Effects of fermented sweet potato residue on nutrient digestibility, meat quality, and intestinal microbes in broilers.

This study aimed to investigate the effects of different proportions of dietary fermented sweet potato residue (FSPR) supplementation as a substitute for corn on the nutrient digestibility, meat quality, and intestinal microbes of yellow-feathered broilers. Experiment 1 (force-feeding) evaluated the nutrient composition and digestibility of mixtures with different proportions of sweet potato residue (70%, 80%, 90%, and 100%) before and after fermentation. In Experiment 2 (metabolic growth), a total of 420 one-day-old yellow-feathered broilers were randomly allocated to 4 groups and fed corn-soybean meal-based diets with 0, 5%, 8%, and 10% FSPR as a substitute for corn. The force-feeding and metabolic growth experiments were performed for 9 and 70 d, respectively. The treatment of 70% sweet potato residue (after fermentation) had the highest levels of crude protein, ether extract, and crude fiber and improved the digestibility of crude protein and amino acids (P < 0.05). Although dietary FSPR supplementation at different levels had no significant effect on growth performance and intestinal morphology, it improved slaughter rate, half-chamber rate, full clearance rate, and meat color, as well as reduced cooking loss in the breast and thigh muscles (P < 0.05). Dietary supplementation with 8% and 10% FSPR increased the serum immunoglobulin M and immunoglobulin G levels in broilers (P < 0.05). Furthermore, 10% FSPR increased the Shannon index and Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-010 and Romboutsia abundances and decreased Sutterella and Megamonas abundances (P < 0.05). Spearman's correlation analysis showed that meat color was positively correlated with Ruminococcaceae_UCG-014 (P < 0.05) and negatively correlated with Megamonas (P < 0.05). Collectively, 70% sweet potato residue (after fermentation) had the best nutritional value and nutrient digestibility. Dietary supplementation with 8% to 10% FSPR as a substitute for corn can improve the slaughter performance, meat quality, and intestinal microbe profiles of broilers. Our findings suggest that FSPR has the potential to be used as a substitute for corn-soybean meals to improve the meat quality and intestinal health of broilers.

Metal-polyphenol coordination nanosheets with synergistic peroxidase-like and photothermal properties for efficient antibacterial treatment.

Bacterial infections pose a serious threat to human health and socioeconomics worldwide. In the post-antibiotic era, the development of novel antimicrobial agents remains a challenge. Polyphenols are natural compounds with a variety of biological activities such as intrinsic antimicrobial activity and antioxidant properties. Metal-polyphenol obtained by chelation of polyphenol ligands with metal ions not only possesses efficient antimicrobial activity but also excellent biocompatibility, which has great potential for application in biomedical and food packaging fields. Herein, we developed metal-polyphenol coordination nanosheets named copper oxidized tannic acid quinone (CuTAQ) possessing efficient antibacterial and anti-biofilm effects, which was synthesized by a facile one-pot method. The synthesis was achieved by chelation of partially oxidized tannic acid (TA) with Cu2+ under mild conditions, which supports low-cost and large-scale production. It was demonstrated that CuTAQ exhibited high antibacterial activity via disrupting the integrity of bacterial cell membranes, inducing oxidative stress, and interfering with metabolism. In addition, CuTAQ exhibits excellent peroxidase catalytic activity and photothermal conversion properties, which play a significant role in enhancing its bactericidal and biofilm scavenging abilities. This study provides insights for rational design of innovative metal-polyphenol nanomaterials with efficient antimicrobial properties.

Two-component system RstAB promotes the pathogenicity of adherent-invasive Escherichia coli in response to acidic conditions within macrophages.

Adherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn's disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.

Therapeutic advantage of teriparatide in very elderly patients with proximal femoral fractures: a functional and BMD analysis.

BACKGROUND: Teriparatide, a recombinant parathyroid hormone, is pivotal in osteoporosis treatment, particularly in post-surgical recovery for hip fractures. This study investigates its efficacy in functional recovery post-hip fracture surgery in elderly patients, a demographic particularly susceptible to osteoporotic fractures. METHODS: In this retrospective cohort study, 150 elderly patients with proximal femoral fractures undergoing open reduction and internal fixation were enrolled. They were categorized into two groups: receiving 20 µg of daily teriparatide injections for 18 months and receiving standard antiresorptive medications during a 24-month follow-up. Detailed records of patient demographics, Fracture Risk Assessment Tool scores, and comorbidities were kept. Key outcomes, including bone mineral density (BMD) and functional scores (Barthel Index and Visual Analog Scale for hip pain), were evaluated at 3 and 24 months post-surgery. RESULTS: Out of the original cohort, 126 patients (20 men and 106 women with an average age of 85.5 ± 9.3 years) completed the study. The teriparatide group exhibited significant enhancements in both functional scores and BMD when compared to the control group. Notably, functional improvements were less pronounced in male patients compared to female patients. Additionally, the incidence of new fractures was markedly lower in the teriparatide group. CONCLUSION: Administering teriparatide daily for 18 months post-surgery for proximal femoral fractures significantly benefits very elderly patients by improving functionality and bone density, with observed differences in recovery between genders. These results reinforce the efficacy of teriparatide as a potent option for treating osteoporosis-related fractures in the elderly and highlight the importance of considering gender-specific treatment and rehabilitation strategies.

Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Overcrowded 14,14'-Bidibenzo[a,j]anthracenes: Challenges in Syntheses and Atypical Property of Lacking Symmetry-Breaking Charge Transfer (SBCT).

14,14'-Bidibenzo[a,j]anthracenes (BDBAs) were prepared by iridium-catalyzed annulation of 5,5'-biterphenylene with alkynes. Overcrowded BDBAs with highly distorted molecular halves and a small interplanar angle between two anthryl moieties (down to approximately 31º, currently the lowest reported value) were verified by X-ray crystallography. The strong intramolecular interactions and electronic couplingsbetween two molecular halves resulted in upfield 1H NMR signals, redshifted absorption and emission bands, and a reduced HOMO-LUMO gap. Photodynamic investigations on BDBAs indicated that the formation of the conventional symmetry-breaking charge transfer (SBCT) state was suspended by restricted rocking around the central C-C bond. Such a mechanism associated with this highly constrained conformation was examined for the first time.

Numerical Simulation and Machine Learning Prediction of the Direct Chill Casting Process of Large-Scale Aluminum Ingots.

The large-scale ingot of the 7xxx-series aluminum alloys fabricated by direct chill (DC) casting often suffers from foundry defects such as cracks and cold shut due to the formidable challenges in the precise controlling of casting parameters. In this manuscript, by using the integrated computational method combining numerical simulations with machine learning, we systematically estimated the evolution of multi-physical fields and grain structures during the solidification processes. The numerical simulation results quantified the influences of key casting parameters including pouring temperature, casting speed, primary cooling intensity, and secondary cooling water flow rate on the shape of the mushy zone, heat transport, residual stress, and grain structure of DC casting ingots. Then, based on the data of numerical simulations, we established a novel model for the relationship between casting parameters and solidification characteristics through machine learning. By comparing it with experimental measurements, the model showed reasonable accuracy in predicting the sump profile, microstructure evolution, and solidification kinetics under the complicated influences of casting parameters. The integrated computational method and predicting model could be used to efficiently and accurately determine the DC casting parameters to decrease the casting defects.

Oral Administration of Antimicrobial Peptide NZ2114 Through the Microalgal Bait Tetraselmis subcordiformis (Wille) Butcher for Improving the Immunity and Gut Health in Turbot (Scophthalmus maximus L.).

Antibiotics are widely used in aquaculture to treat the bacterial diseases. However, the improper use of antibiotics could lead to environmental pollution and development of resistance. As a safe and eco-friendly alternative, antimicrobial peptides (AMPs) are commonly explored as therapeutic agents. In this study, a mutant strain of Tetraselmis subcordiformis containing AMP NZ2114 was developed and used as an oral drug delivery system to reduce the use of antibiotics in turbot (Scophthalmus maximus) aquaculture. The gut, kidney, and liver immune-related genes and their effects on gut digestion and bacterial communities in turbot fed with NZ2114 were evaluated in an 11-day feeding experiment. The results showed that compared with the group fed with wild-type T. subcordiformis, the group fed with T. subcordiformis transformants containing NZ2114 was revealed with decreased levels of both pro-inflammatory factors (TNF-α and IL-1ß), inhibitory effect on Staphylococcus aureus, Vibrio parahaemolyticus, and Vibrio splendidus demonstrated by the in vitro simulation experiments, and increased richness and diversity of the gut microbiota of turbot. In conclusion, our study provided a novel, beneficial, and low-cost method for controlling bacteria in turbot culture through the oral drug delivery systems.

An antimicrobial film of silver/nanocellulose crystal/oxalic acid/polyvinyl alcohol with real-time bactericidal and prevention of biofilm formation properties.

Silver nanoparticles (AgNPs) is an excellent antibacterial agent, which is widely used in medical, food, environmental and other fields, but AgNPs are easy to accumulate in aqueous solution, so their application in various fields is limited. Therefore, it is particularly important to propose a new application method or to prepare a new composite material. In this study, OA/PVA was obtained by cross-linking oxalic acid (OA) with polyvinyl alcohol (PVA). Then Ag/NCC was obtained by in situ reduction of AgNPs on nanocellulose crystals (NCC). Finally, Ag/NCC/OA/PVA composite antimicrobial films with good waterproofing effect were prepared by mixing Ag/NCC with OA/PVA. Subsequently, the films were characterized using SEM, UV-vis, FTIR and XRD, as well as physicochemical properties such as mechanical strength and hydrophilic properties were determined. The results indicated that the Ag/NCC/OA/PVA films possess good light transmittance, mechanical properties, water resistance, antibacterial activity, and biodegradability. The results of the mechanism study showed that Ag/NCC/OA/PVA films can destroy cell integrity, inhibit succinate dehydrogenase (SDH) activity, thereby reducing intracellular ATP levels. And induce a large number of reactive oxygen species (ROS) production, eventually leading to the death of C. sakazakii. In summary, Ag/NCC/OA/PVA film has good physical and chemical properties, antibacterial activity and biocompatibility, and has promising applications in food and medical antibacterial fields.

HIRI-ViT: Scaling Vision Transformer with High Resolution Inputs.

The hybrid deep models of Vision Transformer (ViT) and Convolution Neural Network (CNN) have emerged as a powerful class of backbones for vision tasks. Scaling up the input resolution of such hybrid backbones naturally strengthes model capacity, but inevitably suffers from heavy computational cost that scales quadratically. Instead, we present a new hybrid backbone with HIgh-Resolution Inputs (namely HIRI-ViT), that upgrades prevalent four-stage ViT to five-stage ViT tailored for high-resolution inputs. HIRI-ViT is built upon the seminal idea of decomposing the typical CNN operations into two parallel CNN branches in a cost-efficient manner. One high-resolution branch directly takes primary high-resolution features as inputs, but uses less convolution operations. The other low-resolution branch first performs down-sampling and then utilizes more convolution operations over such low-resolution features. Experiments on both recognition task (ImageNet-1K dataset) and dense prediction tasks (COCO and ADE20K datasets) demonstrate the superiority of HIRI-ViT. More remarkably, under comparable computational cost (  âˆ¼ 5.0 GFLOPs), HIRI-ViT achieves to-date the best published Top-1 accuracy of 84.3% on ImageNet with 448×448 inputs, which absolutely improves 83.4% of iFormer-S by 0.9% with 224×224 inputs.

Maximizing Polysaccharides and Phycoerythrin in Porphyridium purpureum via the Addition of Exogenous Compounds: A Response-Surface-Methodology Approach.

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L-1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L-1), phycoerythrin (102.95 mg L-1), and polysaccharide (1.42 g L-1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.

Cooperation of Different Active Sites to Promote CO2 Electroreduction to Multi-carbon Products at Ampere-Level.

Electroreduction of CO2 to C2+ products provides a promising strategy for reaching the goal of carbon neutrality. However, achieving high selectivity of C2+ products at high current density remains a challenge. In this work, we designed and prepared a multi-sites catalyst, in which Pd was atomically dispersed in Cu (Pd-Cu). It was found that the Pd-Cu catalyst had excellent performance for producing C2+ products from CO2 electroreduction. The Faradaic efficiency (FE) of C2+ products could be maintained at approximately 80.8 %, even at a high current density of 0.8 A cm-2 for at least 20 hours. In addition, the FE of C2+ products was above 70 % at 1.4 A cm-2. Experiments and density functional theory (DFT) calculations revealed that the catalyst had three distinct catalytic sites. These three active sites allowed for efficient conversion of CO2, water dissociation, and CO conversion, ultimately leading to high yields of C2+ products.

Magnolin alleviated DSS-induced colitis by inhibiting ALOX5-mediated ferroptosis.

Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage-associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti-inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 µg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis-associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescent staining, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS-induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5-lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro-inflammatory factors, that is, interleukin-6 and tumor necrosis factor-α (IL-6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5-mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.

Effect of Osteoporosis Treatments on Osteoarthritis Progression in Postmenopausal Women: A Review of the Literature.

PURPOSE OF REVIEW: The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA). RECENT FINDINGS: A total of 40 relevant articles were identified. Studies were categorized into those (1) discussing estrogen and selective estrogen receptor modulators (SERMs), (2) bisphosphonates, (3) parathyroid hormone (PTH) analogs, and (4) denosumab, and (5) prior review articles. A large amount of evidence suggests that estrogen and SERMs are effective at reducing OA symptoms and disease progression. Evidence suggests that bisphosphonates, the most common medications used to treat osteoporosis, can reduce OA symptoms and disease progression. In vivo studies suggest that PTH analogs may improve the cartilage destruction associated with OA; however, few human trials have examined its use for OA. Denosumab is approved to treat osteoporosis, bone metastases, and certain types of breast cancer, but little study has been done with respect to its effect on OA. The current evidence indicates that medications used to treat osteoporosis are also effective for treating OA. Estrogen, SERMs, and bisphosphonates have the most potential as OA therapies. Less is known regarding the effectiveness of PTH analogs and denosumab in OA, and more research is needed.

Salmonella enterica serovar Typhimurium remodels mitochondrial dynamics of macrophages via the T3SS effector SipA to promote intracellular proliferation.

Mitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells' mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.

Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice.

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus.

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.

Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19.

Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated. METHODS: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment. RESULTS: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation. CONCLUSION: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.

Metformin protects ovarian granulosa cells in chemotherapy-induced premature ovarian failure mice through AMPK/PPAR-γ/SIRT1 pathway.

Premature ovarian failure (POF) caused by chemotherapy is a growing concern for female reproductive health. The use of metformin (MET), which has anti-oxidative and anti-inflammatory effects, in the treatment of POF damaged by chemotherapy drugs remains unclear. In this study, we investigated the impact of MET on POF caused by cyclophosphamide (CTX) combined with busulfan (BUS) and M1 macrophages using POF model mice and primary granule cells (GCs). Our findings demonstrate that intragastric administration of MET ameliorates ovarian damage and alleviates hormonal disruption in chemotherapy-induced POF mice. This effect is achieved through the reduction of inflammatory and oxidative stress-related harm. Additionally, MET significantly relieves abnormal inflammatory response, ROS accumulation, and senescence in primary GCs co-cultured with M1 macrophages. We also observed that this protective role of MET is closely associated with the AMPK/PPAR-γ/SIRT1 pathway in cell models. In conclusion, our results suggest that MET can protect against chemotherapy-induced ovarian injury by inducing the expression of the AMPK pathway while reducing oxidative damage and inflammation.

Femoral neck system versus multiple cannulated screws for the fixation of Pauwels classification type II femoral neck fractures in older female patients with low bone mass.

BACKGROUND: Femoral neck fractures in older adult patients are a major concern and often necessitate surgical intervention. This study compared the clinical outcomes of 2 surgical techniques: the femoral neck system (FNS) and cannulated compression screws (CCSs). METHODS: A total of 40 female patients (mean age 73.50 ± 11.55 years) with femoral neck fractures of Pauwels classification type II and receiving surgical fixation between 2020 and 2022 were enrolled. The patients were categorized into an FNS group (n = 12) or a CCS group (n = 28), and surgical duration, intraoperative blood loss, length of hospital stay, and incidence of postoperative adverse events were analyzed. RESULTS: No significant intergroup differences in demographic characteristics were discovered. The mean surgical duration for all patients was 52.88 ± 22.19 min, with no significant difference between the groups. However, the FNS group experienced significantly higher intraoperative blood loss (P = 0.002) and longer hospital stay (P = 0.023) than did the CCS group. The incidence of osteonecrosis was higher in the CCS group, whereas the incidence of nonunion or malunion was higher in the FNS group. The surgical method did not appear to be a significant risk factor. The main risk factor for revision surgery was longer duration until the first adverse event (P = 0.015). CONCLUSION: The FNS does not appear to provide superior surgical outcomes compared with CCSs in older adult women with Pauwels classification type II femoral neck fractures. A longer duration between surgical fixation and the first adverse event before stabilization of the fracture site may be a risk factor for revision surgery.