Exploring the Biological Pathways of Siderophores and Their Multidisciplinary Applications: A Comprehensive Review.

Siderophores are a class of small molecules renowned for their high iron binding capacity, essential for all life forms requiring iron. This article provides a detailed review of the diverse classifications, and biosynthetic pathways of siderophores, with a particular emphasis on siderophores synthesized via nonribosomal peptide synthetase (NRPS) and non-NRPS pathways. We further explore the secretion mechanisms of siderophores in microbes and plants, and their role in regulating bioavailable iron levels. Beyond biological functions, the applications of siderophores in medicine, agriculture, and environmental sciences are extensively discussed. These applications include biological pest control, disease treatment, ecological pollution remediation, and heavy metal ion removal. Through a comprehensive analysis of the chemical properties and biological activities of siderophores, this paper demonstrates their wide prospects in scientific research and practical applications, while also highlighting current research gaps and potential future directions.

Knowledge of neonatal brachial plexus palsy among medical professionals in North America.

PURPOSE: Early referral of neonatal brachial plexus palsy (NBPP) patients to multidisciplinary clinics is critical for timely diagnosis, treatment, and improved functional outcomes. In Saudi Arabia, inadequate knowledge regarding NBPP is a reason for delayed referral. We aimed to evaluate the knowledge of North American healthcare providers (HCPs) regarding the diagnosis, management, and prognosis of NBPP. METHODS: A 12-question survey regarding NBPP was distributed via electronic and paper formats to North American providers from various referring and treating specialties. NBPP knowledge was compared between Saudi Arabian vs. North American providers, referring vs. treating specialties, academic vs. community hospitals, and providers with self-reported confidence vs. nonconfidence in NBPP knowledge. RESULTS: Of the 273 surveys collected, 45% were from referring providers and 55% were from treating providers. Saudi Arabian and North American HCPs demonstrated similar NBPP knowledge except for potential etiologies for NBPP and surgery timing. In North America, referring and treating providers had similar overall knowledge of NBPP but lacked familiarity with its natural history. A knowledge gap existed between academic and community hospitals regarding timing of referral/initiation of physical/occupational therapy (PT/OT) and Horner's syndrome. Providers with self-reported confidence in treating NBPP had greater knowledge of types of NBPP and timing for PT/OT initiation. CONCLUSIONS: Overall, North American providers demonstrated adequate knowledge of NBPP. However, both eastern and western physicians remain overly optimistic in believing that most infants recover spontaneously. This study revealed a unique and universal knowledge gap in NBPP diagnosis, referral, and management worldwide. Continuous efforts to increase NBPP knowledge are indicated.

Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF.

The transcription factor Ets1 is essential for the development/differentiation of invariant Natural Killer T (iNKT) cells at multiple stages. However, its mechanisms of action and target genes in iNKT cells are still elusive. Here, we show that Ets1 is required for the optimal expression of the Vα14Jα18 T cell receptor (TCR) in post-selected thymic iNKT cells and their immediate differentiation. Ets1 is also critical for maintaining the peripheral homeostasis of iNKT cells, which is a role independent of the expression of the Vα14Jα18 TCR. Genome-wide transcriptomic analyses of post-selected iNKT cells further reveal that Ets1 controls leukocytes activation, proliferation differentiation, and leukocyte-mediated immunity. In addition, Ets1 regulates the expression of ICOS and PLZF in iNKT cells. More importantly, restoring the expression of PLZF and the Vα14Jα18 TCR partially rescues the differentiation of iNKT cells in the absence of Ets1. Taken together, our results establish a detailed molecular picture of how Ets1 regulates the stepwise differentiation of iNKT cells.

Interrater reliability of electrodiagnosis in neonatal brachial plexopathy.

INTRODUCTION: We investigated interrater reliability of overall assessment of nerve root lesions by electrodiagnostic testing (EDX) in neonatal brachial plexus palsy (NBPP). METHODS: Two blinded, board-certified reviewers retrospectively reviewed de-identified EDX data from 37 infants with NBPP for 2005-2012. Only nerve conduction and electromyography needle data were included. The examiners independently assigned 1 of 4 nerve root lesion categories: (1) pre-ganglionic lesion (avulsion), (2) post-ganglionic lesion (rupture), (3) normal, or (4) "unable to determine." Simple percentage agreement, the Cohen kappa statistic representing interrater reliability for each nerve root (C5-T1), and overall kappa between examiners were evaluated. RESULTS: Interrater reliabilities were substantial to almost perfect for each nerve root except C5. Considering all nerve roots, overall interrater reliability was substantial (kappa = 0.62); simple percentage agreement was 75% (138/185). CONCLUSIONS: Interrater reliability of nerve root assessment by EDX for infants with NBPP was high for C6-T1 root levels, but less reliable for C5 because of technical factors. Muscle Nerve 55: 69-73, 2017.

Monoclonal antibodies for differentiating infections of three serological-related tospoviruses prevalent in Southwestern China.

BACKGROUND: The thrips-borne tospoviruses Calla lily chlorotic spot virus (CCSV), Tomato zonate spot virus (TZSV) and a new species provisionally named Tomato necrotic spot associated virus (TNSaV) infect similar crops in southwestern China. The symptoms exhibiting on virus-infected crops are similar, which is difficult for distinguishing virus species by symptomatology. The sequences of nucleocapsid proteins (NPs) of CCSV, TNSaV and TZSV share high degrees of amino acid identity with each other, and their serological relationship was currently demonstrated from the responses of the previously reported monoclonal antibodies (MAbs) against the NP of CCSV (MAb-CCSV-NP) and the nonstructural NSs protein of Watermelon silver mottle virus (WSMoV) (MAb-WNSs). Therefore, the production of virus-specific antibodies for identification of CCSV, TNSaV and TZSV is demanded to improve field surveys. METHODS: The NP of TZSV-13YV639 isolated from Crinum asiaticum in Yunnan Province, China was bacterially expressed and purified for producing MAbs. Indirect enzyme-linked immunosorbent assay (ELISA) and immunoblotting were conducted to test the serological response of MAbs to 18 tospovirus species. Additionally, the virus-specific primers were designed to verify the identity of CCSV, TNSaV and TZSV in one-step reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Two MAbs, denoted MAb-TZSV-NP(S15) and MAb-TZSV-NP(S18), were screened for test. MAb-TZSV-NP(S15) reacted with CCSV and TZSV while MAb-TZSV-NP(S18) reacted specifically to TZSV in both indirect ELISA and immunoblotting. Both MAbs can be used to detect TZSV in field-collected plant samples. The epitope of MAb-TZSV-NP(S18) was further identified consisting of amino acids 78-86 (HKIVASGAD) of the TZSV-13YV639 NP that is a highly conserved region among known TZSV isolates but is distinct from TNSaV and TZSV. CONCLUSIONS: In this study, two MAbs targeting to different portions of the TZSV NP were obtained. Unlike MAb-CCSV-NP reacted with TNSaV as well as CCSV and TZSV, both TZSV MAbs can be used to differentiate CCSV, TNSaV and TZSV. The identity of CCSV, TNSaV and TZSV was proven by individual virus-specific primer pairs to indicate the correctness of serological responses. We also proposed an serological detection platform using MAb-CCSV-NP, MAb-TZSV-NP(S15) and MAb-TZSV-NP(S18) to allow researchers and quarantine staff to efficiently diagnose the infections of CCSV, TNSaV and TZSV in China and other countries.

The iNOS/Src/FAK axis contributes to lithium chloride-mediated macrophage migration.

Lithium chloride (LiCl) has long been used as a mood stabilizer for bipolar mood depression patients. However, its biological effects on immune cells are unclear yet. In this study, we observed that upon LiCl stimulation, the motility and the content of total protein tyrosine phosphorylation in RAW264.7 macrophages and murine peritoneal macrophages (PEMs) were significantly increased. The inhibition of LiCl-induced macrophage migration by PP2 (an inhibitor for Src family kinases (SFKs)) suggested the involvement of SFKs in this process. Interestingly, LiCl induced NF-kB activation, and while Src was greatly induced, the expression of its myeloid relatives (i.e. Lyn, Fgr, Hck) was almost unaltered in RAW264.7 cells. Knockdown of Src suppressed LiCl-elicited movement and the level of FAK Pi-Tyr861, which could be reversed by siRNA-resistant Src. Consistent with Src and migration increment was iNOS-dependent in macrophages, markedly reduced Src expression, activity and cell migration were observed in iNOS-null PEMs treated with LiCl. Moreover, FAK knockdown suppressed LiCl-stimulated macrophage motility, suggesting the involvement of FAK in this process. Remarkably, similar increment of iNOS, Src, FAK Pi-Tyr861 and migration ability could also be detected in RAW264.7 treated with other GSK3ß inhibitors (i.e. SB216763 and Kenpaullone). These results corroborate that through inhibition of GSK3ß, the iNOS/Src/FAK axis occupies a critical role in macrophage locomotion in response to LiCl.

Genetic and serological characterization of chrysanthemum stem necrosis virus, a member of the genus Tospovirus.

Chrysanthemum stem necrosis virus (CSNV) is a member of a tentative tospovirus species. In this study, the complete genomic sequence of the Japanese CSNV isolate TcCh07A was determined. The L RNA is 8960 nt long and encodes the 331.0-kDa RNA-dependent RNA polymerase. The M RNA is 4828 nt long and encodes the 34.1-kDa movement protein (NSm) and the 127.7-kDa glycoprotein precursor (Gn/Gc). The S RNA is 2949 nt long and encodes the 52.4-kDa silencing suppressor protein (NSs) and the 29.3-kDa nucleocapsid (N) protein. The N protein of CSNV-TcCh07A was purified from virus-infected plant tissues and used for production of a rabbit polyclonal antiserum (RAs) and a monoclonal antibody (MAb). Results of serological tests by indirect ELISA and western blotting using the prepared RAs and MAb and a previously produced RAs against the N protein of tomato spotted wilt virus (TSWV) indicated that CSNV-TcCh07A, TSWV, tomato chlorotic spot virus, groundnut ringspot virus, alstroemeria necrotic streak virus and impatiens necrotic spot virus are serologically related.

Contribution of functional parameters to patient-rated outcomes after surgical treatment of distal radius fractures.

PURPOSE: Outcomes of distal radius fractures can be measured radiographically, functionally, or via patient-rated questionnaires, but previous studies report conflicting results regarding the relationship between these outcomes. Our specific aim was to explore the role that functional outcomes have in the score of the Michigan Hand Outcomes Questionnaire (MHQ), a patient-rated hand instrument. METHODS: We obtained data for 207 patients. Demographic information was collected as part of the MHQ. Function (wrist motion and grip and pinch strength) was assessed 3 and 6 months after fracture fixation. We applied linear regression analysis to determine each item's contribution to the total MHQ score. RESULTS: After we applied linear regression analysis, we determined that 3 months after fixation, all included factors contributed 37% of the MHQ score. Only the grip strength difference between the injured and uninjured hands was significantly associated, contributing 22% of the MHQ score. Six weeks and 6 months after fixation, all included factors contributed 43% and 34%, respectively, of the MHQ score. No individual factors were significant contributors. CONCLUSIONS: Measured functional outcomes variables account for less than 40% of the total MHQ score. Identifying the unmeasured factors that make up the additional 60% of the total MHQ score would be beneficial in the continued examination of patient-rated outcomes. Furthermore, the use of multiple outcomes assessment modalities should be considered in any study measuring patient-rated outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

ScRNA-Seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation.

While the transcription factor GATA-3 is well-established for its crucial role in T cell development, its specific influence on invariant natural killer T (iNKT) cells remains relatively unexplored. Using flow cytometry and single-cell transcriptomic analysis, we demonstrated that GATA-3 deficiency in mice leads to the absence of iNKT2 and iNKT17 cell subsets, as well as an altered distribution of iNKT1 cells. Thymic iNKT cells lacking GATA-3 exhibited diminished expression of PLZF and T-bet, key transcription factors involved in iNKT cell differentiation, and reduced production of Th2, Th17, and cytotoxic effector molecules. Single-cell transcriptomics revealed a comprehensive absence of iNKT17 cells, a substantial reduction in iNKT2 cells, and an increase in iNKT1 cells in GATA-3-deficient thymi. Differential expression analysis highlighted the regulatory role of GATA-3 in T cell activation signaling and altered expression of genes critical for iNKT cell differentiation, such as Icos, Cd127, Eomes, and Zbtb16. Notably, restoration of Icos, but not Cd127, expression could rescue iNKT cell development in GATA-3-deficient mice. In conclusion, our study demonstrates the pivotal role of GATA-3 in orchestrating iNKT cell effector lineage differentiation through the regulation of T cell activation pathways and Icos expression, providing insights into the molecular mechanisms governing iNKT cell development and function.

Evaluation of Fe3O4-MnO2@RGO magnetic nanocomposite as an effective persulfate activator and metal adsorbent in aqueous solution.

A reduced graphene oxide (RGO) supported Fe3O4-MnO2 nanocomposite (Fe3O4-MnO2@RGO) was successfully prepared for catalytic degradation of oxytetracycline (20 mg/L) by potassium persulfate (PS) and adsorption removal of mixture of Pb2+, Cu2+, and Cd2+ ions (each 0.2 mM) in the synchronous scenario. The removal efficiencies of oxytetracycline, Pb2+, Cu2+, and Cd2+ ions were observed as high as 100%, 99.9%, 99.8%, and 99.8%, respectively, under the conditions of [PS]0 = 4 mM, pH0 = 7.0, Fe3O4-MnO2@RGO dosage = 0.8 g/L, reaction time = 90 min. The ternary composite exhibited higher oxytetracycline degradation/mineralization efficiency, greater metal adsorption capacity (Cd2+ 104.1 mg/g, Pb2+ 206.8 mg/g, Cu2+ 70.2 mg/g), and better PS utilization (62.6%) than its unary and binary counterparts including RGO, Fe3O4, Fe3O4@RGO, and Fe3O4-MnO2. More importantly, the ternary composite had good magnetic recoverability and excellent reusability. Notably, Fe, Mn, and RGO could play a synergistic role in the improvement of pollutant removal. Quenching results indicate that surface bounded SO4•- was the major contributor to oxytetracycline decomposition, and the -OH groups on the composite surface shouldered a significant role in PS activation. The results indicate that the magnetic Fe3O4-MnO2@RGO nanocomposite has a good potential for removing organic-metal co-contaminants in waterbody.

Co-Extraction of Flaxseed Protein and Polysaccharide with a High Emulsifying and Foaming Property: Enrichment through the Sequence Extraction Approach.

A new focus with respect to the extraction of plant protein is that ingredient enrichment should target functionality instead of pursuing purity. Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. Part of the fraction 2 was taken out, followed by adjusting its pH to 4.2. After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. This study provides a reference to promote the high-value utilization of flaxseed meals.

Acute Flaccid Myelitis: Review of Clinical Features, Diagnosis, and Management with Nerve Transfers.

BACKGROUND: Acute flaccid myelitis (AFM) is a devastating neurologic condition in children, manifesting as acute limb weakness and/or paralysis. Despite increased awareness of AFM following initiation of U.S. surveillance in 2014, no treatment consensus exists. The purpose of this systematic review was to summarize the most current knowledge regarding AFM epidemiology, cause, clinical features, diagnosis, and supportive and operative management, including nerve transfer. METHODS: The authors systematically reviewed the literature based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases to search the keywords ("acute flaccid myelitis"), ('acute flaccid myelitis'/exp OR 'acute flaccid myelitis'), and (Acute AND flaccid AND myelitis). Included articles reported on (1) AFM diagnosis and (2) patient-specific data regarding epidemiology, cause, clinical features, diagnostic features, or management of AFM. RESULTS: Ninety-nine articles were included in this review. The precise cause and pathophysiologic mechanism of AFM remain undetermined, but AFM is strongly associated with nonpolio enterovirus infections. Clinical presentation typically comprises preceding viral prodrome, pleocytosis, spinal cord lesions on T2-weighted magnetic resonance imaging, and acute onset of flaccid weakness/paralysis with hyporeflexia in at least one extremity. Supportive care includes medical therapy and rehabilitation. Early studies of nerve transfer for AFM have shown favorable outcomes for patients with persistent weakness. CONCLUSIONS: Supportive care and physical therapy are the foundation of a multidisciplinary approach to managing AFM. For patients with persistent limb weakness, nerve transfer has shown promise for improving function in distal muscle groups. Surgeons must consider potential spontaneous recovery, patient selection, donor nerve availability, recipient nerve appropriateness, and procedure timing.

FLJ10540 is associated with tumor progression in nasopharyngeal carcinomas and contributes to nasopharyngeal cell proliferation, and metastasis via osteopontin/CD44 pathway.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is well-known for its highly metastatic characteristics, but little is known of its molecular mechanisms. New biomarkers that predict clinical outcome, in particular the ability of the primary tumor to develop metastatic tumors are urgently needed. The aim of this study is to investigate the role of FLJ10540 in human NPC development. METHODS: A bioinformatics approach was used to explore the potentially important regulatory genes involved in the growth/metastasis control of NPC. FLJ10540 was chosen for this study. Two co-expression strategies from NPC microarray were employed to identify the relationship between FLJ10540 and osteopontin. Quantitative-RT-PCR, immunoblotting, and immunohistochemistry analysis were used to investigate the mRNA and protein expression profiles of FLJ10540 and osteopontin in the normal and NPC tissues to confirm microarray results. TW01 and Hone1 NPC cells with overexpression FLJ10540 or siRNA to repress endogenous FLJ10540 were generated by stable transfection to further elucidate the molecular mechanisms of FLJ10540-elicited cell growth and metastasis under osteopontin stimulation. RESULTS: We found that osteopontin expression exhibited a positive correlation with FLJ10540 in NPC microarray. We also demonstrated comprehensively that FLJ10540 and osteopontin were not only overexpressed in NPC specimens, but also significantly correlated with advanced tumor and lymph node-metastasis stages, and had a poor 5-year survival rate, respectively. Stimulation of NPC parental cells with osteopontin results in an increase in FLJ10540 mRNA and protein expressions. Functionally, FLJ10540 transfectant alone, or stimulated with osteopontin, exhibited fast growth and increased metastasis as compared to vehicle control with or without osteopontin stimulation. Conversely, knockdown of FLJ10540 by siRNA results in the suppression of NPC cell growth and motility. Treatment with anti-CD44 antibodies in NPC parental cells not only resulted in a decrease of FLJ10540 protein, but also affected the abilities of FLJ10540-elicited cell growth and motility in osteopontin stimulated-NPC cells. CONCLUSIONS: These findings suggest that FLJ10540 may be critical regulator of disease progression in NPC, and the underlying mechanism may involve in the osteopontin/CD44 pathway.

Developing the art of scientific presentation.

PURPOSE: Few guidelines exist regarding the most effective approach to scientific oral presentations. Our purpose is to (1) develop a standardized instrument to evaluate scientific presentations based on a comprehensive review of the available literature regarding the components and organization of scientific presentations and (2) describe the optimal characteristics of scientific presentations. METHODS: At the Sixty-sixth (2011) Annual Meeting of the American Society for Surgery of the Hand, 69 presentations were evaluated by at least 2 independent observers. A rating instrument was developed a priori to examine presentation content (background, methods, results, and conclusions), presentation style (speech, structure, delivery, slide aesthetics), and overall quality. We examined correlations between reviewers' ratings of each component as well as overall perceived quality of the presentation using regression analysis. Intraclass correlation coefficients were calculated to measure the degree of variation because of reviewer disagreement and identify the aspects of presentations that contribute to overall quality. RESULTS: Reviewer agreement was high for presentation content, and less than 1% of variation was caused by reviewer disagreement for background, methods, and conclusions. With respect to presentation style, reviewers agreed most frequently regarding speech and slide appearance, and only 9% and 13%, respectively, of the variation was caused by reviewer disagreement. Disagreement was higher for delivery and presentation structure, and 21% of the variation was attributable to reviewer disagreement. Speaker delivery and slide appearance were the most important predictors of presentation quality, followed by the quality of the presentation of conclusions and background information. Presentation of methods and results were not associated with overall presentation quality. CONCLUSIONS: Distinct aspects of presentation content and style correlate with quality, which can be reliably and objectively measured. By focusing on selected concepts with visually simple slides, speakers can enhance their delivery and may potentially improve the audience's comprehension of the study findings.

Two Laminaria japonica polysaccharides with distinct structure characterization affect gut microbiota and metabolites in hyperlipidemic mice differently.

Our previous study found dietary mannogluconic acid (MA) and fucogalactan sulfate (FS) from Laminaria japonica have distinct structure characterization and potential hypolipidemic effects in vitro. Herein, we compared the benefits of MA and FS on hyperlipidemia. The result showed only FS treatment decreased body weight and serum cholesterol levels. Compared with MA, FS was more effective in mitigating hepatic fat accumulation, promoting GSH-Px activity, reducing the MDA formation, and lowering the level of TNF-α in liver. Gut microbiota and metabolism analysis revealed that FS increased the relative abundance of beneficial bacteria and boosted the level of short chain fatty acids. Particularly, taurine and 3α,7α,12α-trihydroxy-24-oxo-5-ß-cholestanoyl CoA were upregulated by FS, which might attribute to the increased Oscillibacter and thus affect the enterohepatic circulation of bile acids and serum TC level. Therefore, FS with more branches and sulfate ester groups could be a good lipid-lowering dietary supplement.

ZIF-8@GMP-Tb nanocomplex for ratiometric fluorescent detection of alkaline phosphatase activity.

Luminescent metal-organic frameworks (LMOFs) and their functional materials with unique characteristics can provide the basis for the construction of new analytical techniques, which can meet the continuous demand for various fields. In this work, guanosine monophosphate (GMP), terbium ion (Tb3+) and zeolitic imidazolate framework-8 (ZIF-8) are self-assembled to form a ZIF-8@GMP-Tb nanocomplex, which can be utilized as a ratiometric fluorescent probe to monitor alkaline phosphatase (ALP) activity. Specifically, with adding ALP, the fluorescence intensity at 547 nm (one of the characteristic emission peaks of Tb3+) obviously decreased. Meanwhile, the conjugated structure of GMP increased the fluorescence of ZIF-8 (located at 330 nm). The possible mechanism was proposed through the characterization of the materials. Based on the variation of the emission peaks at 330 and 547 nm, the ratiometric fluorescent sensor of ALP has a linear range of 0.25-20 U/L. Moreover, applying this sensing system to the detection of ALP in the human serum sample and ALP inhibitor investigation possesses satisfactory results. This work provides a new perspective for the utilization of ZIF-8 and lanthanide ions in manufacturing simple and sensitive sensors.

In-vitro and in-vivo evaluation of biocompatible polymeric microgels for pH- driven delivery of Ketorolac tromethamine.

The aim of the current study was to prepare glutamic acid crosslinked poly(itaconic acid/methacrylic acid) microgels for pH-responsive delivery of ketorolac tromethamine, using aqueous free radical polymerization technique. The polymerization of polymer with monomers was carried out by a crosslinking agent N', N'-methylene bisacrylamide in the presence of initiator ammonium persulfate. The prepared microgels were characterized for structure, surface morphology, thermal stability, and crystallinity. Similarly, studies such as sol-gel analysis, drug loading, and polymer volume fraction were performed for the fabricated microgels. The pH-sensitivity of the developed microgels was investigated at three different pH values i.e., pH 1.2, 4.6, and 7.4 by swelling and in-vitro drug release studies. Maximum swelling and drug release were found at pH 7.4 as compared to pH 1.2 and 4.6, which indicated the pH-sensitive nature of the prepared microgels. The toxicity of the prepared microgels was evaluated by cell line and HET-CAM test, which demonstrated no toxic effect of the prepared microgels. In-vivo study was carried out on rabbits and high plasma concentration was reported for the drug loaded microgels as compared to drug solution and commercial product Keten. Hence, the prepared microgel system could be employed as an excellent carrier for the controlled drug delivery system.

Integrative Analysis of the Gut Microbiota and Metabolome for In Vitro Human Gut Fermentation Modeling.

This study aimed to find the best in vitro fermentation method by integrative analysis of the gut microbiota and metabolome. We selected five different media: brain heart infusion broth, Luria-Bertani broth, Mueller-Hinton broth, anaerobe basal broth, and anaerobic medium base (AMB). After in vitro fermentation, the gut microbiota and metabolites were analyzed at different culture times. The results showed that different culture media have different effects on the bacterial community structure and metabolites. The integrative analysis of gut microbiota and metabolism also proved that AMB medium is effective in keeping a stable bacterial community structure and producing less metabolites and short-chain fatty acids by simulating the nutrient-poor microenvironment in the human gut during in vitro fermentation. Thus, culturing with AMB medium for 48 h is the most suitable in vitro model for human gut microbiota fermentation, which provides an alternative approach for diet and health research.