Multi-modal triggered-release sonodynamic/chemo/phototherapy synergistic nanocarriers for the treatment of colon cancer.

Most colon cancer patients are diagnosed at an advanced stage, with a grim prognosis. In clinical, various combination therapies have been employed to enhance the efficacy of colon cancer treatment. The essence of combined treatment is the judicious selection and combination of various treatment units. Phototherapy (PT), sonodynamic therapy (SDT), and chemotherapy are treatment modalities that rely on the active molecules to treat tumors, and have been demonstrated to synergistically enhance tumor treatment efficacy. However, the differences in the metabolism of active molecules and hypoxic microenvironment of tumors have limited the synergistic effects of the aforementioned methods. To address this significant issue, in this study, we utilized polydopamine (PDA) as the encapsulated material to form a rigid shell that contains the therapeutic molecules IR-780 and methotrexate (MTX) on the surface of perfluorohexane (PFH) microdroplets through self-assembling method to develop an SDT/chemotherapy/PT combined nanoparticles (SCP NPs). Transmission electron microscopy (TEM) revealed that the nanoparticles exhibited a hollow shell structure, with an average size of approximately 100 nm. SCP NPs have excellent stability and biocompatibility in both in vitro and in vivo. The absorption and emission spectrum of the loaded IR-780 did not exhibit any significant shift, and the photothermal temperature rose to 92°C. Their ultrasonic cavitation effect was good and their cell inhibitory effect of MTX was maintained. SCP NPs can achieve multi-modal triggered release through ultrasound, laser irradiation, and pH, ensuring a simultaneous accumulation of therapeutic molecules in the tumor area and effectively alleviating tumor hypoxia. Additionally, both the near-infrared fluorescence (NIF) signal and the ultrasonic cavitation signal of the nanoparticles can be utilized for tracking and monitoring treatment efficacy. Most notably, SCP NPs exhibited outstanding synergistic treatment effects at low intervention levels, resulting in a 67% cure rate of tumors. These results provide an experimental basis for developing the new clinical treatments for colon cancer.

Revealing the mechanism: the influence of Baicalin on M1/M2 and Th1/Th2 imbalances in mycoplasma gallisepticum infection.

Mycoplasma gallisepticum (MG) is a pathogen that induces chronic respiratory illnesses in chickens, leading to tracheal and lung injury, and eliciting immune reactions that support sustained colonization. Baicalin, a compound found in scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the potential of baicalin in alleviating lung and cell damage caused by MG by restoring imbalances in M1/M2 and Th1/Th2 differentiation and to explore its underlying mechanism. In this research, a model for M1/M2 polarization induced by MG was initially developed. Specifically, infection with MG at a multiplicity of infection (MOI) of 400 for 6 h represented the M1 model, while infection for 10 h represented the M2 model. The polarization markers were subsequently validated using qRT-PCR, ELISA, and Western blot analysis. Baicalin disrupts the activation of M1 cells induced by MG and has the potential to restore the balance between M1 and M2 cells, thereby mitigating the inflammatory damage resulting from MG. Subsequent studies on MG-infected chickens detected imbalances in M1/M2 and Th1/Th2 differentiation in alveolar lavage fluid, as well as imbalances in macrophages and Th cells in the lung. The M1/Th1 model was exposed to MG for 5 d, while the M2/Th2 model was infected with MG for 7 d. The utilization of both light and electron transmission microscopes revealed that the administration of baicalin resulted in a reduction in the number of M1 cells, a decrease in cytoplasmic vacuoles, restoration of mitochondrial swelling and chromatin agglutination, as well as alleviation of alveolar rupture and inflammatory cell infiltration. Furthermore, baicalin restored MG-induced M1/M2 and Th1/Th2 imbalances and inhibited the phosphorylation of p38 and p65 proteins, thereby hindering the activation of the TLR4-p38 MAPK/NF-κB pathway. This study provides insights into the potential long-term effects of baicalin in MG infection and offers a theoretical basis for practical applications.

Microsecond-Scale Transient Thermal Sensing Enabled by Flexible Mo1-xWxS2 Alloys.

Real-time thermal sensing through flexible temperature sensors in extreme environments is critically essential for precisely monitoring chemical reactions, propellant combustions, and metallurgy processes. However, despite their low response speed, most existing thermal sensors and related sensing materials will degrade or even lose their sensing performances at either high or low temperatures. Achieving a microsecond response time over an ultrawide temperature range remains challenging. Here, we design a flexible temperature sensor that employs ultrathin and consecutive Mo1-x W x S2 alloy films constructed via inkjet printing and a thermal annealing strategy. The sensing elements exhibit a broad work range (20 to 823 K on polyimide and 1,073 K on flexible mica) and a record-low response time (about 30 µs). These properties enable the sensors to detect instantaneous temperature variations induced by contact with liquid nitrogen, water droplets, and flames. Furthermore, a thermal sensing array offers the spatial mapping of arbitrary shapes, heat conduction, and cold traces even under bending deformation. This approach paves the way for designing unique sensitive materials and flexible sensors for transient sensing under harsh conditions.

DipR, a GntR/FadR-family transcriptional repressor: regulatory mechanism and widespread distribution of the dip cluster for dipicolinic acid catabolism in bacteria.

Dipicolinic acid is an essential component of bacterial spores for stress resistance, which is released into the environment after spore germination. In a previous study, a dip gene cluster was found to be responsible for the catabolism of dipicolinic acid in Alcaligenes faecalis JQ135. However, the transcriptional regulatory mechanism remains unclear. The present study characterized the new GntR/FadR family transcriptional factor DipR, showing that the dip cluster is transcribed as the six transcriptional units, dipR, dipA, dipBC, dipDEFG, dipH and dipJKLM. The purified DipR protein has six binding sites sharing the 6-bp conserved motif sequence 5'-GWATAC-3'. Site-directed mutations indicated that these motif sequences are essential for DipR binding. Moreover, the four key amino acid residues R63, R67, H196 and H218 of DipR, examined by site-directed mutagenesis, played crucial roles in DipR regulation. Bioinformatics analysis showed that dip clusters including dipR genes are widely distributed in bacteria, are taxon-related, and co-evolved with their hosts. This paper provides new insights into the transcriptional regulatory mechanism of dipicolinic acid degradation by DipR in bacteria.

Exploring the action mechanism and effective components of Yupingfeng powder on influenza based on computational system pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Yupingfeng powder (YPF) is a classic traditional Chinese medicine prescription with a long history of clinical application. However, there is a consensus on the clinical efficacy of YPF in the prevention and treatment of influenza, the underlying pharmacological mechanisms and functional substances have not been thoroughly investigated. AIM OF THE STUDY: This study aimed to elucidate the functional substances and potential mechanisms of YPF against influenza infections by integrating network analysis, metabolomics, computational system pharmacology, and in vitro experiments. MATERIALS AND METHODS: In this study, the active ingredients, related targets, and potential mechanisms of YPF against influenza were identified through network pharmacology and GEO database mining. Combined with metabolomics to corroborate the results of network pharmacology analysis and construct C-T-P-D-M network. Based on this, the key network motifs (KNM) with significance were predicted by system pharmacology algorithm. Finally, the key components as functional substances in the KNM were validated by the coverage of influenza-causing genes and functional pathways, and in vitro experiments. RESULTS: A total of 238 active components and 158 potential target genes intersecting with influenza infection differential genes were screened from YPF. KEGG enrichment analysis indicated that metabolism participated in YPF-provided prevention and treatment on influenza, and metabolomic results further corroborated the significance of the metabolic pathways intervened by YPF included pyruvate metabolism, Valine, leucine and isoleucine degradation, etc. The KNM prediction strategy was computed to include wogonin and isoimperaporin, a group of 48 potential functional components. This functional component group maintained a high degree of consistency with the corresponding C-T network in terms of the coverage of influenza pathogenic genes, and the coverage of functional pathways. Meanwhile, the in vitro results showed that wogonin and isoimperaporin had significant inhibitory effects on inflammation induced by influenza infection, confirming the reliability and accuracy of the KNM prediction strategy. CONCLUSION: YPF against influenza has multi-target and multi-pathway effects, and the underlying mechanisms may be related to metabolism. The pharmacodynamic effects of core components such as wogonin and isoimperaporin on influenza prevention and treatment were confirmed, which represent promising functional candidates for subsequent influenza prevention and treatment, and provide references for the pharmacological and mechanistic analyses of subsequent formulas.

Bone ingrowth induced by gelatin/chitosan internal matrix of 3DP Ti6Al4V scaffold.

Regarding its structural and mechanical adaptability to bone defects, 3D printed (3DP) Ti6Al4V scaffolds are widely used in orthopedics now, purposed to restore the function and mechanical stability of impaired bone. In scaffold fabrication, surface modification is acknowledged as a reliable strategy to enhance the interface interaction between 3DP Ti6Al4V scaffold and bone. Despite its advantage in bone-Ti6Al4V bonding improvement, surface modification lacks the ability to induce bone in-growth efficiently as expected. As an attempt to overcome this challenge, in the current work the inner voids of 3DP Ti6Al4V scaffold were occupied by a gelatin/chitosan porous matrix, purposed to act as a platform for guiding bone ingrowth. Firstly, the gelatin/chitosan matrix was prepared via freeze-drying using genipin as a crosslinker, resulting in a trabecular bone-like interconnected porous network characterized with a gelatin/chitosan ratio dependent swelling capability, degradation and model anti-bacterial drug release behavior. Besides of that, gelatin in the matrix was witnessed to accelerate biomineralization in simulated body fluid. Secondly, a formulated gelatin/chitosan matrix was embedded into 3DP Ti6Al4V scaffold to generate a composite scaffold capable of inducing bone in-growth. The followed studies showed gelatin/chitosan matrix can endow the scaffold with good biological and sustained drug release properties, along with minimal change to the compressive strength of the scaffold. The in vivo experiment results revealed that after 4 weeks of implantation, more new bone formation was witnessed in the inner structure of the composite scaffold than the 3DP Ti6Al4V scaffold, with the average bone volume fraction (BV/TV) value increased from 24.09 % to 46.08 %, the average trabecular bone thickness (Tb. Th) value increased from 0.118 mm to 0.278 mm. Therefore, it was confirmed an inner matrix in 3DP Ti6Al4V scaffold played an essential role in guiding bone in-growth.

Enhancing Field Emission in Air via Ultrascaled Nanorod Electrodes.

Enhancing field emission in ultrascaled electronics improves the device performance and energy efficiency. Conventional lithography defines electrodes with a few-nanometer spacing on the cost of strengthened electron scattering and the reduced field enhancement factor, thus presenting challenges to enhance field emission at a small bias. Here, we used self-assembled nanorods with sub-5 nm spacing as electrodes to overcome these challenges. Intrinsic ballistic transport through high-crystallinity solution-synthesized nanorods minimized charge scattering; meanwhile ultrascaled anisotropic morphologies concentrated local electric fields and thereby lowered the barrier height. Enabled by these structural features, we demonstrated field emission density up to 4.1 × 104 A cm-2 at 1 V in air, more than 10-fold higher than typical molecular and vacuum electronics at similar conditions, and constructed an air-operating electron source with an on/off ratio of 105 at the collector electrode. Energy-efficient high-conductance electron emission suggested the potential of using solution-synthesized nanomaterials in ultrascaled electronics.

Development of a deep learning model for detecting lumbar vertebral fractures on CT images: An external validation.

OBJECTIVE: To develop and externally validate a binary classification model for lumbar vertebral body fractures based on CT images using deep learning methods. METHODS: This study involved data collection from two hospitals for AI model training and external validation. In Cohort A from Hospital 1, CT images from 248 patients, comprising 1508 vertebrae, revealed that 20.9% had fractures (315 vertebrae) and 79.1% were non-fractured (1193 vertebrae). In Cohort B from Hospital 2, CT images from 148 patients, comprising 887 vertebrae, indicated that 14.8% had fractures (131 vertebrae) and 85.2% were non-fractured (756 vertebrae). The AI model for lumbar spine fractures underwent two stages: vertebral body segmentation and fracture classification. The first stage utilized a 3D V-Net convolutional deep neural network, which produced a 3D segmentation map. From this map, region of each vertebra body were extracted and then input into the second stage of the algorithm. The second stage employed a 3D ResNet convolutional deep neural network to classify each proposed region as positive (fractured) or negative (not fractured). RESULTS: The AI model's accuracy for detecting vertebral fractures in Cohort A's training set (n = 1199), validation set (n = 157), and test set (n = 152) was 100.0 %, 96.2 %, and 97.4 %, respectively. For Cohort B (n = 148), the accuracy was 96.3 %. The area under the receiver operating characteristic curve (AUC-ROC) values for the training, validation, and test sets of Cohort A, as well as Cohort B, and their 95 % confidence intervals (CIs) were as follows: 1.000 (1.000, 1.000), 0.978 (0.944, 1.000), 0.986 (0.969, 1.000), and 0.981 (0.970, 0.992). The area under the precision-recall curve (AUC-PR) values were 1.000 (0.996, 1.000), 0.964 (0.927, 0.985), 0.907 (0.924, 0.984), and 0.890 (0.846, 0.971), respectively. According to the DeLong test, there was no significant difference in the AUC-ROC values between the test set of Cohort A and Cohort B, both for the overall data and for each specific vertebral location (all P>0.05). CONCLUSION: The developed model demonstrates promising diagnostic accuracy and applicability for detecting lumbar vertebral fractures.

Transcranial Temporal Interference Stimulation of the Right Globus Pallidus in Parkinson's Disease.

BACKGROUND: Invasive deep brain stimulation (DBS) has been shown to be effective in treating patients with Parkinson's disease (PD), yet its clinical use is limited to patients at the advanced stage of the disease. Transcranial temporal interference stimulation (tTIS) may be a novel nonneurosurgical and safer alternative, yet its therapeutic potential remains unexplored. OBJECTIVE: This pilot study aims to examine the feasibility and safety of tTIS targeting the right globus pallidus internus (GPi) for motor symptoms in patients with PD. METHODS: Twelve participants with mild PD completed this randomized, double-blind, and sham-controlled experiment. Each of them received either 20-minute or sham tTIS of the right GPi. Before and immediately after the stimulation, participants completed the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) in the "medication-on" state to assess the motor symptoms. The blinding efficacy and side effects were also assessed. RESULTS: tTIS was well tolerated by participants, with only mild, transient adverse effects reported. tTIS significantly reduced MDS-UPDRS-III scores by 6.64 points (14.7%), particularly in bradykinesia (23.5%) and tremor (15.3%). The left side showed more significant alleviation in motor symptoms, particularly bradykinesia, compared to the right side. Participants with severer bradykinesia and tremor before stimulation experienced greater improvement after tTIS. CONCLUSION: This pilot study suggests that the tTIS, as a novel noninvasive DBS approach, is feasible and safe for alleviating motor symptoms in mild PD, especially bradykinesia and tremor. Future larger-scale and more definitive studies are needed to confirm the benefits. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

DNA-Based Conductors: From Materials Design to Ultra-Scaled Electronics.

Photolithography has been the foundational fabrication paradigm in current high-performance electronics. However, due to the limitation in fabrication resolution, scaling beyond a 20-nm critical dimension for metal conductors presents a significant challenge for photolithography. Structural DNA nanotechnology emerges as a promising alternative to photolithography, allowing for the site-specific assembly of nano-materials at single-molecule resolution. Substantial progresses have been achieved in the ultra-scaled DNA-based conductors, exhibiting novel transport characteristics and small critical dimensions. This review highlights the structure-transport property relationship for various DNA-based conductors and their potential applications in quantum /semiconductor electronics, going beyond the conventional scope focusing mainly on the shape diversity of DNA-templated metals. Different material synthesis methods and their morphological impacts on the conductivities are discussed in detail, with particular emphasis on the conducting mechanisms, such as insulating, metallic conducting, quantum tunneling, and superconducting. Furthermore, the ionic gating effect of self-assembled DNA structures in electrolyte solutions is examined. This review also suggests potential solutions to address current challenges in DNA-based conductors, encouraging multi-disciplinary collaborations for the future development of this exciting area.

Entropy drives the ligand recognition in G-protein-coupled receptor subtypes.

Achieving ligand subtype selectivity within highly homologous subtypes of G-protein-coupled receptor (GPCR) is critical yet challenging for GPCR drug discovery, primarily due to the unclear mechanism underlying ligand subtype selectivity, which hampers the rational design of subtype-selective ligands. Herein, we disclose an unusual molecular mechanism of entropy-driven ligand recognition in cannabinoid (CB) receptor subtypes, revealed through atomic-level molecular dynamics simulations, cryoelectron microscopy structure, and mutagenesis experiments. This mechanism is attributed to the distinct conformational dynamics of the receptor's orthosteric pocket, leading to variations in ligand binding entropy and consequently, differential binding affinities, which culminate in specific ligand recognition. We experimentally validated this mechanism and leveraged it to design ligands with enhanced or ablated subtype selectivity. One such ligand demonstrated favorable pharmacokinetic properties and significant efficacy in rodent inflammatory analgesic models. More importantly, it is precisely due to the high subtype selectivity obtained based on this mechanism that this ligand does not show addictive properties in animal models. Our findings elucidate the unconventional role of entropy in CB receptor subtype selectivity and suggest a strategy for rational design of ligands to achieve entropy-driven subtype selectivity for many pharmaceutically important GPCRs.

Effect of exogenous selenium on physicochemical, structural, functional, thermal, and gel rheological properties of mung bean (Vigna radiate L.) protein.

Selenium (Se) biofortification during the growth process of mung bean is an effective method to improve the Se content and quality. However, the effect of Se biofortification on the physicochemical properties of mung bean protein is unclear. The objective of this study was to clarify the changes in the composition, Se forms, particle structure, functional properties, thermal stability, and gel properties of mung bean protein at four Se application levels. The results showed that the Se content of mung bean protein increased in a dose-dependent manner, with 7.96-fold (P1) and 8.52-fold (P2) enhancement at the highest concentration. Exogenous Se application promotes the conversion of inorganic Se to organic Se. Among them, selenomethionine (SeMet) and methyl selenocysteine (MeSeCys) replaced Met and Cys through the S metabolic pathway and became the dominant organic Se forms in Se-enriched mung bean protein, accounting for more than 80 % of the total Se content. Exogenous Se at 30 g/hm2 significantly up-regulated protein content and promoted the synthesis of sulfur-containing protein components and hydrophobic amino acids in the presence of increased levels of SeMet and MeSeCys. Meanwhile, Cys and Met substitution altered the sulfhydryl groups (SH), ß-sheets, and ß-turns of protein. The particle size and microstructural characteristics depend on the protein itself and were not affected by exogenous Se. The Se-induced increase in the content of hydrophobic amino acids and ß-sheets synergistically increases the thermal stability of the protein. Moderate Se application altered the functional properties of mung bean protein, which was mainly reflected in the significant increase in oil holding capacity (OHC) and foaming capacity (FC). In addition, the increase in SH and ß-sheets induced by exogenous Se could alter the protein intermolecular network, contributing to the increase in storage modulus (G') and loss modulus (G″), which resulted in the formation of more highly elastic gels. This study further promotes the application of mung bean protein in the field of food processing and provides a theoretical basis for the extensive development of Se-enriched mung bean protein.

Tianhe Zhuifeng Gao reverses inflammatory response and attenuates bone/cartilage destruction in rheumatoid arthritis via PSMC2-RUNX2-COL1A1 axis based on transcriptional regulatory network analysis and experimental validation.

BACKGROUND: Tianhe Zhuifeng Gao (TZG) is an authorized Chinese patent drug with satisfying clinical efficacy, especially for RA patients with cold-dampness syndrome. However, its underlying pharmacological mechanisms remain unclear. METHOD: Anti-arthritic effects of TZG were evaluated using an adjuvant-induced arthritis (AIA) rat model. Transcriptional regulatory network analysis based on synovial tissues obtained from AIA rats, combining with our previous analysis based on whole blood samples from RA patients with cold-dampness syndrome and co-immunoprecipitation were performed to identify involved dominant pathways, which were experimentally verified using AIA-wind-cold-dampness stimulation modified (AIA-M) animal model. RESULTS: TZG treatment dramatically attenuated joint injury and inflammatory response in AIA rats, and PSMC2-RUNX2-COL1A1 axis, which was closely associated with bone/cartilage damage, was inferred to be one of therapeutic targets of TZG against RA. Experimentally, TZG displayed obvious pharmacological effects for alleviating the joint inflammation and destruction through reinstating the body weight, reducing the arthritis score, the limbs diameters, the levels of RF and CRP, and the inflammatory cytokines, recovering the thymus and spleen indexes, diminishing bone and cartilage destruction, as well elevating the pain thresholds of AIA-M rats. In addition, TZG markedly reversed the abnormal energy metabolism in AIA-M rats through enhancing articular temperature, daily water consumption, and regulating expression levels of energy metabolism parameters and hormones. Moreover, TZG also significantly modulated the abnormal expression levels of PSMC2, RUNX2 and COL1A1 proteins in the ankle tissues of AIA-M rats. CONCLUSION: TZG may exert the bone protective effects in RA therapy via regulating bone and cartilage damage-associated PSMC2-RUNX2-COL1A1 axis.

Tri-signal CdS@SiO2 nanoprobes for accurate and sensitive detection of human immunoglobulin G with enhanced flexibility and internal validation.

Accurate and sensitive determination of human immunoglobulin G (HIgG) level is critical for diagnosis and treatment of various diseases, including rheumatoid arthritis, humoral immunodeficiencies, and infectious disease. In this study, versatile tri-signal probes were developed by preparing CdS@SiO2 nanorods that integrate photoluminescence (PL), multi-phonon resonant Raman scattering (MRRS) and infrared absorption (IRA) properties. Through the coating of multiple CdS nanoparticles as cores within SiO2 shells, the PL and MRRS properties of CdS were improved, resulting in a significantly lowered limit of detection (LOD), with the lowest LOD of 12.37 ag mL-1. Integration with the distinctive IRA property of SiO2 shells widened the detection range towards higher concentrations, establishing a final linear range of 50 ag mL-1 to 10 µg mL-1. The remarkable consistency among the three signals highlighted the robust internal verification capability for accurate detection. This approach enhances flexibility in selecting detection methodologies to suit diverse scenarios, facilitating HIgG detection. The tri-signal nanoprobes also exhibited excellent detection selectivity, specificity and repeatability. This study presents a fresh idea for developing high-performance detection strategies.

Association between stress hyperglycemia ratio and in-hospital outcomes: findings from the improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) Project.

BACKGROUND: Stress hyperglycemia ratio (SHR) could provide accurate information on the acute status of hyperglycemia. The relationship between SHR and acute coronary syndrome (ACS) prognosis remains unclear. This study was conducted to identity the association between SHR and in-hospital outcomes in patients with ACS. METHODS: A total of 12,010 patients were eventually enrolled in the study. The relationship between SHR and in-hospital major adverse cardiovascular events (MACEs) was then modeled by restricted cubic spline (RCS) curves, and all patients were divided into three groups according to the results. The multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes, described as odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were also performed on different diseases. RESULTS: The median age of this cohort was 63 (54, 71) years old, and 8942 (74.5%) were male. Group 1 was defined as SHR < 0.6 (n = 426), Group 2 was defined as SHR between 0.6 and 1 (n = 5821), and Group 3 was defined as SHR > 1 (n = 5763). Compared with Group 2, Group 1 (OR = 1.891, 95% CI: 1.028-3.479, P < 0.001) and Group 3 (OR = 1.868, 95% CI: 1.434-2.434, P < 0.001) had higher risks of suffering from in-hospital MACEs. SHR was associated with higher risks of in-hospital MACEs in the subgroups of DM [OR = 2.282, 95% CI: 1.477-3.524). CONCLUSIONS: Both low and high SHR levels were independently associated with in-hospital MACEs. Young males with DM, hypertension, and decreased renal function had much higher risks of suffering from SHR-correlated MACEs.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion.

BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

Changes in the rumen development, rumen fermentation, and rumen microbiota community in weaned calves during steviol glycosides treatment.

Early weaning leads to weaning stress in calves, which hinders healthy growth and development. As an excellent sweetener applied in food, steviol glycosides (STE) has also been shown to exhibit positive biological activity in monogastric animals. Therefore, this study aimed to evaluate the impact of incorporating STE as a dietary supplement on rumen development, fermentation, and microbiota of rumen in weaned calves. This study selected 24 healthy Holstein bull calves and randomly allocated them into two groups (CON and STE). The results indicated that supplementation STE group improved rumen development in weaned calves, as demonstrated by a marked increase in the weight of the rumen, as well as the length and surface area of the rumen papilla. Compared with the CON group, the concentrations of total volatile fatty acids (TVFA), propionate, butyrate, and valerate were higher in the STE group. Moreover, STE treatment increased the relative abundance of Firmicutes and Actinobacteria at the phylum level. At the genus level, the STE group showed a significantly increased relative abundance of Succiniclasticum, Lachnospiraceae_NK3A20_group, and Olsenella, and a decreased relative abundance of Acinetobacter compared to the CON group. Pusillimonas, Lachnospiraceae_NK3A20_group, Olsenella, and Succiniclasticum were significantly enriched in rumen chyme after supplementation with STE, as demonstrated by LEfSe analysis. Overall, our findings revealed that rumen bacterial communities altered in response to the dietary supplementation with STE, and some bacterial taxa in these communities may have positive effects on rumen development during this period.

Hypoxic-Ischemic Encephalopathy: Pathogenesis and Promising Therapies.

Hypoxic-ischemic encephalopathy (HIE) is a brain lesion caused by inadequate blood supply and oxygen deprivation, often occurring in neonates. It has emerged as a grave complication of neonatal asphyxia, leading to chronic neurological damage. Nevertheless, the precise pathophysiological mechanisms underlying HIE are not entirely understood. This paper aims to comprehensively elucidate the contributions of hypoxia-ischemia, reperfusion injury, inflammation, oxidative stress, mitochondrial dysfunction, excitotoxicity, ferroptosis, endoplasmic reticulum stress, and apoptosis to the onset and progression of HIE. Currently, hypothermia therapy stands as the sole standard treatment for neonatal HIE, albeit providing only partial neuroprotection. Drug therapy and stem cell therapy have been explored in the treatment of HIE, exhibiting certain neuroprotective effects. Employing drug therapy or stem cell therapy as adjunctive treatments to hypothermia therapy holds great significance. This article presents a systematic review of the pathogenesis and treatment strategies of HIE, with the goal of enhancing the effect of treatment and improving the quality of life for HIE patients.

Dyslipidemia characterized by low density lipoprotein cholesterol and risk of preterm Birth: A Mendelian randomization study.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality worldwide, and dyslipidemia is associated with preterm birth in observational studies. We use Mendelian randomization (MR) analyses to uncover the causal association between blood lipid levels and preterm birth. METHODS: We extracted uncorrelated (R2 < 0.001) single-nucleotide polymorphisms strongly associated (p < 5 × 10-8) with blood lipids from genome wide association studies of FinnGen database and UK Biobank participants. Inverse variance weighted method was the main MR analysis. Sensitivity analyses including genetic pleiotropy, heterogeneity, and directionality of causality were conducted. RESULTS: The study included 115,082 participants with lipid measurements, 8,507 patients with preterm birth. Increasing apolipoprotein B (odds ratio (OR), 1.12[95 % CI, 1.02-1.23]; p = 0.019), low-density lipoprotein cholesterol (OR, 1.11[95 % CI, 1.00-1.22]; p = 0.040), non-high-density lipoprotein cholesterol (OR, 1.12[95 % CI, 1.01-1.24]; p = 0.026), remnant cholesterol (OR, 1.11[95 % CI, 1.00-1.23]; p = 0.047) and total free cholesterol (OR, 1.11[95 % CI, 1.01-1.23]; p = 0.037) were associated with increased risk of preterm delivery. Moreover, triglycerides in low-density lipoprotein were causally associated with the risk of PTB. Our sensitivity analysis yielded robust results, uncovering no evidence of horizontal pleiotropy or reverse causal relationships. CONCLUSION: Our investigation unveils the adverse impact of dyslipidemia on preterm birth, with a particular emphasis on the detrimental effect of elevated low-density lipoprotein cholesterol.