Modulating macrophage phenotype for accelerated wound healing with chlorogenic acid-loaded nanocomposite hydrogel.

Wound healing involves distinct phases, including hemostasis, inflammation, proliferation, and remodeling, which is a complex and dynamic process. Conventional preparations often fail to meet multiple demands and provide prompt information about wound status. Here, a pH/ROS dual-responsive hydrogel (OHA-PP@Z-CA@EGF) was constructed based on oxidized hyaluronic acid (OHA), phenylboronic acid-grafted ε-polylysine (PP), chlorogenic acid (CA)-loaded ZIF-8 (Z-CA), and epidermal growth factor (EGF), which possesses intrinsic antibacterial, antioxidant, and angiogenic capacities. Due to the Schiff base and Phenylboronate ester bonds, the hydrogel exhibited excellent mechanical properties, strong adhesion, good biodegradability, high biocompatibility, stable rheological properties, and self-healing ability. Moreover, introducing Z-CA as an initiator and nanofiller led to the additional cross-linking of hydrogel through coordination bonds, which further improved the mechanical properties and antioxidant capabilities. Bleeding models of liver and tail amputations demonstrated rapid hemostatic properties of the hydrogel. Besides, the hydrogel regulated macrophage phenotypes via the NF-κB/JAK-STAT pathways, relieved oxidative stress, promoted cell migration and angiogenesis, and accelerated diabetic wound healing. The hydrogel also enabled real-time monitoring of the wound healing stages by colorimetric detection. This multifunctional hydrogel opens new avenues for the treatment and management of full-thickness diabetic wounds.

G-YOLO: A YOLOv7-based target detection algorithm for lightweight hazardous chemical vehicles.

Hazardous chemical vehicles are specialized vehicles used for transporting flammable gases, medical waste, and liquid chemicals, among other dangerous chemical substances. During their transportation, there are risks of fire, explosion, and leakage of hazardous materials, posing serious threats to human safety and the environment. To mitigate these possible hazards and decrease their probability, this study proposes a lightweight object detection method for hazardous chemical vehicles based on the YOLOv7-tiny model.The method first introduces a lightweight feature extraction structure, E-GhostV2 network, into the trunk and neck of the model to achieve effective feature extraction while reducing the burden of the model. Additionally, the PConv is used in the model's backbone to effectively reduce redundant computations and memory access, thereby enhancing efficiency and feature extraction capabilities. Furthermore, to address the problem of performance degradation caused by overemphasizing high-quality samples, the model adopts the WIoU loss function, which balances the training effect of high-quality and low-quality samples, enhancing the model's robustness and generalization performance. Experimental results demonstrate that the improved model achieves satisfactory detection accuracy while reducing the number of model parameters, providing robust support for theoretical research and practical applications in the field of hazardous chemical vehicle object detection.

Current Advances of Nanomaterial-Based Oral Drug Delivery for Colorectal Cancer Treatment.

Colorectal cancer (CRC) is a common malignant tumor, and traditional treatments include surgical resection and radiotherapy. However, local recurrence, distal metastasis, and intestinal obstruction are significant problems. Oral nano-formulation is a promising treatment strategy for CRC. This study introduces physiological and environmental factors, the main challenges of CRC treatment, and the need for a novel oral colon-targeted drug delivery system (OCDDS). This study reviews the research progress of controlled-release, responsive, magnetic, targeted, and other oral nano-formulations in the direction of CRC treatment, in addition to the advantages of oral colon-targeted nano-formulations and concerns about the oral delivery of related therapeutic agents to inspire related research.

Zinc remodels mitochondrial network through SIRT3/Mfn2-dependent mitochondrial transfer in ameliorating spinal cord injury.

Spinal cord injury (SCI) is a traumatic neuropathic condition that results in motor, sensory and autonomic dysfunction. Mitochondrial dysfunction caused by primary trauma is one of the critical pathogenic mechanisms. Moderate levels of zinc have antioxidant effects, promote neurogenesis and immune responses. Zinc normalises mitochondrial morphology in neurons after SCI. However, how zinc protects mitochondria within neurons is unknown. In the study, we used transwell culture, Western blot, Quantitative Real-time Polymerase Chain Reaction (QRT-PCR), ATP content detection, reactive oxygen species (ROS) activity assay, flow cytometry and immunostaining to investigate the relationship between zinc-treated microglia and injured neurons through animal and cell experiments. We found that zinc promotes mitochondrial transfer from microglia to neurons after SCI through Sirtuin 3 (SIRT3) regulation of Mitofusin 2 protein (Mfn2). It can rescue mitochondria in damaged neurons and inhibit oxidative stress, increase ATP levels and promote neuronal survival. Therefore, it can improve the recovery of motor function in SCI mice. In conclusion, our work reveals a potential mechanism to describe the communication between microglia and neurons after SCI, which may provide a new idea for future therapeutic approaches to SCI.

Prevalence of cervical precancers or cancers in women with ASC-H/HSIL cytology according to Aptima HPV (AHPV) assay-detected HPV genotypes and age.

Objective: Aimed to potentially risk-stratify patients with different cervical cytology diagnoses, by HPV genotypes and/or age, we have conducted a series of studies to examine the prevalence of cervical precancers and cancers for women with different cytology diagnoses. This paper will be focusing on patients with ASC-H/HSIL cytology. Methods: In total, 1183 patients aged 20-78 years with atypical squamous cells, cannot rule out HSIL (ASC-H)/HSIL by cytology underwent AHPV assay and cervical biopsy in a developed region in southern China were included in this study. Results: Overall, 59.2% women with ASC-H/HSIL cytology had cervical intraepithelial neoplasia (CIN)2/3 lesions while 1.6% had adenocarcinoma in situ (AIS) lesions. Compared to other groups, HPV-16+ group (80.8%) showed a significantly higher prevalence of CIN2/3 than other genotype+ groups (p<0.0001). Further, HPV-16+ (9.3%) or HPV-18/45+ (6.3%) group showed a significantly higher prevalence of squamous cell carcinoma (SCC) than other genotype+ groups (p<0.0001). The prevalence of AIS glandular lesions in HPV-18/45+ group (13.8%) is significantly higher than other genotype groups (p<0.0001). When stratified by age, younger group showed a significantly higher prevalence of CIN2/3 (p=0.009) while older group presented an obvious higher prevalence of SCC (p<0.0001). Conclusions: In this patient population, among women with ASC-H/HSIL cytology, HPV positive groups are at significantly higher risk of CIN2/3 compared to HPV negative group. Specifically, prevalence of CIN2/3 and SCC is significantly higher in HPV-16+ group while AIS lesions are more prevalent among HPV-18/45+ patients. In addition, younger group showed a significantly higher prevalence of CIN2/3 while older group presented an obvious higher prevalence of SCC.

Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer's Disease.

Background: Oxidative stress induced reactive oxygen species (ROS) and aggregation of amyloid ß (Aß) in the nervous system are significant contributors to Alzheimer's disease (AD). Cerium dioxide and manganese oxide are known as to be effective and recyclable ROS scavengers with high efficiency in neuroprotection. Methods: A hollow-structured manganese-doped cerium dioxide nanoparticle (LMC) was synthesized for loading Resveratrol (LMC-RES). The LMC-RES were characterized by TEM, DLS, Zeta potential, and X-ray energy spectrum analysis. We also tested the biocompatibility of LMC-RES and the ability of LMC-RES to cross the blood-brain barrier (BBB). The antioxidant effects of LMC-RES were detected by SH-SY5Y cells. Small animal live imaging was used to detect the distribution of LMC-RES in the brain tissue of AD mice. The cognitive abilities of mice were tested by water maze and nesting experiments. The effects of LMC-RES in reducing oxidative stress and protecting neurons was also explored by histological analysis. Results: The results showed that LMC-RES had good sustained release effect and biocompatibility. The drug release rate of LMC-RES at 24 hours was 80.9 ± 2.25%. Meanwhile, LMC-RES could cross the BBB and enrich in neurons to exert antioxidant effects. In Aß-induced SH-SY5Y cells, LMC-RES could inhibits oxidative stress through the Nrf-2/HO-1 signaling pathway. In AD model mice, LMC-RES was able to reduce ROS levels, inhibit Aß-induced neurotoxicity, and protect neurons and significantly improve cognitive deficits of AD mice after drug administration. Conclusion: LMC-RES can effectively across the BBB, reduce oxidative stress, inhibit Aß aggregation, and promote the recovery of neurological function.

Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Genetic dissection and genomic prediction for pork cuts and carcass morphology traits in pig.

BACKGROUND: As pre-cut and pre-packaged chilled meat becomes increasingly popular, integrating the carcass-cutting process into the pig industry chain has become a trend. Identifying quantitative trait loci (QTLs) of pork cuts would facilitate the selection of pigs with a higher overall value. However, previous studies solely focused on evaluating the phenotypic and genetic parameters of pork cuts, neglecting the investigation of QTLs influencing these traits. This study involved 17 pork cuts and 12 morphology traits from 2,012 pigs across four populations genotyped using CC1 PorcineSNP50 BeadChips. Our aim was to identify QTLs and evaluate the accuracy of genomic estimated breed values (GEBVs) for pork cuts. RESULTS: We identified 14 QTLs and 112 QTLs for 17 pork cuts by GWAS using haplotype and imputation genotypes, respectively. Specifically, we found that HMGA1, VRTN and BMP2 were associated with body length and weight. Subsequent analysis revealed that HMGA1 primarily affects the size of fore leg bones, VRTN primarily affects the number of vertebrates, and BMP2 primarily affects the length of vertebrae and the size of hind leg bones. The prediction accuracy was defined as the correlation between the adjusted phenotype and GEBVs in the validation population, divided by the square root of the trait's heritability. The prediction accuracy of GEBVs for pork cuts varied from 0.342 to 0.693. Notably, ribs, boneless picnic shoulder, tenderloin, hind leg bones, and scapula bones exhibited prediction accuracies exceeding 0.600. Employing better models, increasing marker density through genotype imputation, and pre-selecting markers significantly improved the prediction accuracy of GEBVs. CONCLUSIONS: We performed the first study to dissect the genetic mechanism of pork cuts and identified a large number of significant QTLs and potential candidate genes. These findings carry significant implications for the breeding of pork cuts through marker-assisted and genomic selection. Additionally, we have constructed the first reference populations for genomic selection of pork cuts in pigs.

Research advances in peptide‒drug conjugates.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

Sugar accumulation enhancement in sorghum stem is associated with reduced reproductive sink strength and increased phloem unloading activity.

Sweet sorghum has emerged as a promising source of bioenergy mainly due to its high biomass and high soluble sugar yield in stems. Studies have shown that loss-of-function Dry locus alleles have been selected during sweet sorghum domestication, and decapitation can further boost sugar accumulation in sweet sorghum, indicating that the potential for improving sugar yields is yet to be fully realized. To maximize sugar accumulation, it is essential to gain a better understanding of the mechanism underlying the massive accumulation of soluble sugars in sweet sorghum stems in addition to the Dry locus. We performed a transcriptomic analysis upon decapitation of near-isogenic lines for mutant (d, juicy stems, and green leaf midrib) and functional (D, dry stems and white leaf midrib) alleles at the Dry locus. Our analysis revealed that decapitation suppressed photosynthesis in leaves, but accelerated starch metabolic processes in stems. SbbHLH093 negatively correlates with sugar levels supported by genotypes (DD vs. dd), treatments (control vs. decapitation), and developmental stages post anthesis (3d vs.10d). D locus gene SbNAC074A and other programmed cell death-related genes were downregulated by decapitation, while sugar transporter-encoding gene SbSWEET1A was induced. Both SbSWEET1A and Invertase 5 were detected in phloem companion cells by RNA in situ assay. Loss of the SbbHLH093 homolog, AtbHLH093, in Arabidopsis led to a sugar accumulation increase. This study provides new insights into sugar accumulation enhancement in bioenergy crops, which can be potentially achieved by reducing reproductive sink strength and enhancing phloem unloading.

Triple Cross-linked Dynamic Responsive Hydrogel Loaded with Selenium Nanoparticles for Modulating the Inflammatory Microenvironment via PI3K/Akt/NF-κB and MAPK Signaling Pathways.

Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri-cross-linked inflammatory microenvironment-responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment-responsive hydrogel (OD-PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano-fillers into the hydrogel results in extra cross-linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple-network is achieved. The hydrogel has injectable, self-healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli-responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH-regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF-κB and MAPK pathways, exerting anti-inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple-network structure provides an effective strategy to treat IDs, holding great promise in clinical application.

LA67 Liposome-Loaded Thermo-Sensitive Hydrogel with Active Targeting for Efficient Treatment of Keloid via Peritumoral Injection.

A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of -27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box-Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development.

[Application of U-Net network in automatic image segmentation of adenoid and airway of nasopharynx].

Objective:To explore the effect of fully automatic image segmentation of adenoid and nasopharyngeal airway by deep learning model based on U-Net network. Methods:From March 2021 to March 2022, 240 children underwent cone beam computed tomography（CBCT） in the Department of Otolaryngology, Head and Neck Surgery, General Hospital of Shenzhen University. 52 of them were selected for manual labeling of nasopharynx airway and adenoid, and then were trained and verified by the deep learning model. After applying the model to the remaining data, compare the differences between conventional two-dimensional indicators and deep learning three-dimensional indicators in 240 datasets. Results:For the 52 cases of modeling and training data sets, there was no significant difference between the prediction results of deep learning and the manual labeling results of doctors（P>0.05）. The model evaluation index of nasopharyngeal airway volume: Mean Intersection over Union（MIOU） s （86.32±0.54）%; Dice Similarity Coefficient（DSC）: （92.91±0.23）%; Accuracy: （95.92±0.25）%; Precision: （91.93±0.14）%; and the model evaluation index of Adenoid volume: MIOU: （86.28±0.61）%; DSC: （92.88±0.17）%; Accuracy: （95.90±0.29）%; Precision: （92.30±0.23）%. There was a positive correlation between the two-dimensional index A/N and the three-dimensional index AV/（AV+NAV） in 240 children of different age groups（P<0.05）, and the correlation coefficient of 9-13 years old was 0.74. Conclusion:The deep learning model based on U-Net network has a good effect on the automatic image segmentation of adenoid and nasopharynx airway, and has high application value. The model has a certain generalization ability.

[Application of virtual endoscopy in the diagnosis of adenoid hypertrophy and the morphologic classification of adenoid].

Objective:To discuss the application of virtual endoscopy in the diagnosis of adenoid hypertrophy and the morphologic classification of adenoid. Methods:The clinical data of 97 children with adenoid hypertrophy admitted to Department of Otorhinolaryngology Head and Neck Surgery, Shenzhen University General Hospital from July 2022 to December 2022 were collected. The virtual endoscopic reconstruction of the nasopharynx was performed by cone beam computed tomography. The results of virtual endoscopic adenoid size measurement were compared with the results of nasopharyngeal CT median sagittal position and nasopharyngeal endoscopy. Virtual endoscopic classification of adenoid based on the size of the adenoids and their relationship with the torus tubarius. Results:The t-test results of the size of adenoids measured by virtual endoscopy and nasopharyngeal CT were t=1.699 and P=0.093, and the results of intra-group correlation coefficient（ICC） analysis were ICC=0.921 and P<0.01. The proportion of adenoids measured by virtual endoscopy and nasopharyngeal CT was highly consistent. The t-test results of the size of adenoids measured virtual endoscopy and nasopharyngeal endoscopy were t=1.543 and P=0.15, and the results of intra-group correlation coefficient（ICC） analysis were ICC=0.900 and P<0.01. The proportion of adenoids measured by virtual endoscopy and nasopharyngeal endoscopy was highly consistent. Among the 97 children, the morphological classification results of adenoids were 48 cases of overall hypertrophy type, 47 cases of central bulge type, and 2 cases of flat thickening type. Conclusion:The diagnosis of adenoid hypertrophy by virtual endoscopy has high accuracy, which not only avoids the invasive operation of traditional nasopharyngeal endoscopy, but also can observe the adenoid condition and its relationship with the torus tubarius from multiple angles. And, the morphological classification of adenoids using virtual endoscopy has guiding significance for perioperative preparation.

[Digital technology and children's maxillofacial management].

The maxillofacial region has multiple functions such as breathing, language, and facial expressions. Children's maxillofacial development is a complex and long process, which is affected by many factors such as genetics, diseases, bad habits and trauma. Early detection, early diagnosis, and early treatment are important concepts in children's maxillofacial management. Digital technology medicine is an emerging technology based on medical imaging and anatomy that has emerged in recent years. The application of this technology in the field of clinical medicine will undoubtedly bring great benefits to children's maxillofacial management. This article summarizes the research on digital technology in children's maxillofacial management, and focuses on the research on children's malocclusion, children's OSA, cleft lip and palate and other related diseases.

Multitudinous components recovery, heavy metals evolution and environmental impact of coal gasification slag: A review.

In recent years, the coal gasification industry has rapidly developed, becoming one of the most promising technologies in the advanced and clean coal chemical industry. As a result, the annual emission of coal gasification fine slag (CGFS) has continuously increased. The present situation of CGFS is regarded as a notorious waste in gasification plants and is rudely landfilled or deposited in slag yards, which leads to a large waste of land resources, the release of dangerous elements, and numerous pollution problems. Although CGFS is classified as industrial solid waste, its unique physical and chemical properties make it a valuable resource that cannot be overlooked. This paper focuses on the resource utilization technology and environmental impact of CGFS. The resource utilization of different components of CGFS has realized the evolution from waste to valuable substances. Moreover, during the disposal and utilization of CGFS, its environmental effects cannot be ignored. The main problems and future research directions are also further proposed. Efforts should be focused on the challenges of the technology, cost, and environmental protection in the application process to achieve industrial application, and ultimately committed to sustainable and green development goals, and promote the sustainable management and conservation of resources.

Development of Novel Paclitaxel-Loaded ZIF-8 Metal-Organic Framework Nanoparticles Modified with Peptide Dimers and an Evaluation of Its Inhibitory Effect against Prostate Cancer Cells.

Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) onto the surface of PTX@ZIF-8 to prepare a nanotargeted drug delivery system (Di-PEG@PTX@ZIF-8) for the treatment of prostate cancer. This study investigated the morphology, particle size distribution, zeta potential, drug loading, encapsulation rate, stability, in vitro release behavior, and cytotoxicity of this targeted drug delivery system, and explored the uptake of Di-PEG@PTX@ZIF-8 by human prostate cancer Lncap cells at the in vitro cellular level, as well as the proliferation inhibition and promotion of apoptosis of Lncap cells by the composite nanoparticles. The results suggest that Di-PEG@PTX@ZIF-8, as a zeolitic imidazolate frameworks-8-loaded paclitaxel nanoparticle, has promising potential for the treatment of prostate cancer, which may provide a novel strategy for the delivery system targeting prostate cancer.