Increase In Weight Research Articles

Rifaximin prophylaxis in MASLD‑hepatocellular carcinoma: Lessons from a negative animal model.

The incidence of hepatocellular carcinoma (HCC) has been rising, particularly among individuals diagnosed with metabolic dysfunction-associated steatotic liver disease. In the present study, the prophylactic effects of rifaximin (RIF) on HCC, inflammatory markers and cardiovascular risk (CVR) were investigated in an animal model. Adult Sprague-Dawley rats were randomly allocated into three groups (n=10, each): Control [standard diet/water plus gavage with vehicle (Veh)], HCC [high-fat choline deficient diet (HFCD)/diethylnitrosamine (DEN) in drinking water/Veh gavage] and RIF [HFCD/DEN/RIF (50 mg/kg/day) gavage] groups. After euthanasia at week 16, biochemical/inflammatory markers and the liver histology were assessed. The results demonstrated that the HCC and RIF animals had a significant increase in fresh liver weight, liver weight/body weight ratio, serum total cholesterol (TC), high-density lipoprotein-cholesterol, triglycerides, hepatic lipid accumulation and hepatic concentration of triglycerides and TC, relative to the controls (P<0.001, for all). Additionally, the HCC and RIF animals had higher plasminogen activator inhibitor, intercellular adhesion molecule-1, E-selectin and CVR scores than the controls (P<0.001, for all). The HCC animals had higher interleukin (IL)-1β (P=0.011), IL-10 (P<0.001), toll-like receptor-2 (P=0.012), lipopolysaccharide-binding protein (P=0.018) and metalloproteinase-2 (P=0.003) levels than the RIF animals. Furthermore, liver steatosis, inflammation and fibrosis, along with increased collagen fiber deposition occurred in the HCC and RIF groups. However, HCC occurred only in 2 RIF rats. In conclusion, although most animals did not develop HCC in the present study, RIF positively affected liver inflammation markers involved in steatohepatitis pathogenesis.

Drugs used in psychiatry causing an increase in body weight in children-a review.

Body weight gain is a prevalent adverse effect observed in psychiatric medication therapy. With the notable increase in mental health diagnoses among children and adolescents over the last decade, exacerbated by the COVID-19 pandemic, the use of medications associated with weight gain poses an additional risk for obesity development. This study aimed to identify psychiatric drugs that may induce weight gain in children as a side effect. Twenty-nine publications were included in this systematic review, investigating the effects of nineteen different drugs on children's weight. The majority of these drugs belonged to atypical antipsychotics and anticonvulsants. Nearly all included articles reported that the examined substances resulted in weight gain in children. As childhood obesity has become a significant problem with various metabolic, psychological and social consequences, it is crucial to carefully consider therapy options. In addition to evaluating effectiveness, it is important to also assess the potential for weight gain. Clinicians and nutrition specialists should individually evaluate patients' nutritional needs, evaluate obesity risk, and provide appropriate dietary guidance to minimalize the risk of weight gain.

Weight Gain in HIV Adults Receiving Antiretroviral Treatment: Current Knowledge and Future Perspectives.

Body weight is impacted by several individual host and environmental factors. In a person living with HIV (PLWH), weight is also influenced by the disease stage. Wasting syndrome is derived from disease progression, and it can be reversed by the effective use of highly active antiretroviral therapy (HAART). Body weight alterations have been studied and compared in several clinical ART trials, and they differ according to antiviral regimens. The newer integrase strand transfer inhibitors (INSTIs), such as bictegravir and dolutegravir, especially when co-administered with tenofovir alafenamide fumarate (TAF), seem to lead to greater weight increases compared to regimens that include tenofovir disoproxil fumarate (TDF), which seem to have an attenuating effect on weight gain. Nevertheless, despite the established association between INSTI and TAF and the negative impact on weight, more recent data suggest a more cautious approach when HAART treatment decisions are taken. In this manuscript, we review weight changes among PLWH receiving HAART and the relevant underlying pathogenic mechanisms described in recent literature. We try to provide a more critical appraisal of the available data and to underline the challenges in assessing the role of HAART in weight changes in both ART initiation and setting switching.

Dynamic Hydration and Viscosity Control of Konjac Glucomannan Enhance Long-Term Antiobesity Effects by Reducing Food Intake in High-Fat-Diet-Fed Mice.

The purpose of this study was to investigate the necessity and importance of dynamic hydration rate and ultimate viscosity control of konjac glucomannan (KGM) for long-term antiobesity effects in C57BL/6J mice on high-fat (HF) diets. KGM supplementation effectively attenuated HF-diet-induced increases in body and tissue weights. The hydration rate and viscosity changes of KGM in the digestive tract were found to have marked impacts on antiobesity effects. KGM with medium hydration and viscosity slowed gastric emptying and intestinal transit, leading to prolonged presence in the lower ileum, increased satiety-related hormones (GLP-1 and PYY), and an 18.27% reduction in daily food intake over 10 weeks (p < 0.05). This resulted in the greatest reduction in weight gain among HF-fed mice. In contrast, KGM with faster hydration and higher viscosity provided only short-term satiety due to rapid dilution. Furthermore, KGM improved metabolic health and altered glycolipid metabolism gene transcription while enriching beneficial gut bacteria; however, no significant differences were observed among the KGM groups in these effects. These findings highlight that synchronizing KGM's hydration rate and viscosity with digestive processes is crucial for regulating satiety and achieving long-term weight loss.

Amending clayey and sandy soils with nano - bio phosphorous for regulating tomato growth, biochemical, and physiological characteristics

Phosphorus is a critical nutrient that significantly enhances tomato production, so maintaining an adequate level of phosphorus plays an essential role in enhancing the growth of tomato by being present in the soil. This study assessed the impact of soil texture and phosphorus content on tomato plant properties using a factorial, complete, randomized design with four replications. Treatments included clayey and sandy soils with varying phosphorus sources: non-phosphorus (P0), calcium phosphate (CaP1 and CaP2), and nano-hydroxyapatite (PN1 and PN2), where 1 indicates a concentration of 0.12 g and 2 indicates a concentration of 0.23 g per 5-kilogram pot of fertilizer. Results indicated that treatments significantly influenced yield parameters such as average fruit weight, juice content, antioxidant activity, and fruit volume. In the clayey soil, CaP2 treatment had a superior effect on yield, average fruit weight, and shoot fresh weight. In comparison with sandy conditions, CaP2 produced a 50% increase in fruit number, 29% increase in average fruit weight, and 91% increase in fruit yield. The treatments then impacted the shoot fresh weight and root length, while the phosphorus concentration appeared to be more dependent on soil type than on phosphorus sources. Similar to the CaP1 and CaP2 treatments, the PN1 treatment in clay soil also resulted in the highest fresh and dry weights of tomato shoots when compared with the control group. Generally, the findings from this study suggest that the use of CaP2 can serve as a reliable method to improve the growth, yield, and fruit quality of tomatoes, especially in clayey soil environments. However, nano-based phosphorous sources need to be tested more to see if they can improve tomato performance in a range of soil conditions. Also, further research should look into the long-term effects of phosphorous interventions on soil health and sustainability.

Selection and genetic parameters of productivity of sheep (&lt;i&gt;ovis aries&lt;/i&gt;) of the Trans-Baikal breed of the Khangil type

The study was conducted to investigate the selection and genetic parameters of productivity of fine-wool sheep of the Trans-Baikal breed of the Khangil typein order to increase the efficiency of the selection process. The relationships between the selected traits (live weight, wool yield) and the exterior and constitutional features were determined using the method of correlation and regression analysis. Of the assessed parameters, the greatest variability was observed for body weight (11.9…19.4 %), wool yield (9.9…11.1 %) and latitudinal linear measurements (8.2…12.4 %). According to the constitution indices, rams differed from ewes by greater leg length, better chest development, stronger skeleton, while ewes were characterized by a more stretched, compact and massive body with a better developed back part. Live weight and wool yield of rams were more closely associated with linear measurements than those of ewes. Live weight of both males and females correlated more strongly with chest girth (respectively +0.916, p 0.001 and +0.740, p 0.001), wool yield – with chest depth in rams (+0.737, p 0.001) and hip width in ewes (+0.469, p 0.001). In Trans-Baikal breed of the Khangil type rams, with an increase in the hip width measurement by 1 cm, it is possible to predict an increase in live weight by 5.50 kg (r = 0.839; p 0.001), in ewes with an increase in chest girth by 1 cm – by 1.04 kg (r = 0.740; p 0.001). The analysis of paired regression equations shows that the live weight of Trans-Baikal breed of the Khangil type ewes is largely determined by the linear measurement of the chest girth: in rams – 83.9 %, in ewes – 54.7 %, the influence of other factors accounts for 16.1 and 45.3 %, respectively. At the same time, in the multivariate regression models, 94.3 and 74.7 % of the change in body weight is explained by the effect of a complex of linear measurements, and the remaining share is attributed to the influence of other factors.

Associations of fetal and infant growth patterns with behavior and cognitive outcomes in early adolescence

AbstractBackgroundFetal life and infancy might be critical periods for brain development leading to increased risks of neurocognitive disorders and psychopathology later in life. We examined the associations of fetal and infant weight growth patterns and birth characteristics with behavior and cognitive outcomes at the age of 13 years.MethodsPopulation‐based prospective cohort study from fetal life until adolescence. Pregnant women with a delivery date between April 2002 and January 2006 were eligible. Follow‐up measurements were available for 4716 children. Fetal weight was estimated in the second and third trimesters of pregnancy by ultrasonography. Infant weight was measured at birth and at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in SD greater than 0.67 between time points. Total, internalizing and externalizing problems and attention‐deficit hyperactivity disorder (ADHD) symptoms were measured using Child Behavior Checklist (CBCL/6–18), autistic traits by the Social Responsiveness Scale (SRS) and intelligence quotient (IQ) by the Wechsler Intelligence Scale for Children‐Fifth Edition (WISC‐V).ResultsOne week longer gestational age at birth was associated with a −0.03 SDS (95% Confidence Interval (CI): −0.04, −0.01) lower total behavior problems score, a −0.02 SDS (95% CI: −0.04, −0.01) lower ADHD symptoms score. Also an increase in birth weight of 500 g was associated with a lower odds of having high externalizing problems (OR 0.92 (95% CI: 0.86, 0.98) and of having a low IQ score (OR 0.79 (95% CI: 0.71, 0.88). Compared to children with normal fetal and infant growth, those with accelerated fetal and infant growth had a 0.27 SDS higher IQ (95% Confidence Interval 0.11, 0.44).ConclusionsBoth fetal and infant weight development are associated with behavioral and cognitive outcomes in early adolescence. Follow‐up studies are needed to assess whether these associations link to later life mental health outcomes.

Systemic lupus international collaborating clinics-2012 and European league against rheumatism/American college of rheumatology-2019 classification criteria for systemic lupus erythematosus associated with childhood-onset auto-immune cytopenia.

Systemic Lupus Erythematosus (SLE) can be diagnosed using the 2012 criteria of the Systemic Lupus International Collaborating Clinics (SLICC) and, more recently, the 2019 criteria of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR). Hematological involvement is scored differently by these classifications. Our objective was to compare both criteria in a cohort of children with autoimmune cytopenia (AIC)-associated SLE. We included 79 patients with childhood-onset AIC as the first manifestations of SLE. The median age at SLE diagnosis was 14.5years (1.1-21.4years). The SLICC criteria were fulfilled by 76/79 (96%) patients and the EULAR/ACR criteria by 72/79 (91%) patients during follow-up. The SLICC and EULAR/ACR criteria were discordant (not concomitantly fulfilled) in 25/79 (32%) patients. Non-hematological clinical manifestations were more frequently observed in SLE diagnosis when the criteria were concordant (30/54, 56%) than when they were not (5/25, 20%) (p = 0.004). In 16/25 (64%) discordant patients, the SLICC criteria allowed earlier diagnosis of SLE. Finally, the attribution of a maximum weight of 6 to the hematological involvement of the EULAR/ACR criteria increased the sensitivity thereof from 63/79 (80%) to 76/79 (96%) in our population. The SLICC 2012 and EULAR/ACR 2019 criteria do not effectively diagnose SLE in children when AIC is the predominant feature. The SLICC criteria appear to be more effective in this population of SLE patients. An increase in the maximum weight of hematological involvement to 6 increases the sensitivity of the EULAR/ACR criteria for SLE diagnosis in children.

Therapeutic oligonucleotide ASC1R shows excellent tolerability and remarkable efficacy in reducing SARS-CoV-2 mRNA levels in C57BL/6 mice

The coronavirus pandemic has resulted in over 775 million cases and 7 million deaths worldwide, driving efforts to develop therapeutic strategies to control the viral infection. Therapeutic oligonucleotides have shown promise in treating many pathological conditions, including those of viral origin. The present study assessed the in vivo efficacy and safety of ASC1R, a novel therapeutic oligonucleotide of unconventional design targeting the conserved viral RdRp sequence essential for replication. In functional studies, ASC1R was administered to transfected C57BL/6 mice at doses of 1 and 10 mg/kg. Safety assessments included acute toxicity evaluations at doses ranging from 30 to 100 mg/kg, and subacute toxicity evaluations of repeated doses of 1 and 10 mg/kg. Evaluations included general clinical observations, findings at necropsy, measurements of organ weight, and histopathological examinations of the liver, lungs, spleen, and kidneys. ASC1R effectively reduced RdRp levels >94 % within 24 hours following a single 1 mg/kg dose, with no observed organ toxicity. Acute and subacute toxicity assessments found that mice receiving high (≥30 mg/kg) or repeated (10 mg/kg for 7 days) doses of ASC1R showed an increase in relative spleen weight, without histopathological changes. The marked ability of a single low dose of ASC1R (1 mg/kg) to reduce viral RNA suggests its potential for clinical applications, balancing therapeutic efficacy with minimal side effects. Our findings indicate that ASC1R has promise as a viable treatment option for patients with COVID-19.

Disruption of canonical AHR-mediated induction of hepatocyte PKM2 expression compromises antioxidant defenses and increases TCDD-induced hepatotoxicity

Metabolic reprogramming by the pyruvate kinase M2 isoform is associated with cell proliferation and reactive oxygen species (ROS) defenses. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant that induces ROS and hepatotoxicity, dose-dependently induces pyruvate kinase muscle isoform M2 (PKM2) in the liver. To further investigate its role in combating TCDD hepatotoxicity, a PkmΔDRE mouse was constructed lacking the dioxin response element mediating aryl hydrocarbon receptor (AHR) induction. TCDD failed to induce hepatic PKM2 in PkmΔDRE mice and in primary hepatocytes isolated from an AHR knockout model (AHRV375Afl/flAlb-CreERT2), demonstrating induction is AHR dependent. Both wild-type (WT) and PkmΔDRE mice exhibited dose-dependent increases in liver weight after treatment with TCDD every 4 days for 28 days. Glutathione (GSH) levels increased in WT mice while oxidized glutathione (GSSG) levels increased in both models with a 24-fold decrease in the GSH/GSSG ratio in PkmΔDRE mice suggesting lower antioxidant and recycling capacity. Moreover, TCDD-induced fibrosis was more severe in PkmΔDRE mice while PkmΔDRE hepatocytes exhibited greater cytotoxicity following co-treatment with TCDD and hydrogen peroxide. TCDD also induced PKM2 in human HepaRG™ cells with AHR enrichment at a conserved DRE core within the locus. These results suggest AHR-mediated PKM2 induction is a novel antioxidant response to TCDD.

Duration of efficacy and effect of implant location in adult queens treated with a 9.4 mg deslorelin subcutaneous implant

Deslorelin is a GnRH-agonist used off-label for contraception in female cats. Little is known about duration and safety of the 9.4 mg subcutaneous implant in the queen as well as its efficacy when placed periumbilically. Fourteen female cats were administered the 9.4 mg deslorelin implant (during interestrus or anestrus) either in interscapular (N = 8) or periumbilical (N = 6) sites, following general and reproductive examination, vaginal cytology, hematology, biochemistry and progesterone assay to ensure health status. All above procedures (except for progesterone assay) were repeated weekly during the first month, then every 2 months until 6 months and then every 6 months until treated cats regained full reproductive function. No side effects were observed in any treated queen. Post implantation estrus occurred in 40 % of the subjects. A significant increase in body weight was observed during treatment (12/14 queens gained weight), particularly at the end of the study. At the end of the study some queens mated, conceived and kittened, proving reversibility of the treatment. The average duration of action of the 9.4 mg deslorelin implant was 790 ± 155 days (range 525–1140 days) with no significant difference in duration or efficacy depending on implantation sites. The 9.4 mg deslorelin implant causes pharmacological sterilization for about 2 years in female cats, is fully reversible and caused no clinically relevant side effects when administered at both interscapular and periumbilical sites.

Response of Different Exogenous Phytohormones to Rice Yield Under Low-Temperature Stress at the Filling Stage

This paper aims to clarify the effects of different exogenous phytohormones on the physiological traits of rice (Oryza sativa L.) at the early stage of irrigation under low-temperature stress. In this study, two types of rice varieties with different temperature sensitivities screened out previously, namely, a cold-tolerant variety (Nan Jing 9108) and a low-temperature-sensitive variety (Hui Liang You 898), were used in pots to simulate the process of low-temperature stress in rice at the early stage of grouting (6–9 days after anthesis) with artificial low-temperature treatments. The experimental treatments were 450 mg L−1 Methyl jasmine acid (MJ), 46 mg L−1 Melatonin (MT), 69 mg L−1 Salicylate (SA), 40 mg L−1 Erythromycin (GA3), 25 mg L−1 Zeatin (Z), 145 mg L−1 Spermidine (SPD), and 5 mg L−1 Abscisic acid (ABA) sprayed on rice before low-temperature stress, while low-temperature treatment without spraying (DK) and conventional planting without spraying (CK) were added as the control. The results showed that compared with the room temperature control (CK, sprayed with deionized water), the low-temperature control (DK, low-temperature treatment, and sprayed with deionized water) all significantly reduced the rice grain yield. Different exogenous hormones sprayed before low-temperature stress could increase rice yield, among which, Z and SPD spraying treatments had a better effect on the yield of Hui Liang You 898, while different exogenous hormone treatments increased the yield of Nan Jing 9108 in an average manner. The Z and SPD treatments increased the yield of Hui Liang You 898 by 24.87% and 26.16% and that of Nan Jing 9108 by 15.87% and 17.80%, respectively. This was mainly attributed to the significant increase in thousand-grain weight and fruiting rate, while there was no significant difference in the number of spikes and number of grains. The different exogenous hormone treatments were able to delay leaf senescence, enhance the photosynthetic production capacity of plants by increasing leaf chlorophyll content, and thus increase the accumulation of photosynthetic assimilation products and population growth rate after flowering. Among them, both Z and SPD treatments resulted in a population growth rate of more than 30% from spike flushing to maturity, which led to a higher dry matter accumulation of the plant at maturity. In addition, in the dry matter distribution of the plant at maturity, the seeds occupied a higher accumulation amount and proportion compared with the respective DK; the SPD treatment resulted in the maximum distribution rate of seeds at maturity of Hui Liang You 898, with an increase of 8.27%, and the Z treatment resulted in the maximum distribution rate of seeds at maturity of Nan Jing 9108, with an increase of 7.34%. At the same time, the Z treatment significantly increased the activities of adenosine diphosphate glucose phosphorylated enzyme (AGP) and starch branching enzyme (SBE) in the grains of both varieties, which resulted in the accumulation of more starch and ultimately increased the rice grain yield. The results verified that different exogenous phytohormones could be used to regulate the insufficiency of grouting caused by low-temperature stress during the grouting and fruiting stages of rice and enriched their agronomic and physiological traits in response at the same time.

Does Marriage Still Make a Difference in Infant Health?

AbstractAlthough a vast literature examines the effects of family structure on school-aged children, adolescents and adults, less attention has been paid to infants. We use a longitudinal sample to disentangle the marriage effects from unobserved fixed characteristics of the mother and various observed confounders. Results from standard cross-sectional regressions tend to overstate the marriage premium. The within-mother analysis shows marriage leads to a small increase in birth weight but still fairly large declines in the risks of low birth weight and small for gestational age. Abstaining from smoking and having early prenatal care help explain how marriage improves infant health.

Exploring the role of genetic variability and exposure to bisphenols and parabens on excess body weight in Spanish children

Gene-environment interaction studies are emerging as a promising tool to shed light on the reasons for the rapid increase in excess body weight (overweight and obesity). We aimed to investigate the influence of several polymorphisms on excess weight in Spanish children according to a short- and long-term exposure to bisphenols and parabens, combining individual approach with the joint effect of them. This case-control study included 144 controls and 98 cases children aged 3–12 years. Thirty SNPs in genes involved in obesity-related pathways, xenobiotic metabolism and hormone systems were genotyped using the GSA microchip technology and qPCRs with Taqman® probes. Levels of bisphenols and parabens in urine and hair were used to assess short- and long-term exposure, respectively, via UHPLC-MS/MS system. LEPR rs9436303 was identified as a relevant risk variant for excess weight (ORDom:AAvsAG+GG=2.65, p<0.001), and this effect persisted across exposure-stratified models. For long-term exposure, GPX1 rs1050450 was associated with increased excess weight at low single paraben exposure (ORGvsA=2.00, p=0.028, p-interaction=0.016), whereas LEPR rs1137101 exhibited a protective function at high co-exposure (ORDom:AAvsAG+GG=0.17, p=0.007, p-interaction=0.043). ESR2 rs3020450 (ORDom:GGvsAG+AA=5.17, p=0.020, p-interaction=0.028) and CYP2C19 rs4244285 (ORDom:GGvsAG+AA=3.54, p=0.039, p-interaction=0.285) were identified as predisposing variants at low and high co-exposure, respectively. In short-term exposure, higher odds were observed for INSIG2 rs7566605 at high bisphenol exposure (ORCvsG=2.97, p=0.035, p-interaction=0.017) and for GSTP1 rs1695 at low levels (ORDom:AAvsAG+GG=5.38, p=0.016, p-interaction=0.016). At low and medium co-exposure, SH2B1 rs7498665 (ORAvsG=0.17, p=0.015, p-interaction=0.085) and MC4R rs17782313 (ORAvsG=0.10, p=0.023, p-interaction=0.045) displayed a protective effect, whereas ESR2 rs3020450 maintained its contributing role (ORGvsA=3.12, p=0.030, p-interaction=0.010). Our findings demonstrate for the first time that understanding the genetic variation in excess weight and how the level of exposure to bisphenols and parabens might interact with it, is crucial for a more in-depth comprehension of the complex polygenic and multifactorial aetiology of overweight and obesity.

Exploration of the Photoluminescence Behavior and Emission Mechanism of Thioester Polyacrylamide Tablets During the Gradual Increase of Molecular Weight.

To enhance the photoluminescence (PL) of unconventional luminescent compounds, particularly their persistent room temperature phosphorescence (p-RTP) performance, compressing the powder into tablets has been demonstrated as a viable approach. Nevertheless, the alterations in the emission capability of PL in compacted tablets have not been comprehensively investigated. In this study, four polyacrylamide (PAM) with controllable molecular weight (MW) are fabricated from powder to tablets, and their PL emission properties are thoroughly examined and compared with corresponding powders to elucidate the emission mechanism. As MW increases, both PL and p-RTP emissions of the tablets gradually intensify, exhibiting significant enhancement compared to the corresponding powder while retaining the characteristic blue shift. Through small angle X-ray scattering (SAXS), construction of molecular models for tablets, detailed analysis of molecular interactions, and theoretical calculations are conducted to reasonably explain these emission phenomena using clustering-triggered emission (CTE) and average packing density promoted emission (PDE) mechanisms. These findings not only advance the understanding of nonconventional luminogens' emission mechanisms but also offer new insights for preparing nonconventional luminescent polymers with controllable p-RTP emission performance.

A Multicenter, Open-Label Study to Evaluate the Long-term Safety and Efficacy of Adjunctive Brexpiprazole 2 mg Daily in Japanese Patients with Major Depressive Disorder.

Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD. An open-label, 52-week study enrolled rollover patients who completed the 6-week, double-blind, randomized, placebo-controlled phase 2/3 BLESS study (NCT03697603), and de novo patients aged ≥ 65 years. Patients were titrated to fixed-dose brexpiprazole 2 mg/day from Week 1. Safety assessments included treatment-emergent adverse events (TEAEs; primary outcome) and clinical and laboratory variables. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale(MADRS), Clinical Global Impression-Improvement (CGI-I) scale, Hamilton Depression Rating Scale (HAM-D) 17-item total score, and Sheehan Disability Scale (SDS) score. In total, 247 patients [rollover, n = 216; de novo (previously unexposed), n = 31] were included in the safety/efficacy populations, and 138 (rollover, n = 132; de novo, n = 6; 55.9%) completed the study. Common TEAEs (incidence ≥ 10%) were weight gain [33.2% (n = 82)], akathisia [23.5% (n = 58)], nasopharyngitis [21.1% (n = 52)], and somnolence [10.5% (n = 26)]. TEAEs leading to treatment discontinuation occurred in 26.7% of patients receiving brexpiprazole and 58.1% of de novo patients. The mean (SD) increase in body weight from baseline to Week 52 [observed cases (OC)] was 4.2 (6.5) kg (n = 138); 44.5% (n = 110) had weight gain ≥ 7% at any postbaseline visit. There were no cases of tardive dyskinesia and no AEs related to suicide/suicide attempts. One death occurred (unknown cause), which was unrelated to study treatment. Improvements in the MADRS total score were observed from baseline over the course of the 52-week study [mean (SD) change at Week 52 (OC): - 7.3 (8.7)] for all patients receiving brexpiprazole. The overall MADRS response rate and remission rate in patients receiving brexpiprazole was 41.3% (n = 57) and 34.8% (n = 48), respectively, at Week 52 (OC). Improvements in CGI-S, HAM-D 17 item total score, and SDS mean scores were also observed from baseline over the 52-week study, with a mean (SD) change from baseline at Week 52 (OC) of - 0.8 (1.0), - 5.9 (6.3), and - 1.0 (2.2), respectively, indicating a sustained improvement in symptoms with long-term brexpiprazole treatment. This is the first study to evaluate the safety profile of brexpiprazole 2 mg/day in Japanese patients with MDD, including older adults, which is similar to previous reports, with no new safety risks, and continued efficacy over 52 weeks. ClinicalTrials.gov (NCT03737474; registered on 29 July 2018).

Discovery of genes that positively affect biomass and stress associated traits in poplar.

Woody biomass serves as a renewable resource for various industries, including pulp and paper production, construction, biofuels, and electricity generation. However, the molecular mechanisms behind biomass traits are poorly understood, which significantly curtails the speed and efficiency of their improvement. We used activation tagging to discover genes that can positively affect tree biomass-associated traits. We generated and screened under greenhouse conditions a population of 2,700 independent activation tagging lines. A total of 761 lines, which had significantly and positively affected at least one biomass-associated trait, were discovered. The tag was positioned in the genome for forty lines which were affected in multiple traits and activation of proximal genes validated for a subset. For two lines we fully recapitulated the phenotype of the original lines through overexpression. Moreover, the overexpression led to more pronounced and additional improvements, not observed in the original lines. Importantly, the overexpression of a Fasciclin-like gene (PtaFLA10) and a Patatin-like gene (PtaPAT) was found to substantially improve biomass, with a 40% increase in dry-stem weight, and enhance drought tolerance, respectively. Additionally, PtaPAT overexpression increased cellulose content, which is crucial for biofuel production. Our work shows that the activation tagging approach applied even on a non-genome saturation scale in a poplar tree can be successfully used for the discovery of genes positively modify biomass productivity. Such dominant forward genetics approaches can aid in biotechnological manipulation of woody biomass traits and help unravel the functions and mechanisms of individual genes, gene families, and regulatory modules.

Anaerobic Degradation of Aromatic and Aliphatic Biodegradable Plastics: Potential Mechanisms and Pathways.

Biodegradable plastics (BDPs) have been widely used as substitutes for traditional plastics, and their environmental fate is a subject of intense research interest. Compared with the aerobic degradation of BDPs, their biodegradability under anaerobic conditions in environmental engineering systems remains poorly understood. This study aimed to investigate the degradability of BDPs composed of poly(butylene adipate-co-terephthalate) (PBAT), poly(lactide acid) (PLA), and their blends, and explore the mechanism underlying their microbial degradation under conditions of anaerobic digestion (AD). The BDPs readily depolymerized under thermophilic conditions but were hydrolyzed at a slow rate under conditions of mesophilic AD. After 45 days of thermophilic AD, a decrease in the molecular weight and significant increase in the production of methane and carbon dioxide production were observed. Network and metagenomics analyses identified AD as reservoirs of plastic-degrading bacteria that produce multiple plastic-degrading enzymes. PETase was identified as the most abundant plastic-degrading enzyme. A potential pathway for the anaerobic biodegradation of BDPs was proposed herein. The polymers of high molecular weight were subjected to abiotic hydrolysis to form oligomers and monomers, enabling subsequent microbial hydrolysis and acetogenesis. Ultimately, complete degradation was achieved predominantly via the pathway involved in the conversion of acetic acid to methane. These findings provide novel insight into the mechanism underlying the anaerobic degradation of BDPs and the microbial resources crucial for the efficient degradation of BDPs.

MOR23 deficiency exacerbates hepatic steatosis in mice.

Hepatic steatosis, a common liver disorder, can progress to severe conditions such as nonalcoholic steatohepatitis and cirrhosis. While olfactory receptors are primarily known for detecting odorants, emerging evidence suggests that they also influence liver lipid metabolism. This study generated a mouse model with a specific knockout of olfactory receptor 23 (MOR23) to investigate its role in hepatic steatosis. MOR23 knockout mice on a normal diet showed a slight increase in liver weight compared to wild-type (WT) mice. When fed a high-fat diet (HFD), these knockout mice exhibited accelerated hepatic steatosis, indicated by increased liver weight and hepatic triglyceride levels. Our findings suggest that the cyclic adenosine monophosphate/protein kinase A/AMP-activated protein kinase pathway is involved in the role of MOR23, leading to the upregulation of peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor-γ coactivator 1-α, and their target β-oxidation genes in the liver. MOR23 also appeared to regulate lipogenesis and free fatty acid uptake in HFD-fed mice, potentially by influencing sterol regulatory element-binding protein 1 activity. Notably, administering a potential MOR23 ligand, cedrene, attenuated hepatic steatosis in WT mice, but these effects were largely nullified in MOR23 knockout mice. These findings provide valuable insights into the invivo role of MOR23 in hepatic steatosis development.

Polymer Brushes Synthesized by the "Grafting-through" Approach: Characterization and Scaling Analysis.

In this study, a combined morphological and scaling analysis of brushes synthesized by the "grafting-through" method was performed, and the possibility of regulation of the thickness was revealed on an example of polyacrylamide brushes. The chemical composition of the surface in the proposed three-step approach was analyzed by photoelectron and infrared spectroscopy. It was shown that the thickness of the dried brush can be tuned in a controlled manner by varying the polymerization temperature. The scaling dependence of the thickness of the dried brushes d on the length of the polymer d ∼ Lv was obtained by comparing reflectometry and dynamic light scattering data. The value of the exponent v = 0.82 corresponds to a rather high grafting density, exceeding the density of mushroom-like (ν ∼ 1/3) brushes and approaching the value for stretched polymer brushes (ν ∼ 1). A 10-fold increase in the polymer molecular weight leads to a slight decrease in grafting density by a factor of 2, which suggests that the "grafting-through" approach allows obtaining brushes with a high grafting density independently of attached polymer chain length. Herein, the possibility of attachment of uniform polymer brush on large substrates with this approach was demonstrated, which means the scalability of the "grafting-through" technique. The considered approach opens up a simple way for surface modification with polymer nanolayers of controlled thickness.