Current research trends on the effect of diabetes mellitus on rotator cuff tendon healing/tendinopathy.

Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.

Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18.

The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses. In rats, intramyocardially injected mRNA remained localized, whereas direct myocardial injection of an adenovirus carrying a reporter gene resulted in diffuse expression and in substantial spillover to the liver, spleen and lungs. Transient expression of TBX18 mRNA in rats led to de novo automaticity and pacemaker properties and, compared with the injection of adenovirus, to substantial reductions in the expression of inflammatory genes and in activated macrophage populations. In rodent and clinically relevant porcine models of complete heart block, intramyocardially injected TBX18 mRNA provided rate-adaptive cardiac pacing for one month that strongly correlated with the animal's sinus rhythm and physical activity. TBX18 mRNA may aid the development of biological pacemakers.

Combinatorial expression of neurexin genes regulates glomerular targeting by olfactory sensory neurons.

Precise connectivity between specific neurons is essential for the formation of the complex neural circuitry necessary for executing intricate motor behaviors and higher cognitive functions. While trans -interactions between synaptic membrane proteins have emerged as crucial elements in orchestrating the assembly of these neural circuits, the synaptic surface proteins involved in neuronal wiring remain largely unknown. Here, using unbiased single-cell transcriptomic and mouse genetic approaches, we uncover that the neurexin family of genes enables olfactory sensory neuron (OSNs) axons to form appropriate synaptic connections with their mitral and tufted (M/T) cell synaptic partners, within the mammalian olfactory system. Neurexin isoforms are differentially expressed within distinct populations of OSNs, resulting in unique pattern of neurexin expression that is specific to each OSN type, and synergistically cooperate to regulate axonal innervation, guiding OSN axons to their designated glomeruli. This process is facilitated through the interactions of neurexins with their postsynaptic partners, including neuroligins, which have distinct expression patterns in M/T cells. Our findings suggest a novel mechanism underpinning the precise assembly of olfactory neural circuits, driven by the trans -interaction between neurexins and their ligands.

CD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators.

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian olfactory receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.

Effect of Mollusca shell extracts on inhibition of kimchi over-acidification.

Mollusca species shell such as oyster shell (OS) and snail shell (SS), are discarded after taking the meat, and the discarded shell causes the environmental problems. Therefore, recycling shell waste could potentially eliminate the environmental problems. This study aimed to evaluate the potential of OS and SS as natural calcium resources. The minerals, calcium, magnesium, potassium, phosphorus and sodium were analyzed in OS and SS extracts. Among them, the calcium content was the highest: 36.87 (%) and 33.42 (%) in the OS and SS extracts, respectively. Further, the content of ionized bioavailable form of calcium in OS and SS was higher than that of CaCO3 under simulated gastrointestinal digestion conditions. Additionally, OS and SS were added to kimchi, and their inhibitory effect on kimchi acidification was evaluated by assessing pH, titratable acidity and microbial analysis. As the results indicated that the addition of OS and SS had little effect on inhibiting the growth of lactic acid bacteria. However, it was confirmed that calcium neutralizes the organic acids produced during fermentation. Overall, the results of this study provide preliminary information on the re-use of OS and SS extracts as ionized natural calcium supplements and fermentation retardants.

Small volar fragment in the lunate fossa leads to volar tilt loss after volar plate fixation for AO/OTA type-C distal radius fracture.

OBJECTIVES: The relationship between volar fragment size and postoperative volar tilt loss in complete articular distal radius fracture is not well known. In this study, we measured precise radiological parameters to help identify other factors that might contribute to volar tilt loss. MATERIAL AND METHODS: We retrospectively reviewed the radiological examinations and charts of 256 patients with distal radial fracture who underwent volar locking plate fixation between March 2014 and July 2022. Radiological parameters were measured based on preoperative CT and immediate postoperative radiographs. Univariate and multivariate linear regression analysis was performed to identify relevant factors associated with volar tilt loss following volar locking plate fixation. The receiver operating characteristic curve was used to identify the cutoff value of the independent parameters. RESULTS: On univariate analysis, 2 radiologic parameters on preoperative CT (volar fragment length at the lunate fossa, and teardrop angle) and 4 on immediate postoperative X-ray (radial inclination, radial length, capitate shift, and volar tilt) were significantly associated with postoperative volar tilt loss. On multivariate linear regression analysis, the risk of volar tilt loss increased as the capitate moved toward the back of the radial shaft. The cut-off for anteroposterior length in the lunate fossa was 6.5 mm. CONCLUSIONS: AO/OTA type-C distal radius fractures with <6.5 mm anteroposterior length in the lunate fossa had significantly higher rates of malunion with dorsal deformity. In addition, preoperative teardrop angle <37.2 ° and immediate postoperative volar tilt <3.7º are also predictors of postoperative volar tilt loss.

Selenium reduction of ubiquinone via SQOR suppresses ferroptosis.

The canonical biological function of selenium is in the production of selenocysteine residues of selenoproteins, and this forms the basis for its role as an essential antioxidant and cytoprotective micronutrient. Here we demonstrate that, via its metabolic intermediate hydrogen selenide, selenium reduces ubiquinone in the mitochondria through catalysis by sulfide quinone oxidoreductase. Through this mechanism, selenium rapidly protects against lipid peroxidation and ferroptosis in a timescale that precedes selenoprotein production, doing so even when selenoprotein production has been eliminated. Our findings identify a regulatory mechanism against ferroptosis that implicates sulfide quinone oxidoreductase and expands our understanding of selenium in biology.

Metabolic shift during fermentation in kimchi according to capsaicinoid concentration.

The cultivar of red pepper used in kimchi contributes to spiciness, red color, and fermentation characteristics. Capsaicinoids are the main components of red pepper. Therefore, understanding changes in metabolites during kimchi fermentation according to capsaicinoid concentration is necessary to control the quality of kimchi. The purpose of this study was to investigate the effect of capsaicinoids on metabolites during kimchi fermentation. To profile the effect of capsaicinoid concentrations on kimchi fermentation, five kimchi samples were prepared using different concentrations of capsaicinoids (4, 12, 30.7, 40.9, and 50.3 mg/kg) and stored at 4 °C for 28 days. During kimchi fermentation, pH, titratable acidity, capsaicinoid concentration, total viable and lactic acid bacteria, free sugars, amino acids, and microbial community were evaluated. Each result was statistically analyzed for changes in capsaicin concentration and fermentation time. The capsaicinoid concentration did not change during kimchi fermentation but the growth of lactic acid bacteria changed. According to the growth of lactic acid bacteria, free sugar, amino acids, and microbial community changed with the capsaicinoid concentration. Overall, the results of this study provide preliminary information on the use of red pepper and capsaicinoids in the kimchi industry.

Tranexamic Acid Can Reduce Early Tendon Adhesions After Rotator Cuff Repair and Is Not Detrimental to Tendon-Bone Healing: A Comparative Animal Model Study.

PURPOSE: To determine the effects of topical tranexamic acid (TXA) administration on tendon adhesions, shoulder range of motion (ROM), and tendon healing in an acute rotator cuff repair rat model. METHODS: A total of 20 Sprague Dawley rats were used. Tendon adhesion, ROM, and biomechanical and histological analysis of tendon-bone healing was conducted at 3 and 6 weeks after surgery. The rats underwent rotator cuff repair surgery on both shoulders and were administered TXA via subacromial injections. The tendon adhesion was evaluated macroscopically and histologically. Biomechanical tendon healing was measured using a universal testing machine, and histological analysis was quantified by H&E, Masson's trichrome, and picrosirius red staining. RESULTS: At 3 weeks after surgery, the adhesion score was significantly lower in the TXA group (2.10 ± 0.32) than in the control group (2.70 ± 0.48) (P = .005), but there was no significant difference between the 2 groups at 6 weeks. Regarding ROM, compared with the control group, the TXA group showed significantly higher external rotation (36.35° ± 4.52° vs 28.42° ± 4.66°, P < .001) and internal rotation (45.35° ± 9.36° vs 38.94° ± 5.23°, P = .013) 3 weeks after surgery. However, at 6 weeks, there were no significant differences in external and internal rotation between the 2 groups. In the biomechanical analysis, no significant differences in gross examination (3 weeks, P = .175, 6 weeks, P = .295), load to failure (3 weeks, P = .117, 6 weeks, P = .295), or ultimate stress (3 weeks, P = .602, 6 weeks, P = .917) were noted between the 2 groups 3 and 6 weeks after surgery. In the histological analysis of tendon healing, no significant differences in the total score (3 weeks, P = .323, 6 weeks, P = .572) were found between the 2 groups 3 and 6 weeks after surgery. CONCLUSIONS: Topical TXA administration showed a beneficial effect in reducing tendon adhesions and improving ROM 3 weeks postoperatively and had no effect at 6 weeks. This suggests that additional intervention with TXA may be useful in achieving long-term improvement in shoulder stiffness. Additionally, TXA may increase tissue ground substance accumulation in the late postoperative period but does not adversely affect tendon-bone interface healing. CLINICAL RELEVANCE: The use of TXA after rotator cuff repair has no effect on tendon-bone interface healing in clinical practice and can improve shoulder stiffness in the early postoperative period. Additional research on the long-term effects is needed.

From odor to oncology: non-canonical odorant receptors in cancer.

Odorant receptors, traditionally associated with olfaction as chemoreceptors, have been increasingly recognized for their presence and diverse functions in various non-nasal tissues throughout the body. Beyond their roles in sensory perception, emerging evidence suggests a compelling interplay between odorant receptors and cancer progression as well. Alongside the canonical GPCR odorant receptors, dysregulation of non-canonical odorant receptors such as trace amine-associated receptors (TAARs), formyl peptide receptors (FPRs), and membrane-spanning 4A family (MS4As) has been observed in various cancer types, suggesting their contributions to cancer progression. The roles of these non-canonical chemoreceptors in cancer are complex, with some receptors promoting tumorigenesis and others acting as tumor-suppressing factors upon activation, depending on the cancer type. These findings shed light on the potential of non-canonical odorant receptors as therapeutic targets and prognostic markers in cancer, inviting further exploration to unravel their precise mechanisms of action and implications in cancer biology. In this review, we provide a comprehensive overview of the intricate relationships between these chemoreceptors and various types of cancer, potentially paving the way for innovative odor-based therapeutics. Ultimately, this review discusses the potential development of novel therapeutic strategies targeting these non-canonical chemoreceptors.

A finite element analysis of stress distribution with various directions of intermaxillary fixation using orthodontic mini-implants and elastics following mandibular advancement with a bilateral sagittal split ramus osteotomy.

OBJECTIVE: This finite element analysis (FEA) aimed to assess the stress distribution in the mandible and fixation system with various directions of the intermaxillary fixation (IMF) using mini-implants (MIs) and elastics following mandibular advancement with a bilateral sagittal split ramus osteotomy (BSSRO). MATERIALS AND METHODS: A total of nine mandibular advancement models were set according to the position of the MIs (1.6 mm in diameter, 8 mm in length) and direction of the IMF elastics (1/4 inch, 5 oz). Major and minor principal stresses in the cortical and cancellous bones, von Mises stresses in the fixation system (miniplate and monocortical screws), and bending angles of the miniplate were analysed. RESULTS: Compressive and tensile stress distributions in the mandible and von Mises stress distributions in the fixation system were greater in models with a Class III IMF elastic direction and a higher IMF elastic force than in models with a Class II IMF elastic direction and a lower IMF elastic force. The bending angle of the miniplate was negligible. CONCLUSIONS: Stress distributions in the bone and fixation system varied depending on the direction, amount of force, and position of IMF elastics and MIs. Conclusively, IMF elastics in the Class II direction with minimal load in the area close to the osteotomy site should be recommended.

Current Research on the Influence of Statin Treatment on Rotator Cuff Healing.

Rotator cuff tears are a condition characterized by damage to the muscles and tendons that connect the scapula and humerus, which are responsible for shoulder rotation and arm lifting. Metabolic factors such as diabetes, thyroid disease, high cholesterol, vitamin D deficiency, obesity, and smoking have been associated with an increased risk of rotator cuff tears. Interestingly, patients with hyperlipidemia, a condition characterized by high levels of cholesterol and other fats in the blood, have been found to have a higher incidence of rotator cuff tears and breakdown of tendon matrix. As a result, statin therapy, which is commonly used to lower cholesterol levels in hyperlipidemia, has been explored as a potential treatment to improve clinical outcomes in rotator cuff tears. However, the results of preclinical and clinical studies on the effects of statins on tendon healing in rotator cuff tears are limited and not well-defined. Moreover, since hyperlipidemia and rotator cuff tears are more prevalent in older individuals, a literature review on the efficacy and safety of statin therapy in this population is needed.

Extracorporeal Blood Treatment Using Functional Magnetic Nanoclusters Mitigates Organ Dysfunction of Sepsis in Swine.

Mitigating sepsis-induced severe organ dysfunction with magnetic nanoparticles has shown remarkable advances in extracorporeal blood treatment. Nevertheless, treating large septic animals remains challenging due to insufficient magnetic separation at rapid blood flow rates (>6 L h-1 ) and limited incubation time in an extracorporeal circuit. Herein, superparamagnetic nanoclusters (SPNCs) coated with red blood cell (RBC) membranes are developed, which promptly capture and magnetically separate a wide range of pathogens at high blood flow rates in a swine sepsis model. The SPNCs exhibited an ultranarrow size distribution of clustered iron oxide nanocrystals and exceptionally high saturation magnetization (≈ 90 emu g-1 ) close to that of bulk magnetite. It is also revealed that CD47 on the RBCs allows the RBC-SPNCs to remain at a consistent concentration in the blood by evading innate immunity. The uniform size distribution of the RBC-SPNCs greatly enhances their effectiveness in eradicating various pathogenic materials in extracorporeal blood. The use of RBC-SPNCs for extracorporeal treatment of swine infected with multidrug-resistant E. coli is validated and found that severe bacteremic sepsis-induced organ dysfunction is significantly mitigated after 12 h. The findings highlight the potential application of RBC-SPNCs for extracorporeal therapy of severe sepsis in large animal models and potentially humans.

CD20 is a mammalian odorant receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators.

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian odorant receptor that recognizes compounds produced by mouse predators. While wild-type mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a novel CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.

Predictors of Vertebral Endplate Fractures after Oblique Lumbar Interbody Fusion.

Background: Cage subsidence after oblique lumbar interbody fusion (OLIF) induces restenosis and adversely affects patient outcomes. Many studies have investigated the causes of subsidence, one of which is endplate fracture (EF). This study aimed to identify predictors of EF after OLIF. Methods: This retrospective study reviewed consecutive patients who underwent OLIF at a single institute between August 2019 and February 2022. A total of 104 patients were enrolled. The patients' demographic data and surgical details were collected through chart reviews. Radiographic variables were measured. Related variables were also analyzed using binomial logistic regression, dividing each group into those with versus without EF. Results: EF occurred at 30 of 164 levels (18.3%), and the binary logistic analysis revealed that sex (odds ratio [OR], 11.07), inferior endplate concave depth (OR, 1.95), disc wedge angle (OR, 1.22), lumbar lordosis (OR, 1.09), pelvic incidence (OR, 1.07), sagittal vertical axis (OR, 1.02), sacral slope (OR, 0.9), L3-4 level (OR, 0.005), and L4-5 level (OR, 0.004) were significantly related to EF. Conclusions: OLIF in older Asian patients should be performed carefully after recognizing the high possibility of EF and confirming the factors that should be considered preoperatively.

Construction of a Compact Array of Microplasma Jet Devices and Its Application for Random Mutagenesis of Rhodosporidium toruloides.

A small and efficient DNA mutation-inducing machine was constructed with an array of microplasma jet devices (7 × 1) that can be operated at atmospheric pressure for microbial mutagenesis. Using this machine, we report disruption of a plasmid DNA and generation of mutants of an oleaginous yeast Rhodosporidium toruloides. Specifically, a compact-sized microplasma channel (25 × 20 × 2 mm3) capable of generating an electron density of greater than 1013 cm-3 was constructed to produce reactive species (N2*, N2+, O, OH, and Hα) under helium atmospheric conditions to induce DNA mutagenesis. The length of microplasma channels in the device played a critical role in augmenting both the volume of plasma and the concentration of reactive species. First, we confirmed that microplasma treatment can linearize a plasmid by creating nicks in vitro. Second, we treated R. toruloides cells with a jet device containing 7 microchannels for 5 min; 94.8% of the treated cells were killed, and 0.44% of surviving cells showed different colony colors as compared to their parental colony. Microplasma-based DNA mutation is energy-efficient and can be a safe alternative for inducing mutations compared to conventional methods using toxic mutagens. This compact and scalable device is amenable for industrial strain improvement involving large-scale mutagenesis.

Metformin increases the expression of proinflammatory cytokines and inhibits supraspinatus fatty infiltration.

BACKGROUND: After a rotator cuff (RC) tendon tear, the supraspinatus (SS) inflammatory response induces fatty infiltration (FI). Metformin has the effect of regulating the initial inflammatory response of atrophic muscles. Therefore, this study aimed to investigate the effect of metformin use on modulating the expression of proinflammatory cytokines and SS FI in an acute RC tear rat model. METHODS: This study used 26 male Sprague-Dawley rats. Animals were randomly divided into two groups: The metformin group received metformin for 5 days after cutting the RC tendon, and the control group was administered only with saline after cutting the tendon. Metformin 50 mg/kg was intraperitoneally injected for 5 days. Three rats in each group were sacrificed 5 days after SS tendon rupture surgery, and 10 rats in each group were sacrificed 14 days after surgery. The SS was sampled 5 days after SS tendon tear surgery, and the expression of proinflammatory cytokines was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). On day 14 after sampling, histological analysis of the SS was performed using hematoxylin and eosin, Masson's trichrome, and picrosirius red staining. RESULTS: On day 5 of surgery, the expression values of interferon gamma (increased 7.2-fold, P < .01), tumor necrosis factor alpha (increased 13-fold, P < .05), interleukin-1ß (increased 4.7-fold, P < .001), and interleukin-6 (increased 4.6-fold, P < .01) increased significantly in the metformin group compared with those in the control group. As a result of Oil Red O staining, SS FI was significantly suppressed in the metformin group compared with that in the control group (metformin group, 305 ± 50.3 µm2, P < .001; control group, 3136 ± 662.8 µm2, P < .001). In addition, the SS volume of the metformin group was not reduced compared with those of the control group, and the morphology and structure of the SS were better preserved. CONCLUSIONS: The results of this study revealed that metformin can increase the expression of proinflammatory cytokines and suppress SS fat infiltration in delayed sutures.

CD20 is a mammalian odorant receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators.

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian odorant receptor that recognizes compounds produced by mouse predators. While wild-type mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a novel CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.

Scalable, Patternable Glass-Infiltrated Ceramic Radiative Coolers for Energy-Saving Architectural Applications.

A huge concern on global climate/energy crises has triggered intense development of radiative coolers (RCs), which are promising green-cooling technologies. The continuous efforts on RCs have fast-tracked notable energy-savings by minimizing solar absorption and maximizing thermal emission. Recently, in addition to spectral optimization, ceramic-based thermally insulative RCs are reported to improve thermoregulation by suppressing heat gain from the surroundings. However, a high temperature co-firing process of ceramic-based thick film inevitably results in a large mismatch of structural parameters between designed and fabricated components, thereby breaking spectral optimization. Here, this article proposes a scalable, non-shrinkable, patternable, and thermally insulative ceramic RC (SNPT-RC) using a roll-to-roll process, which can fill a vital niche in the field of radiative cooling. A stand-alone SNPT-RC exhibits excellent thermal insulation (≈0.251 W m-1  K-1 ) with flame-resistivity and high solar reflectance/long-wave emissivity (≈96% and 92%, respectively). Alternate stacks of intermediate porous alumina/borosilicate (Al2 O3 -BS) layers not only result in outstanding thermal and spectral characteristics, causing excellent sub-ambient cooling (i.e., 7.05 °C cooling), but also non-shrinkable feature. Moreover, a perforated SNPT-RC demonstrates its versatility as a breathable radiative cooling shade and as a semi-transparent window, making it a highly promising technology for practical deployment in energy-saving architecture.