FROM AUTHOR]

The MCS initiative was first introduced in 2013. Since then, two MCS papers have been published: the first proposing a structured approach to consider the impact of drug substance physical properties on manufacturability and the second outlining real world examples of MCS principles. By 2023, both publications had been extensively cited by over 240 publications. This article firstly reviews this citing work and considers how the MCS concepts have been received and are being applied. Secondly, we will extend the MCS framework to continuous manufacture. The review structure follows the flow of drug product development focussing first on optimisation of API properties. The exploitation of links between API particle properties and manufacturability using large datasets seems particularly promising. Subsequently, applications of the MCS for formulation design include a detailed look at the impact of percolation threshold, the role of excipients and how other classification systems can be of assistance. The final review section focusses on manufacturing process development, covering the impact of strain rate sensitivity and modelling applications. The second part of the paper focuses on continuous processing proposing a parallel MCS framework alongside the existing batch manufacturing guidance. Specifically, we propose that continuous direct compression can accommodate a wider range of API properties compared to its batch equivalent. [ABSTRACT FROM AUTHOR]

ABSTRACT Carbapenemase-producing Klebsiella pneumoniae represents a major public health issue globally. Isolates with resistance to the newest drugs, like ceftazidime/avibactam (CZA), are increasingly reported. In this study, we analyzed the evolution of KPC-3-producing sequence type (ST) 512 K. pneumoniae strains isolated at three different times (hospitalization days 45, 56, and 78) from the same patient, two of which were observed in a pericholecystic liver abscess. The three K. pneumoniae isolates (295Kp, 304Kp, and hmv-318Kp) from the same patient were subjected to antimicrobial susceptibility testing, whole-genome sequencing, sedimentation assay, biofilm measurement, serum resistance assay, macrophage phagocytosis, and adhesion assays. KPC-producing isolate hmv-318Kp exhibited carbapenem susceptibility, hypermucoviscous (hmv) colony phenotype and CZA resistance. Virulence markers of hypervirulent Klebsiella were absent. Two non-synonymous mutations were identified in the hmv-318Kp genome comparing with isogenic strains: a single-nucleotide polymorphism (SNP) occurred in the pKpQIL plasmid, changing blaKPC-3 in the blaKPC-31 gene variant, conferring CZA resistance; and a second SNP occurred in the wzc gene of the capsular biosynthesis cluster, encoding a tyrosine kinase, resulting in the F557S Wzc protein mutation. The Klebsiella pneumoniae strain exhibiting an hmv phenotype (hmv-Kp) phenotype has been previously associated with amino acid substitutions occurring in the Wzc tyrosin kinase protein. We observed in vivo evolution of the ST512 strain to CZA resistance and acquisition of hypermucoviscosity. The pathogenetic role of the detected Wzc substitution is not fully elucidated, but other Wzc mutations were previously reported in hmv K. pneumoniae. Wzc mutants may be more frequent than expected and an underreported cause of hypermucoviscosity in K. pneumoniae clinical isolates.IMPORTANCEHere we describe the evolution of KPC-3-producing ST512 K. pneumoniae isolated at three different times from the same patient of which the last one, from a biliary abscess, showed CZA resistance by KPC-31 production and manifested hmv colony phenotype. Hypervirulent Klebsiella pneumoniae (hv-Kp) isolates are increasingly reported worldwide. Their hypervirulent traits are associated with the presence of rmpA/A2 genes and an hmv. In this study, we identified an hmv-Kp that lacked the rmpA-D cluster but showed an amino acid substitution in the Wzc tyrosin kinase protein, involved in the capsular biosynthesis. This hmv-Kp strain emerged in vivo and evolved resistance to ceftazidime/avibactam resistance in a liver abscess of a patient. Our findings suggest that wzc mutations may be underreported, making it challenging to distinguish hv-Kp from “classic” K. pneumoniae with an hmv phenotype.

Abstract Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.

Abstract Here, we conducted a comprehensive analysis of 356 Klebsiella pneumoniae species complex (KpSC) isolates that were classified as classical (cl), presumptive hypervirulent (p-hv) and hypermucoviscous-like (hmv-like). Overall, K. pneumoniae (82.3%), K. variicola (2.5%) and K. quasipneumoniae (2.5%) were identified. These isolates comprised 321 cl-KpSC, 7 p-hv-KpSC and 18 hmv-like-KpSC. A large proportion of cl-KpSC isolates were extended-spectrum-β-lactamases (ESBLs)-producers (64.4%) and 3.4% of isolates were colistin-resistant carrying carbapenemase and ESBL genes. All p-hv-KpSC showed an antibiotic susceptible phenotype and hmv-like isolates were found to be ESBL-producers (8/18). Assays for capsule production and capsule-dependent virulence phenotypes and whole-genome sequencing (WGS) were performed in a subset of isolates. Capsule amount differed in all p-hv strains and hmv-like produced higher capsule amounts than cl strains; these variations had important implications in phagocytosis and virulence. Murine sepsis model showed that most cl strains were nonlethal and the hmv-like caused 100% mortality with 3 × 108 CFUs. Unexpectedly, 3/7 (42.9%) of p-hv strains required 108 CFUs to cause 100% mortality (atypical hypervirulent), and 4/7 (57.1%) strains were considered truly hypervirulent (hv). Genomic analyses confirmed the diverse population, including isolates belonging to hv clonal groups (CG) CG23, CG86, CG380 and CG25 (this corresponded to the ST3999 a novel hv clone) and MDR clones such as CG258 and CG147 (ST392) among others. We noted that the hmv-like and hv-ST3999 isolates showed a close phylogenetic relationship with cl-MDR K. pneumoniae. The information collected here is important to understand the evolution of clinically important phenotypes such as hypervirulent and ESBL-producing-hypermucoviscous-like amongst the KpSC in Mexican healthcare settings. Likewise, this study shows that mgrB inactivation is the main mechanism of colistin resistance in K. pneumoniae isolates from Mexico.

Abstract Background Bacterial surface glycans are assembled by glycosyltransferases (GTs) that transfer sugar monomers to long-chained lipid carriers. Most bacteria employ the 55-carbon chain undecaprenyl phosphate (Und-P) to scaffold glycan assembly. The amount of Und-P available for glycan synthesis is thought to be limited by the rate of Und-P synthesis and by competition for Und-P between phosphoglycosyl transferases (PGTs) and GTs that prime glycan assembly (which we collectively refer to as PGT/GTs). While decreasing Und-P availability disrupts glycan synthesis and promotes cell death, less is known about the effects of increased Und-P availability. Results To determine if cells can maintain higher Und-P levels, we first reduced intracellular competition for Und-P by deleting all known non-essential PGT/GTs in the Gram-negative bacterium Escherichia coli (hereafter called ΔPGT/GT cells). We then increased the rate of Und-P synthesis in ΔPGT/GT cells by overexpressing the Und-P(P) synthase uppS from a plasmid (puppS). Und-P quantitation revealed that ΔPGT/GT/puppS cells can be induced to maintain 3-fold more Und-P than wild type cells. Next, we determined how increasing Und-P availability affects glycan expression. Interestingly, increasing Und-P availability increased endogenous and recombinant glycan expression. In particular, ΔPGT/GT/puppS cells could be induced to express 7-fold more capsule from Streptococcus pneumoniae serotype 4 than traditional E. coli cells used to express recombinant glycans. Conclusions We demonstrate that the biotechnology standard bacterium E. coli can be engineered to maintain higher levels of Und-P. The results also strongly suggest that Und-P pathways can be engineered to increase the expression of potentially any Und-P-dependent polymer. Given that many bacterial glycans are central to the production of vaccines, diagnostics, and therapeutics, increasing Und-P availability should be a foremost consideration when designing bacterial glycan expression systems.

The oil and gas industry frequently uses liquid corrosion inhibitors to reduce equipment and pipeline corrosion. However, this approach requires frequent additions, which are costly in terms of labor and materials. Solid corrosion inhibitor capsules (SCICs) have become an optimal alternative, as they provide long-term corrosion protection. However, the current encapsulation materials need to be modified for improving encapsulation capability. In this study, lauryl acrylate (LA) was grafted onto Ethylene-vinyl-acetates (EVA) to reduce its crystallinity and increase the interface force between EVA and oleic imidazoline (OIM). OIM was then encapsulated using the grafted EVA (EVA-g-LA) to form matrix-type solid capsules that possess the high encapsulation efficiency and long service life. The analysis with a UV–Vis spectrophotometer revealed that OIM had a stable release process from the SCIC matrix. Over a period of 91 days, the released OIM still had a high corrosion inhibition efficiency towards N80 steel (>80%). Using the prepared SCIC can reduce annual anticorrosion costs in oil and gas fields by 70%.

Mannheimia haemolytica is one of the bacterial agents responsible for bovine respiratory disease (BRD). The capability of M. haemolytica to form a biofilm may contribute to the development of chronic BRD infection by making the bacteria more resistant to host innate immunity and antibiotics. To improve therapy and prevent BRD, a greater understanding of the association between M. haemolytica surface components and biofilm formation is needed. M. haemolytica strain 619 (wild-type) made a poorly adherent, low-biomass biofilm. To examine the relationship between capsule and biofilm formation, a capsule-deficient mutant of wild-type M. haemolytica was obtained following mutagenesis with ethyl methanesulfonate to obtain mutant E09. Loss of capsular polysaccharide (CPS) in mutant E09 was supported by transmission electron microscopy and Maneval's staining. Mutant E09 attached to polyvinyl chloride plates more effectively, and produced a significantly denser and more uniform biofilm than the wild-type, as determined by crystal violet staining, scanning electron microscopy, and confocal laser scanning microscopy with COMSTAT analysis. The biofilm matrix of E09 contained predominately protein and significantly more eDNA than the wild-type, but not a distinct exopolysaccharide. Furthermore, treatment with DNase I significantly reduced the biofilm content of both the wild-type and E09 mutant. DNA sequencing of E09 showed that a point mutation occurred in the capsule biosynthesis gene wecB. The complementation of wecB in trans in mutant E09 successfully restored CPS production and reduced bacterial attachment/biofilm to levels similar to that of the wild-type. Fluorescence in-situ hybridization microscopy showed that M. haemolytica formed a poly-microbial biofilm with Histophilus somni and Pasteurella multocida. Overall, CPS production by M. haemolytica was inversely correlated with biofilm formation, the integrity of which required eDNA. A poly-microbial biofilm was readily formed between M. haemolytica, H. somni, and P. multocida, suggesting a mutualistic or synergistic interaction that may benefit bacterial colonization of the bovine respiratory tract.

Capsular polysaccharides are common virulence factors of extracellular, but not intracellular bacterial pathogens, due to the antiphagocytic properties of these surface structures. It is therefore paradoxical that Salmonella enterica subspecies enterica serovar Typhi, an intracellular pathogen, synthesizes a virulence-associated (Vi) capsule, which exhibits antiphagocytic properties. Here, we show that the Vi capsular polysaccharide has different functions when S. Typhi interacts with distinct subsets of host phagocytes. The Vi capsular polysaccharide allowed S. Typhi to selectively evade phagocytosis by human neutrophils while promoting human macrophage phagocytosis. A screen of C-type lectin receptors identified human DC-SIGN as the receptor involved in macrophage binding and phagocytosis of capsulated S. Typhi. Consistent with the anti-inflammatory activity of DC-SIGN, purified Vi capsular polysaccharide reduced inflammatory responses in macrophages. These data suggest that binding of the human C-type lectin receptor DC-SIGN by the Vi capsular polysaccharide contributes to the pathogenesis of typhoid fever. IMPORTANCE Salmonella enterica subspecies enterica serovar Typhi is the causative agent of typhoid fever. The recent emergence of S. Typhi strains which are resistant to antibiotic therapy highlights the importance of vaccination in managing typhoid fever. The virulence-associated (Vi) capsular polysaccharide is an effective vaccine against typhoid fever, but the role the capsule plays during pathogenesis remains incompletely understood. Here, we identify the human C-type lectin receptor DC-SIGN as the receptor for the Vi capsular polysaccharide. Binding of capsulated S. Typhi to DC-SIGN resulted in phagocytosis of the pathogen by macrophages and induction of an anti-inflammatory cytokine response. Thus, the interaction of the Vi capsular polysaccharide with human DC-SIGN contributes to the pathogenesis of typhoid fever and should be further investigated in the context of vaccine development.

Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection. [ABSTRACT FROM AUTHOR]

The aim of the study is to investigate the influence of the appearance of capsules, such as the presence of a complementary color relationship, on dispensed drug identification focusing on the relationship between the letter color and background color of the identification code for capsules. A questionnaire survey was conducted for pharmacists who worked for dispensing in pharmacies and hospitals on the ease of discrimination of each capsule formulation. For each capsule formulation, differences in brightness of printed identification code were measured and evaluated for their correlation with the ease of discrimination of each capsule formulation. The results showed that there was no significant difference in the ease of discrimination based on the number of years of dispensing experience and the experience of difficulty in reading small print in close areas. Whereas, there was a strong positive correlation between the ease of discrimination the difference in brightness between the colors of each text and its background. These results suggest that the difference in brightness between colors of each text and its background is one of the factors affecting the ease of discriminating identification codes since there is a　strong relationship between the ease of discriminating identification codes and the difference in brightness between colors of each text and its background. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing has paved the way in pharmaceutical applications. This innovative methodology presents novel and inventive remedies for patients and the pharmaceutical sector. Moreover, the benefits of this approach encompass the mitigation of adverse effects, customization of formulations for patients with rare medical conditions, and enhancement of therapeutic effectiveness. The objective of our review was to offer a comprehensive survey of the advancements observed in the drug delivery systems that were produced. A thorough inspection has assessed the diverse dosage forms developed using the three-dimensional printing technique (3DP), especially in the last five years. The pharmaceutical industry places significant emphasis on the benefits of developing dosage forms with intricate designs and geometries, incorporating multiple active ingredients, and tailored release profiles due to their versatility and related advantages. Drug delivery systems can be classified into different modalities, tablets, capsules, suppositories, transdermal delivery systems, microneedles, vaginal delivery systems, and nanoscale dosage forms. The utilization of our classification system facilitates researchers' task of evaluating publications and effectively pinpointing further opportunities for research exploration. [ABSTRACT FROM AUTHOR]

This research delves into the morphological and anatomical intricacies of Nigella sativa L. (Ranunculaceae), commonly known as black cumin, through meticulous examination of various accessions collected from diverse geographical regions in India. Morphological studies revealed distinct characteristics such as the linear to lanceolate alternate leaves, black capsule fruit housing seeds, and growth parameters including germination time, maturation period, and yield per plant. Notably, certain accessions exhibited superior attributes in terms of plant height, root length, and seed yield. Anatomical investigations unveiled detailed structures of stems, roots, seeds, and capsules. Stem anatomy exhibited a multi-cornered structure with specific features like uniseriate epidermis with non-glandular trichomes, parenchymatous cortex with chlorenchymatous and sclerenchymatous cells, and distinct vascular bundle arrangements. Root anatomy depicted a circular cross-section with well-defined layers including epidermis, cortex, and xylem with prominent oil droplets. Seed anatomy displayed layers of epidermis, parenchyma, pigmented layer, endosperm, and a central embryo. Moreover, this study identified novel cells in the stem cortex and observed variability in carpel numbers among different accessions. The findings contribute significantly to the understanding of N. sativa morphology and anatomy, shedding light on previously unexplored aspects and emphasizing the need for further investigation into the variability within and among accessions. [ABSTRACT FROM AUTHOR]

During periodontitis, the extracellular capsule of Porphyromonas gingivalis favors alveolar bone loss by inducing Th1 and Th17 patterns of lymphocyte response in the infected periodontium. Dendritic cells recognize bacterial antigens and present them to T lymphocytes, defining their activation and polarization. Thus, dendritic cells could be involved in the Th1 and Th17 response induced against the P. gingivalis capsule. Herein, monocyte-derived dendritic cells were obtained from healthy individuals and then stimulated with different encapsulated strains of P. gingivalis or two non-encapsulated isogenic mutants. Dendritic cell differentiation and maturation were analyzed by flow cytometry. The mRNA expression levels for distinct Th1-, Th17-, or T-regulatory-related cytokines and transcription factors, as well as TLR2 and TLR4, were assessed by qPCR. In addition, the production of IL-1β, IL-6, IL-23, and TNF-α was analyzed by ELISA. The encapsulated strains and non-encapsulated mutants of P. gingivalis induced dendritic cell maturation to a similar extent; however, the pattern of dendritic cell response was different. In particular, the encapsulated strains of P. gingivalis induced higher expression of IRF4 and NOTCH2 and production of IL-1β, IL-6, IL-23, and TNF-α compared with the non-encapsulated mutants, and thus, they showed an increased capacity to trigger Th1 and Th17-type responses in human dendritic cells. [ABSTRACT FROM AUTHOR]

The millimeter-scale capsules with controllable morphology, ultra-low permeability and excellent mechanical stability were fabricated by millifluidics. Viscosity of inner phase was adjusted to control the morphology and properties of the capsules. In detail, as the concentration of polyvinyl alcohol (PVA) increased from 0 to 8% in the inner phase of the capsules, the diameter of capsules decreased from 3.33 ± 0.01 mm to 2.97 ± 0.01 mm, the shell thickness of capsules decreased from 0.183 ± 0.004 mm to 0.155 ± 0.003 mm. While the capsules had round shape and high sphericity. Notably, the capsules with 2% PVA in the inner phase had remarkably decreased water permeability and good morphological stability. Specifically, the end-time of water losing of the capsules was up to 49 days, while the dehydrated capsules maintained spherical appearance, and crushing force of the capsules was up to 13.73 ± 0.79 N, which ensured stability during processing and transportation. This research provides a new strategy for stable encapsulation of small molecules. [ABSTRACT FROM AUTHOR]

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Background: Bacterial surface glycans are assembled by glycosyltransferases (GTs) that transfer sugar monomers to long-chained lipid carriers. Most bacteria employ the 55-carbon chain undecaprenyl phosphate (Und-P) to scaffold glycan assembly. The amount of Und-P available for glycan synthesis is thought to be limited by the rate of Und-P synthesis and by competition for Und-P between phosphoglycosyl transferases (PGTs) and GTs that prime glycan assembly (which we collectively refer to as PGT/GTs). While decreasing Und-P availability disrupts glycan synthesis and promotes cell death, less is known about the effects of increased Und-P availability. Results: To determine if cells can maintain higher Und-P levels, we first reduced intracellular competition for Und-P by deleting all known non-essential PGT/GTs in the Gram-negative bacterium Escherichia coli (hereafter called ΔPGT/GT cells). We then increased the rate of Und-P synthesis in ΔPGT/GT cells by overexpressing the Und-P(P) synthase uppS from a plasmid (puppS). Und-P quantitation revealed that ΔPGT/GT/puppS cells can be induced to maintain 3-fold more Und-P than wild type cells. Next, we determined how increasing Und-P availability affects glycan expression. Interestingly, increasing Und-P availability increased endogenous and recombinant glycan expression. In particular, ΔPGT/GT/puppS cells could be induced to express 7-fold more capsule from Streptococcus pneumoniae serotype 4 than traditional E. coli cells used to express recombinant glycans. Conclusions: We demonstrate that the biotechnology standard bacterium E. coli can be engineered to maintain higher levels of Und-P. The results also strongly suggest that Und-P pathways can be engineered to increase the expression of potentially any Und-P-dependent polymer. Given that many bacterial glycans are central to the production of vaccines, diagnostics, and therapeutics, increasing Und-P availability should be a foremost consideration when designing bacterial glycan expression systems. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the efficiency of hard-gelatin and hard-hydroxypropyl methylcellulose (HPMC) capsules as biodegradable alternative containers to plastic straws in European eel (Anguilla anguilla), gilthead seabream (Sparus aurata) and European sea bass (Dicentrarchus labrax) sperm cryopreservation. Sperm samples from each European eel (n = 12) were diluted 1:8:1 (sperm: extender P1+5 % egg yolk: methanol). Gilthead seabream (n = 12) samples were individually diluted in a cryoprotectant solution of 5 % Me 2 SO + NaCl 1 % plus BSA (10 mg mL−1) at a ratio of 1:6 (sperm: cryoprotectant solution). European sea bass (n = 10) sperm from each male was diluted in non-activating medium (NAM) at a ratio of 1:5.7 (sperm: NAM), and 5 % of Me 2 SO was added. The diluted European eel and sea bass sperm aliquots (0.5 mL) were individually filled in plastic straws (0.5 mL), hard-gelatin, and HPMC capsules (0.68 mL). Gilthead seabream diluted sperm (0.25 mL) were filled in plastic straws (0.25 mL) and identical capsules described. All samples were frozen in liquid nitrogen vapor and stored in a liquid nitrogen tank. Sperm kinetic parameters were evaluated by CASA-Mot software. Sperm membrane integrity was performed using a Live and Dead KIT and an epifluorescence microscope. To quantify DNA damage, the alkaline comet assay was performed and TailDNA (TD-%) and Olive Tail Moment (OTM) were evaluated by CaspLab software. Sperm cryopreservation of the three Mediterranean species in straws, gelatin, or HPMC capsules reduced the kinetic parameters and cell membrane integrity. Generally, the post-thawing samples cryopreserved in straws and capsules did not differ for the kinetic parameters and cell membrane integrity, except for European sea bass sperm, where the samples stored in gelatin capsules showed higher velocities (VCL - 100; VSL - 76; VAP - 90 μm s−1) than the sperm stored in HPMC capsules (VCL - 87; VSL - 59; VAP - 73 μm s−1). The cryopreservation process did not damage the sperm DNA of European eel and European sea bass, regardless of the containers used. On the other hand, gilthead seabream sperm cryopreserved in gelatin (TD - 9.8 %; OTM - 9.7) and HPMC (TD - 11.1 %; OTM - 11.2) capsules showed higher DNA damage than fresh samples (TD - 3.6 %; OTM - 2.7) and the sperm stored in straws (TD - 4.4 %; OTM - 5.2). The hard-gelatin and HPMC biodegradable capsules can be used as an alternative to straws for European eel, gilthead seabream, and European sea bass sperm cryopreservation. • Hard-capsules maintain the cryopreserved sperm motility, as well as plastic straws. • Sperm thawing in an extender did not compromise the cell membrane integrity. • Capsules' thawing process can damage the gilthead seabream sperm DNA. • Alkaline comet assay protocol for European eel sperm worked well. [ABSTRACT FROM AUTHOR]

The bioequivalence (BE) of orally administered capsules versus film tablets containing 20 and 10 mg of rivaroxaban was assessed in 2 single‐dose, open‐label, randomized 2‐way crossover trials with a washout period of at least 1 week. The study for the 10 mg strength was conducted under fasting conditions (n = 68) and the study for the 20 mg strength under fed conditions (n = 52). Blood samples were collected over a 36‐hour period and concentrations were assayed using a liquid chromatography tandem mass spectrometry method. Pharmacokinetic (PK) evaluation was performed with the program Phoenix WinNonlin, for non‐compartmental assessment of data. After administration of 10 mg rivaroxaban under fasting conditions, mean Area Under the time ‐ concentration Curve until the last blood sampling point (AUCt), Area Under the time ‐ concentration Curve until infinity (AUC∞), and maximum plasma concentration (Cmax) were comparable (972 ng/mL*h, 1048 ng/mL*h, and 111 ng/mL, respectively, for the test and 1013 ng/mL*h, 1070 ng/mL*h and 130 ng/mL, respectively, for the reference formulation). Mean AUCt, AUC∞, and Cmax were also comparable under fed conditions after administration of 20 mg rivaroxaban (2145 ng/mL*h, 2198 ng/mL*h and 275 ng/mL, respectively, for the test and 1856 ng/mL*h, 1916 ng/mL*h and 240 ng/mL, respectively, for the reference formulation). The 90% confidence intervals for all PK parameters were within the acceptance range of 80%‐125%, suggesting BE between the generic product and the innovator product in healthy Caucasian male subjects. A clinically relevant difference in the tolerability and safety of the treatments was not detected. Study results indicated that the capsule formulations were bioequivalent with the film tablet formulations. [ABSTRACT FROM AUTHOR]

Blast-furnace-slag aggregate (BFSA), a by-product of the steel industry, is an eco-friendly natural, aggregate substitute used in mortar and concrete. However, research on self-healing cement composites using BFSA is rare. In this study, the compressive strength, chloride-ion-penetration resistance, and crack-recovery properties of self-healing cement mortar samples prepared using cementitious material capsules (CMC) and BFSA of different ratios were examined and compared to a control sample. The test samples were: Control; C05B00 (5 % CMC and 0 % BFSA); C05B25 (5 % CMC and 25 % BFSA); C05B50 (5 % CMC and 50 % BFSA); C10B00 (10 % CMC and 0 % BFSA); C10B25 (10 % CMC and 25 % BFSA); and C10B50 (10 % CMC and 50 % BFSA). The compressive-strength recovery rate of the control stopped increasing after 28 days and was approximately 110 % on day 56 – that of C10B50 was approximately 121 %, (∼10 % greater than that of the control) and continued to increase even after 56 d. The chloride-ion-penetration resistance of C10B50 was excellent; the 28-day total charge was approximately 5858 C (∼ 40.2 % lower than that of the control). The crack-recovery rates, on day 28, of C05B50 and C10B25 were 71 % and 70 %, respectively (∼ 29–30 % higher than that of the control).

The eye lens is a transparent, ellipsoid tissue in the anterior chamber that is required for the fine focusing of light onto the retina to transmit a clear image. The focusing function of the lens is tied to tissue transparency, refractive index, and biomechanical properties. The stiffness and elasticity or resilience of the human lens allows for shape changes during accommodation to focus light from objects near and far. It has long been hypothesized that changes in lens biomechanical properties with age lead to the loss of accommodative ability and the need for reading glasses with age. However, the cellular and molecular mechanisms that influence lens biomechanical properties and/or change with age remain unclear. Studies of lens stiffness and resilience in mouse models with genetic defects or at advanced age inform us of the cytoskeletal, structural, and morphometric parameters that are important for biomechanical stability. In this review, we will explore whether: 1) tissue level changes, including the capsule, lens volume, and nucleus volume, 2) cellular level alterations, including cell packing, suture organization, and complex membrane interdigitations, and 3) molecular scale modifications, including the F-actin and intermediate filament networks, protein modifications, lipids in the cell membrane, and hydrostatic pressure, influence overall lens biomechanical properties.

IntroductionClostridioides difficile infections (CDI) continue to pose a challenge for clinicians. Fecal microbiota transplantation (FMT) is an effective treatment option in CDI. Furthermore, recent and ongoing studies suggest potential benefits of FMT in other diseases as well.MethodsWe would like to present a novel protocol for encapsulation of lyophilized fecal material. Our method provides with better compliance as well as improved flexibility, storage and safety.ResultsFMT was conducted in 28 patients with an overall success rate of 82,14% using apsules containing lyophilized stool. 16 of patients were given capsules with lessened bacteria counts. The success rate in this group was 93,75%.DiscussionThe results highlight the still unanswered questions about the mechanism of action and contribute to a wider use of FMT in the clinical praxis and in research.

Abstract Background The capsule of the zygapophyseal joint plays an important role in motion segmental stability maintenance. Iatrogenic capsule injury is a common phenomenon in posterior approach lumbar interbody fusion operations, but whether this procedure will cause a higher risk of adjacent segment degeneration acceleration biomechanically has yet to be identified. Methods Posterior lumbar interbody fusion (PLIF) with different grades of iatrogenic capsule injury was simulated in our calibrated and validated numerical model. By adjusting the cross-sectional area of the capsule, different grades of capsule injury were simulated. The stress distribution on the cranial motion segment was computed under different loading conditions to judge the potential risk of adjacent segment degeneration acceleration. Results Compared to the PLIF model with an intact capsule, a stepwise increase in the stress value on the cranial motion segment can be observed with a step decrease in capsule cross-sectional areas. Moreover, compared to the difference between models with intact and slightly injured capsules, the difference in stress values was more evident between models with slight and severe iatrogenic capsule injury. Conclusion Intraoperative capsule protection can reduce the potential risk of adjacent segment degeneration acceleration biomechanically, and iatrogenic capsule damage on the cranial motion segment should be reduced to optimize patients’ long-term prognosis.

Abstract Background The hip joint capsule is an essential component of hip joint function and stability, and its thickness is closely associated with certain medical conditions, surgical outcomes, and rehabilitation treatments. Currently, in clinical practice, hip joint capsule thickness is predominantly measured using magnetic resonance imaging (MRI), with limited utilization of ultrasound examinations for this purpose. Methods We retrospectively evaluated patients who visited our Sports Medicine Department between February 2017 and March 2023 and underwent both hip joint MRI and ultrasound imaging on the same side. All patients had undergone preoperative hip joint MRI and ultrasound examinations, with the time gap between the two examinations not exceeding three months. Measurements of hip joint capsule thickness were taken on both MRI and ultrasound images for the same patients to analyze their consistency. Additionally, we measured the alpha angle, lateral center-edge angle, acetabular anteversion angle, and femoral anteversion angle of the patients’ hip joints and analyzed their correlation with hip joint capsule thickness measure by ultrasound. Results A total of 307 patients were included in this study, with hip joint capsule thickness measured by MRI and ultrasound being 5.0 ± 1.2 mm and 5.0 ± 1.5 mm, respectively. The Bland-Altman analysis demonstrates good agreement or consistency. The paired t-test resulted in a p-value of 0.708, indicating no significant statistical difference between the two methods. The correlation analysis between acetabular anteversion angle and ultrasound-measured capsule thickness yielded a p-value of 0.043, indicating acetabular anteversion angle and capsular thickness may have negative correlation. Conclusions The measurements of joint capsule thickness obtained through ultrasound and MRI showed good consistency, suggesting that ultrasound can be used in clinical practice as a replacement for MRI in measuring hip joint capsule thickness. There was a significant correlation between acetabular anteversion angle and hip joint capsule thickness, indicating potential for further research in this area.

Abstract Background The disease caused by Riemerella anatipestifer (R. anatipestifer, RA) results in large economic losses to the global duck industry every year. Serovar-related genomic variation, such as the O-antigen and capsular polysaccharide (CPS) gene clusters, has been widely used for serotyping in many gram-negative bacteria. RA has been classified into at least 21 serovars based on slide agglutination, but the molecular basis of serotyping is unknown. In this study, we performed a pan-genome-wide association study (Pan-GWAS) to identify the genetic loci associated with RA serovars. Results The results revealed a significant association between the putative CPS synthesis gene locus and the serological phenotype. Further characterization of the CPS gene clusters in 11 representative serovar strains indicated that they were highly diverse and serovar-specific. The CPS gene cluster contained the key genes wzx and wzy, which are involved in the Wzx/Wzy-dependent pathway of CPS synthesis. Similar CPS loci have been found in some other species within the family Weeksellaceae. We have also shown that deletion of the wzy gene in RA results in capsular defects and cross-agglutination. Conclusions This study indicates that the CPS synthesis gene cluster of R. anatipestifer is a serotype-specific genetic locus. Importantly, our finding provides a new perspective for the systematic analysis of the genetic basis of the R anatipestifer serovars and a potential target for establishing a complete molecular serotyping scheme.

Background and aim: Zhilong Huoxue Tongyu (ZL) capsule is a classical traditional Chinese medicine (TCM) with satisfactory curative effects. Endothelial cell (EC) dysfunction plays an important role during myocardial fibrosis (MF). But the therapeutic effect of ZL capsule on EC dysfunction remains unknown in the development of MF. This study aims to investigate the effect of ZL capsule on EC dysfunction during MF in vivo. Experimental procedure: The model of MF is established in vivo by injecting isoproterenol for 14 days, simultaneously, we examined the therapeutic effect of ZL capsule on MF in vivo. An integrative approach combining biomarker examination, echocardiography and myocardial fibrosis condition using Hematoxylin-eosin staining, Masson staining, and Sirius red staining were performed to assess the efficacy of ZL capsule against MF. Subsequently, comprehensive immunofluorescence staining was performed to evaluate the therapeutic effect of ZL capsule on EC dysfunction. Results and conclusion: Prior to experiments, analysis of the published single-cell sequencing data was performed and it was discovered that EC dysfunction plays an important role. Further pharmacological results showed that ZL capsule could alleviate fibrosis injury and collagen fiber deposition. The mechanism investigation results showed that the endothelial-to-mesenchymal transition (EndMT) and MHC class-II (MHC-II) expression in EC were improved. In addition, ZL capsule can attenuate the inflammatory response during MF by intervening the activation of CD4+T cell mediated by EC. For the first time, we provided evidence that ZL capsule could improve MF by alleviating EC dysfunction via the regulation of EndMT and expression of MHC-II. Taxonomy (classification by evise): Myocardial fibrosis, Chinese Herbal Medicine, Traditional Medicine, Endothelium, dysfunction, Endothelial-to-mesenchymal transition.