Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway.

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.

Energy drink consumption among medical students in Jordan - prevalence, attitudes, and associated factors: a cross-sectional study.

Background: Energy drinks (ED) are popular beverages that contain high levels of caffeine, sugar, and other supplements, such as vitamins, which are marketed to enhance mental alertness and physical performance. Studies have shown that energy drink consumption is prevalent among medical students. Therefore, this study aimed to assess the prevalence, attitudes, and factors associated with energy drink consumption among medical students in Jordan. Materials and methods: A cross-sectional study was conducted among medical students from six public universities in Jordan. A total of 307 students were included in the study, and data were collected using an expert-validated questionnaire. The collected data were analyzed using SPSS version 25. Results: The study found that 50% of the sample had consumed ED, half of them started consuming them at the age of 16-18, and learned about them from friends. The primary reasons for consuming ED were to stay awake at night and the majority of them increase their consumption during exams to increase alertness. Regular energy drink consumption was significantly associated with being a student at the university located in the south governorate of Jordan (P=0.021), living alone (P=0.000), drinking alcohol (P=0.049), drinking coffee daily (P=0.043), and consuming more than 10 cans of soft drinks weekly (P=0.001). However, sex, age, academic achievement, and smoking status had no significant association with regular energy drink consumption. Students with regular energy drink consumption experienced daytime sleepiness, decreased concentration, fatigue, and reduced performance more than students with no regular energy drink consumption. Conclusion: The prevalence of energy drink consumption among medical students in Jordan is high, with factors such as social influences, lifestyle behaviors, and academic pressure being significant contributors. This study highlights the need for interventions to promote healthy behaviors and raise awareness about the potential harms of ED among medical students.

The Protective Role of Vitamin E against Oxidative Stress and Immunosuppression Induced by Non-Esterified Fatty Acids in Bovine Peripheral Blood Leukocytes.

High levels of non-esterified fatty acids (NEFAs) during the transition period lead to increased oxidative stress and immunosuppression in cows. Feeding them a vitamin-E-supplemented diet reduces reactive oxygen species (ROS) levels in the blood and diminishes immunosuppression in the transition period. However, whether the restoration of immune cell function occurs through the direct action of vitamin E in cells is still a topic that requires further discussion. Therefore, in this experiment, we aimed to investigate the effect of NEFAs on peripheral blood leukocytes (PBLs) and whether vitamin E mitigates the impact of NEFAs. We employed three groups: (1) blank, (2) NEFA only, and (3) pre-culturing with vitamin E before NEFA treatment (VENEFA). In peripheral blood mononuclear cells (PBMCs), there were no differences in vitamin E content among the three groups. However, in the vitamin E pre-treatment group, the vitamin E levels of polymorphonuclear neutrophils (PMNs) were significantly higher than those in the other two groups. NEFA levels increased malondialdehyde (MDA) levels in PBMCs, but pre-treatment with vitamin E reduced accumulation of MDA levels. Regarding the expression of proinflammatory genes, NEFAs increased the expression of interleukin-1ß in PBMCs and colony-stimulating factor 2 in PMNs. Vitamin E pre-treatment restored the increase in interleukin-1ß levels caused by NEFAs in PBMCs. None of the groups affected the phagocytosis of PMNs. Few studies have confirmed that NEFAs cause oxidative stress in bovine PBLs. In summary, this study found that NEFAs induce oxidative stress in PBLs and alter the expression of inflammation-related genes; meanwhile, vitamin E can reduce some of the effects caused by NEFAs. This result may suggest that vitamin E can assist bovine PBLs in resisting the immune suppression caused by an NEB during the transition period.

Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP.

BACKGROUND: Chronic inflammation and metabolic dysfunction are key features of systemic aging, closely associated with the development and progression of age-related metabolic diseases. Bazi Bushen (BZBS), a traditional Chinese medicine used to alleviate frailty, delays biological aging by modulating DNA methylation levels. However, the precise mechanism of its anti-aging effect remains unclear. In this study, we developed the Energy Expenditure Aging Index (EEAI) to estimate biological age. By integrating the EEAI with transcriptome analysis, we aimed to explore the impact of BZBS on age-related metabolic dysregulation and inflammation in naturally aging mice. METHODS: We conducted indirect calorimetry analysis on five groups of mice with different ages and utilized the data to construct EEAI. 12 -month-old C57BL/6 J mice were treated with BZBS or ß-Nicotinamide Mononucleotide (NMN) for 8 months. Micro-CT, Oil Red O staining, indirect calorimetry, RNA sequencing, bioinformatics analysis, and qRT-PCR were performed to investigate the regulatory effects of BZBS on energy metabolism, glycolipid metabolism, and inflammaging. RESULTS: The results revealed that BZBS treatment effectively reversed the age-related decline in energy expenditure and enhanced overall metabolism, as indicated by the aging index of energy expenditure derived from energy metabolism parameters across various ages. Subsequent investigations showed that BZBS reduced age-induced visceral fat accumulation and hepatic lipid droplet aggregation. Transcriptomic analysis of perirenal fat and liver indicated that BZBS effectively enhanced lipid metabolism pathways, such as the PPAR signaling pathway, fatty acid oxidation, and cholesterol metabolism, and improved glycolysis and mitochondrial respiration. Additionally, there was a significant improvement in inhibiting the inflammation-related arachidonic acid-linoleic acid metabolism pathway and restraining the IL-17 and TNF inflammatory pathways activated via senescence associated secretory phenotype (SASP). CONCLUSIONS: BZBS has the potential to alleviate inflammation in metabolic organs of naturally aged mice and maintain metabolic homeostasis. This study presents novel clinical therapeutic approaches for the prevention and treatment of age-related metabolic diseases.

Improvement of performance for flexible film dosimeter by incorporating additive agents.

Objective.To evaluate the reduction in energy dependence and aging effect of the lithium salt of pentacosa-10,-12-diynoic acid (LiPCDA) films with additives including aluminum oxide (Al2O3), propyl gallate (PG), and disodium ethylenediaminetetracetate (EDTA).Approach. LiPCDA films exhibited energy dependence on kilovoltage (kV) and megavoltage (MV) photon energies and experienced deterioration over time. Evaluations were conducted with added Al2O3and antioxidants to mitigate these issues, and films were produced with and without Al2O3to assess energy dependence. The films were irradiated at doses of 0, 3, 6, and 12 cGy at photon energies of 75 kV, 105 kV, 6 MV, 10 MV, and 15 MV. For the energy range of 75 kV to 15 MV, the mean and standard deviation (std) were calculated and compared for the values normalized to the net optical density (netOD) at 6 MV, corresponding to identical dose levels. To evaluate the aging effect, PG and disodium EDTA were incorporated into the films: sample C with 1% PG, sample D with 2% PG, sample E with 0.62% disodium EDTA added to sample D, and sample F with 1.23% disodium EDTA added to sample D.Main results. Films containing Al2O3demonstrated a maximum 15.8% increase in mean normalized values and a 15.1% reduction in std, reflecting a greater netOD reduction at kV than MV energies, which indicates less energy dependence in these films. When the OD of sample 1-4 depending on the addition of PG and disodium EDTA, was observed for 20 weeks, the transmission mode decreased by 8.7%, 8.3%, 29.3%, and 27.3%, respectively, while the reflection mode was 5.4%, 3.0%, 37.0%, and 34.5%, respectively.Significance. Al2O3effectively reduced the voltage and MV energy dependence. PG was more effective than disodium EDTA in preventing the deterioration of film performance owing to the aging effect.

Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS: A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS: Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.

Dynamics of bone mineralization in primiparous sows as a function of dietary phosphorus and calcium during lactation.

To maximize the efficiency of dietary P utilization in swine production, understanding the mechanisms of P utilization in lactating sows is relevant due to their high P requirement and the resulting high inorganic P intake. Gaining a better knowledge of the Ca and P quantities that can be mobilized from bones during lactation, and subsequently replenished during the following gestation, would enable the development of more accurate P requirements incorporating this process of bone dynamics. The objective was to measure the amount of body mineral reserves mobilized during lactation, depending on dietary digestible P and phytase addition and to measure the amount recovered during the following gestation. Body composition of 24 primiparous sows was measured by dual-energy x-ray absorptiometry 2, 14, 26, 70 and 110 days after farrowing. Four lactation diets were formulated to cover nutritional requirements, with the exception of Ca and digestible P: 100% (Lact100; 9.9 g Ca and 3.0 g digestible P/kg), 75% (Lact75), 50% without added phytase (Lact50) and 50% with added phytase (Lact50 + FTU). The gestation diet was formulated to cover the nutritional requirements of Ca and digestible P (8.2 g Ca and 2.6 g digestible P/kg). During the 26 days of lactation, each sow mobilized body mineral reserves. The mean amount of mobilized bone mineral content (BMC) was 664 g, representing 240 g Ca and 113 g P. At weaning, the BMC (g/kg of BW) of Lact50 sows tended to be lower than Lact100 sows (-12.8%, linear Ca and P effect × quadratic time effect) while the BMC of Lact50 + FTU sows remained similar to that of Lact100 sows. During the following gestation, BMC returned to similar values among treatments. Therefore, the sows fed Lact50 could recover from the higher bone mineral mobilization that occurred during lactation. The P excretion was reduced by 40 and 43% in sows fed Lact50 and Lact50 + FTU, respectively, relative to sows fed Lact100. In conclusion, the quantified changes in body composition during the lactation and following gestation of primiparous sows show that bone mineral reserves were mobilized and recovered and that its degree was dependent on the dietary P content and from phytase supplementation during lactation. In the future, considering this potential of the sows' bone mineralization dynamics within the factorial assessment of P requirement and considering the digestible P equivalency of microbial phytase could greatly limit the dietary use of inorganic phosphates and, thus, reduce P excretion.

Longitudinal change of energy expenditure, body composition and dietary habits in Progressive Supranuclear Palsy patients.

INTRODUCTION: Alterations in metabolic status, body composition, and food intake are present in all neurodegenerative diseases. Aim of this study was to detect the progression of these changes in Progressive Supranuclear Palsy (PSP). METHODS: We conducted a longitudinal study of 15 patients with PSP. The assessments were performed at baseline (T0) and after 7(IQR = 5) months of follow-up (T1). We collected anthropometric measures including body weight, height, body mass index and waist circumference, metabolic parameters through indirect calorimeters, body composition using bioimpedance analysis, and dietary habits with a validated questionnaire. PSP-rating scale (PSP-rs) was used to evaluate disease severity and dysphagia. RESULTS: The majority of patients (66.66%) presented PSP-Richardson Syndrome and 33.33% the other variant syndromes of the disease. At T1 there was a decrease in intake of total daily calories (p < 0.001), proteins (p < 0.001), fibers (p = 0.001), calcium (p = 0.008), iron (p < 0.001), zinc (0.034), vitamin E (p = 0.006) and folates (p = 0.038) compared to T0. No other changes were found. As for T1 data, no significant differences were shown according to disease phenotypes or the presence of clinically significant dysphagia for solids. CONCLUSIONS: Within a mid-term follow up, PSP patients presented reduced caloric and proteins intake regardless the presence of dysphagia. The PSP-rs is likely not adequate to assess dysphagia, which should be investigated by specific clinical scales or instrumental examinations. With the goal of maintaining adequate nutritional status, the administration of protein and vitamin supplements should be considered even in the absence of dysphagia evidenced by the rating scales.

The use of biofield energy therapy as complementary and alternative medicine in human health care system: a narrative review and potential mechanisms.

INTRODUCTION: There has been accumulating interest in the application of biofield therapy as complementary and alternative medicine (CAM) to treat various diseases. The practices include reiki, qigong, blessing, prayer, distant healing, known as biofield therapies. This paper aims to state scientific knowledge on preclinical and clinical studies to validate its potential use as an alternative medicine in the clinic. It also provides a more in-depth context for understanding the potential role of quantum entanglement in the effect of biofield energy therapy. CONTENT: A comprehensive literature search was performed using the different databases (PubMed, Scopus, Medline, etc.). The published English articles relevant to the scope of this review were considered. The review gathered 45 papers that were considered suitable for the purpose. Based on the results of these papers, it was concluded that biofield energy therapy was effective in treating different disease symptoms in preclinical and clinical studies. SUMMARY: Biofield therapies offer therapeutic benefits for different human health disorders, and can be used as alternative medicine in clinics for the medically pluralistic world due to the growing interest in CAM worldwide. OUTLOOK: The effects of the biofield energy therapies are observed due to the healer's quantum thinking, and transmission of the quantum energy to the subject leads to the healing that occurs spiritually through instantaneous communication at the quantum level via quantum entanglement.

Salvia miltiorrhiza ameliorates endometritis in dairy cows by relieving inflammation, energy deficiency and blood stasis.

Introduction: According to traditional Chinese veterinary medicine, endometritis is caused by a combination of Qi deficiency, blood stasis, and external evil invasion. Salvia miltiorrhiza is a traditional Chinese medicine that counteracts blood stasis and has additional demonstrated effects in boosting energy and restraining inflammation. Salvia miltiorrhiza has been employed in many traditional Chinese prescriptions that have proven effective in healing clinical dairy cow endometritis. Methods: the in vivo effect of Salvia miltiorrhiza in treating endometritis was evaluated in dairy cows. In addition, bovine endometrial epithelium cell inflammation and rat blood stasis models were employed to demonstrate the crosstalk between energy, blood circulation and inflammation. Network analysis, western blotting, qRT-PCR and ELISA were performed to investigate the molecular mechanism of Salvia miltiorrhiza in endometritis treatment. Results: The results demonstrate that treatment with Salvia miltiorrhiza relieves uterine inflammation, increases blood ATP concentrations, and prolongs blood clotting times. Four of the six Salvia miltiorrhiza main components (SMMCs) (tanshinone IIA, cryptotanshinone, salvianolic acid A and salvianolic acid B) were effective in reversing decreased ATP and increased IL-1ß, IL-6, and IL-8 levels in an in vitro endometritis model, indicating their abilities to ameliorate the negative energy balance and external evil invasion effects of endometritis. Furthermore, in a blood stasis rat model, inflammatory responses were induced in the absence of external infection; and all six SMMCs inhibited thrombin-induced platelet aggregation. Network analysis of SMMC targets predicted that Salvia miltiorrhiza may mediate anti-inflammation via the Toll-like receptor signaling pathway; anti-aggregation via the Platelet activation pathway; and energy balance via the Thermogenesis and AMPK signaling pathways. Multiple molecular targets within these pathways were verified to be inhibited by SMMCs, including P38/ERK-AP1, a key molecular signal that may mediate the crosstalk between inflammation, energy deficiency and blood stasis. Conclusion: These results provide mechanistic understanding of the therapeutic effect of Salvia miltiorrhiza for endometritis achieved through Qi deficiency, blood stasis, and external evil invasion.

Cost-effectiveness analysis of minimally invasive surgical treatments for benign prostatic hyperplasia: implications for Japan's public healthcare system.

AIMS: Benign prostatic hyperplasia (BPH) represents a significant public health issue in Japan. This study evaluated the lifetime cost-effectiveness of water vapor energy therapy (WAVE) versus prostatic urethral lift (PUL) for men with moderate-to-severe BPH from a public healthcare payer's perspective in Japan. MATERIALS AND METHODS: A decision analytic model compared WAVE to PUL among males in Japan. Clinical effectiveness and adverse event (AE) inputs were obtained from a systematic literature review. Resource utilization and cost inputs were derived from the Medical Data Vision database and medical service fee national data in Japan. Experts reviewed and validated model input parameters. One-way and probabilistic sensitivity analyses were conducted to determine how changes in the values of uncertain parameters affect the model results. RESULTS: Throughout patients' lifetimes, WAVE was associated with higher quality-adjusted life years (0.920 vs. 0.911 year 1; 15.564 vs. 15.388 lifetime) and lower total costs (¥734,134 vs. ¥888,110 year 1; ¥961,595 vs. ¥1,429,458 lifetime) compared to PUL, indicating that WAVE is a more effective and less costly (i.e. dominant) treatment strategy across all time horizons. Lifetime cost-savings for the Japanese healthcare system per patient treated with WAVE instead of PUL were ¥467,863. The 32.7% cost difference between WAVE and PUL was predominantly driven by lower WAVE surgical retreatment rates (4.9% vs. 19.2% for WAVE vs PUL, respectively, at 5 years) and AE rates (hematuria 11.8% vs. 25.7%, dysuria 16.9% vs. 34.3%, pelvic pain 2.9% vs. 17.9%, and urinary incontinence 0.4% vs. 1.3% for WAVE vs PUL, respectively, at 3 months). Model findings were robust to changes in parameter input values. LIMITATIONS: The model represents a simplification of complex factors involved in resource allocation decision-making. CONCLUSIONS: Driven by lower retreatment and AE rates, WAVE was a cost-effective and cost-saving treatment for moderate-to-severe BPH in Japan compared to PUL, providing better outcomes at lower costs to the healthcare system.

Benign prostatic hyperplasia (BPH) is an important public health issue in Japan, given its high prevalence and potential morbidity in a rapidly aging population. This study compared the clinical and economic outcomes of two minimally invasive surgical treatments for BPH (water vapor energy therapy [WAVE] vs. prostatic urethral lift [PUL]) for patients in Japan. Clinical effectiveness and adverse event (AE) information from published medical literature, and real-world health services and cost data from Japan, were used to estimate the impact of the two treatments. Compared to PUL, WAVE was found to provide better clinical outcomes and quality-of-life for patients whilst costing less to the Japanese healthcare system. Patients treated with WAVE had higher lifetime quality-adjusted life years vs. patients treated with PUL (15.564 vs. 15.388). Lifetime cost-savings for the Japanese healthcare system per patient treated with WAVE instead of PUL were estimated to be ¥467,863. The 32.7% cost difference between WAVE and PUL was predominantly driven by lower retreatment rates for WAVE (surgical retreatment rate was 4.9% vs. 19.2% for WAVE vs. PUL, respectively, at 5 years) and AE rates (AE rates at 3 months for WAVE vs. PUL, respectively, were: hematuria 11.8% vs. 25.7%, dysuria 16.9% vs. 34.3%, pelvic pain 2.9% vs. 17.9%, and urinary incontinence 0.4% vs. 1.3%). These findings provide evidence-based insights for clinicians, payers, and health policymakers to further define the role of WAVE for BPH in Japan.

Thermodynamic Analysis to Evaluate the Effect of Diet on Brain Glucose Metabolism: The Case of Fish Oil.

Inefficient glucose metabolism and decreased ATP production in the brain are linked to ageing, cognitive decline, and neurodegenerative diseases (NDDs). This study employed thermodynamic analysis to assess the effect of fish oil supplementation on glucose metabolism in ageing brains. Data from previous studies on glucose metabolism in the aged human brain and grey mouse lemur brains were examined. The results demonstrated that Omega-3 fish oil supplementation in grey mouse lemurs increased entropy generation and decreased Gibbs free energy across all brain regions. Specifically, there was a 47.4% increase in entropy generation and a 47.4 decrease in Gibbs free energy in the whole brain, indicating improved metabolic efficiency. In the human model, looking at the specific brain regions, supplementation with Omega-3 polyunsaturated fatty acids (n-3 PUFAs) reduced the entropy generation difference between elderly and young individuals in the cerebellum and particular parts of the brain cortex, namely the anterior cingulate and occipital lobe, with 100%, 14.29%, and 20% reductions, respectively. The Gibbs free energy difference was reduced only in the anterior cingulate by 60.64%. This research underscores that the application of thermodynamics is a comparable and powerful tool in comprehending the dynamics and metabolic intricacies within the brain.

Unexpected early loosening of rectangular straight femoral Zweymüller stems with an alumina-reduced surface after total hip arthroplasty-a prospective, double-blind, randomized controlled trial.

BACKGROUND: Alumina particles from the grit blasting of Ti-alloy stems are suspected to contribute to aseptic loosening. An alumina-reduced stem surface was hypothesized to improve osseointegration and show comparable short-term outcomes to those of a standard stem. METHODS: In this prospective, double-blind, randomized trial, 26 standard (STD) and 27 experimental new technology (NT) stems were implanted. The latter were additionally treated by acid etching and ice blasting to remove alumina particles from the grit-blasting process. Follow-up occurred at 12 and 24 months. Bone mineral density (BMD) around the stem was measured by a dual-energy x-ray absorptiometry device (DEXA). Radiographs were reviewed for alterations. Clinical scoring comprised the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Harris Hip Score (HHS). Survival rates were calculated up to 50 months. RESULTS: Lower mean BMD and more severe cortical hypertrophies were found in the NT group. At 12 months, radiolucent lines were observed mostly in the metaphyseal zone for both groups, with a progression tendency in the NT group at 24 months. At 12 months, pain scores and the WOMAC total and physical activity scores were significantly lower in the NT group, without any differences thereafter. The number of NT stem revisions amounted to 6 (24%) and 11 (41%) at 24 and 50 months, respectively. CONCLUSION: In the NT group, unexpected catastrophic failure rates of 41% caused by early aseptic loosening were noted within 50 months. Compared with the STD stems, NT stems lead to poor clinical and radiographic results. LEVEL OF EVIDENCE: II. TRIAL REGISTRATION: NCT05053048.

Hypothalamic POMC neuron-specific knockout of MC4R affects insulin sensitivity by regulating Kir2.1.

BACKGROUND: Imbalance in energy regulation is a major cause of insulin resistance and diabetes. Melanocortin-4 receptor (MC4R) signaling at specific sites in the central nervous system has synergistic but non-overlapping functions. However, the mechanism by which MC4R in the arcuate nucleus (ARC) region regulates energy balance and insulin resistance remains unclear. METHODS: The MC4Rflox/flox mice with proopiomelanocortin (POMC) -Cre mice were crossed to generate the POMC-MC4Rflox/+ mice. Then POMC-MC4Rflox/+ mice were further mated with MC4Rflox/flox mice to generate the POMC-MC4Rflox/flox mice in which MC4R is selectively deleted in POMC neurons. Bilateral injections of 200 nl of AAV-sh-Kir2.1 (AAV-sh-NC was used as control) were made into the ARC of the hypothalamus. Oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure were measured by using the CLAMS; Total, visceral and subcutaneous fat was analyzed using micro-CT. Co-immunoprecipitation assays (Co-IP) were used to analyze the interaction between MC4R and Kir2.1 in GT1-7 cells. RESULTS: POMC neuron-specific ablation of MC4R in the ARC region promoted food intake, impaired energy expenditure, leading to increased weight gain and impaired systemic glucose homeostasis. Additionally, MC4R ablation reduced the activation of POMC neuron, and is not tissue-specific for peripheral regulation, suggesting the importance of its central regulation. Mechanistically, sequencing analysis and Co-IP assay demonstrated a direct interaction of MC4R with Kir2.1. Knockdown of Kir2.1 in POMC neuron-specific ablation of MC4R restored the effect of MC4R ablation on energy expenditure and systemic glucose homeostasis, indicating by reduced body weight and ameliorated insulin resistance. CONCLUSION: Hypothalamic POMC neuron-specific knockout of MC4R affects energy balance and insulin sensitivity by regulating Kir2.1. Kir2.1 represents a new target and pathway that could be targeted in obesity.

Tuning Germanane Band Gaps via Cyanoethyl Functionalization for Cutting-Edge Photoactive Cathodes: Photoenhanced Hybrid Zinc-Ion Capacitor Evaluation.

Energy harvesting and storing by dual-functional photoenhanced (photo-E) energy storage devices are being developed to battle the current energy hassles. In this research work, our investigations on the photoinduced efficiency of germanane (Ge-H) and its functionalized analogue cyanoethyl (Ge-C2-CN) are assessed as photocathodes in photo-E hybrid zinc-ion capacitors (ZICs). The evaluated self-powered photodetector devices made by these germanene-based samples revealed effective performances in photogenerated electrons and holes. The photo-E ZICs findings provided a photoinduced capacitance enhancement of ∼52% (for Ge-H) and ∼26% (for Ge-C2-CN) at a scan rate of 10 mV s-1 under 100 mW cm-2 illumination with 435 nm wavelength. Further characterizations demonstrated that the photo-E ZIC with Ge-C2-CN supply higher specific capacitance (∼6000 mF g-1), energy density (∼550 mWh kg-1), and power density (∼31,000 mW kg-1), compared to the Ge-H. In addition, capacitance retention of photo-E ZIC with Ge-C2-CN is ∼91% after 3000 cycles which is almost 6% greater than Ge-H. Interestingly, the photocharging voltage response in photo-E ZIC made by Ge-C2-CN is 1000 mV, while the photocharging voltage response with Ge-H is approximately 970 mV. The observed performances in Ge-H-based photoactive cathodes highlight the pivotal role of such two-dimensional materials to be applied as single architecture in new unconventional energy storage systems. They are particularly noteworthy when compared to the other advanced photo-E supercapacitors and could even be enhanced greatly with other suitable inorganic and organic functional precursors.

Exogenous chlorogenic acid inhibits quality deterioration in fresh-cut potato slices.

Fresh-cut potatoes are prone to surface browning and physiological degradation. Chlorogenic acid (CGA), a natural phenolic antioxidant, has demonstrated preservative properties in various postharvest products. However, the underlying mechanisms of its application on maintaining quality remain unclear. Therefore, the effect of exogenous CGA treatment on quality deterioration of potato slices and the mechanisms involved were investigated. Results revealed CGA treatment retarded the browning coloration, suppressed microbial growth and inhibited the declines in starch, and ascorbic acid contents in potato slices. Meanwhile, the treatment activated the phenylpropanoid pathway but decreased the activities of phenolic decomposition-related enzymes such as polyphenol oxidase (PPO) and tyrosinase and downregulated StPPO expression. Moreover, the treated slices exhibited reduced accumulation of reactive oxygen species and increased activity of antioxidant enzymes. Additionally, they displayed enhanced 2,2-diphenyl-1-picrylhydrazyl radicals scavenging capacity and higher ATP levels. Therefore, these findings indicated that CGA treatment was effective for quality maintenance and antioxidant capacity enhancement in fresh-cut potatoes, thereby providing potential strategies for the preservation and processing of fresh-cut produce.

Acquired hypothalamic obesity: A clinical overview and update.

Hypothalamic obesity (HO) is a rare and complex disorder that confers substantial morbidity and excess mortality. HO is a unique subtype of obesity characterized by impairment in the key brain pathways that regulate energy intake and expenditure, autonomic nervous system function, and peripheral hormonal signalling. HO often occurs in the context of hypothalamic syndrome, a constellation of symptoms that follow from disruption of hypothalamic functions, for example, temperature regulation, sleep-wake circadian control, and energy balance. Genetic forms of HO, including the monogenic obesity syndromes, often impact central leptin-melanocortin pathways. Acquired forms of HO occur as a result of tumours impacting the hypothalamus, such as craniopharyngioma, surgery or radiation to treat those tumours, or other forms of hypothalamic damage, such as brain injury impacting the region. Risk for severe obesity following hypothalamic injury is increased with larger extent of hypothalamic damage or lesions that contain the medial and posterior hypothalamic nuclei that support melanocortin signalling pathways. Structural damage in these hypothalamic nuclei often leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue, the collective effect of which is rapid weight gain. Individuals with hyperphagia are perpetually hungry. They do not experience fullness at the end of a meal, nor do they feel satiated after meals, leading them to consume larger and more frequent meals. To date, most efforts to treat HO have been disappointing and met with limited, if any, long-term success. However, new treatments based on the distinct pathophysiology of disturbed energy homeostasis in acquired HO may hold promise for the future.

Novel Human Milk Fat Substitutes Based on Medium- and Long-Chain Triacylglycerol Regulate Thermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL/6J Mice.

Human milk is naturally rich in medium- and long-chain triacylglycerols (MLCT), accounting for approximately 30% of the total fat. However, infant formula fat is prepared using a physical blend of vegetable oils, which rarely contains MLCT, similar to human milk. The differences in MLCT between human milk and infant formulas may cause different lipid metabolisms and physiological effects on infants, which are unknown. This study aimed to analyze the metabolic characteristics of formula lipid containing novel human milk fat substitutes based on MLCT (FL-MLCT) and compare their effects with those of the physical blend of vegetable oils (FL-PB) on lipid metabolism and gut microbiota in mice. Compared with the FL-PB group, the FL-MLCT group showed increased energy expenditure, decreased serum triacylglycerol level, and significantly lower aspartate aminotransferase level, epididymal and perirenal fat weight, and adipocyte size. Moreover, the abundances of Firmicutes/Bacteroidota, Actinobacteriota, and Desulfovibrionaceae were significantly decreased in the FL-MLCT group. Novel human milk fat substitutes MLCT could inhibit visceral fat accumulation, improve liver function, and modulate the mice gut microbiota composition, which may contribute to controlling obesity.

Discovery of novel IDO1/TDO2 dual inhibitors: a consensus Virtual screening approach with molecular dynamics simulations, and binding free energy analysis.

The pursuit of effective cancer immunotherapy drugs remains challenging, with overexpression of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) allowing cancer cells to evade immune attacks. While several IDO1 inhibitors have undergone clinical testing, only three dual IDO1/TDO2 inhibitors have reached human trials. Hence, this study focuses on identifying novel IDO1/TDO2 dual inhibitors through consensus structure-based virtual screening (SBVS). ZINC15 natural products library was refined based on molecular descriptors, and the selected compounds were docked to the holo form IDO1 and TDO2 using two different software programs and ranked according to their consensus docking scores. The top-scoring compounds underwent in silico evaluations for pharmacokinetics, toxicity, CYP3A4 affinity, molecular dynamics (MD) simulations, and MM-GBSA binding free energy calculations. Five compounds (ZINC00000079405/10, ZINC00004028612/11, ZINC00013380497/12, ZINC00014613023/13, and ZINC00103579819/14) were identified as potential IDO1/TDO2 dual inhibitors due to their high consensus docking scores, key residue interactions with the enzymes, favorable pharmacokinetics, and avoidance of CYP3A4 binding. MD simulations of the top three hits with IDO1 indicated conformational changes and compactness, while MM-GBSA analysis revealed strong binding free energy for compounds 10 (ΔG: -20.13 kcal/mol) and 11 (ΔG: -16.22 kcal/mol). These virtual hits signify a promising initial step in identifying candidates as supplementary therapeutics to immune checkpoint inhibitors in cancer treatment. Their potential to deliver potent dual inhibition of IDO1/TDO2, along with safety and favorable pharmacokinetics, makes them compelling. Validation through in vitro and in vivo assays should be conducted to confirm their activity, selectivity, and preclinical potential as holo IDO1/TDO2 dual inhibitors.Communicated by Ramaswamy H. Sarma.

Carbon neutrality in wastewater treatment plants: An integrated biotechnological-based solution for nutrients recovery, odour abatement and CO2 conversion in alternative energy drivers.

Wastewater treatment plants play a crucial role in water security and sanitation, ensuring ecosystems balance and avoiding significant negative effects on humans and environment. However, they determine also negative pressures, including greenhouse gas and odourous emissions, which should be minimized to mitigate climate changes besides avoiding complaints. The research has been focused on the validation of an innovative integrated biological system for the sustainable treatment of complex gaseous emissions from wastewater treatment plants. The proposed system consists of a moving bed biofilm reactor coupled with an algal photobioreactor, with the dual objective of: i) reducing the inlet concentration of the odourous contaminants (in this case, hydrogen sulphide, toluene and p-xylene); ii) capturing and converting the carbon dioxide emissions produced by the degradation process into exploitable algal biomass. The first reactor promoted the degradation of chemical compounds up to 99.57% for an inlet load (IL) of 22.97 g m-3 d-1 while the second allowed the capture of the CO2 resulting from the degradation of gaseous compounds, with biofixation rate up to 81.55%. The absorbed CO2 was converted in valuable feedstocks, with a maximum algal biomass productivity in aPBR of 0.22 g L-1 d-1. Dairy wastewater has been used as alternative nutrient source for both reactors, with a view of reusing wastewater while cultivating biomass, framing the proposed technology in a context of a biorefinery within a circular economy perspective. The biomass produced in the algal photobioreactor was indeed characterized by a high lipid content, with a maximum percentage of lipids per dry weight biomass of 35%. The biomass can therefore be exploited for the production of alternative and clean energy carrier. The proposed biotechnology represents an effective tool for shifiting the conventional plants in carbon neutral platform for implementing principles of ecological transition while achieving high levels of environmental protection.