Role of Corn Peptide Powder in Lipopolysaccharide-Induced Inflammatory Responses in 3T3-L1 Adipocytes.

Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing obesity-related disorders, but its impact on reducing inflammation is unknown. Hence, this study examined the possible protective effects of corn peptide powder (CPP) against the harmful effects of lipopolysaccharide (LPS), with a particular emphasis on reducing oxidative damage and inflammation in adipocytes. Hence, mature 3T3-L1 adipocytes underwent exposure to 10 ng/mL LPS, with or without CPP (10 and 20 µg/mL). LPS stimulation increased reactive oxygen species and superoxide anion generation. However, this effect was reduced in a dose-dependent manner by pretreatment with CPP. CPP treatment elevated the mRNA expressions of the antioxidant enzymes manganese superoxide dismutase (mnSOD) and glutathione peroxidase 1 (Gpx1) while reducing the mRNA expressions of the cytosolic reactive oxygen species indicators p40 and p67 (NADPH oxidase 2). In addition, CPP inhibited the monocyte chemoattractant protein-1, tumor necrosis factor-alpha, Toll-like receptor 4, and nuclear factor kappa B mRNA expressions induced by LPS. These findings demonstrate that CPP may ameliorate adipocyte dysfunction by suppressing oxidative damage and inflammatory responses through a new mechanism known as Toll-like receptor 4/nuclear factor kappa B-mediated signaling.

The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Comparison of Clinical and Radiological Outcomes after Vertebroplasty and Balloon Kyphoplasty in the Treatment of Osteoporotic Vertebral Compression Fractures.

BACKGROUND: Vertebroplasty (VP) and balloon kyphoplasty (KP) are effective means with which to improve pain and function in osteoporotic vertebral compression fractures. However, the risk of complications after these procedures is poorly understood, with concerns regarding adjacent vertebral fractures. This study retrospectively investigated the clinical and radiological outcomes of these procedures. METHODS: A total of 115 patients who experienced their first vertebral fracture were treated with VP (N=63) or KP (N=52) at the Dankook University Hospital between January 2013 and December 2022. The clinical outcomes were evaluated using the visual analog scale (VAS) preoperative and at 1-year follow-up. Radiological comparisons were performed for kyphosis correction, vertebral height restoration, and postoperative cement leakage. RESULTS: KP was more effective than VP, especially for vertebral body height restoration and kyphotic angle reduction (P<0.05). However, the incidence of cement leakage, new adjacent vertebral fractures, and improvement in pain assessed by VAS did not differ statistically between the 2 groups (P>0.05). CONCLUSIONS: Considering that KP was performed on fractures with severe deformity, no differences were observed in the clinical outcomes and incidence of adjacent vertebral fractures compared Considering that KP was performed for fractures with severe deformity, there was no difference in clinical outcomes and incidence of adjacent vertebral fractures compared to VP. Improvements in radiological measurements were demonstrated. Therefore, KP may be a good treatment option for pain relief and long-term prognosis in patients with high-compressive-rate vertebral fractures.

Unlocking synergies: Harnessing the potential of biological methane sequestration through metabolic coupling between Methylomicrobium alcaliphilum 20Z and Chlorella sp. HS2.

A halotolerant consortium between microalgae and methanotrophic bacteria could effectively remediate in situ CH4 and CO2, particularly using saline wastewater sources. Herein, Methylomicrobium alcaliphilum 20Z was demonstrated to form a mutualistic association with Chlorella sp. HS2 at a salinity level above 3.0%. Co-culture significantly enhanced the growth of both microbes, independent of initial inoculum ratios. Additionally, increased methane provision in enclosed serum bottles led to saturated methane removal. Subsequent analyses suggested nearly an order of magnitude increase in the amount of carbon sequestered in biomass in methane-fed co-cultures, conditions that also maintained a suitable cultural pH suitable for methanotrophic growth. Collectively, these results suggest a robust metabolic coupling between the two microbes and the influence of the factors other than gaseous exchange on the assembled consortium. Therefore, multi-faceted investigations are needed to harness the significant methane removal potential of the identified halotolerant consortium under conditions relevant to real-world operation scenarios.

Knee Joint Line Obliquity With Adaptational Hip and Ankle Joint Orientation After Medial Open Wedge High Tibial Osteotomy.

BACKGROUND: Time-dependent postoperative changes in knee joint line obliquity (KJLO) and subsequent adaptational changes in the hip and ankle joints have not been fully proven after medial open wedge high tibial osteotomy (MOWHTO). PURPOSE: To investigate the serial postoperative changes in KJLO and subsequent adaptational changes in the hip and ankle joints over time after MOWHTO. STUDY DESIGN: Case series, Level of evidence, 4. METHODS: A total of 92 patients who underwent MOWHTO between April 2015 and December 2020 were evaluated. Radiographic parameters, including KJLO, ankle joint line obliquity (ALO), hip abduction angle (HAA), joint line convergence angle, weightbearing line ratio, and hip-knee-ankle angle, were analyzed in time sequence (preoperatively and 3, 6, 12, and 24 months postoperatively). Repeated-measures analysis of variance and post hoc analysis were used to demonstrate alterations and the statistical significance of KJLO and other related radiographic parameters over time. RESULTS: The mean KJLO values were -1.9°, -2.1°, -2.7°, and -3.2° at 3, 6, 12, and 24 months postoperatively, respectively, indicating that there was consistent increase in valgus tilting of KJLO from 6 to 24 months (P < .001 for both 6-12 months and 12-24 months). ALO and HAA showed significant changes from 6 to 12 months (ALO, P < .001; HAA, P = .002), but not between 12 and 24 months (ALO: -3.0°, -2.7°, -1.9°, and -1.6°; HAA: -0.8°, -0.9°, -1.5°, and -1.8° at 3, 6, 12, and 24 months, respectively). The mean joint line convergence angle, weightbearing line ratio, and hip-knee-ankle angle did not change significantly from 3 months to 24 months postoperatively. CONCLUSION: There was a consistent increase in valgus tilting of the postoperative KJLO from 6 to 24 months after MOWHTO. The adaptive ALO and HAA significantly changed between 6 and 12 months and were maintained until 24 months after MOWHTO. It is necessary to consider the adaptive change when hip or ankle surgery is planned within this period.

Proximal row carpectomy with interposition arthroplasty using both capsular flap and acellular human dermal matrix.

BACKGROUND: In cases of wrist arthritis, proximal row carpectomy (PRC) has been widely utilized and shown favorable long-term outcomes. However, its applicability is limited in cases where arthritis extends to the lunate fossa or capitate. Recently, surgical approaches combining various methods of interposition arthroplasty have been introduced to overcome these drawbacks. The purpose of this study was to perform PRC and interposition arthroplasty with dorsal capsule and acellular dermal matrix(ADM),and analyze the clinical outcomes of these procedures. METHODS: Fourteen cases who underwent PRC and interposition arthroplasty using both dorsal capsular flap and ADM were retrospectively recruited. The researchers assessed the patients' Visual Analog Scale (VAS) pain score, Disabilities of the Arm, Shoulder and Hand (DASH) scores, range of motion (ROM), retear, and radiocarpal distance (RCD). RESULTS: One year post-surgery, both the VAS pain scores, DASH scores, and ROM showed statistically significant improvement compared to before the surgery. Upon reviewing the radiological results, the postoperative mean RCD was 4.8 ± 0.8 mm and one year follow up mean RCD was 3.6 ± 0.5 mm at one year post-surgery. Moreover, in the one year follow-up, there was no observed failure of the allodermis graft in any of the cases. CONCLUSION: The PRC and interposition arthroplasty with ADM demonstrated significantly improved clinical outcomes after surgery, showing a maintain of RCD without graft failure effectively.

In Vitro Anti-Inflammatory and Skin Protective Effects of Codium fragile Extract on Macrophages and Human Keratinocytes in Atopic Dermatitis.

Codium fragile has been traditionally used in oriental medicine to treat enterobiasis, dropsy, and dysuria, and it has been shown to possess many biological properties. Atopic dermatitis (AD) is one of the types of skin inflammation and barrier disruption, which leads to chronic inflammatory skin diseases. In the current investigation, the protective effects of C. fragile extract (CFE) on anti-inflammation and skin barrier improvement were investigated. In LPS-stimulated RAW 264.7 cells, nitric oxide generation and the expression levels of interleukin (IL)-1ß, IL-4, IL-6, iNOS, COX-2, and tumor necrosis factor-alpha (TNF)-α were reduced by CFE. CFE also inhibited the phosphorylation of NF-κB-p65, ERK, p-38, and JNK. Additionally, CFE showed inhibitory activity on TSLP and IL-4 expression in HaCaT cells stimulated with TNF-α/interferon-gamma (IFN-γ). Enhanced expression of factors related to skin barrier function, FLG, IVL, and LOR, was confirmed. These findings implied that CFE may be used as a therapeutic agent against AD due to its skin barrier-strengthening and anti-inflammatory activities, which are derived from natural marine products.

Novel Signal Peptides and Episomal Plasmid System for Enhanced Protein Secretion in Engineered Bacteroides Species.

The genus Bacteroides, a predominant group in the human gut microbiome, presents significant potential for microbiome engineering and the development of live biotherapeutics aimed at treating gut diseases. Despite its promising capabilities, tools for effectively engineering Bacteroides species have been limited. In our study, we have made a breakthrough by identifying novel signal peptides in Bacteroides thetaiotaomicron and Akkermansia muciniphila. These peptides facilitate efficient protein transport across cellular membranes in Bacteroides, a critical step for therapeutic applications. Additionally, we have developed an advanced episomal plasmid system. This system demonstrates superior protein secretion capabilities compared to traditional chromosomal integration plasmids, making it a vital tool for enhancing the delivery of therapeutic proteins in Bacteroides species. Initially, the stability of this episomal plasmid posed a challenge; however, we have overcome this by incorporating an essential gene-based selection system. This novel strategy not only ensures plasmid stability but also aligns with the growing need for antibiotic-free selection methods in clinical settings. Our work, therefore, not only provides a more robust secretion system for Bacteroides but also sets a new standard for the development of live biotherapeutics.

Engineered Methylococcus capsulatus Bath for efficient methane conversion to isoprene.

Isoprene has numerous industrial applications, including rubber polymer and potential biofuel. Microbial methane-based isoprene production could be a cost-effective and environmentally benign process, owing to a reduced carbon footprint and economical utilization of methane. In this study, Methylococcus capsulatus Bath was engineered to produce isoprene from methane by introducing the exogenous mevalonate (MVA) pathway. Overexpression of MVA pathway enzymes and isoprene synthase from Populus trichocarpa under the control of a phenol-inducible promoter substantially improved isoprene production. M. capsulatus Bath was further engineered using a CRISPR-base editor to disrupt the expression of soluble methane monooxygenase (sMMO), which oxidizes isoprene to cause toxicity. Additionally, optimization of the metabolic flux in the MVA pathway and culture conditions increased isoprene production to 228.1 mg/L, the highest known titer for methanotroph-based isoprene production. The developed methanotroph could facilitate the efficient conversion of methane to isoprene, resulting in the sustainable production of value-added chemicals.

Changes in ankle and hip joints following medial opening-wedge high tibial osteotomy affect knee joint line obliquity.

PURPOSE: This study aimed to measure the change in knee joint line obliquity (KJLO) and the changes in radiologic parameters of the ankle and hip joints after medial opening-wedge high tibial osteotomy (MOWHTO), and to evaluate the correlation and causal relationship between these parameters. METHODS: This study evaluated 109 patients who underwent MOWHTO between April 2015 and December 2021. Radiologic parameters, including KJLO, medial proximal tibial angle (MPTA), ankle joint line obliquity (AJLO), and hip abduction angle (HAA), were analysed before and 1 year after MOWHTO. Multiple linear regression analysis was used to identify independent variables that significantly affected the change in KJLO after MOWHTO. Receiver operating characteristic (ROC) analysis was used to evaluate the cutoff value for a change in KJLO that exceeded 5° postoperatively, and the predicting values of radiologic parameters. RESULTS: Multiple linear regression analysis showed that changes in MPTA, AJLO, and HAA (ß = 0.440, P < 0.001; ß = - 0.310, P < 0.001; ß = 0.164, P = 0.035, respectively) were predictors of the change in KJLO after MOWHTO. ROC analysis showed that the threshold value for a change in KJLO which exceeded 5° postoperatively was 4.6° (66.7% sensitivity, 63.8% specificity, P = 0.025). Moreover, ROC curves for predicting a change in KJLO of > 4.6° showed that the AUC was significantly higher for the change in MPTA than that of the other two parameters (P = 0.011 for AJLO and P < 0.001 for HAA). CONCLUSION: MOWHTO increases the KJLO by valgization of the proximal tibia and causes hip adduction and ankle valgization. The postoperative ankle valgization after MOWHTO could reduce the increase in KJLO, counteracting the effects of proximal tibial valgization and hip adduction. Therefore, the effects of the hip and ankle joints should be considered to achieve an optimal KJLO and satisfactory clinical outcomes after MOWHTO. LEVEL OF STUDY: Cohort study, IV.

Serial change of femoral and tibial tunnel width after anterior cruciate ligament reconstruction with allograft.

PURPOSE: To investigate progressive tunnel widening and its correlation with postoperative outcomes after anterior cruciate ligament (ACL) reconstruction using allografts. METHODS: Sixty-five patients who underwent ACL reconstruction using a tibialis anterior allograft between 2015 and 2017 were enrolled. Femoral and tibial tunnel widths were measured on anteroposterior (AP) and lateral radiographs immediately and at 3, 6, 12, and 24 months postoperatively. Average femoral and tibial tunnel widths in AP and lateral views were calculated at three different measurement points. Tunnel widening was calculated as the difference in tunnel width immediately and 2 years postoperatively. The correlation between tunnel widening and the postoperative results was analysed. RESULTS: Tunnel width changes between immediate and 2 years postoperatively were as follows, in AP and lateral views, respectively: femur, 3.0 mm ± 1.5 mm and 2.4 mm ± 1.4 mm; and tibia, 2.8 mm ± 1.4 mm and 2.9 mm ± 1.5 mm. Femoral tunnel widths significantly increased until 1 year, but not from 1 to 2 years postoperatively. Tibial tunnel width significantly increased until 2 years postoperatively. In all tunnels, the increments in tunnel widening decreased over time. Increased knee laxity significantly correlated with greater femoral tunnel widening in AP (r = 0.346, P = 0.006) and lateral views (r = 0.261, P = 0.049). CONCLUSION: Femoral tunnel widths gradually increased until 1 year postoperatively, and tibial tunnel widths increased until 2 years after ACL reconstruction with allografts. The tunnel widening rate gradually decreased over time. Femoral tunnel widening of 3.7 mm and 3.2 mm on AP and lateral views, respectively, were the cut-off values for postoperative knee laxity. LEVEL OF EVIDENCE: Level III.

Weight Is a Predictor of Delayed Operation Time in Primary Isolated Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Few studies have evaluated the impact of obesity on operation time in patients with ACL reconstruction. The purpose of this study was to understand the effect of obesity on operation time in patients with arthroscopic anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 103 patients were included. The mean pure operation time was 45.9 ± 13.4 min. Considering that 15 min incremental increases in operation time are an independent risk factor for complications, all patients were classified into two groups according to operation time: more or less than 61 min. Demographic data were compared between both groups. Pure operation time was defined as operative time without suture time (pure operation time = suture start time - operation start time). Correlation analysis between demographic data and pure operation time was performed, and multiple linear regression analysis was used to identify the predictors of pure operation time. RESULTS: The pure operation time ≥61 min group (n = 34) had a 14.7 kg higher weight and 4.5 kg/m2 higher body mass index (BMI) than those with pure operation time < 61 min (n = 69). Weight (r = 0.635, p < 0.001) and BMI (r = 0.584, p < 0.001) were positively correlated with operation time. Multiple linear regression analysis showed that weight (ß = 0.635, p < 0.001) was the only predictor of operation time. A weight of 74.25 kg was a cut-off value for a pure operation time of >61 min. CONCLUSIONS: The weight and BMI of the group with pure operation time of ≥61 min were 14.7 kg and 4.5 kg/m2 higher, respectively. The weight of patients with ACL tears was a factor affecting delay in the operation time. Patients weighing over 74.25 kg were more likely to delay ACL reconstruction.

Colored reflectors to improve coincidence timing resolution of BGO-based time-of-flight PET detectors.

Time-of-flight (TOF) positron emission tomography (PET) detectors improve the signal-to-noise ratio of PET images by limiting the position of the generation of two 511 keV gamma-rays in space using the arrival time difference between the two photons. Unfortunately, bismuth germanate (BGO), widely used in conventional PET detectors, was limited as a TOF PET scintillator due to the relatively slow decay time of the scintillation photons. However, prompt Cerenkov light in BGO has been identified in addition to scintillation photons. Using Cerenkov photons for timing has significantly improved the coincidence timing resolution (CTR) of BGO. Based on this, further research on improving the CTR for a BGO-based TOF PET system is being actively conducted. Wrapping materials for BGO pixels have primarily employed white reflectors to most efficiently collect scintillation light. White reflectors have customarily been used as reflectors for BGO pixels even after Cerenkov light began to be utilized for timing calculations in pixel-level experiments. However, when the arrival-time differences of the two 511 keV annihilations photons were measured with pure Cerenkov radiators, painting the lateral sides of the radiators black can improve CTR by suppressing the reflection of Cerenkov photons. The use of BGO for TOF PET detectors requires simultaneously minimizing scintillation loss for good energy information and suppressing reflected Cerenkov photons for better timing performance. Thus, reflectors for BGO pixels should be optimized for better timing and energy performance. In this study, colored polytetrafluoroethylene (PTFE) tapes with discontinuous reflectance values at specific wavelengths were applied as a BGO reflector. We hypothesized that CTR could be enhanced by selectively suppressing reflected Cerenkov photons with an optimum colored reflector on the BGO pixel while minimizing scintillation photon loss. CTRs were investigated utilizing white and three colors (yellow, red, and green) PTFE tapes as a reflector. In addition, black-painted PTFE tape and enhanced specular reflector film were investigated as reference reflector materials. When 3 × 3 × 20 mm3BGO pixels were wrapped with the yellow PTFE reflector, the CTR was significantly improved to 365 ± 5 ps from 403 ± 14 ps measured with the conventional white PTFE reflector. Adequate energy information was still obtained with only 4.1% degradation in light collection compared to the white reflector. Colored reflectors show the possibility to further improve CTR for BGO pixels with optimum reflectance design.

Scientific evidence of foods that improve the lifespan and healthspan of different organisms.

Age is a risk factor for numerous diseases. Although the development of modern medicine has greatly extended the human lifespan, the duration of relatively healthy old age, or 'healthspan', has not increased. Targeting the detrimental processes that can occur before the onset of age-related diseases can greatly improve health and lifespan. Healthspan is significantly affected by what, when and how much one eats. Dietary restriction, including calorie restriction, fasting or fasting-mimicking diets, to extend both lifespan and healthspan has recently attracted much attention. However, direct scientific evidence that consuming specific foods extends the lifespan and healthspan seems lacking. Here, we synthesized the results of recent studies on the lifespan and healthspan extension properties of foods and their phytochemicals in various organisms to confirm how far the scientific research on the effect of food on the lifespan has reached.

On timing-optimized SiPMs for Cherenkov detection to boost low cost time-of-flight PET.

Objective.Recent SiPM developments and improved front-end electronics have opened new doors in TOF-PET with a focus on prompt photon detection. For instance, the relatively high Cherenkov yield of bismuth-germanate (BGO) upon 511 keV gamma interaction has triggered a lot of interest, especially for its use in total body positron emission tomography (PET) scanners due to the crystal's relatively low material and production costs. However, the electronic readout and timing optimization of the SiPMs still poses many questions. Lab experiments have shown the prospect of Cherenkov detection, with coincidence time resolutions (CTRs) of 200 ps FWHM achieved with small pixels, but lack system integration due to an unacceptable high power uptake of the used amplifiers.Approach.Following recent studies the most practical circuits with lower power uptake (<30 mW) have been implemented and the CTR performance with BGO of newly developed SiPMs from Fondazione Bruno Kessler tested. These novel SiPMs are optimized for highest single photon time resolution (SPTR).Main results.We achieved a best CTR FWHM of 123 ps for 2 × 2 × 3 mm3and 243 ps for 3 × 3 × 20 mm3BGO crystals. We further show that with these devices a CTR of 106 ps is possible using commercially available 3 × 3 × 20 mm3LYSO:Ce,Mg crystals. To give an insight in the timing properties of these SiPMs, we measured the SPTR with black coated PbF2of 2 × 2 × 3 mm3size. We confirmed an SPTR of 68 ps FWHM published in literature for standard devices and show that the optimized SiPMs can improve this value to 42 ps. Pushing the SiPM bias and using 1 × 1 mm2area devices we measured an SPTR of 28 ps FWHM.Significance.We have shown that advancements in readout electronics and SiPMs can lead to improved CTR with Cherenkov emitting crystals. Enabling time-of-flight with BGO will trigger a high interest for its use in low-cost and total-body PET scanners. Furthermore, owing to the prompt nature of Cherenkov emission, future CTR improvements are conceivable, for which a low-power electronic implementation is indispensable. In an extended discussion we will give a roadmap to best timing with prompt photons.

Change in Cartilage Status of Medial Compartment after Open-Wedge High Tibial Osteotomy without Cartilage Regeneration Procedure: Second Look Arthroscopic Assessment.

This study investigated the rate of cartilage regeneration after an open-wedge high tibial osteotomy (HTO) without cartilage regeneration by second-look arthroscopy. This study included patients who underwent an open-wedge HTO between July 2014 and March 2019. A total of 65 patients were enrolled. Pre- and postoperative (second-look arthroscopy) hip-knee-ankle (HKA) angle and tibial slope were measured. All patients underwent arthroscopic examination prior to osteotomy. Medial femoral condyle (MFC) and medial tibial plateau (MTP) articular cartilage were evaluated according to the International Cartilage Repair Society (ICRS) grading system. After 26.5 months, second-look arthroscopy was performed with plate removal to identify the cartilage status of the MFC and MTP. The preoperative HKA angle (6.4° ± 2.7°) was well corrected postoperatively (-2.7° ± 2.7°, p < 0.001). In terms of MFC on second-look arthroscopy, 29 patients (44.6%) showed an improved ICRS grade, 31 patients (47.7%) were maintained, and 5 patients (7.7%) showed a worse ICRS grade since the prior operation. In the MTP group, 19 patients (29.2%) improved, 44 patients (67.7%) were maintained, and 2 patients (3.1%) worsened. Approximately 44.6% and 29.2% of patients showed improved cartilage statuses on the MFC and MTP after open-wedge HTO without any cartilage regeneration procedures. Cartilage regenerations in both the MFC and MTP did not influence clinical outcomes.

Femoral Tunnel Position Affects Postoperative Femoral Tunnel Widening after Anterior Cruciate Ligament Reconstruction with Tibialis Anterior Allograft.

This study aims to identify potential factors for both femoral and tibial tunnel widening (TW) and to investigate the effect of TW on postoperative outcomes after anterior cruciate ligament (ACL) reconstruction with a tibialis anterior allograft. A total 75 patients (75 knees) who underwent ACL reconstruction with tibialis anterior allografts were investigated between February 2015 and October 2017. TW was calculated as the difference in tunnel widths between the immediate and 2-year postoperative measurements. The risk factors for TW, including demographic data, concomitant meniscal injury, hip-knee-ankle angle, tibial slope, femoral and tibial tunnel position (quadrant method), and length of both tunnels, were investigated. The patients were divided twice into two groups depending on whether the femoral or tibial TW was over or less than 3 mm. Pre- and 2-year follow-up outcomes, including the Lysholm score, International Knee Documentation Committee (IKDC) subjective score, and side-to-side difference (STSD) of anterior translation on stress radiographs, were compared between TW ≥ 3 mm and TW < 3 mm. The femoral tunnel position depth (shallow femoral tunnel position) was significantly correlated with femoral TW (adjusted R2 = 0.134). The femoral TW ≥ 3 mm group showed greater STSD of anterior translation than the femoral TW < 3 mm group. The shallow position of the femoral tunnel was correlated with the femoral TW after ACL reconstruction using a tibialis anterior allograft. A femoral TW ≥ 3 mm showed inferior postoperative knee anterior stability.

High Cell-Density Cultivation of Methylococcus capsulatus Bath for Efficient Methane-Derived Mevalonate Production.

The engineered Methylococcus capsulatus Bath presents a promising approach for converting methane, a potent greenhouse gas, into valuable chemicals. High cell-density culture (HCDC) is necessary for high-titer growth-associated bioproducts, but it often requires time-consuming and labor-intensive optimization processes. In this study, we aimed to achieve efficient HCDC of M. capsulatus Bath by measuring the residual nutrient levels during bioreactor operations and analyzing the specific uptake of each medium component. By controlling the concentrations of nutrients, particularly calcium and phosphorus via intermittent feeding, we achieved a high cell density of 28.2 g DCW/L and a significantly elevated production of mevalonate at a concentration of 1.8 g/L from methane. Our findings demonstrate that the methanotroph HCDC approach presented herein offers a promising strategy for promoting sustainable development, with an exceptional g-scale production titer for value-added synthetic biochemicals.

A Genetically Encoded Biosensor for the Detection of Levulinic Acid.

Levulinic acid (LA) is a valuable chemical used in fuel additives, fragrances, and polymers. In this study, we proposed possible biosynthetic pathways for LA production from lignin and poly(ethylene terephthalate). We also created a genetically encoded biosensor responsive to LA, which can be used for screening and evolving the LA biosynthesis pathway genes, by employing an LvaR transcriptional regulator of Pseudomonas putida KT2440 to express a fluorescent reporter gene. The LvaR regulator senses LA as a cognate ligand. The LA biosensor was first examined in an Escherichia coli strain and was found to be non-functional. When the host of the LA biosensor was switched from E. coli to P. putida KT2440, the LA biosensor showed a linear correlation between fluorescence intensity and LA concentration in the range of 0.156-10 mM LA. In addition, we determined that 0.156 mM LA was the limit of LA detection in P. putida KT2440 harboring an LA-responsive biosensor. The maximal fluorescence increase was 12.3-fold in the presence of 10 mM LA compared to that in the absence of LA. The individual cell responses to LA concentrations reflected the population-averaged responses, which enabled high-throughput screening of enzymes and metabolic pathways involved in LA biosynthesis and sustainable production of LA in engineered microbes.

Low-dose RaDiation therapy for patients with KNee osteoArthritis (LoRD-KNeA): a protocol for a sham-controlled randomised trial.

INTRODUCTION: Low-dose radiation therapy (LDRT) for osteoarthritis (OA) has been performed for several decades. However, supporting evidence from randomised studies using modern methodologies is lacking, and a recently published randomised study failed to show the significant benefit of LDRT. The presented trial aims to evaluate the efficacy and safety of LDRT for patients with knee OA. METHODS AND ANALYSIS: This prospective, multicentre, randomised trial will be conducted in the Republic of Korea. A total of 114 participants will be randomly assigned (1:1:1) to receive sham irradiation, 0.3 Gy/6 fractions of LDRT or 3 Gy/6 fractions of LDRT. Key inclusion criteria are primary knee OA with Kellgren-Lawrence grade 2-3 and visual analogue scale 50-90 when walking at the baseline. The primary endpoint is the rate of responders at 4 months after LDRT according to the OARSI-OMERACT criteria. Concomitant use of analgesics is prohibited until the primary efficacy evaluation is scheduled. ETHICS AND DISSEMINATION: Currently, approval from the Ministry of Food and Drug Safety of the Republic of Korea and the institutional review board of each participating hospital has been obtained. Patient enrolment began in October 2022 and is ongoing at three participating sites. The results will be disseminated to academic audiences and the public via publication in an international peer-reviewed journal and presentation at conferences. This trial will provide valuable information on the safety and efficacy of LDRT for patients with knee OA. TRIAL REGISTRATION NUMBER: NCT05562271.