Pazopanib attenuated bleomycin-induced pulmonary fibrosis via suppressing TGF-ß1 signaling pathway.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a high mortality rate and limited treatment efficacy. Nintedanib, a tyrosine kinase inhibitor, is clinically used to treat pulmonary fibrosis. At present, only nintedanib is on the market for the treatment of pulmonary fibrosis. Pazopanib is a drug for the treatment of renal cell carcinoma and advanced soft tissue sarcoma. Methods: In this study, we explored whether pazopanib can attenuate bleomycin (BLM)-induced pulmonary fibrosis and explored its antifibrotic mechanism. In vivo and in vitro investigations were carried out to investigate the efficacy and mechanism of action of pazopanib in pulmonary fibrosis. Results: In vivo experiments showed that pazopanib can alleviate pulmonary fibrosis caused by BLM, reduce the degree of collagen deposition and improve lung function. In vitro experiments showed that pazopanib suppressed transforming growth factor-ß1 (TGF-ß1)-induced myofibroblast activation and promoted apoptosis and autophagy in myofibroblasts. Further mechanistic studies demonstrated that pazopanib inhibited the TGF-ß1/Smad and non-Smad signaling pathways during fibroblast activation. Conclusions: In conclusion, pazopanib attenuated BLM-induced pulmonary fibrosis by suppressing the TGF-ß1 signaling pathway. Pazopanib inhibits myofibroblast activation, migration, autophagy, apoptosis, and extracellular matrix (ECM) buildup by downregulating the TGF-ß1/Smad signal route and the TGF-ß1/non-Smad signal pathway. It has the same target as nintedanib and is a tyrosine kinase inhibitor.

Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019.

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Radiation polymerization for the preparation of universal coatings: remarkable anti-fogging and frost-resisting performance.

Hydrophilic anti-fogging coatings have attracted considerable attention due to their ease of preparation and excellent fog resistance. In this study, a hydrophilic anti-fogging coating based on the random copolymer p(AA-co-SAS) was prepared using acrylic acid (AA) and sodium allylsulfonate (SAS) as monomers through radiation polymerization. The introduction of SAS successfully transformed the random copolymer from a gel state into a film-forming polymer solution. The presence of AA structural units in p(AA-co-SAS) improved the film-forming properties of the polymer solution. Additionally, there was a positive correlation between the proportion of SAS structural units in the random copolymer and the scratch hardness and wetting properties of the coating. After coating polycarbonate (PC) sheets, the surface hydrophilicity was significantly enhanced, with the contact angle of PC-AA10/SAS5 decreasing from 100.1° to 18.8° within 50 seconds. The outstanding wetting properties endowed the coating with exceptional anti-fogging and frost-resisting performance. It exhibited optimal transparency under both testing conditions and demonstrated good stability during cyclic testing. Tape adhesion tests indicated that the adhesion between the coating and PC reached a 5B level. When AA10/SAS5 was applied to PET film, glass, and PMMA goggles, all samples showed excellent anti-fog performance. Even after being naturally placed for one year under ambient conditions, the PMMA goggles still maintained good performance in the anti-fog and frost resistance tests. The remarkable comprehensive properties of the polymer coating based on p(AA-co-SAS) suggest enormous potential applications in industries such as packaging, healthcare, and optical equipment.

Resolution-increased fiber-optic strain sensor with a large dynamic range driven by white light.

The white light interferometer is advantageous for wavelength division multiplexing (WDM), but the excessive noise floor limits its application in practicality. In this Letter, we propose a fiber-optic sensor driven by a broadband light source, which uses a fiber-optic Fabry-Perot cavity and a reference interferometer to enhance strain resolution. In the experiment, the strain resolution of a 5.86 m resonant sensor is 18.5 fɛ/H z at 1.5 kHz, while the maximum detectable signal is over 230 rad at 1 kHz. With low cost, this method provides a new, to the best of our knowledge, solution for WDM sensing arrays with a large dynamic range.

Enzyme Engineering Renders Chlorinase the Activity of Fluorinase.

Organofluorine compounds have attracted substantial attention owing to their wide application in agrochemistry. Fluorinase (FlA) is a unique enzyme in nature that can incorporate fluorine into an organic molecule. Chlorinase (SalL) has a similar mechanism as fluorinase and can use chloride but not fluoride as a substrate to generate 5'-chloro-deoxyadenosine (5'-ClDA) from S-adenosyl-l-methionine (SAM). Therefore, identifying the features that lead to this selectivity for halide ions is highly important. Here, we engineered SalL to gain the function of FlA. We found that residue Tyr70 plays a key role in this conversion through alanine scanning. Site-saturation mutagenesis experiments demonstrated that Y70A/C/S/T/G all exhibited obvious fluorinase activity. The G131S mutant of SalL, in which the previously thought crucial residue Ser158 for fluoride binding in FlA was introduced, did not exhibit fluorination activity. Compared with the Y70T single mutant, the double mutant Y70T/W129F increased 5'-fluoro-5-deoxyadenosine (5'-FDA) production by 76%. The quantum mechanics (QM)/molecular mechanics (MM) calculations suggested that the lower energy barriers and shorter nucleophilic distance from F- to SAM in the mutants than in the SalL wild-type may contribute to the activity. Therefore, our study not only renders SalL the activity of FlA but also sheds light on the enzyme selectivity between fluoride versus chloride.

Enzyme-responsive controlled-release materials for food preservation and crop protection - A review.

The adoption of environmentally friendly and efficient methods to control food spoilage and crop diseases has become a new worldwide trend. In the medical field, various enzyme-responsive controlled-release drug formulations have been developed for precision therapy. Recently, these materials and techniques have also begun to be applied in the fields of food preservation and agricultural protection. This review of contemporary research focuses on applications of enzyme-responsive controlled-release materials in the field of food preservation and crop protection. It covers a variety of composite controlled-release materials triggered by different types of enzymes and describes in detail their composition and structure, controlled-release mechanisms, and practical application effects. The enzyme-responsive materials have been employed to control foodborne pathogens, fungi, and pests. These enzyme-responsive controlled-release materials exhibit excellent capabilities for targeted drug delivery. Upon contact with microorganisms or pests, the polymer shell of the material is degraded by secreted enzymes from these organisms, thereby releasing drugs that kill or inhibit the organisms. In addition, multi-enzyme sensitive carriers have been created to improve the effectiveness and broad spectrum of the delivery system. The increasing trend towards the use of enzyme-responsive controlled-release materials has opened up countless possibilities in food and agriculture.

The haplotype-resolved T2T genome of teinturier cultivar Yan73 reveals the genetic basis of anthocyanin biosynthesis in grapes.

Teinturier grapes are characterized by the typical accumulation of anthocyanins in grape skin, flesh, and vegetative tissues, endowing them with high utility value in red wine blending and nutrient-enriched foods developing. However, due to the lack of genome information, the mechanism involved in regulating teinturier grape coloring has not yet been elucidated and their genetic utilization research is still insufficient. Here, the cultivar 'Yan73' was used for assembling the telomere-to-telomere (T2T) genome of teinturier grapes by combining the High Fidelity (HiFi)， Hi-C and ultralong Oxford Nanopore Technologies (ONT) reads. Two haplotype genomes were assembled, at the sizes of 501.68 Mb and 493.38 Mb, respectively. In the haplotype 1 genome, the transposable elements (TEs) contained 32.77% of long terminal repeats (LTRs), while in the haplotype 2 genome, 31.53% of LTRs were detected in TEs. Furthermore, obvious inversions were identified in chromosome 18 between the two haplotypes. Transcriptome profiling suggested that the gene expression patterns in 'Cabernet Sauvignon' and 'Yan73' were diverse depending on tissues, developmental stages, and varieties. The transcription program of genes in the anthocyanins biosynthesis pathway between the two cultivars exhibited high similarity in different tissues and developmental stages, whereas the expression levels of numerous genes showed significant differences. Compared with other genes, the expression levels of VvMYBA1 and VvUFGT4 in all samples, VvCHS2 except in young shoots and VvPAL9 except in the E-L23 stage of 'Yan73' were higher than those of 'Cabernet Sauvignon'. Further sequence alignments revealed potential variant gene loci and structure variations of anthocyanins biosynthesis related genes and a 816 bp sequence insertion was found in the promoter of VvMYBA1 of 'Yan73' haplotype 2 genome. The 'Yan73' T2T genome assembly and comparative analysis provided valuable foundations for further revealing the coloring mechanism of teinturier grapes and the genetic improvement of grape coloring traits.

[Synthesis and application of the methyl analogues of S-adenosyl-L-methionine].

Methylation plays a vital role in biological systems. SAM (S-adenosyl-L-methionine), an abundant cofactor in life, acts as a methyl donor in most biological methylation reactions. SAM-dependent methyltransferases (MTase) transfer a methyl group from SAM to substrates, thereby altering their physicochemical properties or biological activities. In recent years, many SAM analogues with alternative methyl substituents have been synthesized and applied to methyltransferases that specifically transfer different groups to the substrates. These include functional groups for labeling experiments and novel alkyl modifications. This review summarizes the recent progress in the synthesis and application of SAM methyl analogues and prospects for future research directions in this field.

Establishment and validation of a novel lysosome-related gene signature for predicting prognosis and immune landscape in hepatocellular carcinoma.

BACKGROUND: Recent studies have shown that lysosomes not only provide energy for tumor cell growth, but also participate in the occurrence and development of malignant tumors by regulating various ways of tumor cell death. However, the role of lysosome associated genes (LSAGs) in hepatocellular carcinoma (HCC) remains unclear. METHODS: Transcriptome data and clinical data of HCC were downloaded from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. We identified differential expression of LSAGs by comparing tumor tissue with normal liver tissue. Subsequently, we used univariate COX analysis and least absolute shrinkage and selection operator (LASSO) COX regression to construct the prognostic feature of LSAGs. Kaplan-Meier survival curve and receiver operating characteristic curve were used to evaluate the predictive ability of LSAGs feature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional enrichment analysis of risk differential genes. The relationship between LSAGs score and tumor microenvironment and chemotherapy drug sensitivity was analyzed. Finally, the cellular communication of tumor cells with high and low expression of model LSAGs was explored. RESULTS: We identified sixteen prognostic associated LSAGs, four of which were selected to construct prognostic feature of LSAGs. Patients in the low LSAGs group had a better prognosis than those in the high LSAGs group. GO and KEGG analyses showed that risk differential genes were enriched in leukocyte migration, cytokine-cytokine receptor interaction and PI3K-Akt signaling pathway. The group with low LSAGs score had lower immune score. Patients in the high LSAGs group were more sensitive to drugs for chemotherapy. In addition, tumor cells with high expression of model LSAGs showed stronger association with immune cells through the interleukin-2 (IL2), fibroblast growth factor (FGF), adiponectin, and bone morphogenetic proteins (BMP) signaling pathways. CONCLUSION: We established a LSAGs signature that had the ability to predict clinical prognosis and immune landscape, proposing potential therapeutic targets for HCC.

Factors associated with delayed diagnosis of Crohn's disease: A systematic review and meta-analysis.

Background: Delayed diagnosis is a major barrier to the effective management of Crohn's disease (CD). Several studies have investigated factors responsible for delays in diagnosis, but no meta-analyses have systematically assessed the impact of these factors. Aim: To assess the impact of various factors on the delayed diagnosis of CD. Methods: PubMed, EMBASE, and Web of Science databases were searched to identify observational studies published before April 2022 that assessed factors associated with delays in CD diagnosis. Further, we excluded review articles, case reports, or commentaries without original data. We pooled effect siee distinct samples. The assessment of study quality was performed utilizing the Newcastle-Ottawa Scale, while the presence of between-study heterogeneity was investigated. For a visual appraisal of potential publication bias, a funnel plot was employed. The study protocol was registered with PROSPERO, CRD42022322251. Results: A total of 18 studies were included in the paper, covering 13 countries. The study sample consisted of 9669 cases. Ileal CD (OR = 1.46, 95 % CI = 1.21-1.76), smoking at the time of diagnosis (OR = 1.19, 95 % CI = 1.02-1.38), and use of NSAIDs (OR = 1.34, 95 % CI = 1.04-1.72) were significantly associated with a delay in CD diagnosis. However, no significant associations were observed between diagnostic delay and sex, age, endoscopic ileocolonoscopy, or diarrhea. Funnel plot analysis, indicating potential risks of publication bias, suggested the existence of unpublished or unreported study findings. Conclusion: The findings suggest that ileal CD, use of NSAIDs, and smoking are risk factors for the delayed diagnosis of CD. Enhancing education of patients and primary care providers about these factors is warranted.

Primary malignant bone tumors incidence, mortality, and trends in China from 2000 to 2015.

BACKGROUND: Primary malignant bone tumors are uncommon, and their epidemiological features are rarely reported. We aimed to study the incidence and death characteristics of bone tumors from 2000 to 2015. METHODS: Population-based cancer registries submitted registry data to National Central Cancer Registry of China (NCCRC). The data collected from 501 local cancer registries in China were assessed using NCCRC screening methods and criteria. Incidence and mortality rates of primary bone tumor were stratified by age group, gender, and area. Age-standardized incidence and mortality rates were adjusted using the Chinese standard population in 2000 and Segi's world population. The annual percentage change (APC) in rate was calculated using the Joinpoint Regression Program. RESULTS: Data from 368 registries met quality control criteria, of which 134 and 234 were from urban and rural areas, respectively. The data covered 309,553,499 persons. The crude incidence, age-standardized incidence, and crude mortality rates were 1.77, 1.35, and 1.31 per 100,000, respectively. Incidence and mortality rates were higher in males than those in females; they showed downward trends, with declines of 2.2% and 4.8% per year, respectively, and the rates in urban areas were lower than those in rural areas. Significant declining trends were observed in urban areas. Stable trends were seen in rural areas during 2000 to 2007, followed by downward trends. Age-specific incidence and mortality rates showed stable trends in the age group of 0 to 19 years, and downward trends in the age group elder than 19 years. CONCLUSIONS: The incidence and mortality rates of primary malignant bone tumors in rural areas were higher compared to those in urban areas. Targeted prevention measures are required to monitor and control bone tumor incidence and improve the quality of life of affected patients. This research can provide a scientific basis for the prevention and control of bone tumors, as well as basic information for follow-up research.

Exosome-derived miR-372-5p promotes stemness and metastatic ability of CRC cells by inducing macrophage polarization.

Colorectal cancer (CRC) is the most common malignancy in the digestive system, and tumor metastasis is the main cause of death in clinical patients with CRC. It has been shown that exosomes promote phenotypic changes in macrophages and tumor metastasis in the CRC tumor microenvironment. In this study, we used miRNA-seq technology to screen out the highly expressed miR-372-5p among the miRNAs differentially expressed in plasma exosomes of clinical CRC patients. It was found that miR-372-5p highly expressed in HCT116 exosomes could be phagocytosed by macrophages and promote their polarization into M2 macrophages by regulating the PTEN/AKT pathway. Meanwhile, co-culture of CRC cells with conditioned medium (CM) of macrophages enhanced the EMT, stemness and metastasis of CRC cells. Mechanistically, CRC cells exosome-derived miR-372-5p induced polarized M2 macrophages to secrete chemokine C-X-C-Motif Ligand 12 (CXCL12), which activated the WNT/ß-catenin pathway to promote the EMT, stemness and metastatic ability of CRC cells. In summary, this study elucidated the molecular mechanism of exosomal miR-372-5p promoting metastasis and stemness in CRC, which may provide new therapeutic targets for CRC metastasis and prognosis assessment.

The alleviating effect and mechanism of GLP-1 on ulcerative colitis.

Ulcerative Colitis (UC) is a major type of chronic inflammatory bowel disease of the colonic mucosa and exhibits progressive morbidity. The incidence and prevalence of UC is increasing worldwide. The global burden of UC, which can substantially reduce quality of life, is clearly increasing. These data highlight the need for research into prevention of UC and innovations in health-care systems to manage this complex and costly disease. Glucagon-like peptide-1 (GLP-1), a new antidiabetic drug, is used to treat Type 2 Diabetes Mellitus (T2DM). Accumulating evidence suggests that GLP-1 has additional roles other than glucose-lowering effects. Despite the abundance of GLP-1 research, studies in UC have been less consistent, especially body weight; for example, body weight, colon length, colon injury score, intestinal microbiota, remain to be studied further. To date, the molecular mechanism of the protective effect of GLP-1 on UC remains obscure. The effect of GLP-1 was studied by using a dextran sulfate sodium (DSS)-induced colitic mice and lipopolysaccharide (LPS) treated RAW264.7 cells (macrophage cell line) under in vivo and in vitro conditions, respectively. Our results indicate that GLP-1 significantly relieves ulcerative colitis as it represses the production of proinflammatory mediators. In addition, GLP-1 blocks the activation of the protein kinase B (AKT)/nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. GLP-1 also alleviates DSS-induced injury to the intestinal mucosa and dysbiosis of gut microbiota. Altogether, GLP-1 has protection effect on ulcerative colitis. Thus, GLP-1 can be considered as a potential therapeutic candidate for the treatment of UC.

Colorectal cancer tumor cell-derived exosomal miR-203a-3p promotes CRC metastasis by targeting PTEN-induced macrophage polarization.

(1) Background: Tumor-associated macrophages (TAMs) are important immunocytes associated with liver metastasis of colorectal cancer (CRLM). However, the molecular processes underpinning the interaction between the TME and the tumour-derived exosomal miRNAs in CRLM are not being fully understood; (2) Methods: Transmission electron microscopy was utilized to confirm the existence of exosomes after differential ultracentrifugation. To determine the roles of exosomal miR-203a-3p, an in vivo and in vitro investigation was conducted. The mechanism by which exosomal miR-203a-3p governs the interaction between CRC cells and M2 macrophages was investigated using a dual-luciferase reporter assay, western blot, and other techniques; (3) Results: Overexpression of miR-203a-3p was associated with poor prognosis and liver metastasis in CRC patients. Exosomal miR-203a-3p was upregulated in the plasma of CRC patients and highly metastatic CRC cells HCT116, and it could be transported to macrophages via exosomes. Exosomal miR-203a-3p induced M2 polarization of macrophages by controlling PTEN and activating the PI3K/Akt signaling pathway. M2-polarized macrophages secreted the CXCL12, which increased cancer metastasis and resulted in pre-metastatic niches in CRLM by CXCL12/CXCR4/NF-κB signaling pathway. Co-culture of macrophages with miR-203a-3p-transfected or exosome-treated cells increased the ability of HCT116 cells to metastasize both in vitro and in vivo; (4) Conclusions: Exosomes produced by highly metastatic CRC cells and rich in miR-203a-3p may target PTEN and alter the TME, promoting liver metastasis in CRC patients. These findings offer fresh understanding of the liver metastatic process in CRC.

Prognostic Prediction Value and Biological Functions of Non-Apoptotic Regulated Cell Death Genes in Lung Adenocarcinoma.

Objective To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.Methods Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software. Results We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, p53 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4, JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes. Conclusion The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

Layered Double Hydroxide-Loaded miR-30a for the Treatment of Breast Cancer In Vitro and In Vivo.

MicroRNAs (miRNAs) play an essential role in cancer therapy, but the disadvantages of its poor inherent stability, rapid clearance, and low delivery efficiency affect the therapeutic efficiency. Loading miRNAs by nanoformulations can improve their bioavailability and enhance therapeutic efficiency, which is an effective miRNA delivery strategy. In this study, we synthesized layered double hydroxides (LDH), which are widely used as carriers of drugs or genes due to the characteristics of good biocompatibility, high loading capacity, and pH sensitivity. We loaded the suppressor oncogene miR-30a on LDH nanomaterials (LDH@miR-30a) and determined the mass ratio of miRNA binding to LDH by agarose gel electrophoresis. LDH@miR-30a was able to escape the lysosomal pathway and was successfully phagocytosed by breast cancer SKBR3 cells and remained detectable in the cells after 24 h of co-incubation. In vitro experiments showed that LDH@miR-30a-treated SKBR3 cells showed decreased proliferation and cell cycle arrest in the G0/G1 phase and LDH@miR-30a was able to regulate the epithelial-mesenchymal transition (EMT) process and inhibit cell migration and invasion by targeting SNAI1. Meanwhile, in vivo experiments showed that nude mice treated with LDH@miR-30a showed a significant reduction in their solid tumors and no significant impairment of vital organs was observed. In conclusion, LDH@miR-30a is an effective drug delivery system for the treatment of breast cancer.

Indoor Visible Light Positioning System Based on Point Classification Using Artificial Intelligence Algorithms.

In RSSI-based indoor visible light positioning systems, when only RSSI is used for trilateral positioning, the receiver height needs to be known to calculate distance. Meanwhile, the positioning accuracy is greatly affected by multi-path effect interference, with the influence of the multi-path effect varying across different areas of the room. If only one single processing is used for positioning, the positioning error in the edge area will increase sharply. In order to address these problems, this paper proposes a new positioning scheme, which uses artificial intelligence algorithms for point classification. Firstly, height estimation is performed according to the received power data structure from different LEDs, which effectively extends the traditional RSSI trilateral positioning from 2D to 3D. The location points in the room are then divided into three categories: ordinary points, edge points and blind points, and corresponding models are used to process different types of points, respectively, to reduce the influence of the multi-path effect. Next, processed received power data are used in the trilateral positioning method for calculating the location point coordinates, and to reduce the room edge corner positioning error, so as to reduce the indoor average positioning error. Finally, a complete system is built in an experimental simulation to verify the effectiveness of the proposed schemes, which are shown to achieve centimeter-level positioning accuracy.

Glycolysis-based drug delivery nanosystems for therapeutic use in tumors and applications.

Tumor cells are able to use glycolysis to produce energy under hypoxic conditions, and even under aerobic conditions, they rely mainly on glycolysis for energy production, the Warburg effect. Conventional tumor therapeutic drugs are unidirectional, lacking in targeting and have limited therapeutic effect. The development of a large number of nanocarriers and targeted glycolysis for the treatment of tumors has been extensively investigated in order to improve the therapeutic efficacy. This paper reviews the research progress of nanocarriers based on targeting key glycolytic enzymes and related transporters, and combines nanocarrier systems with other therapeutic approaches to provide a new strategy for targeted glycolytic treatment of tumors, providing a theoretical reference for achieving efficient targeted treatment of tumors.

Intensity Equalization of Bidirectional Fiber Laser Based on a Non-Reciprocal Optical Attenuator.

The application of a bidirectional laser requires the laser intensity in both directions to be balanced. However, the CW and CCW light intensities in current bidirectional erbium-doped fiber laser experiments differ due to the gain competition effect. There is no report on equalizing the intensity in the CW and CCW directions. This paper proposes a bidirectional non-reciprocal optical attenuator using the Faraday optical rotation effect. Continuous attenuation adjustment is realized by changing the angle between the polarizer's transmission axis and the linear polarized light. In this study, we analyzed the influence of different parameters on the device's performance, built a non-reciprocal attenuator, and tested the bidirectional attenuation curve, which was consistent with the simulation results. The device was integrated into a bidirectional fiber laser, and the light intensity in both directions was balanced through non-reciprocal adjustment. Combined with closed-loop control, the average intensity difference fluctuation between the two directions was controlled at 0.28% relative to the average power, realizing stable long-term bidirectional fiber laser intensity equalization.

Predicting the risk factors of diabetic ketoacidosis-associated acute kidney injury: A machine learning approach using XGBoost.

Objective: The purpose of this study was to develop and validate a predictive model based on a machine learning (ML) approach to identify patients with DKA at increased risk of AKI within 1 week of hospitalization in the intensive care unit (ICU). Methods: Patients diagnosed with DKA from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database according to the International Classification of Diseases (ICD)-9/10 code were included. The patient's medical history is extracted, along with data on their demographics, vital signs, clinical characteristics, laboratory results, and therapeutic measures. The best-performing model is chosen by contrasting the 8 Ml models. The area under the receiver operating characteristic curve (AUC), sensitivity, accuracy, and specificity were calculated to select the best-performing ML model. Results: The final study enrolled 1,322 patients with DKA in total, randomly split into training (1,124, 85%) and validation sets (198, 15%). 497 (37.5%) of them experienced AKI within a week of being admitted to the ICU. The eXtreme Gradient Boosting (XGBoost) model performed best of the 8 Ml models, and the AUC of the training and validation sets were 0.835 and 0.800, respectively. According to the result of feature importance, the top 5 main features contributing to the XGBoost model were blood urea nitrogen (BUN), urine output, weight, age, and platelet count (PLT). Conclusion: An ML-based individual prediction model for DKA-associated AKI (DKA-AKI) was developed and validated. The model performs robustly, identifies high-risk patients early, can assist in clinical decision-making, and can improve the prognosis of DKA patients to some extent.