Prussian blue nanoparticles coated with tumor cell membranes for precise photothermal therapy and subsequent inflammation reduction.

The utilization of photothermal agents (PTAs) in photothermal therapy (PTT) is faced with challenges such as immune clearance and inadequate concentration, which consequently result in residual tumors and an increased risk of recurrence and metastasis. Conversely, excessive treatment can lead to heightened inflammation and inevitable harm to adjacent healthy tissues. To address these issues, we developed a nanosystem (M@PB) consisting of Prussian blue coated with tumor cell membrane for precise photothermal therapy (PTT) and subsequent reduction of inflammation. This system not only evades immune attack due to the homologous biological characteristics of the encapsulating cell membrane but also exhibits active targeting capabilities towards homologous tumors. Furthermore, it effectively reduces excessive phototoxicity by leveraging the distinctive photothermal and anti-inflammatory characteristics of PB nanoparticles. The resulting M@PB nanosystem demonstrates effective photothermal ablation under 808 nm laser irradiation while mitigating the inflammatory response through inhibiting of local production of inflammatory mediators. Our study provides valuable insights into achieving targeted PTT with high efficiency while minimizing post-treatment inflammatory responses.

Combined transcriptomics and metabolomics to reveal the effects of copper exposure on the liver of rainbow trout(Oncorhynchus mykiss).

Copper (Cu) is recognized as an essential trace elements for the body; However, excessive levels of Cu can lead to toxic effects. We investigated the effects of Cu2+(75 µg/L, 150 µg/L, and 300 µg/L) on the rainbow trout liver. Combination of transcriptome and metabolome analyses, the regulatory mechanisms of the liver under Cu stress were elucidated. The results showed that Cu affected the antioxidant levels, leading to disruptions in the normal tissue structure of the liver. Combined transcriptome and metabolome analyses revealed significant enrichment of the insulin signaling pathway and the adipocytokine signaling pathway. Additionally, Cu2+ stress altered the amino acid metabolism in rainbow trout by reducing serine and arginine levels while increasing proline content. Apoptosis is inhibited and autophagy and lipid metabolism are suppressed; In summary, Cu2+ stress affects energy and lipid metabolism, and the reduction of serine and arginine represents a decrease in the antioxidant capacity, whereas the increase in proline and the promotion of apoptosis potentially serving as crucial strategies for Cu2+ resistance in rainbow trout. These findings provided insights into the regulatory mechanisms of rainbow trout under Cu2+ stress and informed the prevention of heavy metal pollution and the selection of biomarkers under Cu pollution.

Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer.

BACKGROUND: Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. RESULTS: Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated "M@P-PDR"), which acted as "Nano-targeted cells" to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with "Nano-targeted cells"-based cocktail therapy. CONCLUSION: "Nano-targeted cells"-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.

Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor.

BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. RESULTS: The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSIONS: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.

Renal Safety of Intra-Arterial Treatment after Acute Ischemic Stroke with Multimodal CT Imaging selection.

BACKGROUND: Multimodal computed tomography imaging is used to identify eligible patients for intra-arterial treatment. A concern with this method is the multiple use of iodinated contrast material which presents a possible risk of renal toxicity. We compared the safety of intra-arterial treatment versus intravenous treatment during acute ischemic stroke treatment with a focus on renal safety. METHODS: Adult acute ischemic stroke patients who underwent a baseline Multimodal computed tomography, then intra-arterial treatment and/or intravenous treatment were identified. Primary outcomes were acute kidney injury and changes in serum creatinine at 24-72 hours (Δ serum creatinine). RESULTS: A total of 184 patients received intra-arterial treatment, while 68 received intravenous treatment. There were no differences in mean serum creatinine in the 24-72-hour time period, 24-hour urine volume, or rates of acute kidney injury, dialysis, or mortality. Univariate regression analysis identified diabetes mellitus, operation duration and times of embolectomy as predictors of creatinine increase while the multiple regression model identified diabetes mellitus as the only significant predictor. CONCLUSIONS: There were no significant differences in renal safety between the intra-arterial treatment and intravenous treatment groups. Diabetes mellitus may be a predictor of acute kidney injury. The use of Multimodal computed tomography imaging in the selection of patients who could benefit from endovascular therapy is safe.

Bioconversion of duck blood cell: process optimization of hydrolytic conditions and peptide hydrolysate characterization.

BACKGROUND: As the protein-laden by-product, red blood cells (RBCs) from poultry blood is a potential source of protein used as food and feed ingredient. However, RBC was currently underutilized. Therefore, it is an urgent need to develop feasible and cost-effective methods for converting poultry waste into nutritional and functional products. RESULTS: To take full advantage of this poultry waste, peptide hydrolysate was produced by deep controllable bioconversion of RBC, by means of synergistic combination of neutrase and flavourzyme. In this work, the functional properties and antioxidant activity of peptide hydrolysate were also characterized. The degree of hydrolysis (DH) was optimized using response surface methodology, and optimal hydrolysis conditions were found to be: temperature 51 °C, substrate concentration 14% (w/v), initial pH 7.0, and time 7.5 h. The red blood cell hydrolysate (RBCH) obtained not only possessed plentiful small peptides (< 3 kDa, 68.14%), but also was abundant in essential amino acids, accounting for over 50% of total amino acids. In addition to its excellent solubility (> 80%), emulsifying and foaming properties, RBCH also exhibited notable antioxidant activities, such as DPPH (2,2-diphenyl- 1-picrylhydrazyl) radical-scavenging activity (IC50, 4.16 mg/mL), reducing power, metal chelating ability and inhibiting lipid peroxidation. CONCLUSIONS: RBCH enriched in small peptides has the potential to be a new food additive with outstanding functional and antioxidant properties, and a process was established for converting poultry waste into peptide hydrolysate using neutrase and flavourzyme.

Enhancement of thermoalkaliphilic xylanase production by Pichia pastoris through novel fed-batch strategy in high cell-density fermentation.

BACKGROUND: Xylanase degrades xylan into monomers of various sizes by catalyzing the endohydrolysis of the 1,4-ß-D-xylosidic linkage randomly, possessing potential in wide industrial applications. Most of xylanases are susceptible to be inactive when suffering high temperature and high alkaline process. Therefore, it is necessary to develop a high amount of effective thermoalkaliphilic xylanases. This study aims to enhance thermoalkaliphilic xylanase production in Pichia pastoris through fermentation parameters optimization and novel efficient fed-batch strategy in high cell-density fermentation. RESULTS: Recombinant xylanase activity increased 12.2%, 7.4%, 12.0% and 9.9% by supplementing the Pichia pastoris culture with 20 g/L wheat bran, 5 mg/L L-histidine, 10 mg/L L-tryptophan and 10 mg/L L-methionine in shake flasks, respectively. Investigation of nutritional fermentation parameters, non-nutritional fermentation parameters and feeding strategies in 1 L bioreactor and 1 L shake flask revealed that glycerol and methanol feeding strategies were the critical factors for high cell density and xylanase activity. In 50 L bioreactor, a novel glycerol feeding strategy and a four-stage methanol feeding strategy with a stepwise increase in feeding rate were developed to enhance recombinant xylanase production. In the initial 72 h of methanol induction, the linear dependence of xylanase activity on methanol intake was observed (R2 = 0.9726). The maximum xylanase activity was predicted to be 591.2 U/mL, while the actual maximum xylanase activity was 560.7 U/mL, which was 7.05 times of that in shake flask. Recombinant xylanase retained 82.5% of its initial activity after pre-incubation at 80 °C for 50 min (pH 8.0), and it exhibited excellent stability in the broad temperature (60-80 °C) and pH (pH 8.0-11.0) ranges. CONCLUSIONS: Efficient glycerol and methanol fed-batch strategies resulting in desired cell density and xylanase activity should be applied in other P. pastoris fermentation for other recombinant proteins production. Recombinant xylanases with high pH- and thermal-stability showed potential in various industrial applications.

Protective effects of various ratios of DHA/EPA supplementation on high-fat diet-induced liver damage in mice.

BACKGROUND: A sedentary lifestyle and poor diet are risk factors for the progression of non-alcoholic fatty liver disease. However, the pathogenesis of hepatic lipid accumulation is not completely understood. Therefore, the present study explored the effects of dietary supplementation of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on a high-fat diet-induced lipid metabolism disorder and the concurrent liver damage. METHODS: Using high-fat diet-fed C57BL/6 J mice as the animal model, diets of various ratios of DHA/EPA (2:1, 1:1, and 1:2) with an n-6/n-3 ratio of 4:1 were prepared using fish and algae oils enriched in DHA and/or EPA and sunflower seed oils to a small extent instead of the high-fat diet. RESULTS: Significantly decreased hepatic lipid deposition, body weight, serum lipid profile, inflammatory reactions, lipid peroxidation, and expression of adipogenesis-related proteins and inflammatory factors were observed for mice that were on a diet supplemented with DHA/EPA compared to those in the high-fat control group. The DHA/EPA 1:2 group showed lower serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol levels, lower SREBP-1C, FAS, and ACC-1 relative mRNA expression, and higher Fra1 mRNA expression, with higher relative mRNA expression of enzymes such as AMPK, PPARα, and HSL observed in the DHA/EPA 1:1 group. Lower liver TC and TG levels and higher superoxide dismutase levels were found in the DHA/EPA 2:1 group. Nonetheless, no other notable effects were observed on the biomarkers mentioned above in the groups treated with DHA/EPA compared with the DHA group. CONCLUSIONS: The results showed that supplementation with a lower DHA/EPA ratio seems to be more effective at alleviating high-fat diet-induced liver damage in mice, and a DHA/EPA ratio of 1:2 mitigated inflammatory risk factors. These effects of n-3 polyunsaturated fatty acids (PUFA) on lipid metabolism may be linked to the upregulation of Fra1 and attenuated activity of c-Jun and c-Fos, thus ultimately reducing the severity of the lipid metabolism disorder and liver damage to some extent.

Association between cardiometabolic index and testosterone among adult males: a cross-sectional analysis from National Health and Nutrition Examination Survey 2013-2016.

Background: Cardiometabolic index (CMI) is a well-promising indicator for predicting obesity-related diseases. Testosterone decline and deficiency importantly affect men's health, and may be associated with obesity and excessive deposition of visceral adipose tissue. We aimed to explore the association between CMI and serum testosterone in US adult males. Methods: The present cross-sectional study was conducted among adult males with complete data about CMI and testosterone in 2013-2016 National Health and Nutrition Examination Survey (NHANES). CMI was calculated as follows: triglyceride (TG) (mmol/L)/high-density lipid-cholesterol (HDL-C) (mmol/L) × waist-to-height ratio (WHtR). Multivariable regression and subgroup analyses were conducted to explore the association between CMI and testosterone. Results: We included 2,209 male participants for the final analysis. After adjusting for confounders, CMI was found to show a negative correlation between testosterone [minimally adjusted model: ß=-10.56, 95% confidence interval (CI): -12.76, -8.36, P<0.001, fully adjusted model: ß=-0.04 (-4.88, 4.81), P=0.99]. Multivariate-adjusted beta also showed testosterone levels were significantly lower in the two highest CMI groups (Q3, Q4) compared to the lowest group (Q1). In the subgroup populations, the relationship between CMI and testosterone was affected by age, race, education level, hypertension, and smoking status (P-interaction <0.05). Furthermore, receiver operating characteristic (ROC) curve analysis indicated that triglyceride-glucose-body mass index (TyG-BMI) (0.67, 95% CI: 0.65, 0.70) was the best predictor of low testosterone (results), although CMI was comparable in its predictive value (0.68, 95% CI: 0.65, 0.71). Conclusions: Higher CMI scores were associated with lower testosterone levels in adult males in the United States, with this correlation being influenced by factors such as age, race, education level, hypertension, and smoking status. CMI was comparable to other metabolic indexes for predicting testosterone deficiency, although TyG-BMI was the best overall predictor.

Chronic cold stress promotes inflammation and ER stress via inhibiting GLP-1R signaling, and exacerbates the risk of ferroptosis in the liver and pancreas.

The cold climates in autumn and winter threatens human health. The aim of this study was to reveal the effects of prolonged cold exposure on the liver and pancreas based on GLP-1R signaling, oxidative stress, endoplasmic reticulum (ER) stress and ferroptosis by Yorkshire pig models. Yorkshire pigs were divided into the control group and chronic cold stress (CCS) group. The results showed that CCS induced oxidative stress injury, activated Nrf2 pathway and inhibited the expression of GLP-1R in the liver and pancreas (P < 0.05). The toll-like receptor 4 (TLR4) pathway was activated in the liver and pancreas, accompanied by the enrichment of IL-1ß and TNF-α during CCS (P < 0.05). Moreover, the kinase RNA-like endoplasmic reticulum kinase (PERK), inositol requiring kinase 1 (IRE1), X-box-binding protein 1 (XBP1) and eukaryotic initiation factor 2α (eIF2α) expression in the liver and pancreas was up-regulated during CCS (P < 0.05). In addition, CCS promoted the prostaglandin-endoperoxide synthase 2 (PTGS2) expression and inhibited the ferritin H (FtH) expression in the liver. Summarily, CCS promotes inflammation, ER stress and apoptosis by inhibiting the GLP-1R signaling and inducing oxidative stress, and exacerbates the risk of ferroptosis in the liver and pancreas.

Associations of sedentary behaviors with mental health outcomes in a cohort of patients with minor ischemic stroke.

OBJECTIVE: The relationship between sedentary behaviors and functional outcomes of acute ischemic stroke (AIS) has been previously reported. However, it remains unclear whether sedentary behaviors are associated with mental health outcomes in AIS patients. Therefore, the objective of this study was to investigate the mental health outcomes in patients with minor AIS one year after stroke onset. METHODS: This cross-sectional study recruited 1230 patients with minor AIS (NIHSS ≤ 5) from three hospitals in China. One year after discharge, patients were interviewed using face-to-face questionnaires, including the PHQ-9, GAD-7, and ISI, to assess symptoms of depression, anxiety, and insomnia, respectively. Participants were categorized into the long sedentary time group and the short sedentary time group based on the median sedentary time of all participants. The associations between leisure sedentary time and mental health outcomes were investigated. RESULTS: Participants with a long leisure sedentary time had higher PHQ-9, GAD-7, and ISI scores than those with a short sedentary time. Longer sedentary time was associated with an increased risk of experiencing symptoms of major depression (RR, 95% CI: 1.79, 1.47 to 2.18), anxiety (RR, 95% CI: 3.28, 2.08 to 5.18), and insomnia (RR, 95% CI: 2.58, 2.03 to 3.28) one year after a minor AIS. CONCLUSION: Excessive sedentary time is associated with long-term mental health conditions after stroke. Therefore, reducing the sedentary time might be helpful for preventing poststroke depression, anxiety, and insomnia.

Combined healthy lifestyles and risk of depressive symptoms: A baseline survey in China.

BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.

Characteristics of glucose and lipid metabolism and the interaction between gut microbiota and colonic mucosal immunity in pigs during cold exposure.

BACKGROUND: Cold regions have long autumn and winter seasons and low ambient temperatures. When pigs are unable to adjust to the cold, oxidative damage and inflammation may develop. However, the differences between cold and non-cold adaptation regarding glucose and lipid metabolism, gut microbiota and colonic mucosal immunological features in pigs are unknown. This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation. Moreover, the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs. RESULTS: Cold and non-cold-adapted models were established by Min and Yorkshire pigs. Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models (Yorkshire pigs), decreasing plasma glucose concentrations. In this case, cold exposure enhanced the ATGL and CPT-1α expression to promote liver lipolysis and fatty acid oxidation. Meanwhile, the two probiotics (Collinsella and Bifidobacterium) depletion and the enrichment of two pathogens (Sutterella and Escherichia-Shigella) in colonic microbiota are not conducive to colonic mucosal immunity. However, glucagon-mediated hepatic glycogenolysis in cold-adapted pig models (Min pigs) maintained the stability of glucose homeostasis during cold exposure. It contributed to the gut microbiota (including the enrichment of the Rikenellaceae RC9 gut group, [Eubacterium] coprostanoligenes group and WCHB1-41) that favored cold-adapted metabolism. CONCLUSIONS: The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa. During non-cold adaptation, cold-induced glucose overconsumption promotes thermogenesis through lipolysis, but interferes with the gut microbiome and colonic mucosal immunity. Furthermore, glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.

Identification of DNA-binding protein based multiple kernel model.

DNA-binding proteins (DBPs) play a critical role in the development of drugs for treating genetic diseases and in DNA biology research. It is essential for predicting DNA-binding proteins more accurately and efficiently. In this paper, a Laplacian Local Kernel Alignment-based Restricted Kernel Machine (LapLKA-RKM) is proposed to predict DBPs. In detail, we first extract features from the protein sequence using six methods. Second, the Radial Basis Function (RBF) kernel function is utilized to construct pre-defined kernel metrics. Then, these metrics are combined linearly by weights calculated by LapLKA. Finally, the fused kernel is input to RKM for training and prediction. Independent tests and leave-one-out cross-validation were used to validate the performance of our method on a small dataset and two large datasets. Importantly, we built an online platform to represent our model, which is now freely accessible via http://8.130.69.121:8082/.

Occurrence and ecological risk assessment of 16 phthalates in surface water of the mainstream of the Yangtze River, China.

Phthalic acid esters (PAEs), a class of typical endocrine disruptors, have received considerable attention due to their widespread applications and adverse effects on biological health. In this study, 30 water samples, along the mainstream of the Yangtze River (YR), were collected from Chongqing (upper stream) to Shanghai (estuary) from May to June in 2019. The total concentrations of 16 targeted PAEs ranged from 0.437 to 20.5 µg/L, with an average of 1.93 µg/L, where dibutyl phthalate (DBP, 0.222-20.2 µg/L), bis (2-ethylhexyl) phthalate (DEHP, 0.254-7.03 µg/L), and diisobutyl phthalate (DIBP, 0.0645-0.621 µg/L) were the most abundant PAEs. According to the pollution level in the YR to assess the ecological risk posed by PAEs, the results showed medium risk level of PAEs in the YR, among which DBP and DEHP posed a high ecological risk to aquatic organisms. The optimal solution for DBP and DEHP is found in ten fitting curves. The PNECSSD of them is 2.50 µg/L and 0.34 µg/L, respectively.

High glucose induces inflammatory cytokine through protein kinase C-induced toll-like receptor 2 pathway in gingival fibroblasts.

Toll-like receptors (TLRs) play a key role in innate immune response and inflammation, especially in periodontitis. Meanwhile, hyperglycemia can induce inflammation in diabetes complications. However, the activity of TLRs in periodontitis complicated with hyperglycemia is still unclear. In the present study, high glucose (25 mmol/l) significantly induced TLR2 expression in gingival fibroblasts (p<0.05). Also, high glucose increased nuclear factor kappa B (NF-κB) p65 nuclear activity, tumor necrosis factor-α (TNF-α) and interleukin-lß (IL-1ß) levels. Protein kinase C (PKC)-α and δ knockdown with siRNA significantly decreased TLR2 and NF-κB p65 expression (p<0.05), whereas inhibition of PKC-ß had no effect on TLR2 and NF-κB p65 under high glucose (p<0.05). Additional studies revealed that TLR2 knockdown significantly abrogated high-glucose-induced NF-κB expression and inflammatory cytokine secretion. Collectively, these data suggest that high glucose stimulates TNF-α and IL-1ß secretion via inducing TLR2 through PKC-α and PKC-δ in human gingival fibroblasts.

An Analysis of the Motivation Mechanism of the Formation of Corporate Health Strategic Innovation Capability Based on the K-Means Algorithm.

Improving enterprises' independent innovation capability is critical to improving their competitive strength, industries' independent innovation capability, industries' international competitiveness, and countries' independent innovation capability, as well as building an innovative country. It is now the era of strategic innovation. Many growing businesses are focused on strategic innovation, but they overlook the issue of ensuring that strategic innovation is implemented. Management and innovation are perennial themes in the long-term development of businesses. The most pressing issue in enterprises' strategic innovation activities is how to combine their strategic direction with their superior ability and choose a strategic innovation path that is appropriate for their development. This paper uses data mining theory to establish the K-means clustering algorithm to identify the best strategic orientation of enterprise innovation strategic direction selection based on the existing advantages and capabilities of enterprises based on the analysis of the direction of enterprise strategic innovation.

Expression profiling of mRNA and functional network analyses of genes regulated by human papilloma virus E6 and E7 proteins in HaCaT cells.

Human papillomavirus (HPV) oncogenes E6 and E7 are essential for HPV-related cancer development. Here, we developed a cell line model using lentiviruses for transfection of the HPV16 oncogenes E6 and E7 and investigated the differences in mRNA expression during cell adhesion and chemokine secretion. Subsequently, RNA sequencing (RNA-seq) analysis was performed to explore the differences in mRNA expression. Compared to levels in the control group, 2,905 differentially expressed mRNAs (1,261 downregulated and 1,644 upregulated) were identified in the HaCaT-HPV16E6E7 cell line. To predict the functions of these differentially expressed genes (DEGs) the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used. Protein-protein interactions were established, and the hub gene was identified based on this network. Real-time quantitative-PCR (RT-qPCR) was conducted to confirm the levels of 14 hub genes, which were consistent with the RNA-seq data. According to this, we found that these DEGs participate in the extracellular matrix (ECM), cell adhesion, immune control, and cancer-related signaling pathways. Currently, an increasing number of clinicians depend on E6/E7mRNA results to make a comprehensive judgment of cervical precancerous lesions. In this study, 14 hub genes closely related to the expression of cell adhesion ability and chemokines were analyzed in HPV16E6E7-stably expressing cell lines, which will open up new research ideas for targeting E6E7 in the treatment of HPV-related cancers.

The clinical effect and safety of new preoperative fasting time guidelines for elective surgery: a systematic review and meta-analysis.

Background: Traditional fasting and no drinking schemes (fasting for 8-12 hours and no drinking for 4-6 hours) affect the metabolism of the body. The new guidelines put forward by the American Association of Anesthesiologists (fasting for 6 hours, no drinking for 2 hours) obviously reduce the time of fasting and no drinking, but the clinical efficacy and safety need to be further confirmed. In this study, a meta-analysis of randomized controlled trials (RCTs) using the new guidelines and traditional protocols was conducted to provide an evidence-based foundation for elective surgery. Methods: The articles were searched in PubMed, EBSCO, MEDLINE, Science Direct, Cochrane Library, CNKI, China Biomedical Resources Database, Wanfang Database, Weipu, and Western Biomedical Journal Literature Database. RCTs related to fasting before surgery during the screening period were selected. Chinese and English search keywords included elective surgery, preoperative, fasting and no drinking, patient comfort, thirst, hunger, collapse, hypoglycemia, preoperative gastric volume, preoperative gastric juice pH, and intraoperative gastric volume. The RevMan 5.3 software provided by Cochrane collaboration network was used to evaluate the quality of included documents. Two professionals independently screened the literature, extracted data, and assessed the risk of bias. Results: A total of 6 studies were included. The incidence of hunger in patients undergoing elective surgery in the experimental group and control group was significantly different [Z=3.90; relative risk (RR) =0.58; 95% confidence interval (CI): 0.44, 0.76; P<0.0001]. The incidence of thirst was significantly different between the experimental group and control group (Z=7.22; RR =0.21; 95% CI: 0.13, 0.32; P<0.00001). Discussion: Meta-analysis results confirmed that the new guidelines can significantly reduce the hunger and thirst of patients, improve their satisfaction after surgery, and can be applied clinically.

Plasma Calprotectin Is Predictive for Short-Term Functional Outcomes of Acute Ischemic Stroke.

Background: Blood-based prognostic biomarkers of acute ischemic stroke (AIS) are limiting. Calprotectin is suggested to be involved in directing post-stroke inflammatory conditions. However, the pathological alteration of circulating calprotectin in AIS is yet to be thoroughly elucidated. Therefore, this study aimed to investigate the levels and clinical relevance of calprotectin in AIS. Methods: This study recruited 271 patients with AIS within 24 h since symptom onset and 145 non-stroke healthy controls (HC) from February 1, 2018, to Dec 31, 2020. Patients were followed up for 2 weeks for observation of functional outcomes, as determined by the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Plasma calprotectin concentrations were determined by ELISA. Results: Plasma calprotectin concentrations were significantly higher in patients with AIS compared with controls [patients vs. control: median (IQR) 54.2 (39.01-99.04) vs. 50.04 (35.42-61.22), p < 0.001]. Besides, patients with poor prognosis, as defined by mRS ≥ 3, had significantly higher calprotectin levels than patients with good prognosis [poor prognosis patients vs. good prognosis patients: median (IQR) 61.99 (47.52-108) vs. 43.36 (33.39-60.2), p < 0.001]. Plasma calprotectin levels were positively associated with the disease severity of AIS, as reflected by infarction volume and NIHSS score at baseline. Furthermore, baseline calprotectin was found to be independently associated with poor prognosis [odds ratio (OR): 1.02, 95% CI: 1.01-1.03] and disease progression (OR: 1.03, 95% CI: 1.02-1.04) of AIS during a 2-week follow-up, with adjustment of possible confounding factors. Conclusion: Plasma calprotectin is associated with short-term functional outcomes of AIS.