Lactiplantibacillus plantarum LM1001 Improves Digestibility of Branched-Chain Amino Acids in Whey Proteins and Promotes Myogenesis in C2C12 Myotubes.

Lactiplantibacillus plantarum is a valuable potential probiotic species with various proven health-beneficial effects. L. plantarum LM1001 strain was selected among ten strains of L. plantarum based on proteolytic activity on whey proteins. L. plantarum LM1001 produced higher concentrations of total free amino acids and branched-chain amino acids (Ile, Leu, and Val) than other L. plantarum strains. Treatment of C2C12 myotubes with whey protein culture supernatant (1%, 2% and 3%, v/v) using L. plantarum LM1001 significantly increased the expression of myogenic regulatory factors, such as Myf-5, MyoD, and myogenin, reflecting the promotion of myotubes formation (p<0.05). L. plantarum LM1001 displayed ß-galactosidase activity but did not produce harmful ß-glucuronidase. Thus, the intake of whey protein together with L. plantarum LM1001 has the potential to aid protein digestion and utilization.

Anatomical assessments of injectate spread stratified by the volume of the intertransverse process block at the T2 level.

BACKGROUND: This cadaveric study aimed to analyze injectate spread to target nerves during a single-injection, ultrasound-guided intertransverse process block. METHODS: An ultrasound-guided intertransverse process block with three different injectate volumes was administered to 12 cadavers. Each hemithorax was subjected to computer-generated random allocation of 10, 15, or 20 mL ultrasound-guided, single-injection intertransverse process block at the T2 vertebral level. Latex dye solution was injected into each hemithorax in accordance with the allocated volume. The presence of dye at the nerve root in the sympathetic chain and intercostal nerves at various injection levels was examined via dissection. RESULTS: Injectate spread into the dorsal rami was observed in seven of eight (87.5%), seven of eight (87.5%), and all eight (100%) of the 10, 15, and 20 mL specimens, respectively. In all 20 mL specimens, consistent staining of the dorsal rami, spinal nerve, and dorsal root ganglion was observed. CONCLUSIONS: An injectate volume of 20 mL was required for consistent staining of the dorsal rami, spinal nerve, and dorsal root ganglion in an intertransverse process block. Although an augmented injectate volume was associated with an increased likelihood of target nerve staining, consistent staining of the sympathetic ganglion, rami communicans, and ventral ramus was not observed, even at a volume of 20 mL. The current study presents initial findings suggesting that as opposed to a sympathetic ganglion block, a 20 mL intertransverse process block may act as a feasible substitute for dorsal root ganglion, spinal nerve, and medial branch blocks within a clinical context.

KL-Biome (Postbiotic Formulation of Lactiplantibacillus plantarum KM2) Improves Dexamethasone-Induced Muscle Atrophy in Mice.

Sarcopenia refers to an age-related decrease in muscle mass and strength. The gut-muscle axis has been proposed as a promising target to alleviate muscle atrophy. The effect of KL-Biome-a postbiotic preparation comprising heat-killed Lactiplantibacillus plantarum KM-2, its metabolites, and an excipient (soybean powder)-on muscle atrophy was evaluated using dexamethasone (DEX)-induced atrophic C2C12 myoblasts and C57BL/6J mice. KL-Biome significantly downregulated the expression of genes (Atrogin-1 and MuRF1) associated with skeletal muscle degradation but increased the anabolic phosphorylation of FoxO3a, Akt, and mTOR in C2C12 cells. Oral administration of KL-Biome (900 mg/kg) for 8 weeks significantly improved muscle mass, muscle function, and serum lactate dehydrogenase levels in DEX-treated mice. KL-Biome administration increased gut microbiome diversity and reversed DEX-mediated gut microbiota alterations. Furthermore, it significantly increased the relative abundances of the genera Subdologranulum, Alistipes, and Faecalibacterium prausnitzii, which are substantially involved in short-chain fatty acid production. These findings suggest that KL-Biome exerts beneficial effects on muscle atrophy by regulating gut microbiota.

One-step detection of procollagen type III N-terminal peptide as a fibrosis biomarker using fluorescent immunosensor (quenchbody).

BACKGROUND: Procollagen type III N-terminal peptide (P-III-NP) is a fibrosis biomarker associated with liver and cardiac fibrosis. Despite the value of P-III-NP as a biomarker, its analysis currently relies on enzyme-linked immunosorbent assays (ELISA) and radioimmunoassays (RIA), which require more than 3 h. To facilitate early diagnosis and treatment through rapid biomarker testing, we developed a one-step immunoassay for P-III-NP using a quenchbody, which is a fluorescence-labeled immunosensor for immediate signal generation. RESULTS: To create quenchbodies, the total mRNA of P-III-NP antibodies was extracted from early-developed hybridoma cells, and genes of variable regions were obtained through cDNA synthesis, inverse PCR, and sequencing. A single-chain variable fragment (scFv) with an N-terminal Cys-tag was expressed in E. coli Shuffle T7, resulting in a final yield of 9.8 mg L-1. The fluorescent dye was labeled on the Cys-tag of the anti-P-III-NP scFv using maleimide-thiol click chemistry, and the spacer arm lengths between the maleimide-fluorescent dyes were compared. Consequently, a TAMRA-C6-labeled quenchbody exhibited antigen-dependent fluorescence signals and demonstrated its ability to detect P-III-NP at concentrations as low as 0.46 ng mL-1 for buffer samples, 1.0 ng mL-1 for 2 % human serum samples. SIGNIFICANCE: This one-step P-III-NP detection method provides both qualitative and quantitative outcomes within a concise 5-min timeframe. Furthermore, its application can be expanded using a 96-well platform and human serum, making it a high-throughput and sensitive method for testing fibrotic biomarkers.

Clinical Outcomes of Coronavirus Disease 2019 in People Living With Human Immunodeficiency Virus in South Korea: A Nationwide Population-Based Cohort Study.

BACKGROUND: We aimed to compare the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) in people living with human immunodeficiency virus (HIV) (PLWH) with those in people living without HIV (PLWoH). METHODS: This nationwide descriptive epidemiological study was conducted in South Korea between January 2020 and February 2022. The National Health Insurance claim data, comprising the data of the entire Korean population, were collected through the Health Insurance Review and Assessment Service. RESULTS: Among 3,653,808 individuals who were diagnosed with COVID-19, 1311 (0.04%) were PLWH. All PLWH received antiretroviral therapy, and 26.47% had more than one underlying disease other than HIV infection. The overall in-hospital mortality rates of PLWH and PLWoH were 0.76% and 0.25%, respectively (P = 0.002). According to the Cox proportional hazard model, no significant difference was observed in the in-hospital mortality rate (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 0.70-4.67) between the PLWH and PLWoH. However, progression to severe or critical COVID-19 was more common in PLWH (HR: 2.70, 95% CI: 1.37-5.33). In PLWH diagnosed with COVID-19, a multivariable Cox regression analysis found old age (≥ 60 years) (HR: 6.9, 95% CI: 2.57-18.56) and diabetes mellitus (HR: 5.13, 95% CI: 2.02-13.00) as the independent risk factors for severe or critical COVID-19. CONCLUSIONS: PLWH had a significantly higher risk of developing severe or critical COVID-19 compared with PLWoH. Our findings suggest the need for implementing tailored strategies to decrease the impact of COVID-19 on PLWH.

Nanoscale-Confined Synthesis of 2D Metal Compounds for Electrochemical Applications.

2D metal compounds, such as transition metal dichalcogenides (TMDs), layered double hydroxides (LDHs), and MXenes, are emerging as important electrocatalyst materials in the transition to a sustainable energy future. Aided by their high surface area, electrical conductivity, and tunable electronic properties, these materials have provided a crucial research thrust in enhancing the efficiency of green hydrogen production, fuel cells, and carbon reduction processes. Most importantly, the synthesis of nanostructured 2D compounds, while challenging, is the key to optimizing their catalytic performance. Recent advancements in this field have highlighted the potential of 2D metal compounds in revolutionizing energy conversion technologies, which entails the discovery of new material compositions, the development of novel synthetic routes, and the integration of these materials into practical energy conversion systems. This review presents an overview of the distinctive characteristics of nanoscale-confined 2D metal compounds, the challenges encountered in their synthesis, and electrochemical applications.

TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction.

Adipose tissue (AT) adapts to overnutrition in a complex process, wherein specialized immune cells remove and replace dysfunctional and stressed adipocytes with new fat cells. Among immune cells recruited to AT, lipid-associated macrophages (LAMs) have emerged as key players in obesity and in diseases involving lipid stress and inflammation. Here, we show that LAMs selectively express transmembrane 4 L six family member 19 (TM4SF19), a lysosomal protein that represses acidification through its interaction with Vacuolar-ATPase. Inactivation of TM4SF19 elevates lysosomal acidification and accelerates the clearance of dying/dead adipocytes in vitro and in vivo. TM4SF19 deletion reduces the LAM accumulation and increases the proportion of restorative macrophages in AT of male mice fed a high-fat diet. Importantly, male mice lacking TM4SF19 adapt to high-fat feeding through adipocyte hyperplasia, rather than hypertrophy. This adaptation significantly improves local and systemic insulin sensitivity, and energy expenditure, offering a potential avenue to combat obesity-related metabolic dysfunction.

Effect of air temperature on serum 25-hydroxyvitamin D concentrations: A single institutional large-scale study in Korea.

Vitamin D deficiency is a worldwide health issue especially in women. Serum vitamin D concentrations vary depending on the weather. However, the ideal vitamin D supplementation strategy related to weather remains uncertain. We aimed to investigate the relationship between climate factors and serum 25-hydroxy vitamin D [25(OH)D] concentrations. This study included 11,272 women aged 20-79 who visited a health promotion center for annual checkups between January 2013 and December 2015. We reviewed medical records and collected daily meteorological data. We analyzed the association between serum 25(OH)D concentration and climate factors using simple and multiple regression models and then predicted serum 25(OH)D concentration using multiple fractional polynomial models. The median age of the participants was 51 years (20-79 years), and the mean serum 25(OH)D level was 17.4 ± 8.6 ng/mL. The serum 25(OH)D concentration was lower in young women than in older women. The proportions of women with adequate 25(OH)D levels were 14.9% and 47.0% in the age groups 20-29 and 70-79, respectively. The maximum level of predicted log 25(OH)D was found in September, and the minimum was found in January. In multiple regression analysis, age and monthly mean temperature were associated with 25(OH)D concentrations. Serum 25(OH)D level was predicted using the following formula: log (25(OH)D) = 2.144 + 0.009 × age + 0.018 × ((temperature + 12.4)/10)2 (P < 0.001, adjusted R2 = 0.091). Serum 25(OH)D concentrations changed according to air temperature. An adequate strategy for vitamin D supplementation, based on air temperature, is necessary to maintain healthy serum 25(OH)D levels.

A New Equation to Estimate Peripherally Inserted Central Catheter Length.

Background and Objectives: Peripherally inserted central catheter (PICC) placement plays an important role in clinical practice. This study aimed to provide an equation for the proper estimation of catheter length in cases of PICC placement without imaging guidance in relation to patient height, weight, sex, and age. Materials and Methods: For 1137 PICC placement cases in both arm veins of 954 patients at a single center, the elbow crease to the cavoatrial junction length (ECL) was calculated as follows: ECL = (PICC length) + (distance from the elbow crease to the puncture site). We analyzed the relationship between ECL and patient characteristics and suggested a new equation for ECL based on height, weight, sex, and age. Results: The average ECL was 48.0 ± 2.4 cm in the right side and 51.0 ± 3.0 cm in the left side. ECL in the right arm was significantly correlated with patient height, sex, and age, whereas the ECL in the left arm was additionally significantly correlated with patient weight. The ECL (cm) prediction model was as follows: right ECL = 26.32 + 1.33 × (female = 1, male = 2) - 0.02 × age (years) + 0.13 × height (cm); left ECL = 22.09 + 1.28 × (female = 1, male = 2) + 0.02 × age (years) + 0.14 × height (cm) + 0.042 × weight (kg). Conclusions: The appropriate PICC length was predicted based on the patient's height, weight, sex, and age. The equations in our study can help predict the optimal catheter length and can be automatically calculated using computerized patient information for bedside procedures in PICC.

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells.

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Mucosal TLR5 activation controls healthspan and longevity.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Roles of Heterojunction and Cu Vacancies in the Au@Cu2-xSe for the Enhancement of Electrochemical Nitrogen Reduction Performance.

The utilization of hydrogen (H2) as a fuel source is hindered by the limited infrastructure and storage requirements. In contrast, ammonia (NH3) offers a promising solution as a hydrogen carrier due to its high energy density, liquid storage capacity, low cost, and sustainable manufacturing. NH3 has garnered significant attention as a key component in the development of next-generation refueling stations, aligning with the goal of a carbon-free economy. The electrochemical nitrogen reduction reaction (ENRR) enables the production of NH3 from nitrogen (N2) under ambient conditions. However, the low efficiency of the ENRR is limited by challenges such as the electron-stealing hydrogen evolution reaction (HER) and the breaking of the stable N2 triple bond. To address these limitations and enhance ENRR performance, we prepared Au@Cu2-xSe electrocatalysts with a core@shell structure using a seed-mediated growth method and a facile hot-injection method. The catalytic activity was evaluated using both an aqueous electrolyte of KOH solution and a nonaqueous electrolyte consisting of tetrahydrofuran (THF) solvent with lithium perchlorate and ethanol as proton donors. ENRR in both aqueous and nonaqueous electrolytes was facilitated by the synergistic interaction between Au and Cu2-xSe (copper selenide), forming an Ohmic junction between the metal and p-type semiconductor that effectively suppressed the HER. Furthermore, in nonaqueous conditions, the Cu vacancies in the Cu2-xSe layer of Au@Cu2-xSe promoted the formation of lithium nitride (Li3N), leading to improved NH3 production. The synergistic effect of Ohmic junctions and Cu vacancies in Au@Cu2-xSe led to significantly higher ammonia yield and faradaic efficiency (FE) in nonaqueous systems compared to those in aqueous conditions. The maximum NH3 yields were approximately 1.10 and 3.64 µg h-1 cm-2, with the corresponding FE of 2.24 and 67.52% for aqueous and nonaqueous electrolytes, respectively. This study demonstrates an attractive strategy for designing catalysts with increased ENRR activity by effectively engineering vacancies and heterojunctions in Cu-based electrocatalysts in both aqueous and nonaqueous media.

Periodontitis of maxillary teeth screened by community periodontal index is associated with chronic rhinosinusitis defined by EPOS 2020 guideline.

We aimed to evaluate the association between periodontitis in the upper jaw and chronic rhinosinusitis (CRS) using the nationwide Korean National Health and Nutrition Examination Survey (KNHANES) data. In this cross-sectional study, data of KNHANES participants enrolled between 2008 and 2012 were reviewed. Periodontitis of the upper teeth was diagnosed by dentists according to the community periodontal index with standardized methods. CRS was diagnosed by otorhinolaryngologists according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 with nasal endoscopy findings. We also evaluated the association between periodontitis and CRS according to smoking and drinking status. Univariate and multivariate logistic regression analyses were performed. Overall, 28,761 participants were eligible for analysis, and 210 were diagnosed with CRS. Periodontitis was associated with CRS diagnosis (odds ratio [OR] = 1.391, 95% confidence interval [CI] = 1.013-1.912). Non-drinkers showed no significant association between periodontitis and CRS (OR = 1.142, 95% CI 0.746-1.749). However, among drinkers, periodontitis was significantly associated with CRS (OR = 1.733, 95% CI 1.091-2.753). The number of smokers with CRS was not statistically sufficient and a logistic regression model based on smoking status could not be generated. Individuals with periodontitis in the upper jaw may need to consult an otorhinolaryngologist for comorbid CRS especially according to drinking status.

Salvage of failed direct lateral sacroiliac joint fixation using a new percutaneous lateral-oblique transfixation technique with two variable-threaded screws: a multicenter case report of three cases.

Background: The direct lateral trans-gluteal muscle splitting transiliac approach was popularized to fixate the sacroiliac joint (SIJ) using three cannulated triangular titanium implants (TTIs) wedges. Publications support efficacy of the direct lateral approach but a paucity of literature to help surgeons revise these implants when they fail. Intuitively the implants can be removed but require an open incision and dissection through the gluteal muscles and scar tissue which can lead to muscle and neurovascular injuries. Our objective was to evaluate the clinical outcome, measured by patient-reported Visual Analog Score (VAS), of three patients who had failed direct lateral SIJ fusions each using three implants and describe a revision technique using a new percutaneous lateral-oblique transfixation technique with two variable-threaded screws while preserving the original implants. Case Description: Two separate orthopedic spine surgeons at different hospitals performed the technique using two SacroFuse® screws for SIJ revision fusion in three patients who had clinical symptoms and radiographic findings of SIJ pseudoarthrosis after direct lateral approach. One 61 years old male patient had a previous surgery with three lateral threaded screw implants. Two females with ages 47 and 40 years old had three TTI wedges. Follow-up from 10 to 26 months. Patients discharged home the same day. Mean procedure time of 20 minutes with blood loss less than five cc. Incision size was approximately 1 inch. Each patient had a 12 mm × 60 mm and a 12 mm × 50 mm screw filled with NanoFuse Biologics synthetic bioactive glass and demineralized bone matrix. Prior implants were left in place. There was an 89% decrease in mean VAS score of 9.5 to 1. Conclusions: This is a clinically valuable report because until now there was no reconstructive surgery to revise direct lateral implants other than removal with potential neurovascular risks. This is the first article to demonstrate a lateral-oblique transfixation technique with two variable-threaded screws for successful salvage of SIJ pseudoarthrosis after direct lateral fixation without implant removal. The Sacrix technique achieved immediate stability and long-term fusion documented on computed tomography (CT) scan as early as 6 months.

Influence of shift work on periodontitis according to the occupation group.

This study aimed to investigate the effects of shift work on periodontal disease in blue-and white-collar workers and to examine the interaction effects between occupation and work patterns. Data were collected from the Korea National Health and Nutrition Examination Survey conducted by the Korean Ministry of Health and Welfare for a total of nine years from 2007 to 2015. Participants with missing outcome variables were excluded from the analysis and a total of 32,336 participants were included in the final analysis. Univariable odds ratios (OR) were calculated using a logistic regression model with 95% confidence interval (CI). A multivariable logistic regression analysis was performed using the backward elimination method. The CONTRAST statement was used to analyze the interaction effect between occupation and work patterns. Multivariable logistic regression analysis revealed that interaction effects are present between the terms, occupational type and work pattern. Crude OR of shift work for periodontitis was 1.269 [CI 1.213-1.327, P < 0.05]. However, following adjustment for multiple confounding factors and the interaction effect term considered, this OR (1.269) increased to 1.381 [CI 1.253-1.523] in white-collar group while it decreased to 1.198 [1.119-1.283] in blue-collar. Crude OR of blue-collar (OR = 3.123, CI 2.972-3.281, P < 0.05) decreased to 1.151 [CI 1.049-1.262] when interaction effect to the shift work was considered. Shift work pattern increases the risk for periodontitis and this adverse effect is greater when white-collar workers are engaged comparing to blue-collar. The result of this study suggests that 24/7 lifestyle of the modern society poses health risks to the relevant people and the potential harm can be greater to white-collar workers.

False-positive supraclavicular lymph node detected on chest computed tomography in oncology patients: Clinical implication based on subsequent neck ultrasonography and ultrasonography-guided tissue sampling.

PURPOSE: The purpose of this study was to assess the prevalence and clinical implications of false-positive supraclavicular lymph node (LN) detected on chest computed tomography (CT), using subsequent neck ultrasonography (US) and US-guided tissue sampling. METHODS: Among 172 patients with suspected supraclavicular LNs identified on CT, 87 underwent neck US or US-guided tissue sampling. Receiver operating characteristic curve and logistic regression analyses were performed to determine the diagnostic performance of US and independent predictors of false-positive LNs. RESULTS: Among 87 patients, 49 (56.3%) were pathologically confirmed as metastases, 26 (29.9%) were negative for malignancy, and 12 (13.8%) had pseudolesions or schwannomas. The diagnostic indices were as follows: sensitivity, 91.8%; specificity, 92.3%; PPV, 95.7%; NPV, 85.7%; and accuracy, 92.0% (AUC = 0.921; 95% CI: 0.832-0.970, p < 0.001). The false-positive group had a higher mean age than the true-positive group (mean age, 69.8 ± 9.2 vs. 63.9 ± 9.8, p = 0.003). Logistic regression analyses revealed that age ≥ 65 years was the only independent predictor of false-positive LNs (OR = 4.391; 95% CI: 1.037-18.582; p = 0.044). CONCLUSION: Subsequent US can be helpful for evaluating suspicious supraclavicular LNs detected on CT to establish appropriate management, especially in older patients.

Production and engineering of nanobody-based quenchbody sensors for detecting recombinant human growth hormone and its isoforms.

Due to athletes' misuse of recombinant human growth hormone (rhGH) for performance improvement, the World Anti-Doping Agency has designated rhGH as a prohibited substance. This study focuses on the development and improvement of a simple and fast rhGH detection method using a fluorescence-incorporated antibody sensor "Quenchbody (Q-body)" that activates upon antigen binding. Camelid-derived nanobodies were used to produce stable Q-bodies that withstand high temperatures and pH levels. Notably, pituitary human growth hormone (phGH) comprises two major isoforms, namely 22 and 20 kDa GH, which exist in a specific ratio, and the rhGH variant shares the same sequence as the 22 kDa GH isoform. Therefore, we aimed to discriminate rhGH abuse by analyzing its specific isoform ratio. Two nanobodies, NbPit (recognizing phGH) and NbRec (preferentially recognizing 22 kDa rhGH), were used to develop the Q-bodies. Nanobody production in Escherichia coli involved the utilization of a vector containing 6xHis-tag, and Q-bodies were obtained using a maleimide-thiol reaction between the N-terminal of the cysteine tag and a fluorescent dye. The addition of tryptophan residue through antibody engineering resulted in increased fluorescence intensity (FI) (from 2.58-fold to 3.04-fold). The limit of detection (LOD) was determined using a fluorescence response, with TAMRA-labeled NbRec successfully detecting 6.38 ng/ml of 22 kDa rhGH while unable to detect 20 kDa GH. However, ATTO520-labeled NbPit detected 7.00 ng/ml of 20 kDa GH and 2.20 ng/ml 22 kDa rhGH. Q-bodies successfully detected changes in the GH concentration ratio from 10 to 40 ng/ml in human serum within 10 min without requiring specialized equipment and kits. Overall, these findings have potential applications in the field of anti-doping measures and can contribute to improved monitoring and enforcement of rhGH misuse, ultimately enhancing fairness and integrity in competitive sports.

Measured sodium excretion is associated with cardiovascular outcomes in non-dialysis CKD patients: results from the KNOW-CKD study.

Background: There are insufficient studies on the effect of dietary salt intake on cardiovascular (CV) outcomes in chronic kidney disease (CKD) patients, and there is no consensus on the sodium (Na) intake level that increases the risk of CV disease in CKD patients. Therefore, we investigated the association between dietary salt intake and CV outcomes in CKD patients. Methods: In the Korean cohort study for Outcome in patients with CKD (KNOW-CKD), 1,937 patients were eligible for the study, and their dietary Na intake was estimated using measured 24h urinary Na excretion. The primary outcome was a composite of CV events and/or all-cause death. The secondary outcome was a major adverse cardiac event (MACE). Results: Among 1,937 subjects, there were 205 (10.5%) events for the composite outcome and 110 (5.6%) events for MACE. Compared to the reference group (urinary Na excretion< 2.0g/day), the group with the highest measured 24h urinary Na excretion (urinary Na excretion ≥ 8.0g/day) was associated with increased risk of both the composite outcome (hazard ratio 3.29 [95% confidence interval 1.00-10.81]; P = 0.049) and MACE (hazard ratio 6.28 [95% confidence interval 1.45-27.20]; P = 0.013) in a cause-specific hazard model. Subgroup analysis also showed a pronounced association between dietary salt intake and the composite outcome in subgroups of patients with abdominal obesity, female, lower estimated glomerular filtration rate (< 60 ml/min per 1.73m2), no overt proteinuria, or a lower urinary potassium-to-creatinine ratio (< 46 mmol/g). Conclusion: A high-salt diet is associated with CV outcomes in non-dialysis CKD patients.

Tumor lipid metabolism: a mechanistic link between diet and cancer progression.

The potential for 'anti-cancer' diets to markedly alter cancer risk and prognosis has captured the imagination of patients, physicians, and researchers alike, but many of these dietary recommendations come from correlative studies that attribute certain diets to altered cancer risk. While provocative, little is known about the molecular mechanisms behind how these dietary interventions impact cancer progression. Within this context, however, changes in tumor lipid metabolism are emerging as a key contributor. In this review, we examine the current understanding of lipid metabolism in the tumor microenvironment (TME), suggesting how diet-induced changes in lipid composition may regulate tumor progression and therapeutic efficacy. By dissecting various cellular pathways involved in lipid metabolism, we highlight how diet modulates the balance between saturated and unsaturated fatty acid (FA) species in tumors to impact cancer cell and stromal cell function. Finally, we describe how current cancer therapies may synergize with diet to improve therapeutic efficacy.

The Fatal Role of Enterohaemorrhagic Escherichia coli Shiga Toxin-associated Extracellular Vesicles in Host Cells.

Enterohemorrhagic Escherichia coli (EHEC) is a specific subset of Shiga toxin-producing Escherichia coli (STEC) strains that are characterized by their ability to cause bloody diarrhea (hemorrhagic colitis) and potentially life-threatening, extraintestinal complications such as hemolytic uremic syndrome (HUS), which is associated with acute renal failure., contributing to severe clinical outcomes. The Shiga toxins (Stxs), produced by EHEC, are primary virulence factors. These potent cytotoxins are composed of one enzymatically active A subunit (StxA) and five receptor-binding B subunits (StxB). Although the toxins are primarily associated with cytotoxic effects, they also elicit other pathogenic consequences due to their induction of a number of biological processes, including apoptosis through ER-stress, pro-inflammatory responses, autophagy, and post-translational modification (PTM). Moreover, several studies have reported the association between Stxs and extracellular vesicles (EVs), including microvesicles and exosomes, demonstrating that Stx-containing EVs secreted by intoxicated macrophages are taken up by recipient cells, such as toxin-sensitive renal proximal tubular epithelial cells. This mechanism likely contributes to the spreading of Stxs within the host, and may exacerbate gastrointestinal illnesses and kidney dysfunction. In this review, we summarize recent findings relating to the host responses, in different types of cells in vitro and in animal models, mediated by Stxs-containing exosomes. Due to their unique properties, EVs have been explored as therapeutic agents, drug delivery systems, and diagnostic tools. Thus, potential therapeutic applications of EVs in EHEC Stxs-mediated pathogenesis are also briefly reviewed.