A global transcriptional activator involved in the iron homeostasis in cyanobacteria.

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.

Influence of starch spherulites with different allomorphs and morphologies on reducing gastrointestinal digestibility in bread.

This study aimed to enhance the resistance of bread to gastrointestinal digestion by partially substituting wheat flour with starch spherulites. Three types of starch spherulites, specifically A-type (exhibiting an A-type crystalline pattern with mostly positive birefringence), B(-)-type (B-type crystalline with negative birefringence), and B(+)-type (B-type crystalline with positive birefringence), were investigated. The A-, B(-)-, and B(+)-type spherulites showed significantly higher resistant starch contents of 63.5, 63.8, and 89.2 %, respectively, compared to the control wheat flour (7.4 %). The melting temperatures of A-type and B(+)-type spherulites were notably higher than those of the control wheat flour, suggesting the potential preservation of certain enzyme-resistant starch during the baking process. The partial substitution of wheat flour with spherulites resulted in a denser crumb structure, increased bread hardness and chewiness, and a pale brown color in the case of B(+)-type spherulite. However, these variations in physicochemical properties did not significantly impact consumer acceptability. Remarkably, in bread containing A- or B(+)-type spherulite, residual ordered spherulite structures were present after baking, as confirmed by differential scanning calorimetry. This resulted in significantly lower digestibility during in vitro gastrointestinal digestion. These findings are useful for the rational design of bread with sustained glucose release during gastrointestinal digestion.

Heterologous Expression and Characterization of a pH-Stable Chitinase from Micromonospora aurantiaca with a Potential Application in Chitin Degradation.

To promote the bioconversion of marine chitin waste into value-added products, we expressed a novel pH-stable Micromonospora aurantiaca-derived chitinase, MaChi1, in Escherichia coli and subsequently purified, characterized, and evaluated it for its chitin-converting capacity. Our results indicated that MaChi1 is of the glycoside hydrolase (GH) family 18 with a molecular weight of approximately 57 kDa, consisting of a GH18 catalytic domain and a cellulose-binding domain. We recorded its optimal activity at pH 5.0 and 55 °C. It exhibited excellent stability in a wide pH range of 3.0-10.0. Mg2+ (5 mM), and dithiothreitol (10 mM) significantly promoted MaChi1 activity. MaChi1 exhibited broad substrate specificity and hydrolyzed chitin, chitosan, cellulose, soluble starch, and N-acetyl chitooligosaccharides with polymerization degrees ranging from three to six. Moreover, MaChi1 exhibited an endo-type cleavage pattern, and it could efficiently convert colloidal chitin into N-acetyl-D-glucosamine (GlcNAc) and (GlcNAc)2 with yields of 227.2 and 505.9 mg/g chitin, respectively. Its high chitin-degrading capacity and exceptional pH tolerance makes it a promising tool with potential applications in chitin waste treatment and bioactive oligosaccharide production.

Human gut-associated Bifidobacterium species salvage exogenous indole, a uremic toxin precursor, to synthesize indole-3-lactic acid via tryptophan.

Indole in the gut is formed from dietary tryptophan by a bacterial tryptophan-indole lyase. Indole not only triggers biofilm formation and antibiotic resistance in gut microbes but also contributes to the progression of kidney dysfunction after absorption by the intestine and sulfation in the liver. As tryptophan is an essential amino acid for humans, these events seem inevitable. Despite this, we show in a proof-of-concept study that exogenous indole can be converted to an immunomodulatory tryptophan metabolite, indole-3-lactic acid (ILA), by a previously unknown microbial metabolic pathway that involves tryptophan synthase ß subunit and aromatic lactate dehydrogenase. Selected bifidobacterial strains converted exogenous indole to ILA via tryptophan (Trp), which was demonstrated by incubating the bacterial cells in the presence of (2-13C)-labeled indole and l-serine. Disruption of the responsible genes variedly affected the efficiency of indole bioconversion to Trp and ILA, depending on the strains. Database searches against 11,943 bacterial genomes representing 960 human-associated species revealed that the co-occurrence of tryptophan synthase ß subunit and aromatic lactate dehydrogenase is a specific feature of human gut-associated Bifidobacterium species, thus unveiling a new facet of bifidobacteria as probiotics. Indole, which has been assumed to be an end-product of tryptophan metabolism, may thus act as a precursor for the synthesis of a host-interacting metabolite with possible beneficial activities in the complex gut microbial ecosystem.

Wheat bran arabinoxylans: Chemical structure, extraction, properties, health benefits, and uses in foods.

Wheat bran (WB) is a well-known and valuable source of dietary fiber. Arabinoxylan (AX) is the primary hemicellulose in WB and can be isolated and used as a functional component in various food products. Typically, AX is extracted from the whole WB using different processes after mechanical treatments. However, WB is composed of different layers, namely, the aleurone layer, pericarp, testa, and hyaline layer. The distribution, structure, and extractability of AX vary within these layers. Modern fractionation technologies, such as debranning and electrostatic separation, can separate the different layers of WB, making it possible to extract AX from each layer separately. Therefore, AX in WB shows potential for broader applications if it can be extracted from the different layers separately. In this review, the distribution and chemical structures of AX in WB layers are first discussed followed by extraction, physicochemical properties, and health benefits of isolated AX from WB. Additionally, the utilization of AX isolated from WB in foods, including cereal foods, packaging film, and the delivery of food ingredients, is reviewed. Future perspectives on challenges and opportunities in the research field of AX isolated from WB are highlighted.

Synthesis of ß,ß-Dithioketones by Merging C-C and C-S Bond Cleavage in [1 + 1 + 1 + 1 + 1 + 1] Annulation.

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of ß,ß-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

Investigation on Mechanism of Microstructure Evolution during Multi-Process Hot Forming of GH4169 Superalloy Forging.

Typically, in the manufacturing of GH4169 superalloy forgings, the multi-process hot forming that consists of pre-deformation, heat treatment and final deformation is required. This study focuses on the microstructural evolution throughout hot working processes. Considering that δ phase can promote nucleation and limit the growth of grains, a process route was designed, including pre-deformation, aging treatment (AT) to precipitate sufficient δ phases, high temperature holding (HTH) to uniformly heat the forging, and final deformation. The results show that the uneven strain distribution after pre-deformation has a significant impact on the subsequent refinement of the grain microstructure due to the complex coupling relationship between the evolution of the δ phase and recrystallization behavior. After the final deformation, the fine-grain microstructure with short rod-like δ phases as boundaries is easy to form in the region with a large strain of the pre-forging. However, necklace-like mixed grain microstructure is formed in the region with a small strain of the pre-forging. In addition, when the microstructure before final deformation consists of mixed grains, dynamic recrystallization (DRX) nucleation behavior preferentially depends on kernel average misorientation (KAM) values. A large KAM can promote the formation of DRX nuclei. When the KAM values are close, a smaller average grain size of mixed-grain microstructure is more conductive to promote the DRX nucleation. Finally, the interaction mechanisms between δ phase and DRX nucleation are revealed.

Efficacy and safety of fibrin sealant application in patients undergoing thyroidectomy: a systematic review and meta-analysis.

Various studies have focused on the application of fibrin sealants (FS) in thyroid surgery. Utilizing a meta-analysis, this systematic review analyzed the findings of recent randomized controlled trials on the safety and efficacy of FS in patients who underwent thyroidectomy. The Cochrane Library, Web of Science, Embase, PubMed, and Medline databases were searched for relevant studies, without any language restrictions. Seven randomized controlled trials were included in the originally identified 69 studies. Overall, 652 patients received FS during thyroid surgery; their outcomes were compared with those of conventionally treated patients. The primary outcomes were total volume of wound drainage, length of hospitalization, and operative time. Significant differences were observed in the total volume of wound drainage (mean deviation (MD): -29.75, 95% confidence interval (CI): -55.39 to -4.11, P = 0.02), length of hospitalization (MD: -0.84, 95% CI: -1.02 to -0.66, P < 0.00001), and surgery duration (MD: -7.60, 95% CI: -14.75 to -0.45, P = 0.04). Secondary outcomes were seroma and hypoparathyroidism development. The risk of hypoparathyroidism did not differ between the FS and conventional groups (I = 0%, relative risk = 1.31, P = 0.38). Analysis of "seroma formation that required invasive treatment" indicated that FS showed some benefit (I2 = 8%, relative risk 0.44, P = 0.15). Heterogeneity among the different trials limited their conclusions. The meta-analysis showed that although FS use did not significantly reduce seroma or hypoparathyroidism incidence in patients after thyroidectomy, it significantly reduced the total drainage volume, length of hospitalization, and duration of surgery.

Changes in the structure and enzyme binding of starches during in vitro enzymatic hydrolysis using mammalian mucosal enzyme mixtures.

Starches are hydrolyzed into monosaccharides by mucosal α-glucosidases in the human small intestine. However, there are few studies assessing the direct digestion of starch by these enzymes. The objective of this study was to investigate the changes in the structure and enzyme binding of starches during in vitro hydrolysis by mammalian mucosal enzymes. Waxy maize (WMS), normal maize (NMS), high-amylose maize (HAMS), waxy potato (WPS), and normal potato (NPS) starches were examined. The order of the digestion rate was different compared with other studies using a mixture of pancreatic α-amylase and amyloglucosidase. NPS was digested more than other starches. WPS was more digestible than WMS. Hydrolyzed starch from NPS, NMS, WPS, WMS, and HAMS after 24 h was 66.4, 64.2, 61.7, 58.7, and 46.2 %, respectively. Notably, a significant change in the morphology, reduced crystallinity, and a decrease in the melting enthalpy of the three starches (NPS, NMS, and WPS) after 24 h of hydrolysis were confirmed by microscopy, X-ray diffraction, and differential scanning calorimetry, respectively. The bound enzyme fraction of NPS, NMS, and WPS increased as hydrolysis progressed. In contrast, HAMS was most resistant to hydrolysis by mucosal α-glucosidases in terms of digestibility, changes in morphology, crystallinity, and thermal properties.

Effects of Aging Treatment on the Microstructures and Mechanical Properties of a TC18 Alloy.

In the present work, the effects of aging treatment on the microstructures of a TC18 alloy are studied. The influence of aging treatment on the tensile properties and failure mechanisms is systematically analyzed. It is found that the size and morphology of the primary α (αp) phases are insensitive to aging temperature and time. Furthermore, the aging temperature and time dramatically influence the precipitation of the secondary α (αs) phases. Massive αs phases precipitate and gradually coarsen, and finally weave together by increasing the aging temperature or extending the aging time. The variations in αp and αs phases induced by aging parameters also affect the mechanical properties. Both yield strength (YS) and ultimate tensile strength (UTS) first increase and then decrease by increasing the aging temperature and time, while ductility first decreases and then increases. There is an excellent balance between the strengths and ductility. When the aging temperature is changed from 450 to 550 °C, YS varies from 1238.6 to 1381.6 MPa, UTS varies from 1363.2 to 1516.8 MPa, and the moderate elongation ranges from 9.0% to 10.3%. These results reveal that the thickness of αs phases is responsible for material strengths, while the content of α phases can enhance material ductility. The ductile characteristics of the alloy with coarser αs phases are more obvious than those with thinner αs phases. Therefore, the aging treatment is helpful for the precipitation and homogeneous distribution of αs phases, which are essential for balancing the strengths and ductility of the studied Ti alloy.

Modular intercalary prosthetic reconstruction for malignant and metastatic tumours of the proximal femur.

To illustrate the surgical technique and explore clinical outcomes of the reconstruction for the malignant and metastatic bone tumour of proximal femur with metallic modular intercalary prosthesis. Sixteen patients who underwent modular intercalary prosthetic reconstruction after tumour resection were included from April 2012 and October 2020. Prosthesis and screws parameters, resected bone length and residual bone length, clinical outcomes and survivorship were analyzed. All patients were followed up for an average of 19 months (range 1-74). In our series, 12 patients died of the progression of the primary disease at the final follow-up. The cumulative survivorship since the treatment of proximal femoral metastasis was 78.6% (11 patients) at 6 months and 38.5% (5 patients) at 1 year. The mean MSTS score was 22.25 ± 4.55 among all patients. There were no cases of loosening or breakage of the prostheses, plates or screws, despite the various measurements of prostheses and residual bones. Modular intercalary prosthetic reconstruction was an effective method for malignant tumour of the proximal femur, including the advantages of providing early pain relief, quickly restoring postoperative function, required a short operation time, and preserving the adjacent joints.

Limitations and modifications in the clinical application of calcium sulfate.

Calcium sulfate and calcium sulfate-based biomaterials have been widely used in non-load-bearing bone defects for hundreds of years due to their superior biocompatibility, biodegradability, and non-toxicity. However, lower compressive strength and rapid degradation rate are the main limitations in clinical applications. Excessive absorption causes a sharp increase in sulfate ion and calcium ion concentrations around the bone defect site, resulting in delayed wound healing and hypercalcemia. In addition, the space between calcium sulfate and the host bone, resulting from excessively rapid absorption, has adverse effects on bone healing or fusion techniques. This issue has been recognized and addressed. The lack of sufficient mechanical strength makes it challenging to use calcium sulfate and calcium sulfate-based biomaterials in load-bearing areas. To overcome these defects, the introduction of various inorganic additives, such as calcium carbonate, calcium phosphate, and calcium silicate, into calcium sulfate is an effective measure. Inorganic materials with different physical and chemical properties can greatly improve the properties of calcium sulfate composites. For example, the hydrolysis products of calcium carbonate are alkaline substances that can buffer the acidic environment caused by the degradation of calcium sulfate; calcium phosphate has poor degradation, which can effectively avoid the excessive absorption of calcium sulfate; and calcium silicate can promote the compressive strength and stimulate new bone formation. The purpose of this review is to review the poor properties of calcium sulfate and its complications in clinical application and to explore the effect of various inorganic additives on the physicochemical properties and biological properties of calcium sulfate.

Unveiling the significance of gastric digestion in gastrointestinal fate of octenylsuccinylated starch-stabilized emulsions.

The importance of gastric digestion in starch-based emulsion is often overshadowed compared to intestinal digestion, despite acknowledging the activity of salivary α-amylase in the stomach. This study aimed to address this gap by investigating the digestion of starch-based emulsions through orogastrointestinal digestion experiments. Our observations revealed the crucial role of salivary α-amylase, which hydrolyzed ∼8 %, ∼56 %, and âˆ¼ 28 % of starch in emulsions stabilized by octenylsuccinylated maize starch (OMS-E), gelatinized OMS (GOMS-E), and retrograded OMS (ROMS-E), respectively, during the gastric phase. Consequently, ∼23 % of the oil in GOMS-E underwent lipolysis during this phase, whereas ∼13 and âˆ¼ 6 % of the oil was lipolyzed in OMS-E and ROMS-E, respectively. These phenomena significantly influenced their small intestinal digestion and the bioaccessibility of encapsulated curcumin. Notably, GOMS-E exhibited ∼28 % lower curcumin bioaccessibility than that of curcumin encapsulated in OMS-E or ROMS-E. This difference was attributed to premature gastric digestion and subsequent encapsulant release in the case of GOMS-E. This understanding can be utilized to manipulate the delivery and digestion of starch-based emulsions. Importantly, our findings highlight the necessity of considering gastric amylolysis and lipolysis when investigating the gastrointestinal fate of starch-based emulsions.

[Molecular identification of animal species of Bufonis Venenum from secretions].

The animal species is one of the key factors affecting the quality of Bufonis Venenum. The quality of Bufonis Venenum derived from Bufo bufo gargarizans is significantly higher than that from B. melanostictus. Since Bufonis Venenum is from secretions, the conventional identification methods are difficult to identify the animal species due to the lack of the appearance and morphology of the animals. The rapid development of molecular identification technology has provided new methods for the identification of Bufonis Venenum. However, because of the low content and serve degradation of residual DNA in secretions, the research on the molecular identification of Chinese medicinal materials from secretions remains to be carried out. To understand the animal species of Bufonis Venenum, this study collected 83 samples of Bufonis Venenum, including 7 commercially available samples, 5 reference medicinal materials, and 71 animal samples from which Bufonis Venenum was prepared according to the method in the 2020 edition of the Chinese Pharmacopoeia. Different DNA extraction methods were used and compared, and the mitochondrial 16S rRNA gene fragments were amplified, on the basis of which the phylogenetic trees were built. Finally, molecular identification of the animal species of the samples was performed. The results showed that the DNA extracted from Bufonis Venenum by the reagent kit had good quality, and 16S rRNA sequences were successfully amplified from 80 out of the 83 samples. In addition, 71 16S rRNA sequences of the animal species of Bufonis Venenum were downloaded from GenBank. The phylogenetic trees constructed based on the neighbor-joining(NJ) method and the Bayesian inference(BI) method showed that the samples derived from B. bufo gargarizans and B. melanostictus were clustered into separate monophyletic clades, with the support of 100%(NJ) and 1.00(BI), respectively. The animal species of both commercially available samples and reference medicinal materials were B. bufo gargarizans. In conclusion, DNA can be extracted from Bufonis Venenum derived from secretions, and the 16S rRNA gene sequences can be amplified, which can be used for molecular identification of the animal species of Bufonis Venenum. The findings provide a reference for the quality control of Bufonis Venenum and the identification of animal species of medicinal materials derived from secretions.

Early double-balloon enteroscopy was not related to better clinical outcomes in patients with suspected overt small bowel bleeding.

BACKGROUND: Device-assisted enteroscopy has been used for over 20 years for the management of patients with suspected small bowel bleeding. Unlike esophagogastroduodenoscopy and colonoscopy, the appropriate timing of enteroscopy is still unknown. In recent guidelines, early enteroscopy is suggested to maximize diagnostic yield and therapeutic yield in patients with suspected small bowel bleeding. However, few studies have identified its influence on clinical outcomes, including mortality or rebleeding rate. We conducted this study to evaluate the influence of the timing of double-balloon enteroscopy on clinical outcomes in patients with suspected small bowel bleeding. METHODS: Patients with overt small bowel bleeding who underwent double-balloon enteroscopy from January 2013 to February 2021 were retrospectively reviewed. Patients were categorized into an early enteroscopy group (≤14 days) and a nonearly enteroscopy group (>14 days). Clinical outcomes, including short-term mortality and rebleeding rate, long-term mortality and rebleeding rate, diagnostic yield, and therapeutic yield, were analyzed. RESULTS: A total of 100 patients (mean age, 66.2 years; 53% male) were included, and 44 patients were stratified into the early enteroscopy group. The diagnostic yield, therapeutic yield, mortality, and rebleeding rate were similar between two groups. In multivariate conditional logistic regression analysis, there were no significant differences between two groups regarding the 30-day rebleeding rate (adjusted odds ratio [aOR], 1.43; 95% CI, 0.47-4.33), 90-day rebleeding rate (aOR, 1.18; 95% CI, 0.47-2.94), 30-day mortality rate (aOR, 1.29; 95% CI, 0.21-8.13), 90-day mortality rate (aOR, 1.94; 95% CI, 0.48-7.87), and 90-day bleeding-related mortality (aOR, 2.18; 95% CI, 0.24-19.52). The Kaplan-Meier survival curve analysis showed that the timing of DBE was not associated with the long-term rebleeding rate or mortality rate ( p = 0.57 and 0.83, respectively). CONCLUSION: The timing of enteroscopy did not influence the clinical outcomes, including the short-term mortality rate, short-term rebleeding rate, long-term mortality rate, and rebleeding rate, in patients with suspected overt small bowel bleeding.

A Comparison between Chicago Classification Versions 3.0 and 4.0 and Their Impact on Manometric Diagnoses in Esophageal High-Resolution Manometry Cases.

High-resolution manometry (HRM) facilitates the detailed evaluation of esophageal motility. In December 2020, Chicago classification (CC) version 4.0 introduced modifications to improve consistency and accuracy. We conducted this study to compare the differences in the interpretations of HRM examinations between CC 3.0 and 4.0. Consecutive HRM records at a Taiwan tertiary medical center, including wet swallows and MRS performed in both supine and sitting positions from October 2019 to May 2021, were retrospectively reviewed and analyzed using both CC versions 3.0 and 4.0. A total of 105 patients were enrolled, and 102 patients completed the exam, while three could not tolerate HRM sitting up. Refractory gastroesophageal reflux disease (GERD) symptoms (n = 65, 63.7%) and dysphagia (n = 37, 36.3%) were the main indications. A total of 18 patients (17.6%) were reclassified to new diagnoses using CC 4.0. Of the 11 patients initially diagnosed with absent contractility, 3 (27.3%) were reclassified as having Type 1 achalasia. Of the 18 patients initially diagnosed with IEM, 6 (33.3%) were reclassified as normal. The incidence of diagnosis changes was similar in both the dysphagia and refractory GERD symptoms groups (21.6% versus 15.3%, p = 0.43). The use of CC 4.0 led to changes in the diagnoses of esophageal motility disease, irrespective of examination indications. Early adoption improves the accuracy of diagnoses and affects patient management.

Bone protective effect of sinomenine against monosodium iodoacetate induced knee and hip injury in rat model: an inflammatory pathway.

PURPOSE: Osteoarthritis (OA) is a degenerative joint disease which is categorized via destruction of joint cartilage and it also affects the various joints, especially knees and hips. Sinomenine active phytoconstituents isolated from the stem of Sinomenium acutum and already proof anti-inflammatory effect against the arthritis model of rodent. In this experimental protocol, we scrutinized the anti-osteoarthritis effect of sinomenine against monosodium iodoacetate (MIA) induced OA in rats. METHODS: MIA (3 mg/50 µL) was used for inducing the OA in the rats, and rats received the oral administration of sinomenine (2.5, 5 and 7.5 mg/kg body weight) up to the end of the experimental study (four weeks). The body and organs weight were estimated. Aggrecan, C-terminal cross-linked telopeptide of type II collagen (CTX-II), glycosaminoglycans (GCGs), monocyte chemoattractant protein-1 (MCP-1), Interferon gamma (IFN-γ), antioxidant, inflammatory cytokines, inflammatory mediators and matrix metalloproteinases (MMP) were analyzed. RESULTS: Sinomenine significantly (P < 0.001) boosted the body weight and reduced the heart weight, but the weight of spleen and kidney remain unchanged. Sinomenine significantly (P < 0.001) reduced the level of nitric oxide, MCP-1 and improved the level of aggrecan, IFN-γ and GCGs. Sinomenine remarkably upregulated the level of glutathione, superoxide dismutase and suppressed the level of malonaldehyde. It effectually modulated the level of inflammatory cytokines and inflammatory mediators and significantly (P < 0.001) reduced the level of MMPs, like MMP-1, 2, 3, 9 and 13. CONCLUSIONS: Sinomenine is a beneficial active agent for the treatment of OA disease.

Topological electronic states in holey graphyne.

We unveil that the holey graphyne (HGY), a two-dimensional carbon allotrope where benzene rings are connected by two -C≡C- bonds fabricated recently in a bottom-up way, exhibits topological electronic states. Using first-principles calculations and Wannier tight-binding modeling, we discover a higher-order topological invariant associated withC2symmetry of the material, and show that the resultant corner modes appear in nanoflakes matching to the structure of precursor reported previously, which are ready for direct experimental observations. In addition, we find that a band inversion between emergentg-like andh-like orbitals gives rise to a nontrivial topology characterized byZ2invariant protected by an energy gap as large as 0.52 eV, manifesting helical edge states mimicking those in the prominent quantum spin Hall effect, which can be accessed experimentally after hydrogenation in HGY. We hope these findings trigger interests towards exploring the topological electronic states in HGY and related future electronics applications.

Safety and Tolerability of Intra-Articular Injection of Adipose-Derived Mesenchymal Stem Cells GXCPC1 in 11 Subjects With Knee Osteoarthritis: A Nonrandomized Pilot Study Without a Control Arm.

The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 106 GXCPC1, N = 5) and high dose (4 × 107 GXCPC1, N = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = -7.773 to -2.561t at 12 weeks compared to baseline) and knee function (95% CI = -24.297 to -10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study.