Ninjin'yoeito reduces fatigue-like conditions by alleviating inflammation of the brain and skeletal muscles in aging mice.

Fatigue can lead to several health issues and is particularly prevalent among elderly individuals with chronic inflammatory conditions. Ninjin'yoeito, a traditional Japanese herbal medicine, is used to address fatigue and malaise, anorexia, and anemia. This study aimed to examine whether relieving inflammation in the brain and skeletal muscle of senescence-accelerated mice prone 8 (SAMP8) could reduce fatigue-like conditions associated with aging. First, SAMP8 mice were divided into two groups, with and without ninjin'yoeito treatment. The ninjin'yoeito-treated group received a diet containing 3% ninjin'yoeito for a period of 4 months starting at 3 months of age. At 7 months of age, all mice underwent motor function, treadmill fatigue, and behavioral tests. They were then euthanized and the skeletal muscle weight, muscle cross-sectional area, and concentration of interleukin (IL)-1ß and IL-1 receptor antagonist (IL-1RA) in both the brain and skeletal muscle were measured. The results showed that the ninjin'yoeito-treated group had higher motor function and spontaneous locomotor activity than the untreated group did and ran for significantly longer in the treadmill fatigue test. Moreover, larger muscle cross-sectional area, lower IL-1ß concentrations, and higher IL-1RA concentrations were observed in both the brain and skeletal muscle tissues of the ninjin'yoeito-treated group than in the untreated group. The results suggest that ninjin'yoeito improves age-related inflammatory conditions in both the central and peripheral tissues and reduces fatigue.

A retrospective study of the prevalence of isolated prolongation of activated partial thromboplastin time in the preoperative setting.

BACKGROUND: Isolated prolongation of activated partial thromboplastin time (APTT) has various causes including inheritable bleeding disorders, and has medical significance as it can lead to the cancelation of surgery. However, even an emergency surgery can be conducted in a patient presenting with severe APTT prolongation, provided careful evaluation and appropriate measures are taken. Hence, the identification of the underlying etiology of the prolonged APTT is crucial. To date, little evidence exists regarding the prevalence of isolated APTT prolongation in Japanese patients undergoing surgery. Herein, we aimed to clarify the prevalence of isolated prolongation of APTT in the preoperative setting and to identify the reasons underlying isolated, severely prolonged APTT. METHODS: Preoperative coagulation data of all elective and emergent patients who presented to the anesthetic department between January 1, 2020, and June 30, 2023, were retrospectively collected. Isolated prolongation of APTT was defined as an APTT ≥ 37 s with an international normalized ratio of prothrombin time < 1.2. The underlying etiology of the patient with isolated, severely prolonged APTT (≥ 46 s) was investigated, and canceled surgical procedures in relation to the isolated APTT prolongation were searched. RESULTS: Overall, 10,684 measurements from 9413 patients were included, of which 725 (6.8%) were identified as having isolated APTT prolongation. The reasons for the severely prolonged APTT (n = 60) were miscellaneous, with the most frequently detected etiology being antiphospholipid antibody positivity. Preoperative isolated APTT prolongation contributed to the cancellation of surgery in elective five cases. CONCLUSIONS: We clarified the prevalence of preoperative isolated prolongation of APTT. The presence of antiphospholipid antibody was the most frequently detected etiology of the patient with isolated, severely prolonged APTT. The present study provides an important dataset regarding the isolated prolongation of APTT in East Asian patients undergoing surgery.

Association of taurine intake with changes in physical fitness among community-dwelling middle-aged and older Japanese adults: an 8-year longitudinal study.

Introduction: Taurine has diverse valuable biological functions, including antioxidant activity and regulation of osmotic pressure. Maintaining physical fitness from middle age is important for healthy life expectancy. Although taurine administration improves muscle endurance and strength, its role in maintenance remains unclear. We aimed to clarify the longitudinal taurine intake association with fitness changes. Methods: Participants comprised men and women aged ≥40 years who participated in the third (2002-2004; Baseline) and seventh (2010-2012; Follow-up) waves of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) and completed a 3-day dietary weights recording survey at baseline. A table of taurine content was prepared for 751 foods (including five food groups: Seaweed; Fish and shellfish; Meat; Eggs; and Milk and dairy products) from the Standard Tables of Food Composition in Japan (1,878 foods) 2010. Four physical fitness items (knee extension muscle strength, sit-and-reach, one-leg standing with eyes closed, and maximum walking speed) were measured at baseline and follow-up. We analyzed the association of taurine intake with physical fitness change, employing a general linear model (GLM) and trend tests for baseline taurine intake and follow-up fitness change. Adjustments included baseline variables: sex, age, height, weight, educational level, self-rated health, smoking status, depressive symptoms, and clinical history. Results: The estimated average daily taurine intake (standard deviation) was 207.5 (145.6) mg/day at the baseline. When examining the association with the four physical fitness parameters, higher taurine intake positively increased the change in knee extension muscle strength (T1; 0.1, T2; 0.8, T3; 1.1 (kgf) GLM, p < 0.05; p for trend <0.05) and reduced the decline in knee extension muscle strength in the subgroup analysis of participants aged ≥65 years (T1: -1.9, T2: -1.7, T3: -0.4 kgf; GLM p < 0.05, p for trend <0.05). No relationship was found between taurine intake and the remaining three fitness factors. Conclusion: Estimation of taurine intake showed that dietary taurine intake potentially contributes to the maintenance of knee extension muscle strength over 8 years among Japanese community-dwelling middle-aged and older individuals. This is the first study to investigate the association of dietary taurine intake with muscle strength.

Comparative study on clinical outcomes in autologous chondrocyte implantation using three-dimensional cultured JACC® with collagen versus periosteum coverings.

This study investigates the efficacy of a collagen membrane as a substitute for autologous periosteum in atelocollagen-assisted autologous chondrocyte implantation (ACI) using J-TEC autologous cultured cartilage (JACC®). Sixty-nine patients with knee joint chondral defects underwent ACI using JACC®-34 with periosteum-covered ACI (P-ACIs) and 35 with collagen-covered ACI (C-ACIs). Clinical outcomes were compared through patient-reported measures, International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) scores at second-look arthroscopy one year postoperatively, and adverse event incidence. Postoperative subjective scores significantly improved up to two years, with no significant differences between P-ACI and C-ACI groups. However, C-ACI exhibited a lower adverse event rate (p = 0.034) and significantly higher ICRS CRA scores (p = 0.0001). Notably, C-ACI outperformed P-ACI in both femoral condyle and trochlea assessments (p = 0.0157 and 0.0005, respectively). While clinical outcomes were comparable, the use of a collagen membrane demonstrated superiority in ICRS CRA during second-look arthroscopy and adverse event occurrence.

Real-world short-term outcomes of prostate urethral lift in Japan: A prospective cohort study.

OBJECTIVES: We report the first prospective trial of prostatic urethral lift for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in Japan. METHODS: This prospective study was conducted at a single institution and included patients with benign prostatic hyperplasia who underwent prostatic urethral lift based on the Japanese surgical indication. The primary efficacy endpoint was reduced international prostatic symptoms score in the early postoperative period after prostatic urethral lift. To assess efficacy, international prostatic symptoms score, quality of life, sexual health inventory for men, and uroflowmetry were evaluated 2 weeks before, 2 weeks after, and 6 weeks after surgery. RESULTS: We enrolled 120 elderly men. The patients experienced significantly reduced international prostatic symptoms scores from 15 at the baseline to 13 at 2 weeks, and to 10 at 6 weeks, respectively. The peak flow rates did not change significantly at any time point. Three patients had serious adverse events of grade 3a in the Clavien-Dindo classification. Four patients were evaluated for sexual function, and none had ejaculatory dysfunction. CONCLUSION: In the Japanese population, prostatic urethral lift is reliably performed under local anesthesia and rapidly improves symptoms.

Overall reaction mechanism of photocatalytic CO2 reduction on a Re(i)-complex catalyst unit of a Ru(ii)-Re(i) supramolecular photocatalyst.

Rhenium(i) complexes fac-[ReI(diimine)(CO)3(L)]n+ are mostly used and evaluated as photocatalysts and catalysts in both photochemical and electrochemical systems for CO2 reduction. However, the selective reduction mechanism of CO2 to CO is unclear, although numerous mechanistic studies have been reported. A Ru(ii)-Re(i) supramolecular photocatalyst with fac-[ReI(diimine)(CO)3{OC(O)OCH2CH2NR2}] (R = C2H4OH) as a catalyst unit (RuC2Re) exhibits very high efficiency, selectivity, and durability of CO formation in photocatalytic CO2 reduction reactions. In this work, the reaction mechanism of photocatalytic CO2 reduction using RuC2Re is fully clarified. Time-resolved IR (TR-IR) measurements using rapid-scan FT-IR spectroscopy with laser flash photolysis verify the formation of RuC2Re(COOH) with a carboxylic acid unit, i.e., fac-[ReI(diimine)(CO)3(COOH)], in the photocatalytic reaction solution. Additionally, this important intermediate is detected in an actual photocatalytic reaction using steady state irradiation. Kinetics analysis of the TR-IR spectra and DFT calculations demonstrated the reaction mechanism of the conversion of the one-electron reduced species of RuC2Re with a fac-[ReI(diimine˙-)(CO)3{OC(O)OCH2CH2NR2}]- unit, which was produced via the photochemical reduction of RuC2Re by 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole (BIH), to RuC2Re(COOH). The kinetics of the recovery processes of the starting complex RuC2Re from RuC2Re(COOH) accompanying the release of CO and OH- was also clarified. As a side reaction of RuC2Re(COOH), a long-lived carboxylate-ester complex with a fac-[ReI(diimine)(CO)3(COOC2H4NR2)] unit, which was produced by the nucleophilic attack of TEOA to one of the carbonyl ligands of RuC2Re(CO) with a fac-[ReI(diimine)(CO)4]+ unit, was formed during the photocatalytic reaction. This complex works not only as a precursor in another minor CO formation process but also as an external photosensitiser that photochemically reduces the other complexes i.e., RuC2Re, RuC2Re(COOH), and the intermediate that is reductively converted to RuC2Re(COOH).

Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

Evaluation of adipogenesis over time using a novel bioabsorbable implant without the addition of exogenous cells or growth factors.

Background: Breast reconstruction is crucial for patients who have undergone mastectomy for breast cancer. Our bioabsorbable implants comprising an outer poly-l-lactic acid mesh and an inner component filled with collagen sponge promote and retain adipogenesis in vivo without the addition of exogenous cells or growth factors. In this study, we evaluated adipogenesis over time histologically and at the gene expression level using this implant in a rodent model. Methods: The implants were inserted in the inguinal and dorsal regions of the animals. At 1, 3, 6, and 12 months post-operation, the weight, volume, and histological assessment of all newly formed tissue were performed. We analyzed the formation of new adipose tissue using multiphoton microscopy and RNA sequencing. Results: Both in the inguinal and dorsal regions, adipose tissue began to form 1 month post-operation in the peripheral area. Angiogenesis into implants was observed until 3 months. At 6 months, microvessels matured and the amount of newly generated adipose tissue peaked and was uniformly distributed inside implants. The amount of newly generated adipose tissue decreased from 6 to 12 months but at 12 months, adipose tissue was equivalent to the native tissue histologically and in terms of gene expression. Conclusions: Our bioabsorbable implants could induce normal adipogenesis into the implants after subcutaneous implantation. Our implants can serve as a novel and safe material for breast reconstruction without requiring exogenous cells or growth factors.

Outcomes of Barlow mitral valve repaired by robot-assisted keyhole surgery.

Objective: To present our strategy and the clinical outcomes of robot-assisted Barlow mitral valve keyhole surgery. Methods: From May 2015 to March 2022, a total of 1281 patients underwent mitral valve repair at our institution, including 763 with robotics surgeries. Of these, 124 patients with Barlow mitral valve (49 ± 12 years, male/female ratio = 81:43) were treated using robotic assistance and included in this study. Results: All operations were completed using 3 to 5 keyholes. Neochordae implantation using the loop technique was the first option, and resection was performed only in cases with an intrinsic risk of developing systolic anterior motion. Neochordae implantation was performed in 118 cases (95.1%) using 6.6 ± 3.0 neochordae. Posterior leaflet resection was performed in 27 (21.7%) patients. Operation time was 177 ± 42 minutes, cardiopulmonary bypass time was 127 ± 25 minutes, and aorta crossclamp time was 76 ± 16 minutes. Blood transfusion was required in 5 cases (4%). None of the patients required a conversion to valve replacement. The postoperative complications included bleeding (n = 4), stroke (n = 1), and infection (n = 2). Mitral valve regurgitation 1 week after repair was none or trivial in 122 cases (98.3%), mild in 2 cases (1.7%), and more than moderate in 0 cases. Freedom from reoperation was 99.2% during the follow-up period of 36 ± 21 months. One patient required reoperation due to infective endocarditis. Conclusions: Robot-assisted keyhole surgery using the loop-first concept was adequate to help achieve satisfactory and safe perioperative outcomes for Barlow mitral valve.

Predictive Value of the Hemoglobin-Geriatric Nutritional Risk Index in Patients with Heart Failure.

Malnutrition prevails among patients with heart failure (HF), increasing the likelihood of functional decline. We assessed the predictive value of the Hemoglobin-Geriatric Nutritional Risk Index (H-GNRI)-combining hemoglobin and the Geriatric Nutritional Risk Index (GNRI)-on prognosis in older patients with HF. We used the JMDC multicenter database to examine the potential associations between malnutrition risk and other outcome measures. The patients were categorized as low- (H-GNRI score = 0), intermediate- (H-GNRI score = 1), or high-risk (H-GNRI score = 2) based on their H-GNRI scores. The primary outcome measure was the Barthel Index (BI) gain; the secondary outcomes included the BI at discharge, the BI efficiency, length of hospital stay, in-hospital mortality, discharge to home or a nursing home, and hospitalization-associated disability. We analyzed 3532 patients, with 244 being low-risk, 952 being intermediate-risk, and 2336 being high-risk patients. The high-risk group of patients had significantly lower BI values at discharge, lower BI gains, reduced BI efficiency values, and prolonged hospital stays compared to those in the low-risk group. The high-risk patients also had higher in-hospital mortality rates, lower rates of discharge to home or a nursing home, and greater incidences of a hospitalization-associated disability in comparison to the low-risk group. The H-GNRI may serve as a valuable tool for determining prognoses for patients with HF.

Preparation and isolation of mono-Nb substituted Keggin-type phosphomolybdic acid and its application as an oxidation catalyst for isobutylaldehyde and Wacker-type oxidation.

The potassium and proton mixed salt of mono-Nb substituted Keggin-type phosphomolybdate, KH3[PMo11NbO40], was isolated in a pure form by reacting Keggin-type phosphomolybdic acid (H3[PMo12O40]) and potassium hexaniobate (K8Nb6O19) in water, followed by freeze-drying. The all protonic form, H4[PMo11NbO40], was isolated via proton exchange with H-resin and subsequent freeze-drying. The most crucial factor to isolate KH3[PMo11NbO40] and H4[PMo11NbO40] in pure forms is the evaporation of water using the freeze-drying method. Using a similar procedure, the potassium salt of the di-Nb substituted compound K5[PMo10Nb2O40] was isolated. H4[PMo11NbO40] exhibited high catalytic activity for oxidizing isobutylaldehyde to methacrolein and moderate catalytic activity for the Wacker-type oxidation of allyl phenyl ether when combined with Pd(OAc)2.

Reproducibility and Robustness of a Liver Microphysiological System PhysioMimix LC12 under Varying Culture Conditions and Cell Type Combinations.

The liver is one of the key organs for exogenous and endogenous metabolism and is often a target for drug- and chemical-driven toxicity. A wide range of experimental approaches has been established to model and characterize the mechanisms of drug- and chemical-induced hepatotoxicity. A number of microfluidics-enabled in vitro models of the liver have been developed, but the unclear translatability of these platforms has hindered their adoption by the pharmaceutical industry; to achieve wide use for drug and chemical safety evaluation, demonstration of reproducibility and robustness under various contexts of use is required. One of these commercially available platforms is the PhysioMimix LC12, a microfluidic device where cells are seeded into a 3D scaffold that is continuously perfused with recirculating cell culture media to mimic liver sinusoids. Previous studies demonstrated this model's functionality and potential applicability to preclinical drug development. However, to gain confidence in PhysioMimix LC12's robustness and reproducibility, supplementary characterization steps are needed, including the assessment of various human hepatocyte sources, contribution of non-parenchymal cells (NPCs), and comparison to other models. In this study, we performed replicate studies averaging 14 days with either primary human hepatocytes (PHHs) or induced pluripotent stem cell (iPSC)-derived hepatocytes, with and without NPCs. Albumin and urea secretion, lactate dehydrogenase, CYP3A4 activity, and metabolism were evaluated to assess basal function and metabolic capacity. Model performance was characterized by different cell combinations under intra- and inter-experimental replication and compared to multi-well plates and other liver platforms. PhysioMimix LC12 demonstrated the highest metabolic function with PHHs, with or without THP-1 or Kupffer cells, for up to 10-14 days. iPSC-derived hepatocytes and PHHs co-cultured with additional NPCs demonstrated sub-optimal performance. Power analyses based on replicate experiments and different contexts of use will inform future study designs due to the limited throughput and high cell demand. Overall, this study describes a workflow for independent testing of a complex microphysiological system for specific contexts of use, which may increase end-user adoption in drug development.

Synthesis and Conformational Behaviors of Unnatural Peptides Alternating Chiral and Achiral α,α-Disubstituted α-Amino Acid Units.

The development of peptidomimetics to modulate the conformational profile of peptides has been extensively studied in the fields of biological and medicinal chemistry. However, large-scale synthesis of peptidomimetics with both an ordered sequence and a controlled secondary structure is highly challenging. In this paper, the framework of peptidomimetics has been designed to be alternating an achiral α,α-disubstituted α-amino acid unit and a chiral α-methylphenylalanine unit. The polymers are synthesized via invented Ugi reaction-based polycondensation technique. The chiral higher-order structures of the alternating peptides are evaluated mainly through circular dichroism (CD) spectroscopy. The UV-Vis and CD spectra of the polymers in three solvents are systematically measured at various temperatures. The anisotropic factors of CD (gCD ) values are calculated to know the chiroptical response. The results indicate the characteristic conformational behaviors. In a polar solvent, the hydrogen bonds between the N-H group of MePhe unit and the C=O of α,α-diphenylglycine unit outweigh the intraresidue hydrogen bonds in α,α-diphenylglycine unit, leading to the formation of a prevailing preferred-handed 310 -helical conformation. On the other hand, in a less polar solvent, the intrachain hydrogen bonds switch to intraresidue hydrogen bonds in α,α-diphenylglycine unit, which make the polymer adopting a prevailing extended planar C5 -conformation.

Relation between athletic club affiliation from school age and future serum free testosterone levels in Japan: A cross-sectional study.

Background and Aims: Testosterone deficiency is often related to geriatric syndrome including erectile dysfunction, osteo-porosis, depression, cognitive impairment, cardiovascular diseases and frailty. Despite the existence of many studies on short-term exercise and serum testosterone levels, few research have focused on exercise habits from young age and testosterone values in middle-aged male. In this study, we investigated whether belonging to an athletic club from school age could predict serum-free testosterone (FT) levels. Methods: The subjects were 1609 middle-aged male outpatients aged 40 years or older (median: 61 years, interquartile range: 54-69) who visited our hospital. Participants had their FT values measured in the morning hours during the period from December 2007 to June 2009. A questionnaire survey on exercise habits was conducted at the same time as the measurements. The exercise habit questionnaire was created based on whether the patients belonged to an athletic club in (a) elementary school, (b) junior high school, (c) high school, (d) college, (e) adult life, and (f) at the time of the test. Results: There was only one positive response to the questionnaire among 456 patients (28% of total), followed by zero for 358 patients (22% of total). The number of patients with low-testosterone levels (FT < 8.5 pg/mL) according to the Japanese diagnostic criteria for late-onset of hypogonadism was 839 (52.1%). In multivariate analysis, it was shown that with low-testosterone levels (FT < 8.5 pg/mL), age (odds ratio [OR]: 1.065, 95% confidence interval [CI]: 1.052-1.079; p < 0.001), hypertension (OR: 3.489, 95% CI: 2.728-4.462; p < 0.001), type-2 diabetes (OR: 3.035, 95% CI: 2.296-4.01; p < 0.001), and dyslipidemia (OR: 2.039, 95% CI: 1.558-2.668; p < 0.001) were risk factors, and more than two positive responses to the questionnaire (OR: 0.886, 95% CI: 0.802-0.980; p = 0.018) were also a significant independent factor. Conclusion: A sports club membership during school years may affect future testosterone levels.

Development of new bioabsorbable implants with de novo adipogenesis.

Poly-L-lactic acid (PLLA) mesh implants containing collagen sponge (CS) were replaced with autologous adipose tissue regeneration in vivo. Herein, we investigated the optimal external frames and internal fillings using poly (lactic-co-ε-caprolactone) (P (LA/CL)), PLLA, and low-molecular-weight PLLA (LMW-PLLA) as the external frame and polyglycolic acid (PGA) nanosheets and CS as the internal filling. We prepared six implants: P (LA/CL) with PGA nano, PLLA with PGA nano, PLLA with CS, PLLA with 1/2 CS, PLLA with 1/4 CS, and LMW-PLLA with CS, and evaluated adipogenesis at 6 and 12 months using a rat inguinal model. The internal spaces in the P (LA/CL) and LMW-PLLA implants collapsed at 6 months, whereas those in the other four implants collapsed at 12 months. Adipose tissue regeneration was not significantly different between the PLLA-implanted groups at 6 and 12 months and was greater than that in the P (LA/CL) with PGA nano and LMW-PLLA with CS groups. The PGA nanosheet inside PLLA was comparable to the CS inside PLLA in the regeneration of adipose tissue and macrophage infiltration. In summary, PLLA is a promising external frame material in which the internal space can be replaced with adipose tissue. Thus, PGA nanosheets are an alternative internal filling material for adipose tissue regeneration.

Long term observation of de novo adipogenesis using novel bioabsorbable implants with larger size in a porcine model.

Introduction: The regeneration of adipose tissue in patients after breast cancer surgery would be desirable without the use of growth factors or cells to avoid potential recurrence and metastasis. We reported that prolate spheroidal-shaped poly-L-lactic acid (PLLA) mesh implants of approximately 18-mm polar diameter and 7.5-mm greatest equatorial diameter containing collagen sponge (CS) would be replaced by regenerated adipose tissue after implantation, thereby suggesting an innovative method for breast reconstruction. Our study aimed to evaluate the adipose tissue regeneration ability of implant aggregates in a porcine model. Methods: We prepared implant aggregates consisting of thirty PLLA mesh implants containing CS packed in a woven poly (glycolic acid) bag. The implant aggregates were inserted under the mammary glands in the porcine abdomen for a year. Single and double groups were classified by inserting either one or two implant aggregates on each side of the abdomen, respectively. Results: In both groups, the volume of the implant aggregates decreased over time, and the formation of adipose tissue peaked between 6 and 9 months. Histologically, the formation of adipose tissue was confirmed in the area that was in contact with native adipose tissue. Conclusions: Our implant aggregates could induce the autologous adipose tissue after long term implantation in vivo, without the use of any growth factor or cell treatment, presenting a potential novel method of breast reconstruction.

Improving image quality with super-resolution deep-learning-based reconstruction in coronary CT angiography.

OBJECTIVES: To evaluate the effect of super-resolution deep-learning-based reconstruction (SR-DLR) on the image quality of coronary CT angiography (CCTA). METHODS: Forty-one patients who underwent CCTA using a 320-row scanner were retrospectively included. Images were reconstructed with hybrid (HIR), model-based iterative reconstruction (MBIR), normal-resolution deep-learning-based reconstruction (NR-DLR), and SR-DLR algorithms. For each image series, image noise, and contrast-to-noise ratio (CNR) at the left main trunk, right coronary artery, left anterior descending artery, and left circumflex artery were quantified. Blooming artifacts from calcified plaques were measured. Image sharpness, noise magnitude, noise texture, edge smoothness, overall quality, and delineation of the coronary wall, calcified and noncalcified plaques, cardiac muscle, and valves were subjectively ranked on a 4-point scale (1, worst; 4, best). The quantitative parameters and subjective scores were compared among the four reconstructions. Task-based image quality was assessed with a physical evaluation phantom. The detectability index for the objects simulating the coronary lumen, calcified plaques, and noncalcified plaques was calculated from the noise power spectrum (NPS) and task-based transfer function (TTF). RESULTS: SR-DLR yielded significantly lower image noise and blooming artifacts with higher CNR than HIR, MBIR, and NR-DLR (all p < 0.001). The best subjective scores for all the evaluation criteria were attained with SR-DLR, with significant differences from all other reconstructions (p < 0.001). In the phantom study, SR-DLR provided the highest NPS average frequency, TTF50%, and detectability for all task objects. CONCLUSION: SR-DLR considerably improved the subjective and objective image qualities and object detectability of CCTA relative to HIR, MBIR, and NR-DLR algorithms. CLINICAL RELEVANCE STATEMENT: The novel SR-DLR algorithm has the potential to facilitate accurate assessment of coronary artery disease on CCTA by providing excellent image quality in terms of spatial resolution, noise characteristics, and object detectability. KEY POINTS: • SR-DLR designed for CCTA improved image sharpness, noise property, and delineation of cardiac structures with reduced blooming artifacts from calcified plaques relative to HIR, MBIR, and NR-DLR. • In the task-based image-quality assessments, SR-DLR yielded better spatial resolution, noise property, and detectability for objects simulating the coronary lumen, coronary calcifications, and noncalcified plaques than other reconstruction techniques. • The image reconstruction times of SR-DLR were shorter than those of MBIR, potentially serving as a novel standard-of-care reconstruction technique for CCTA performed on a 320-row CT scanner.

Structures of a FtsZ single protofilament and a double-helical tube in complex with a monobody.

FtsZ polymerizes into protofilaments to form the Z-ring that acts as a scaffold for accessory proteins during cell division. Structures of FtsZ have been previously solved, but detailed mechanistic insights are lacking. Here, we determine the cryoEM structure of a single protofilament of FtsZ from Klebsiella pneumoniae (KpFtsZ) in a polymerization-preferred conformation. We also develop a monobody (Mb) that binds to KpFtsZ and FtsZ from Escherichia coli without affecting their GTPase activity. Crystal structures of the FtsZ-Mb complexes reveal the Mb binding mode, while addition of Mb in vivo inhibits cell division. A cryoEM structure of a double-helical tube of KpFtsZ-Mb at 2.7 Å resolution shows two parallel protofilaments. Our present study highlights the physiological roles of the conformational changes of FtsZ in treadmilling that regulate cell division.

A cancer-associated METTL14 mutation induces aberrant m6A modification, affecting tumor growth.

The methyltransferase-like 3 (METTL3)-/METTL14-containing complex predominantly catalyzes N6-methyladenosine (m6A) modification, which affects mRNA stability. Although the METTL14 R298P mutation is found in multiple cancer types, its biological effects are not completely understood. Here, we show that the heterozygous R298P mutation promotes cancer cell proliferation, whereas the homozygous mutation reduces proliferation. Methylated RNA immunoprecipitation sequencing analysis indicates that the R298P mutation reduces m6A modification at canonical motifs. Furthermore, this mutation induces m6A modification at aberrant motifs, which is evident only in cell lines harboring the homozygous mutation. The aberrant recognition of m6A modification sites alters the methylation efficiency at surrounding canonical motifs. One example is c-MET mRNA, which is highly methylated at canonical motifs close to the aberrantly methylated sites. Consequently, c-MET mRNA is severely destabilized, reducing c-Myc expression and suppressing cell proliferation. These data suggest that the METTL14 R298P mutation affects target recognition for m6A modification, perturbing gene expression patterns and cell growth.