Netrin-1 Is an Important Mediator in Microglia Migration.

Microglia migrate to the cerebral cortex during early embryonic stages. However, the precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating the motility of diverse cells. In this paper, we found that Netrin-1 promoted microglial BV2 cell migration in vitro. Mechanism studies indicated that the activation of GSK3ß activity contributed to Netrin-1-mediated microglia migration. Furthermore, Integrin α6/ß1 might be the relevant receptor. Single-cell data analysis revealed the higher expression of Integrin α6 subunit and ß1 subunit in microglia in comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, and Dscam. Microscale thermophoresis (MST) measurement confirmed the high binding affinity between Integrin α6/ß1 and Netrin-1. Importantly, activation of Integrin α6/ß1 with IKVAV peptides mirrored the microglia migration and GSK3 activation induced by Netrin-1. Finally, conditional knockout (CKO) of Netrin-1 in radial glial cells and their progeny led to a reduction in microglia population in the cerebral cortex at early developmental stages. Together, our findings highlight the role of Netrin-1 in microglia migration and underscore its therapeutic potential in microglia-related brain diseases.

"How difficult it is to change dietary behaviour" experience of older people with sarcopenic obesity: a qualitative study.

BACKGROUND: Dietary intervention is an important method to manage sarcopenic obesity, but the implementation in real world is difficult to achieve an ideal condition. This study aimed to the experiences of older people with sarcopenic obesity during the implementation of dietary behavioural change (DBC) intervention. METHODS: This study is a semi-structured individual interview embedded within a pilot randomized controlled trial on community-dwelling older people with sarcopenic obesity. Purposive sampling was applied to invite 21 participants who had received a 15-week DBC intervention. The interviews were audio-recorded and transcribed verbatim. Content analysis was performed to analyze the data. RESULTS: The themes for facilitators included: (a) Attach importance to self's health; (b) Family's support; (c) Concern self's body shape; (d) Instructor's support; (e) Regular food diary taken. The themes for barriers included: (a) Difficulties of taking food diary; (b) Difficulties of calculating the food amount; (c) Yield to offspring's appetite; (d) Misjudging self's or family's appetite. CONCLUSION: Support from family members and instructor, caring about self's health and body image facilitated the intervention implementation. The complication of food amount estimation and diary record, personal sacrifice for next generations, and previous living experience were barriers for implementing the intervention. Overall, the older people with sarcopenic obesity can accept the design of DBC intervention program and have great willing to join.

Spatial accumulation of lignin monomers and cellulose underlying stalk strength in maize.

Lodging largely affects yield, quality and mechanical harvesting of maize. Stalk strength is one of the major factors that affect maize lodging. Although plant cell wall components including lignin and cellulose were known to be associated with stalk strength and lodging resistance, spatial accumulation of specific lignin monomers and cellulose in different tissues and their association with stalk strength in maize was not clearly understood. In this study, we found that both G and S lignin monomers accumulate highest in root, stem rind and leaf vein. Consistently, most lignin biosynthetic genes were expressed higher in root and stem than in other tissues. However, cellulose appears to be lowest in root. There are only mild changes of G lignin and cellulose in different internodes. Instead, we noticed a dramatic decrease of S-lignin accumulation and lignin biosynthetic gene expression in 2nd to 4th internodes wherein stem breakage usually occurs, thereby revealing a few candidate lignin biosynthetic genes associated with stalk strength. Moreover, stalk strength is positively correlated with G, S lignin, and cellulose, but negatively correlated with S/G ratio based on data of maize lines with high or low stalk strength. Loss-of-function of a caffeic acid o-methyltransferase (COMT), which is involved in S lignin biosynthesis, in the maize bm3 mutant, leads to lower stalk strength. Our data collectively suggest that stalk strength is determined by tissue-specific accumulation of lignin monomers and cellulose, and manipulation of the cell wall components by genetic engineering is vital to improve maize stalk strength and lodging resistance.

[Damage and changes in expression of autophagy related factors LC3 and p62 of condylar cartilage in fluorosis mouse].

PURPOSE: To study the damage and the expression of LC3 and p62 of condylar cartilage in fluorosis mouse. METHODS: Thirty 4-week-old male C57BL/6 mice were randomly divided into control group and the experimental group with 15 animals in each group. The control group received regular drinking water and the experimental group received a fluoride concentration of 75 mg/L drinking water for 8 weeks. The structure of condylar cartilage was observed through modified safranine O-fast green FCF cartilage stain kit. Immunohistochemistry was used to detect the expression of MMP-13, type Ⅱ collagen and LC3 and p62. Two-way analysis of variance test was conducted for analysis of semi-quantitative results of immunohistochemistry using SPSS 22.0 software package. RESULTS: Compared with the control group, the fibrocartilage layer of the experimental group became thinner, the condrocytes were smaller, and the staining became deeper.Immunohistochemistry results showed that the expression of MMP-13 and LC3 increased; the expression of type Ⅱ collagen and p62 decreased in the experimental group. CONCLUSIONS: There was degeneration of the condylar cartilage and autophagy in mice with drinking water containing 75 mg/L fluoride.

Photoresponsive Multirole Nanoweapon Camouflaged by Hybrid Cell Membrane Vesicles for Efficient Antibacterial Therapy of Pseudomonas aeruginosa-Infected Pneumonia and Wound.

Exploring effective antibacterial approaches for targeted treatment of pathogenic bacterial infections with reduced drug resistance is of great significance. Combinational treatment modality that leverages different therapeutic components can improve the overall effectiveness and minimize adverse effects, thus displaying considerable potential against bacterial infections. Herein, red blood cell membrane fuses with macrophage membrane to develop hybrid cell membrane shell, which further camouflages around drug-loaded liposome to fabricate biomimetic liposome (AB@LRM) for precise antibacterial therapy. Specifically, photoactive agent black phosphorus quantum dots (BPQDs) and classical antibiotics amikacin (AM) are loaded in AB@LRM to accurately target the inflammatory sites through the guidance of macrophage membrane and long residence capability of red blood cell membrane, eventually exerting efficacious antibacterial activities. Besides, due to the excellent photothermal and photodynamic properties, BPQDs act as an efficient antibacterial agent when exposed to near-infrared laser irradiation, dramatically increasing the sensitivity of bacteria to antibiotics. Consequently, the synergistic sterilizing effect produced by AB@LRM further restricts bacterial resistance. Upon laser irradiation, AB@LRM shows superior anti-inflammatory and antibacterial properties in models of P. aeruginosa-infected pneumonia and wounds. Hence, this light-activatable antibacterial nanoplatform with good biocompatibility presents great potential to advance the clinical development in the treatment of bacterial infections.

The effect of group art therapy on the stress coping ability of Chinese international students in South Korea: using the person-in-the-rain test.

Introduction: This study aimed to determine the effectiveness of group therapy on the stress coping skills of Chinese students in Korea using a pre-test post-test control group design. Methods: Thirty participants were randomly placed into an experimental group (EG; n = 15) and a control group (CG; n = 15). The EG completed eight 120-min sessions of group art therapy. The Person-in-the-Rain (PITR) drawing test was conducted with both groups before and after the EG completed art therapy. Results: The test revealed that EG members demonstrated lower stress and significantly higher stress resources and coping abilities than the CG members after the intervention. The group art therapy program improved the EG participants' ability to deal with stress. Discussion: This study's findings may offer insights useful for determining how best to provide psychological and emotional support to international students who have left their home countries and are continuing their academic journeys abroad.

In-situ Formation of a LiF-rich Interphase for Graphite Anode Operated at Low Temperatures.

Inorganic LiF is generally a desirable component in solid electrolyte interface (SEI) for graphite anode due to its electronic insulation, low Li+ diffusion barrier, high modulus and good chemical stability. Herein, fluorinated carbon (CFx) was incorporated into graphite material, which exhibited a high discharge potential prior to electrolyte decomposition and in-situ formed a crystalline LiF-based SEI with improved Li+ diffusion rate. The optimized graphite anode therefore demonstrated a fast-charging capability with 124 mAh g-1 at high rate of 8 C and a remarkable capacity retention of 83.8% at the low temperature of -30 oC compared to that at 25 oC. Furthermore, the optimized graphite|LiFePO4 full cell exhibited a significantly high discharge capacity of 109 mAh g-1 at -30 oC, corresponding to a notable 77.3% room-temperature capacity retention. These findings highlight a facile strategy to attain a LiF-rich SEI for high-performance lithium-ion batteries.

Apelin Receptor Homodimerisation Inhibits Hippocampal Neuronal Autophagy via G Protein-Dependent Signalling in Vascular Dementia.

Vascular dementia (VD), a progressive vascular cognitive impairment, is characterised by the presence of cerebral hypoperfusion, increased blood-brain barrier permeability, and white matter lesions. Although current treatment strategies primarily focus on risk factors such as hypertension, diabetes, and heart disease, efficient and targeted therapies are lacking and the underlying mechanisms of VD remain unclear. We previously discovered that Apelin receptors (APJ), which are G protein-coupled receptors (GPCRs), can homodimerize and generate signals that are distinct from those of APJ monomers in VD rats. Apelin-13 reduces the level of APJ homodimers and leads to the proliferation of endogenous neural stem cells in the hippocampal dentate gyrus area, suggesting that it has a neuroprotective role. In this study, we established a rat and cellular oxygen-glucose deprivation/reoxygenation VD model to investigate the impact of APJ homodimerisation on autophagy. We found that APJ homodimers protect against VD by inhibiting autophagy through the Gαq and PI3K/Akt/mTOR pathways upon Gαi signalling, both in vivo and in vitro. This discovery provides a promising therapeutic target for chronic cerebral ischaemia-reperfusion diseases and an experimental foundation for the development of drugs that target APJ homodimers.

Effect of Nanoparticle Curvature on Its Interaction with Serum Proteins.

The size or the curvature of nanoparticles (NPs) plays an important role in regulating the composition of the protein corona. However, the molecular mechanisms of how curvature affects the interaction of NPs with serum proteins still remain elusive. In this study, we employ all-atom molecular dynamics simulations to investigate the interactions between two typical serum proteins and PEGylated Au NPs with three different surface curvatures (0, 0.1, and 0.5 nm-1, respectively). The results show that for proteins with a regular shape, the binding strength between the serum protein and Au NPs decreases with increasing curvature. For irregularly shaped proteins with noticeable grooves, the binding strength between the protein and Au NPs does not change obviously with increasing curvature in the cases of smaller curvature. However, as the curvature continues to increase, Au NPs may act as ligands firmly adsorbed in the protein grooves, significantly enhancing the binding strength. Overall, our findings suggest that the impact of NP curvature on protein adsorption may be nonmonotonic, which may provide useful guidelines for better design of functionalized NPs in biomedical applications.

Chromosome-level genome assembly of Aquilaria yunnanensis.

Aquilaria yunnanensis is an endangered agarwood-producing tree currently listed on the IUCN Red List of Threatened Species. The agarwood it produces has important medicinal and economic value, but its population has sharply declined due to human destruction and habitat reduction. Therefore, obtaining genomic information on A. yunnanensis is beneficial for its protection work. We assembled a chromosome-level reference genome of A. yunnanensis by using BGI short reads, PacBio HiFi long reads, coupled with Hi-C technology. The final genome assembly of A. yunnanensis is 847.04 Mb, with N50 size of 99.68 Mb, in which 805.49 Mb of the bases were anchored on eight pseudo-chromosomes. Two gapless pseudo-chromosomes were detected in the assembly. A total of 27,955 protein-coding genes as well as 74.65% repetitive elements were annotated. These findings may provide valuable resources in conservation, functional genomics, and molecular breeding of A. yunnanensis, as well as the molecular phylogenetics and evolutionary patterns in Aquilaria.

Associations of gallbladder and gallstone parameters with clinical outcomes in patients with cirrhosis.

Background: Morphologic changes in the gallbladder and gallstones are common in cirrhotic patients, but their associations with outcomes of cirrhotic patients are unclear. Methods: We retrospectively enrolled 206 cirrhotic patients and measured their gallbladder length and width, gallbladder wall thickness, presence of gallstones, and gallstones' length and width in axial contrast-enhanced computed tomography (CT) images. X-tile software was utilized to calculate the optimal cutoff values of these parameters for evaluating survival and hepatic decompensation events in the cirrhosis group. Their associations with survival were explored by Cox regression analyses and Kaplan-Meier curve analyses. Their associations with hepatic decompensation events were evaluated by competing risk analyses and Nelson-Aalen cumulative risk curve analyses where death was a competing event. Results: Cirrhotic patients with gallbladder length < 72 mm had a significantly higher cumulative survival rate than those with a length of ≥ 72 mm (P = 0.049 by log-rank test), but gallbladder width, gallbladder wall thickness, presence of gallstones, and gallstones' length and width were not significantly associated with survival (P = 0.10, P = 0.14, P = 0.97, P = 0.73, and P = 0.73 by log-rank tests, respectively). Cirrhotic patients with gallbladder wall thickness < 3.4 mm had a significantly lower cumulative rate of hepatic decompensation events than those with a wall thickness of ≥ 3.4 mm (P = 0.02 by Gray's test), but gallbladder length and width, presence of gallstones, and gallstones' length and width were not significantly associated with hepatic decompensation events (P = 0.15, P = 0.15, P = 0.54, P = 0.76, and P = 0.54 by Gray's tests, respectively). Conclusion: Changes in gallbladder length and gallbladder wall thickness, rather than gallstone parameters, may be in parallel with the long-term outcomes of cirrhotic patients.

The abundant fraction of soil microbiomes regulates the rhizosphere function in crop wild progenitors.

The rhizosphere influence on the soil microbiome and function of crop wild progenitors (CWPs) remains virtually unknown, despite its relevance to develop microbiome-oriented tools in sustainable agriculture. Here, we quantified the rhizosphere influence-a comparison between rhizosphere and bulk soil samples-on bacterial, fungal, protists and invertebrate communities and on soil multifunctionality across nine CWPs at their sites of origin. Overall, rhizosphere influence was higher for abundant taxa across the four microbial groups and had a positive influence on rhizosphere soil organic C and nutrient contents compared to bulk soils. The rhizosphere influence on abundant soil microbiomes was more important for soil multifunctionality than rare taxa and environmental conditions. Our results are a starting point towards the use of CWPs for rhizosphere engineering in modern crops.

Marginal fit and retention force of zirconia resin-bonded fixed dental prostheses in the posterior region with different designs.

Background/purpose: Retainer debonding of resin-bonded fixed dental prostheses (RBFDPs) is one of the major reasons for their lower survival rates than fixed dental prostheses (FDPs) with full-coverage crowns. Recent advances in milling technology have enabled the fabrication of RBFDPs with complex retainers (D-shaped designs). This study aimed to assess the marginal fit and retention force of zirconia RBFDPs with inlay-, L-, and D-shaped designs to clarify their clinical applications. Materials and methods: Three abutment teeth models without maxillary second premolars were created using inlay-, L-, and D-shaped retainer designs. The zirconia RBFDPs were designed and fabricated according to the manufacturer's instructions (n = 10). The marginal gap was measured using the silicone replica technique. Zirconia frameworks were bonded to the abutment teeth using resin cement. Tensile test was conducted after thermal cycling and dynamic loading tests. The loads during debonding or fracture were recorded. The failure pattern was analyzed by observing the fracture surface using a scanning electron microscope. Results: D-shaped RBFDPs showed a significantly larger marginal gap than inlay- and L-shaped RBFDPs (P < 0.05). However, the mean marginal values were clinically acceptable (<120 µm). The D-shaped model exhibited the highest tensile strength in the tensile tests. The inlay-shaped and most of the D-shaped RBFDPs experienced debonding with cohesive failure, whereas the L-shaped RBFDPs showed fractures near the connector. Conclusion: The D-shaped retainer design was superior to the inlay- and L-shaped designs with respect to the inhibition of retainer debonding. However, the marginal fitness needs to be improved.

Exploring Anthracycline-Induced Cardiotoxicity from the Perspective of Protein Quality Control.

Anthracyclines are effective anticancer drugs; however, their use is restricted because of their dose-dependent, time-dependent and irreversible myocardial toxicity. The mechanism of anthracycline cardiotoxicity has been widely studied but remains unclear. Protein quality control is crucial to the stability of the intracellular environment and, ultimately, to the heart because cardiomyocytes are terminally differentiated. Two evolutionarily conserved mechanisms, autophagy, and the ubiquitin-proteasome system, synergistically degrade misfolded proteins and remove defective organelles. Recent studies demonstrated the importance of these mechanisms. Further studies will reveal the detailed metabolic pathway and metabolic control of the protein quality control mechanism integrated into anthracycline-induced cardiotoxicity. This review provides theoretical support for clinicians in the application and management of anthracyclines.

Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside.

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment of advanced HCC, but problems such as drug resistance and immune-related adverse events still exist in clinical practice. The immunosuppressive tumor microenvironment (TME) of HCC restricts the efficacy of immunotherapy and is essential for HCC progression and metastasis. Therefore, it is necessary to elucidate the mechanisms behind immunosuppressive TME to develop and apply immunotherapy. This review systematically summarizes the pathogenesis of HCC, the formation of the highly heterogeneous TME, and the mechanisms by which the immunosuppressive TME accelerates HCC progression and metastasis. We also review the status of HCC immunotherapy and further discuss the existing challenges and potential therapeutic strategies targeting immunosuppressive TME. We hope to inspire optimizing and innovating immunotherapeutic strategies by comprehensively understanding the structure and function of immunosuppressive TME in HCC.

Effects of Tongluo Jiedu prescription on immune function and oxidative stress in patients with oral cancer.

BACKGROUND: Oral cancer, which is caused by mucous membrane variation, represents a prevalent malignant tumor in the oral and maxillofacial region, posing a significant threat to patients' lives and safety. While surgical intervention stands as a cornerstone treatment for oral cancer patients, it carries the risk of incomplete treatment or high rates of postoperative recurrence. Hence, a multifaceted approach incorporating diverse treatment modalities is essential to enhance patient prognosis. AIM: To analyze the application effect of Tongluo Jiedu prescription as adjuvant therapy and its influence on patient prognosis in patients with oral cancer. METHODS: Eighty oral cancer patients in our hospital were selected and divided into the observation group and control group by a random number table. The control group was treated with continuous arterial infusion chemotherapy of cisplatin and 5-fluorouracil. The observation group was additionally given Tongluo Jiadu prescription. The inflammatory stress level, peripheral blood T-cell subsets, and immune function of the two groups were subsequently observed. SPSS 21.0 was used for data analysis. RESULTS: The observation group demonstrated lower levels of interleukin-6 and C-reactive protein, and a higher level of tumor necrosis factor in comparison to the control group. After treatment, the immune function in the observation group was significantly better than in the control group. CONCLUSION: Tongluo Jiedu prescription can improve the immune function and oxidative stress level of patients with oral cancer and accelerate the recovery process.

Inversion of soil organic carbon content based on the two-point machine learning method.

Soil organic carbon (SOC) is vital for the global carbon cycle and environmentally sustainable development. Meanwhile, the fast, convenient remote sensing technology has become one of the notable means to monitor SOC content. Nowadays, limitations are found in the inversion of SOC content with high-precision and complex spatial relationships based on scarce ground sample points. It is restrained by the spatial difference in the relationship between SOC content and remote sensing spectra due to the problem of different spectra for the same substance and the influence of topographic and environment (e.g. vegetation and climate). In this regard, the two-point machine learning (TPML) method, which can overcome above problems and deal with complex spatial heterogeneity of relationships between SOC and remote sensing spectra, is used to invert the SOC content in Hailun County, Heilongjiang Province, combined with derived variables from Sentinel-1, Sentinel-2, topography and environment. Based on 10-fold cross-validation and t-test, results indicate that the TPML method boasts the highest inversion accuracy, followed by random forest, gradient boosting regression tree, partial least squares regression and support vector machine. The average r, MAE, RMSE, and RPD of TPML are 0.854, 0.384 %, 0.558 %, and 1.918. Further, the TPML method has been proven to be equal to evaluating the uncertainty of inversion results, by comparing the actual and theoretical error of the inversion result in one subset. The spatial inversion result of SOC content with 10 m resolution by TPML is smoother and has more real details than other models, which are consistent with the distribution of SOC content in different land use types. This study provides both theoretical and technical guidance for using TPML method combined with spectral information of remote sensing to predict soil attributes and offer accurate uncertainty estimation, thereby opening up the opportunity for low-cost, high-precision, and large-scale SOC inversion.

Erector spinae plane block versus paravertebral block on postoperative quality of recovery in obese patients undergoing laparoscopic sleeve gastrectomy: a randomized controlled trial.

Purpose: To compare the impact of erector spinae plane block (ESPB) and paravertebral block (PVB) on the quality of postoperative recovery (QoR) of patients following laparoscopic sleeve gastrectomy (LSG). Methods: A total of 110 patients who underwent elective LSG under general anesthesia were randomly assigned to receive either ultrasound-guided bilateral ESPB or PVB at T8 levels. Before anesthesia induction, 40 mL of 0.33% ropivacaine was administered. The primary outcome was the QoR-15 score at 24 hours postoperatively. Results: At 24 hours postoperatively, the QoR-15 score was comparable between the ESPB and PVB groups (131 (112-140) vs. 124 (111-142.5), P = 0.525). Consistently, there was no significant difference in QoR-15 scores at 48 hours postoperatively, numerical rating scale (NRS) pain scores at any postoperative time points, time to first ambulation, time to first anal exhaust, postoperative cumulative oxycodone consumption, and incidence of postoperative nausea and vomiting (PONV) between the two groups (all P > 0.05). No nerve block-related complications were observed in either group. Conclusion: In patients undergoing LSG, preoperative bilateral ultrasound-guided ESPB yields comparable postoperative recovery to preoperative bilateral ultrasound-guided PVB.

Clinical potential of serum prostaglandin A2 as a novel diagnostic biomarker for hepatocellular cancer.

BACKGROUND: Hepatocellular cancer (HCC) is one of the most harmful tumors to human health. Currently, there is still a lack of highly sensitive and specific HCC biomarkers in clinical practice. In this study, we aimed to explore the diagnostic performance of prostaglandin A2 (PGA2) for the early detection of HCC. METHODS: Untargeted metabolomic analyses on normal control (NC) and HCC participants in the discovery cohort were performed, and PGA2 was identified to be dysregulated in HCC. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detecting serum PGA2 was established and applied to validate the dysregulation of PGA2 in another independent validation cohort. Receiver operating characteristic (ROC), decision curve analysis (DCA) and some other statistical analyses were performed to evaluate the diagnostic performance of PGA2 for HCC. RESULTS: At first, PGA2 was found to be dysregulated in HCC in untargeted metabolomic analyses. Then a precise quantitative LC-MS/MS method for PGA2 has been established and has passed rigorous method validation. Targeted PGA2 analyses confirmed that serum PGA2 was decreased in HCC compared to normal-risk NC and high-risk cirrhosis group. Subsequently, PGA2 was identified as a novel biomarker for the diagnosis of HCC, with an area under the ROC curve (AUC) of 0.911 for differentiating HCC from the combined NC + cirrhosis groups. In addition, PGA2 exhibited high performance for differentiating small-size (AUC = 0.924), early-stage (AUC = 0.917) and AFP (-) HCC (AUC = 0.909) from the control groups. The combination of PGA2 and AFP might be useful in the surveillance of risk population for HCC and early diagnosis of HCC. CONCLUSION: This study establishes that PGA2 might be a novel diagnostic biomarker for HCC.