The associations of daily steps and body mass index with incident gastroesophageal reflux disease in older adults.

Background: High body mass index (BMI) is a major risk factor of gastroesophageal reflux disease (GERD), a prevalent morbidity of older adulthood linked to lower quality of life and an increased risk of esophageal cancers. Daily stepping behavior, the most common physical activity of older adulthood, is associated with an array of favorable health outcomes, sometimes independent of high BMI. Whether stepping behavior is associated with the incidence of GERD independently or in combination with BMI is currently unclear. Materials and methods: We followed 442 individuals (58.4% female) aged 65-91 years enrolled in the Physical Activity and Aging Study. Baseline steps were obtained by pedometer and categorized by tertiles (lower, middle, upper), while BMI was categorized into normal weight, overweight, and obesity. To explore joint associations, daily steps were dichotomized into "high steps" (middle/upper tertiles) and "low steps" (lower tertile), while BMI was dichotomized into normal weight and overweight/obesity. The joint exposure categories included "low steps and overweight/obesity," "low steps and normal weight," "high steps and overweight/obesity," and "high steps and normal weight." Results: We identified 35 (7.9%) cases of GERD over a mean follow-up of 2.5 years. Compared to the lower tertile of steps, the hazard ratios (HRs) [95% confidence intervals (95% CIs)] of GERD were 0.44 (0.20-0.96) and 0.17 (0.05-0.54) for the middle and upper tertiles, respectively, after adjusting for confounders (including BMI). Compared to normal weight, the HRs (95% CIs) of GERD were 1.35 (0.54-3.37) and 3.00 (1.19-7.55) for overweight and obesity, respectively, after adjusting for confounders (including steps). In a joint analysis, compared to "low steps and overweight/obesity," the HRs (95% CIs) of GERD were 0.32 (0.10-1.00), 0.23 (0.10-0.54), and 0.20 (0.07-0.58) for "low steps and normal weight," "high steps and overweight/obesity," and "high steps and normal weight," respectively. Conclusion: Higher daily steps were associated with a lower risk of GERD in older adults, independent of BMI. Since accumulating steps through walking is an achievable and acceptable modality of physical activity in older adulthood, future lifestyle interventions designed to achieve high daily steps counts may have favorable implications for the development of GERD in older adults of any BMI status.

NEK2 plays an essential role in porcine embryonic development by maintaining mitotic division and DNA damage response via the Wnt/ß-catenin signalling pathway.

NIMA-related kinase 2 (NEK2) is a serine/threonine protein kinase that regulates mitosis and plays pivotal roles in cell cycle regulation and DNA damage repair. However, its function in porcine embryonic development is unknown. In this study, we used an NEK2-specific inhibitor, JH295 (JH), to investigate the role of NEK2 in embryonic development and the underlying regulatory mechanisms. Inhibition of NEK2 after parthenogenesis activation or in vitro fertilization significantly reduced the rates of cleavage and blastocyst formation, the numbers of trophectoderm and total cells and the cellular survival rate compared with the control condition. NEK2 inhibition delayed cell cycle progression at all stages from interphase to cytokinesis during the first mitotic division; it caused abnormal nuclear morphology in two- and four-cell stage embryos. Additionally, NEK2 inhibition significantly increased DNA damage and apoptosis, and it altered the expression levels of DNA damage repair- and apoptosis-related genes. Intriguingly, NEK2 inhibition downregulated the expression of ß-catenin and its downstream target genes. To validate the relationship between Wnt/ß-catenin signalling and NEK2 during porcine embryonic development, we cultured porcine embryos in JH-treated medium with or without CHIR99021, a Wnt activator. CHIR99021 co-treatment strongly restored the developmental parameters reduced by NEK2 inhibition to control levels. Our findings suggest that NEK2 plays an essential role in porcine embryonic development by regulating DNA damage repair and normal mitotic division via the Wnt/ß-catenin signalling pathway.

Enhancement of porcine in vitro embryonic development through luteolin-mediated activation of the Nrf2/Keap1 signaling pathway.

BACKGROUND: Oxidative stress, caused by an imbalance in the production and elimination of intracellular reactive oxygen species (ROS), has been recognized for its detrimental effects on mammalian embryonic development. Luteolin (Lut) has been documented for its protective effects against oxidative stress in various studies. However, its specific role in embryonic development remains unexplored. This study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying mechanism. RESULTS: After undergoing parthenogenetic activation (PA) or in vitro fertilization, embryos supplemented with 0.5 µmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates, with an increase in total cell numbers and a decrease in the apoptosis rate compared to the control. Measurements on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the control. Moreover, Lut supplementation significantly augmented mitochondrial content and membrane potential. Intriguingly, activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut, leading to the upregulation of antioxidant-related gene transcription levels. To further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development, we cultured PA embryos in a medium supplemented with brusatol, with or without the inclusion of Lut. The positive effects of Lut on developmental competence were negated by brusatol treatment. CONCLUSIONS: Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence, and offers insight into the mechanisms regulating early embryonic development.

Increasing Lifestyle Walking by 3000 Steps per Day Reduces Blood Pressure in Sedentary Older Adults with Hypertension: Results from an e-Health Pilot Study.

Increasing daily steps by an additional 3000 steps/day on 5 days/week equates to ~150 min/week of aerobic physical activity to meet the physical activity guidelines; however, its effectiveness for blood pressure control in older adults with hypertension is unknown. A 20-week, single-arm, pilot e-health lifestyle walking intervention was conducted in 21 sedentary older adults (73 ± 5 years old) with hypertension (13 female, 8 male) to investigate the effectiveness of increasing daily steps by an additional 3000 steps/day for blood pressure control. The intervention consisted of two phases, with behavior change assistance provided during the first active phase (weeks 1-10) to help reach step goals and minimal assistance provided during the second self-maintenance phase (weeks 11-20). Nineteen participants (91%) completed both the 10- and 20-week assessments. The participants wore the pedometer for ≥10 h on 97% of the days over 20 weeks. They significantly increased average steps/day from 3899 ± 2198 at baseline to 6512 ± 2633 at 10 weeks and 5567 ± 2587 at 20 weeks. After 20 weeks, both systolic (137 ± 10 to 130 ± 11 mm Hg, p < 0.001) and diastolic (81 ± 6 to 77 ± 6 mm Hg, p = 0.01) blood pressure improved. The response was consistent in participants with (n = 8) and without (n = 13) anti-hypertensive medication. The results of our lifestyle walking intervention are encouraging for reducing blood pressure in older adults with hypertension; however, larger randomized, controlled trials need to be performed to confirm these findings.

Development of lung cancer risk prediction models based on F-18 FDG PET images.

OBJECTIVE: We aimed to evaluate whether the degree of F-18 fluorodeoxyglucose (FDG) uptake in the lungs is associated with an increased risk of lung cancer and to develop lung cancer risk prediction models using metabolic parameters on F-18 FDG positron emission tomography (PET). METHODS: We retrospectively included 795 healthy individuals who underwent F-18 FDG PET/CT scans for a health check-up. Individuals who developed lung cancer within 5 years of the PET/CT scan were classified into the lung cancer group (n = 136); those who did not were classified into the control group (n = 659). The healthy individuals were then randomly assigned to either the training (n = 585) or validation sets (n = 210). Clinical factors including age, sex, body mass index (BMI), and smoking history were collected. The standardized uptake value ratio (SUVR) and metabolic heterogeneity (MH) index were obtained for the bilateral lungs. Logistic regression models including clinical factors, SUVR, and MH index were generated to quantify the probability of lung cancer development using a training set. The prediction models were validated using a validation set. RESULTS: The lung SUVR and lung MH index in the lung cancer group were significantly higher than in the control group (p < 0.001 and p < 0.001, respectively). In the combined prediction model 1, age, sex, BMI, smoking history, and lung SUVR were significantly associated with lung cancer development (age: OR 1.07, p < 0.001; male: OR 2.08, p = 0.015; BMI: OR 0.93, p = 0.057; current or past smoker: OR 5.60, p < 0.001; lung SUVR: OR 1.13, p < 0.001). In the combined prediction model 2, age, sex, BMI, smoking history, and lung MH index showed a significant association with lung cancer development (age: OR 1.06, p < 0.001; male: OR 1.87, p = 0.045; BMI: OR 0.93, p = 0.010; current or past smoker: OR 4.78, p < 0.001; lung MH index: OR 1.33, p < 0.001). In the validation data, combined prediction models 1 and 2 exhibited very good discrimination [area under the receiver operator curve (AUC): 0.867 and 0.901, respectively]. CONCLUSIONS: The metabolic parameters on F-18 FDG PET are related to an increased risk of lung cancer. Metabolic parameters can be used as biomarkers to provide information independent of the clinical parameters, related to lung cancer risk.

Pure uric acid stone prediction model using the variant coefficient of stone density measured by thresholding 3D segmentation-based methods: A multicenter study.

Urinary stones are common urological diseases with increasing prevalence and incidence worldwide. Among the various types of stones, uric acid stones can be dissolved by oral chemolysis without any surgical procedure. Therefore, our study demonstrates that variant coefficient of stone density measured by thresholding a three-dimensional segmentation-based method from noncontrast computed tomography images can be used to identify pure uric acid stones from non-pure uric acid stones. This study provides a preoperative pure uric acid stone prediction model that could reduce invasive procedural treatments. The pure uric acid stone prediction model may offer optimized clinical decision-making for patients with urinary stones. BACKGROUND AND OBJECTIVES: While most urinary stones are managed with interventional therapy, uric acid (UA) stones can be dissolved by oral chemolysis without invasive procedures. This study aimed to develop and validate a pure UA (pUA) stone prediction model using a variant coefficient of stone density (VCSD) measured by thresholding a three-dimensional (3D) segmentation-based method. METHODS: Patients with urolithiasis treated at Keimyung University Dongsan Hospital between January 2017 and December 2020 were divided into training and internal validation sets, and patients from Kyungpook National University Hospital between January 2017 and December 2018 were used as an external validation set. Each stone was segmented by a thresholding 3D segmentation-based method using an attenuation threshold of 130 Hounsfield units. VCSD was calculated as the stone heterogeneity index divided by the mean stone density. RESULTS: A total of 1175 urinary stone cases in 1023 patients were enrolled in this study. Of these, 224 (19.1%) were pUA stone cases. Among the potential predictors, thresholding 3D segmentation-based VCSD, age, sex, radio-opacity, hypertension, diabetes, and urine pH were identified as independent pUA stone predictors, and VCSD was the most powerful indicator. The pUA stone prediction model showed good discrimination, yielding area under the receiver operating characteristic curve of 0.960 (95% confidence interval (CI): 0.940-0.979, P < 0.001), 0.931 (95% CI: 0.875-0.987, P < 0.001), and 0.938 (95% CI: 0.912-0.965, P < 0.001) in the training, internal validation, and external validation sets, respectively. CONCLUSIONS: VCSD measured using 3D segmentation was a decisive independent predictive factor for pUA stones. Furthermore, the established prediction model with VCSD can serve as a noninvasive preoperative tool to identify pUA stones.

Luteolin supplementation during porcine oocyte maturation improves the developmental competence of parthenogenetic activation and cloned embryos.

Luteolin (Lut), a polyphenolic compound that belongs to the flavone subclass of flavonoids, possesses anti-inflammatory, cytoprotective, and antioxidant activities. However, little is known regarding its role in mammalian oocyte maturation. This study examined the effect of Lut supplementation during in vitro maturation (IVM) on oocyte maturation and subsequent developmental competence after somatic cell nuclear transfer (SCNT) in pigs. Lut supplementation significantly increased the proportions of complete cumulus cell expansion and metaphase II (MII) oocytes, compared with control oocytes. After parthenogenetic activation or SCNT, the developmental competence of Lut-supplemented MII oocytes was significantly enhanced, as indicated by higher rates of cleavage, blastocyst formation, expanded or hatching blastocysts, and cell survival, as well as increased cell numbers. Lut-supplemented MII oocytes exhibited significantly lower levels of reactive oxygen species and higher levels of glutathione than control MII oocytes. Lut supplementation also activated lipid metabolism, assessed according to the levels of lipid droplets, fatty acids, and ATP. The active mitochondria content and mitochondrial membrane potential were significantly increased, whereas cytochrome c and cleaved caspase-3 levels were significantly decreased, by Lut supplementation. These results suggest that Lut supplementation during IVM improves porcine oocyte maturation through the reduction of oxidative stress and mitochondria-mediated apoptosis.

Cadmium exposure impairs oocyte meiotic maturation by inducing endoplasmic reticulum stress in vitro maturation of porcine oocytes.

Cadmium (Cd) is toxic metal that can induce various diseases, such as cardiovascular, nervous, and reproductive systems. This study investigated the effect of Cd exposure on porcine oocyte maturation and the underlying mechanism. Porcine cumulus-oocyte complexes were exposed various Cd concentration and tauroursodeoxycholic acid (TUDCA), an inhibitor of endoplasmic reticulum (ER) stress during in vitro maturation (IVM). After IVM, we evaluated meiotic maturation, ER stress, and oocyte quality by Cd exposure. Cd exposure inhibited cumulus cell expansion and meiotic maturation, increased oocyte degeneration, and induced ER stress. The levels of spliced XBP1 and ER stress-associated transcripts, markers of ER stress, were elevated in Cd-treated cumulus-oocyte complexes and denuded oocytes during IVM. Moreover, Cd-induced ER stress impaired oocyte quality by disrupting mitochondrial function and elevating intracellular reactive oxygen species levels while decreasing ER function. Interestingly, TUDCA supplementation significantly decreased the expression of ER stress-related genes and increased the quantity of ER compared with the Cd treatment. Additionally, TUDCA was also able to rescue excessive levels of ROS and restore normal mitochondrial function. Moreover, the addition of TUDCA under Cd exposure greatly ameliorated Cd-mediated detrimental effects on meiotic maturation and oocyte quality, including cumulus cell expansion and MII rate. These findings suggest that Cd exposure during IVM impairs the meiotic maturation of oocytes by inducing of ER stress.

Restoration of Developmental Competence in Low-Quality Porcine Cumulus-Oocyte Complexes through the Supplementation of Sonic Hedgehog Protein during In Vitro Maturation.

The sonic hedgehog (SHH) pathway is an important signaling pathway for mammalian ovarian folliculogenesis and oocyte maturation. A previous study demonstrated that low-quality porcine cumulus-oocyte complexes (COCs) have low developmental competence, with lower SHH signaling protein expression before and after in vitro maturation (IVM) than high-quality COCs. However, there is no reported evidence on the restorative effects of SHH protein supplementation during the IVM of low-quality porcine COCs. Therefore, this study investigated the effects of SHH protein supplementation on the IVM of low-quality porcine COCs, as assessed by brilliant cresyl blue (BCB) staining. To examine this, we designed four groups: (i) BCB- (low-quality), (ii) BCB- + SHH, (iii) BCB+ (high-quality), and (iv) BCB+ + SHH. While the supplementation of SHH protein with high-quality COCs had no effect, supplementation with low-quality COCs significantly improved cumulus cell expansion, metaphase II rate, and subsequent embryo development following parthenogenetic activation. Our results provide the first evidence that the low developmental competence of low-quality porcine COCs can be improved by supplementation with the SHH protein. These results indicate that an active SHH signaling pathway is required for the acquisition of developmental competence in porcine COCs.

Expression of the melatonergic system during meiotic maturation of cynomolgus monkey cumulus-oocyte complexes.

BACKGROUND: Melatonin is a multifunctional hormone synthesized in the pineal gland and peripheral reproductive tissues that regulates many biological processes. There is increasing evidence for a role of melatonin in oocyte maturation and embryonic development in various mammals. However, no study has reported evidence for the existence of melatonergic system, such as melatonin synthesis enzymes, melatonin membrane receptors, or melatonin binding sites in non-human primate cumulus-oocyte complexes (COCs). METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry were performed to detect transcripts and proteins of the rate-limiting enzyme in melatonin synthesis (arylalkylamine N-acetyltransferase, AANAT), melatonin membrane receptors (MT1 and MT2), and a melatonin binding site (NRH: quinone oxidoreductase 2, NQO2) in cynomolgus monkey COCs. RESULTS: RT-PCR analyses revealed the presence of AANAT, MT1, MT2, and NQO2 transcripts in granulosa cells, germinal vesicle (GV)- and metaphase II (MII)-stage cumulus cells, and oocytes. Immunocytochemistry revealed the presence of AANAT, MT1, MT2, and NQO2 proteins in GV- and MII-stage COCs. CONCLUSIONS: Our results provide the first evidence for the existence of the rate-limiting enzyme required for melatonin synthesis, melatonin membrane receptors, and a melatonin binding site in non-human primate COCs.

Performance Enhancement in Powder-Fabricated Cu2(ZnSn)Se4 Solar Cell by Roll Compression.

Despite the improved conversion efficiency of Cu2(ZnSn)Se4 (CZTSe) solar cells, their roll-to-roll fabrication nonetheless leads to low performance. The selenization time and temperature are typically considered major parameters for a powder-based CZTSe film; meanwhile, the importance of the densification during the roll-to-roll process is often overlooked. The densification process is related to the porosity of the light-absorbing layer, where high porosity lowers cell performance. In this study, we fabricated a dense CZTSe absorber layer as a method of controlling the compression of a powder precursor (Cu1.7(Zn1.2Sn1.0)S4.0 (CZTS)) during the roll-press process. The increased particle packing density of the CZTS layer was crucial in sintering the powder layer into a dense film and preventing severe selenization of the Mo back electrode. The pressed absorber layer of the CZTSe solar cell exhibited a more uniform chemical composition determined using dynamic secondary ion mass spectrometry (SIMS). Under the AM 1.5G illumination condition, the power conversion efficiency of the pressed solar cell was 6.82%, while the unpressed one was 4.90%.

Anethole improves the developmental competence of porcine embryos by reducing oxidative stress via the sonic hedgehog signaling pathway.

BACKGROUND: Anethole (AN) is an organic antioxidant compound with a benzene ring and is expected to have a positive impact on early embryogenesis in mammals. However, no study has examined the effect of AN on porcine embryonic development. Therefore, we investigated the effect of AN on the development of porcine embryos and the underlying mechanism. RESULTS: We cultured porcine in vitro-fertilized embryos in medium with AN (0, 0.3, 0.5, and 1 mg/mL) for 6 d. AN at 0.5 mg/mL significantly increased the blastocyst formation rate, trophectoderm cell number, and cellular survival rate compared to the control. AN-supplemented embryos exhibited significantly lower reactive oxygen species levels and higher glutathione levels than the control. Moreover, AN significantly improved the quantity of mitochondria and mitochondrial membrane potential, and increased the lipid droplet, fatty acid, and ATP levels. Interestingly, the levels of proteins and genes related to the sonic hedgehog (SHH) signaling pathway were significantly increased by AN. CONCLUSIONS: These results revealed that AN improved the developmental competence of porcine preimplantation embryos by activating SHH signaling against oxidative stress and could be used for large-scale production of high-quality porcine embryos.

Associations of cardiorespiratory fitness and body mass index with incident restrictive spirometry pattern.

OBJECTIVES: Restrictive spirometry pattern (RSP) suggests an impairment of lung function associated with a significantly increased risk of premature mortality. We evaluated the independent and joint associations of cardiorespiratory fitness (CRF) and body mass index with incident RSP. METHODS: Data from the Aerobics Centre Longitudinal Study included 12 360 participants (18-82 years). CRF was assessed by maximal treadmill test and categorised into five groups. Body mass index was categorised into normal weight (<25.0 kg/m2), overweight (25.0-29.9 kg/m2) or obesity (≥30.0 kg/m2). RSP was defined as the simultaneous occurrence of forced expiratory volume in 1 s/force vital capacity ≥lower limit of normal and forced vital capacity

Prognostic value of the metabolic score obtained via [18F]FDG PET/CT and a new prognostic staging system for gastric cancer.

We developed and validated a new staging system that includes metabolic information from pretreatment [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) for predicting disease-specific survival (DSS) in gastric cancer (GC) patients. Overall, 731 GC patients undergoing preoperative [18F]FDG PET/CT were enrolled and divided into the training (n = 543) and validation (n = 188) cohorts. A metabolic score (MS) was developed by combining the maximum standardized uptake value (SUVmax) of the primary tumor (T_SUVmax) and metastatic lymph node (N_SUVmax). A new staging system incorporating the MS and tumor-node-metastasis (TNM) stage was developed using conditional inference tree analysis. The MS was stratified as follows: score 1 (T_SUVmax ≤ 4.5 and N_SUVmax ≤ 1.9), score 2 (T_SUVmax > 4.5 and N_SUVmax ≤ 1.9), score 3 (T_SUVmax ≤ 4.5 and N_SUVmax > 1.9), and score 4 (T_SUVmax > 4.5 and N_SUVmax > 1.9) in the training cohort. The new staging system yielded five risk categories: category I (TNM I, II and MS 1), category II (TNM I, II and MS 2), category III (TNM I, II and MS ≥ 3), category IV (TNM III, IV and MS ≤ 3), and category V (TNM III, IV and MS 4) in the training cohort. DSS differed significantly between both staging systems; the new staging system showed better prognostic performance in both training and validation cohorts. The MS was an independent prognostic factor for DSS, and discriminatory power of the new staging system for DSS was better than that of the conventional TNM staging system alone.

Arsenic exposure during porcine oocyte maturation negatively affects embryonic development by triggering oxidative stress-induced mitochondrial dysfunction and apoptosis.

Arsenic (AS), an environmental contaminant, is a known human carcinogen that can cause cancer of the lung, liver, and skin. Furthermore, AS induces oxidative stress and mitochondrial impairments in mammalian cells. However, limited information is available on the effect of AS exposure on oocyte maturation of porcine, whose anatomy, physiology, and metabolism are similar to those of human. Therefore, we examined the effect of AS exposure on the in vitro maturation (IVM) of porcine oocytes and the possible underlying mechanisms. Cumulus-cell enclosed oocytes were cultured with or without AS for maturation, and then were used for analyses. This study indicated that AS under a concentration of 1 µM significantly increased the abnormal expansion of cumulus cells and the number of oocytes maintained in meiotic arrest. In addition, AS exposure significantly reduced subsequent development of embryos and increased the rate of apoptosis of blastocysts following parthenogenetic activation (PA) and in vitro fertilization (IVF). Moreover, AS exposure induced oxidative stress with increased reactive oxygen species (ROS), and decreased glutathione (GSH), leading to reduced mitochondrial membrane potential, mitochondrial quantity, DNA damage, excessive autophagy activity, and early apoptosis in porcine oocytes. Taken together, the results demonstrated that AS exposure exerts several negative effects, such as meiotic defects and embryo developmental arrest by causing mitochondrial dysfunction and apoptosis via inducing oxidative stress.

Associations between cardiorespiratory fitness and diverticulitis in older adults.

OBJECTIVES: Examine the independent and joint associations of cardiorespiratory fitness (CRF) and body mass index (BMI) with the prevalence of diverticulitis in older adults. METHODS: 476 older adults (61% Female; 71 ± 5 years) with no history of myocardial infarction, stroke, cancer, inflammatory bowel disease, or diabetes were included in this cross-sectional study. Diverticulitis cases were identified by self-reported physician diagnosis from the medical history questionnaire. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of the prevalence of diverticulitis by tertiles of CRF and BMI category. CRF and BMI were further dichotomized into either "unfit" (the lowest one-third of CRF), "fit" (the upper two-thirds of CRF), "overweight/obese" (BMI ≥25.0 kg/m2), or "normal-weight" (BMI <25.0 kg/m2) to investigate the joint association of CRF and BMI with diverticulitis. RESULTS: Thirty-five (7.4%) participants were identified as having diverticulitis. Compared with the lowest CRF tertile, the ORs (95% CIs) of diverticulitis were 0.52 (0.22-1.22) and 0.33 (0.12-0.94) in the middle and upper CRF tertiles, respectively, after adjusting for potential confounders. After further adjustment for BMI, the association was no longer significant with ORs (95% CIs) of 0.55 (0.23-1.33) and 0.37 (0.12-1.10) in middle and upper CRF tertiles, respectively. Compared with the normal-weight group, the ORs (95% CIs) of diverticulitis were 2.86 (1.05-7.79) and 2.98 (0.95-9.35) in the overweight and obese groups, respectively, after adjusting for possible confounders and CRF. Compared with the "unfit and overweight/obese" group in the joint analysis, the OR (95% CI) of diverticulitis was 0.16 (0.04-0.61) in the "fit and normal-weight" group. CONCLUSIONS: Older adults who maintain higher CRF and lower BMI may have significantly lower odds of diverticulitis, with the lowest odds found in the normal-weight and fit older adults.

Production of Prosaikogenin F, Prosaikogenin G, Saikogenin F and Saikogenin G by the Recombinant Enzymatic Hydrolysis of Saikosaponin and their Anti-Cancer Effect.

The saponins of Bupleurum falcatum L., saikosaponins, are the major components responsible for its pharmacological and biological activities. However, the anti-cancer effects of prosaikogenin and saikogenin, which are glycoside hydrolyzed saikosaponins, are still unknown due to its rarity in plants. In this study, we applied two recombinant glycoside hydrolases that exhibit glycoside cleavage activity with saikosaponins. The two enzymes, BglPm and BglLk, were cloned from Paenibacillus mucilaginosus and Lactobacillus koreensis, and exhibited good activity between 30-37 °C and pH 6.5-7.0. Saikosaponin A and D were purified and obtained from the crude B. falcatum L. extract using preparative high performance liquid chromatography technique. Saikosaponin A and D were converted into saikogenin F via prosaikogenin F, and saikogenin G via prosaikogenin G using enzyme transformation with high ß-glycosidase activity. The two saikogenin and two prosaikogenin compounds were purified using a silica column to obtain 78.1, 62.4, 8.3, and 7.5 mg of prosaikogenin F, prosaikogenin G, saikogenin F, and saikogenin G, respectively, each with 98% purity. The anti-cancer effect of the six highly purified saikosaponins was investigated in the human colon cancer cell line HCT 116. The results suggested that saikosaponins and prosaikogenins markedly inhibit the growth of the cancer cell line. Thus, this enzymatic technology could significantly improve the production of saponin metabolites of B. falcatum L.

Hyaluronidase 6 Does Not Affect Cumulus-Oocyte Complex Dispersal and Male Mice Fertility.

Glycosylphosphatidylinositol-anchored sperm hyaluronidases (HYAL) assist sperm penetration through the cumulus-oocyte complex (COC), but their role in mammalian fertilization remains unclear. Previously, we demonstrated that sperm from HYAL 5 and 7 double-knockout (dKO) mice produced significantly less offspring than sperm from wild-type mice due to defective COC dispersal. However, the HYAL6 gene remained active in the sperm from the dKO mice, indicating that they were not entirely infertile. This study explored the role of HYAL6 in fertilization by analyzing HYAL6-mutant mice. In this mouse model, HYAL5 and HYAL7 were present in the HYAL6-knockout sperm, and they could disperse hyaluronic acid. We found that HYAL6 was present on the surface of sperm. However, male mice lacking the HYAL6 gene had normal fertility, testicular integrity, and sperm characteristics. Furthermore, in vitro fertilization assays demonstrated that HYAL6-deficient epididymal sperm functioned normally. Therefore, HYAL6 is dispensable for fertilization.

Expansion of the prime editing modality with Cas9 from Francisella novicida.

Prime editing can induce a desired base substitution, insertion, or deletion in a target gene using reverse transcriptase after nick formation by CRISPR nickase. In this study, we develop a technology that can be used to insert or replace external bases in the target DNA sequence by linking reverse transcriptase to the Francisella novicida Cas9, which is a CRISPR-Cas9 ortholog. Using FnCas9(H969A) nickase, the targeting limitation of existing Streptococcus pyogenes Cas9 nickase [SpCas9(H840A)]-based prime editing is dramatically extended, and accurate prime editing is induced specifically for the target genes in human cell lines.

Microbial production of 2-pyrone-4,6-dicarboxylic acid from lignin derivatives in an engineered Pseudomonas putida and its application for the synthesis of bio-based polyester.

Lignin valorization depends on microbial upcycling of various aromatic compounds in the form of a complex mixture, including p-coumaric acid and ferulic acid. In this study, an engineered Pseudomonas putida strain utilizing lignin-derived monomeric compounds via biological funneling was developed to produce 2-pyrone-4,6-dicarboxylic acid (PDC), which has been considered a promising building block for bioplastics. The biosynthetic pathway for PDC production was established by introducing the heterologous ligABC genes under the promoter Ptac in a strain lacking pcaGH genes to accumulate a precursor of PDC, i.e., protocatechuic acid. Based on the culture optimization, fed-batch fermentation of the final strain resulted in 22.7 g/L PDC with a molar yield of 1.0 mol/mol and productivity of 0.21 g/L/h. Subsequent purification of PDC at high purity was successfully implemented, which was consequently applied for the novel polyester.