A portable smartphone detection of ctDNA using MnB2 nanozyme and paper-based analytical device.

The development of point-of-care testing (POCT) for circulating tumor DNA (ctDNA) is meaningful for the non-invasive cancers screening and diagnosis, particularly in resource-limited settings. The microfluidic paper-based analytical device (µPAD) provides an ideal platform, its application in ctDNA assays remains underexplored. In this work, a multifunctional µPAD was manufactured, which can enhance the efficiency and reduce the cost of ctDNA sensing. Additionally, a smartphone-based application analysis was fabricated for convenient, portable detection and colorimetric signal readout. Moreover, the novel oxidase-like MnB2 nanozyme was introduced in the sandwiches sensing strategy, utilizing its catalytic properties to effectively generate a colorimetric signal. The use of MnB2 nanozyme in sensing application is relatively novel, and its catalytic performance and mechanism was thoroughly evaluated via experiment and density functional theory (DFT) calculations. After optimizing the detection conditions, the proposed biosensor exhibited satisfactory results. Furthermore, the method was successfully used to detect ctDNA in tumor cell lysates and peripheral blood samples from tumor-bearing mice. The results were consistent with standard qPCR method, affirming the reliability of our POCT analysis device in ctDNA detection. Thus, this work not only provides a paper-based POCT device and intelligent analysis tool for portable cancers diagnosis, but it also paves a new application path for MnB2 nanozyme in the sensing filed.

Dissecting microenvironment in cystadenomas and hepatic cysts based on single nucleus RNA-sequencing data.

Hepatic cystadenoma is a rare disease, accounting for about 5% of all cystic lesions, with a high tendency of malignant transformation. The preoperative diagnosis of cystadenoma is difficult, and some cystadenomas are easily misdiagnosed as hepatic cysts at first. Hepatic cyst is a relatively common liver disease, most of which are benign, but large hepatic cysts can lead to pressure on the bile duct, resulting in abnormal liver function. To better understand the difference between the microenvironment of cystadenomas and hepatic cysts, we performed single-nuclei RNA-sequencing on cystadenoma and hepatic cysts samples. In addition, we performed spatial transcriptome sequencing of hepatic cysts. Based on nucleus RNA-sequencing data, a total of seven major cell types were identified. Here we described the tumor microenvironment of cystadenomas and hepatic cysts, particularly the transcriptome signatures and regulators of immune cells and stromal cells. By inferring copy number variation, it was found that the malignant degree of hepatic stellate cells in cystadenoma was higher. Pseudotime trajectory analysis demonstrated dynamic transformation of hepatocytes in hepatic cysts and cystadenomas. Cystadenomas had higher immune infiltration than hepatic cysts, and T cells had a more complex regulatory mechanism in cystadenomas than hepatic cysts. Immunohistochemistry confirms a cystadenoma-specific T-cell immunoregulatory mechanism. These results provided a single-cell atlas of cystadenomas and hepatic cyst, revealed a more complex microenvironment in cystadenomas than in hepatic cysts, and provided new perspective for the molecular mechanisms of cystadenomas and hepatic cyst.

Cost-effectiveness of immune checkpoint inhibitors in treating metastatic urothelial cancer.

Objectives: Immune checkpoint inhibitor (ICI) is an important treatment option for metastatic urothelial carcinoma (mUC) patients. A lot of clinical evidence proved the survival benefits of ICI, but cost-effectiveness of the treatment remains unclear. This study evaluates the cost-effectiveness of the ICIs treatment in different sequences among mUC patients. Methods: We retrospectively analyzed mUC patients who had been treated at our hospital between January 2016 and December 2020. These patients received chemotherapy with or without ICI treatment (Pembrolizumab, Atezolizumab, Nivolumab, Durvalumab, or Avelumab). The patients were divided into three different groups: receiving chemotherapy alone, receiving a combination of first-line ICI and chemotherapy (ICI combination therapy), and receiving chemotherapy as the first-line treatment followed by second-line ICI therapy (Subsequent ICI therapy). The primary endpoint was cost per life day, while lifetime medical costs and overall survival were also evaluated. Results: The 74 enrolled patients had a median age of 67.0 years, with 62.2% being male. Of these patients, 23 had received chemotherapy only, while the remaining patients had received combined therapy with ICI in either first-line or as subsequent agents (37 patients had ever received atezolizumab, 18 pembrolizumab, 1 Durvalumab, 1 Nivolumab, and 1 Avelumab separately.). Fifty-five patients (74.3%, 55/74) received cisplatin amongst all the patients who underwent chemotherapy. Median overall survival was 27.5 months (95% CI, 5.2-49.9) in the first-line ICI combination therapy group, and 8.9 months (95% CI, 7.1-10.8) in the chemotherapy only. Median overall survival for the subsequent ICI therapy group was not reached. The median lifetime cost after metastatic UC diagnosis was USD 31,221. The subsequent ICI therapy group had significantly higher costs when compared with the ICI combination therapy group (155.8 USD per day, [IQR 99.0 to 220.5] v 97.8 USD per day, [IQR 60.8 to 159.19], p = 0.026). Higher insurance reimbursement expenses for the subsequent ICI therapy group were observed when compared with the ICI combination therapy group. Conclusion: Our real-world data suggests that first line use of ICI combined with chemotherapy demonstrates better cost-effectiveness and similar survival outcomes for mUC patients, when compared with subsequent ICI therapy after chemotherapy.

Effects of Hericium erinaceus polysaccharide in porcine IPEC-J2 intestinal epithelial cells against apoptosis induced by oxidative stress.

This study was intended to investigate whether Hericium erinaceus polysaccharides (HEP) prevent oxidative stress and apoptosis of intestinal porcine epithelial cells from jejunum (IPEC-J2 cells) induced by hydrogen peroxide (H2O2). Crude HEP were extracted and purified by chromatography. The ultraviolet and infrared spectra and monosaccharide composition of HEP were analyzed. Reactive oxygen species (ROS) generation was quantified by flow cytometry method, and lactate dehydrogenase (LDH) and malondialdehyde (MDA) production were determined by TBARS. Also, apoptosis was analyzed by flow cytometry method and the apoptosis-related regulatory molecules were determined by microplate or western blotting method. Our results showed that pretreatment of IPEC-J2 cells with HEP significantly scavenged ROS and reduced LDH and MDA production. HEP also reduced apoptosis and kept polarity of the mitochondrial membrane potential. Moreover, HEP increased the content of caspase-3 and PARP, and protein expression of Bcl-2, while inhibited Bax and Bad and reduced the content of caspase-9 and release of CytC. Meanwhile, HEP inhibited the protein expression of TNFR1, FAS, and FASL, and decreased the content of caspase-8. The results indicated that HEP had a protective effect against oxidative stress in IPEC-J2 cells and the underlying mechanism was reducing apoptosis via mitochondrial and death receptor pathways.

Malfunction endostapler trapped on renal vein - Nightmare scenario for surgeon.

The utilization of endostapler devices has become standard practice for renal vein ligation during laparoscopic nephroureterectomy. While exceptionally rare, malfunctions can occur in these devices. In the video, we present a malfunctioning endostapler that became trapped on the renal vein. Fortunately, this catastrophic event was successfully managed without conversion to open surgery or massive blood loss and was recorded on video. We propose a structured management flow chart for addressing GIA malfunction, aiming to assist surgeons in navigating through this potentially life-threatening situation.

LncHLEF promotes hepatic lipid synthesis through miR-2188-3p/GATA6 axis and encoding peptides and enhances intramuscular fat deposition via exosome.

Long noncoding RNAs (lncRNAs) have emergingly been implicated in mammalian lipid metabolism. However, their biological functions and regulatory mechanisms underlying adipogenesis remain largely elusive in chicken. Here, we systematically characterized the genome-wide full-length lncRNAs in the livers of pre- and peak-laying hens, and identified a novel intergenic lncRNA, lncHLEF, an RNA macromolecule with a calculated molecular weight of 433 kDa. lncHLEF was primarily distributed in cytoplasm of chicken hepatocyte and significantly up-regulated in livers of peak-laying hens. Functionally, lncHLEF could promote hepatocyte lipid droplet formation, triglycerides and total cholesterol contents. Mechanistically, lncHLEF could not only serve as a competitive endogenous RNA to modulate miR-2188-3p/GATA6 axis, but also encode three small functional polypeptides that directly interact with ACLY protein to enable its stabilization. Importantly, adeno-associated virus-mediated liver-specific lncHLEF overexpression resulted in increased hepatic lipid synthesis and intramuscular fat (IMF) deposition, but did not alter abdominal fat (AbF) deposition. Furthermore, hepatocyte lncHLEF could be delivered into intramuscular and abdominal preadipocytes via hepatocyte-secreted exosome to enhance intramuscular preadipocytes differentiation without altering abdominal preadipocytes differentiation. In conclusion, this study revealed that the lncHLEF could promote hepatic lipid synthesis through two independent regulatory mechanisms, and could enhance IMF deposition via hepatocyte-adipocyte communications mediated by exosome.

Successful rescue pneumovesicoscopic surgery for post-Deflux® vesicoureteral junction obstruction.

BACKGROUND: Vesicoureteral junction (VUJ) obstruction after Deflux® subureteral injection for vesicoureteral reflux (VUR) is rare and minimally invasive management has not been reported. This work investigated the patients who underwent Deflux® injection for VUR and identified those with subsequent VUJ obstruction. METHODS: Medical records of matched patients from October 2003 to March 2022 were reviewed, and parameters were retrospectively studied. All patients underwent Deflux® injection. The injection was performed under general anesthesia using the same manner. For patients complicated with VUJ obstruction, the symptoms, signs, management, images, renal ultrasounds, Tc-99m dimercaptosuccinic acid renal scintigraphy, histology of VUJ region, and outcomes were documented and reported. VUJ stenosis was diagnosed by performing renal ultrasound and magnetic resonance imaging. RESULTS: Totally 407 patients (554 ureterorenal units) received Dx/HA injections for VUR. VUJ obstruction was found in three patients (four ureterorenal units). Originally, three were grade V VUR, and one was grade IV. The repeated injection was not a risk factor for VUJ obstruction. The overall incidence of VUJ obstruction post-Dx/HA injection was 0.7% by ureter. The incidences were 0%, 0.75%, and 2.25% for grade I-III, IV, and V VUR, respectively. After the initial conversion case of pneumovesicoscopic ureteral reimplantation, the procedure was performed smoothly and successfully in the two following cases. CONCLUSIONS: Pneumovesicoscopic ureteral reimplantation offers an alternative for VUJ obstruction following Dx/HA injection for VUR. Fibrosis and foreign-body reaction may influence the feasibility. High-grade VUR and young age of injection were related to VUJ obstruction.

Context-aware augmentation for liver lesion segmentation: shape uniformity, expansion limit and fusion strategy.

Background: Data augmentation with context has been an effective way to increase the robustness and generalizability of deep learning models. However, to our knowledge, shape uniformity, expansion limit, and fusion strategy of context have yet to be comprehensively studied, particularly in lesion segmentation of medical images. Methods: To examine the impact of these factors, we take liver lesion segmentation based on the well-known deep learning architecture U-Net as an example and thoroughly vary the context shape, the expansion bandwidth as well as three representative fusion methods. In particular, the context shape includes rectangular, circular and polygonal, the expansion bandwidth is scaled by a maximum value of 2 compared to the lesion size, and the context fusion weighting strategy is composed of average, Gaussian and inverse Gaussian. Results: Studies conducted on a newly constructed high-quality and large-volume dataset show that (I) uniform context improves lesion segmentation, (II) expanding the context with either 5 or 7 pixels yields the highest performance for liver lesion segmentation, depending on the lesion size, and (III) an unevenly distributed weighting strategy for context fusion is appreciated but in the opposite direction, depending on lesion size as well. Conclusions: Our findings and newly constructed dataset are expected to be useful for liver lesion segmentation, especially for small lesions.

Unilateral Bi/Multi-Portal Endoscopy for the Treatment of Complicated Lumbar Degenerative Diseases with Utilization of Uniaxial Spinal Endoscope, Instead of Arthroscope: Technique Note and Clinical Results.

Objective: This article aims to discuss a novel surgical strategy, referred to as unilateral bi/multi-portal endoscopy (UME), which used a uniaxial spinal endoscope instead of an arthroscope in the traditional unilateral biportal endoscopy (UBE) surgical procedure in our study of the treatment of complicated lumbar degenerative diseases. Methods: This retrospective study included 42 patients diagnosed with high-migrated lumbar disc herniation and bilateral spinal stenosis who underwent UME surgery from January 2021 to December 2021. Patients included 20 men and 22 women, with an average age of 55.97±14.92 years. The average follow-up period was 13.19 months. The demographic data, operation time (min), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry Disability Index (ODI) scores were used to evaluate the surgical outcomes. Three-dimensional CT scans and MRI were conducted to evaluate the radiographic improvement. Results: A total of 26 patients were diagnosed with lumbar disc herniation and 16 with lumbar spinal stenosis. All 42 patients underwent UME surgery and achieved satisfactory outcomes. The operation time was 154.46±46.09 min. The average follow-up time was 13.19±1.33 months. The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 3.84±1.00 and 0.70±0.46, respectively (P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 6.46±1.08 and 1.03±0.64, respectively (P <0.05). Significant differences existed between preoperative ODI scores (58.70±11.22%) and the last follow-up ODI scores (9.24±3.04%; P<0.05). All patients achieved significant pain relief and functional improvement after the surgery. No severe complications occurred, except for two cases of postoperative dysesthesia and one case suffered from vertebral compression fractures induced by a postoperative accidental injury. Symptoms of numbness disappeared within one week with treatment using dexamethasone and neurotrophic drugs. The vertebral fracture case recovered with percutaneous kyphoplasty treatment. Conclusion: This study suggests that UME is a promising treatment strategy for high-migrated disc herniation and bilateral spinal stenosis.

HIF-1α/MMP-9 promotes spinal cord central sensitization in rats with bone cancer pain.

Bone cancer pain (BCP) is one of the most prevalent and serious symptoms of patients with cancer. Currently, the medical interventions used for the treatment of BCP do not act with optimal safety and efficacy. In this study, we appraised whether the hypoxia-inducible factor 1α (HIF-1α)/metalloproteinase-9 (MMP9) axis activates the PI3K/AKT pathway, resulting in elevated spinal cord central sensitization and aggravated BCP. BCP rats were established by tibial injection of Walker 256 cells, followed by different interventions in rats using HIF-1ɑ inhibitor LW6 or antibody treatments. After treatment with LW6 or antibody against HIF-1α, central sensitization in the spinal cord tissues of rats was inhibited, and pain perception in rats was reduced. Moreover, the activation of glial cells in the spinal cord tissues was ameliorated. The expression of MMP9 was remarkably suppressed in spinal cord tissues after inhibition of HIF-1ɑ activity, and the activity of the PI3K/AKT signaling pathway was inhibited. Further activation of MMP9 expression suppressed the alleviating effect of HIF-1ɑ inhibitor LW6 or antibody on pain perception in rats inoculated with tumors. Taken together, our studies suggest a HIF-1α/MMP9-mediated activation of PI3K/AKT in the spinal cord tissues, resulting in increased pain perception in a rat model with BCP.

Clinical significance and immune landscape of a novel ferroptosis-related prognosis signature in osteosarcoma.

BACKGROUND: Osteosarcoma is a malignant tumor that usually occurs in adolescents aged 10-20 years and is associated with poor prognosis. Ferroptosis is an iron-dependent cell death mechanism that plays a vital role in cancer. METHODS: Osteosarcoma transcriptome data were downloaded from the public database TARGET and from previous studies. A prognostic risk score signature was constructed using bioinformatics analysis, and its efficacy was determined by analyzing typical clinical features. The prognostic signature was then validated with external data. Differences in immune cell infiltration between high- and low-risk groups were analyzed. The potential of the prognostic risk signature as a predictor of immunotherapy response was evaluated using the GSE35640 (melanoma) dataset. Five key genes expression were measured by real-time PCR and western blot in human normal osteoblasts and osteosarcoma cells. Moreover, malignant biological behaviors of osteosarcoma cells were tested by modulating gene expression level. RESULTS: We obtained 268 ferroptosis-related genes from the online database FerrDb and published articles. Transcriptome data and clinical information of 88 samples in the TARGET database were used to classify genes into two categories using clustering analysis, and significant differences in survival status were identified. Differential ferroptosis-related genes were screened, and functional enrichment showed that they were associated with HIF-1, T cells, IL17, and other inflammatory signaling pathways. Prognostic factors were identified by univariate Cox regression and LASSO analysis, and a 5-factor prognostic risk score signature was constructed, which was also applicable for external data validation. Experimental validation indicated that the mRNA and protein expression level of MAP3K5, LURAP1L, HMOX1 and BNIP3 decreased significantly, though meanwhile MUC1 increased in MG-63 and SAOS-2 cells compared with hFOB1.19 cells. Cell proliferation and migration ability of SAOS-2 were affected based on alterations of signature genes. CONCLUSIONS: Significant differences in immune cell infiltration between high- and low-risk groups indicated that the five ferroptosis-related prognostic signature was constructed and could be used to predict the response to immunotherapy in osteosarcoma.

Endovascular therapy for acute ischemic stroke in patients with active malignancy: a meta-analysis with trial sequential analysis.

BACKGROUND: Active malignancy has a poorer prognosis and more deaths in patients with acute ischemic stroke (AIS). The outcomes of endovascular therapy (EVT) remain controversial in patients with AIS and active malignancy. METHODS: We searched PubMed, Cochrane, and Embase for articles published up to June 1, 2022. The primary outcome was good functional outcome at 3 months and successful reperfusion between patients with cancer and AIS and control patients. The secondary and safety outcomes included mortality at 3 months, in-hospital mortality, symptomatic intracerebral hemorrhage (sICH), any ICH, and subarachnoid hemorrhage (SAH). RESULTS: Twelve studies involving 5944 patients with AIS secondary to EVT were included (389 patients having active malignancy). The OR of good functional outcome at 3 months was 0.53 (95% CI 0.41 to 0.67) between the two groups. The OR of successful reperfusion between the two groups was 0.90 (95% CI 0.63 to 1.30). Compared with patients without cancers, those with cancers had a higher risk of mortality at 3 months (OR 3.64; 95% CI 2.35 to 6.27) and in-hospital mortality (OR 3.46; 95% CI 1.71 to 7.01). Despite a higher point estimate regarding any ICH (OR 1.41; 95% CI 1.01 to 1.96) and SAH (OR 2.53; 95% CI 1.10 to 5.81), sICH (OR 0.85; 95% CI 0.51 to 1.42) was not significant. CONCLUSION: Although a quarter of patients with active malignancy and AIS regained functional independence, physicians and patients should consider whether to apply EVT in patients with active malignancy.

Integrated Proteotranscriptomics Reveals Differences in Molecular Immunity between Min and Large White Pig Breeds.

Long-term selection or evolution is an important factor governing the development of disease resistance in pigs. To better clarify the molecular mechanisms underlying different levels of disease resistance, we used transcriptomics and proteomics analysis to characterize differences in the immunities between six resistant (Min pig) and six susceptible (Large White, LW) pigs which were raised in the same environment. A total of 135 proteins and 791 genes were identified as being differentially expressed between the Large White and Min pig groups. Protein expression clustering and functional analysis revealed that proteins related to immune system process, humoral immune response, the B cell receptor signaling pathway, lymphocyte-mediated immunity, and innate immune responses were more highly expressed in Min pigs. Transcriptome gene set enrichment analysis was used to reveal that pathways of cell adhesion molecules and antigen processing and presentation are significantly enriched in Min pigs. Integrated proteomics and transcriptomics data analysis identified 16 genes that are differentially expressed at both the mRNA and protein levels. In addition, 13 out of these 16 genes were related to the quantitative trait loci of immune diseases, including neural EGFL-like 2 (NELL2) and lactate dehydrogenase B (LDHB), which are involved in innate immunity. Correlation analysis between the genes/proteins and cytokines shows upregulated proteins in LW pigs in association with immunosuppressive/pro-inflammatory cytokines, such as interleukin (IL) 10, IL6, and tumor necrosis factor alpha. This was further validated using parallel reaction monitoring analysis. In summary, we discovered several potential candidate pathways and key genes/proteins involved in determining differences in disease resistance between the two studied pig breeds, which could provide new insights into the breeding of pigs for disease resistance.

Selection of rice and maize varieties with low cadmium accumulation and derivation of soil environmental thresholds in karst.

Cadmium (Cd) is considered the primary dietary toxic element. Previous studies have demonstrated significant differences in heavy metal accumulation among crop species. However, this information in karst areas with low heavy metal activity is missing. In this study, the uptake and accumulation characteristics of cadmium in soil-crop samples of group 504 in the core karst region of East Asia were analyzed. Cadmium low-accumulating maize and rice were screened using cluster and Pareto analytic methods. In addition, a new method, the species-sensitive distribution model (SSD), was proposed, which could be used to estimate the environmental threshold for cadmium in regional cropland. The results showed that both maize and rice soils in the research area were contaminated with varying degrees of cadmium. The total concentrations of cadmium ω(T-Cd) in maize and rice fields are 0.18-1.32 and 0.20-4.42 mg kg-1, respectively. The ω(T-Cd) of heavy metals in maize kernels and rice grains is 0.002-0.429 and 0.003-0.393 mg kg-1, respectively. The bioaccumulation factor (BCF) of cadmium in maize ranged from 0.0079 to 0.9701, with a coefficient of variation of 1.71; the BCF of cadmium in rice ranged from 0.0074 to 0.1345, with a coefficient of variation of 0.99. According to cluster and Pareto analyses, the maize crop varieties with low cadmium accumulation suitable for local cultivation were screened as JHY809, JDY808, AD778, SN3H and SY13, and the rice varieties were DMY6188, GY725, NY6368, SY451 and DX4103. In addition, the environmental cadmium threshold ranges of 0.30-10.05 mg kg-1 and 0.89-24.39 mg kg-1 for maize and rice soils, respectively, were deduced in this study. This threshold will ensure that 5-95% of maize and rice will not be contaminated with cadmium in the soil.

Characteristics, Health Risk Assessment, and Transfer Model of Heavy Metals in the Soil-Food Chain in Cultivated Land in Karst.

Heavy metal(loid) contamination of farmland is a crucial agri−environmental problem that threatens food safety and human health. In this study, we examined the contamination levels of heavy metals (As, Pb, Cd, Hg, Cr) in farmland and foods (rice, maize, and cabbage) in the core of Asia's largest karst region and assessed the potential health risks of consumption of these three foods. In addition, we developed a predictive transfer model of heavy metals in the soil−food chain through multiple regression equations. The results reveal that the soil heavy metals in the study area showed high accumulation characteristics, and the average concentration exceeded the national background value by 1.6−130 times, among which Cd pollution was the most serious. The order of contamination of the three soils in the study area was cabbage land > maize land > rice land. The order of potential risk of toxic elements in all three soils was Cd > Hg > As > Pb > Cr. The results of the risk assessment of agricultural consumption indicated a high carcinogenic and noncarcinogenic risk for the local population. The top contributor to carcinogenic risk was Cr, followed by As. Cd is the major noncarcinogenic contributor in maize and cabbage, and the noncarcinogenic contribution in rice is mainly caused by As. The risk was higher in children than in adults and was the highest for rice consumption. In addition, the predictive transfer model showed that the Cd levels in the three foods showed sufficient predictability and reasonable simulations of Cd concentrations in rice, maize, and cabbage throughout the study area. It could allow decision-making on the need for remediation strategies to reduce the risk of metal contamination of agricultural land in potentially high−risk areas of karst.

SCO-spondin-derived peptide NX210 rescues neurons from cerebral ischemia/reperfusion injury through modulating the Integrin-ß1 mediated PI3K/Akt pathway.

Ischemic stroke is a common condition with high morbidity and mortality, causing irreversible neuronal damage and seriously affecting neurological function. There has been no ideal effective treatment so far. The NX210 peptide is derived from the thrombospondin type 1 repeat (TSR) sequence of SCO-spondin, and has been reported to exert various neurogenic properties. This study investigated whether NX210 had therapeutic effects and possible underlying mechanisms against cerebral ischemia/reperfusion (I/R). Therefore, primary embryonic rat cortical neurons and Sprague-Dawley (SD) rats that were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively, were treated with or without NX210. We found that NX210 reduced OGD/R-induced cell viability loss and cytotoxicity. NX210 decreased cerebral infarct volume and brain edema, ameliorated neurological dysfunction, attenuated oxidative stress damage, and diminished neuronal apoptosis in MCAO/R rats. Furthermore, western blot analysis shown that treatment with NX210 up-regulated the expression of Integrin-ß1, phosphorylated-PI3K (p-PI3K) and phosphorylated-Akt (p-Akt). The Integrin-ß1 specific inhibitor, ATN-161, was used to identify pathways involved. The anti-oxidation activities and anti-apoptosis of NX210 was reversed by treatment with ATN-161. Overall, our results indicated that NX210 prevents oxidative stress and neuronal apoptosis in cerebral I/R via upregulation of the Integrin-ß1/PI3K/Akt signaling pathway. These results indicated that NX210 may be a promising therapeutic candidate for ischemic stroke.

[Health Risk Assessment and Environmental Benchmark of Heavy Metals in Cultivated Land in Mountainous Area of Northwest Guizhou Province].

An extensive investigation of heavy metal (Cd, Hg, As, Pb, and Cr) levels in 137 pairs of soil-maize/rice samples was conducted in cultivated land from a typical karst mountain area in the Northwest of Guizhou Province. A health risk assessment model was used to assess the health risks of those areas, and the environmental benchmarks of heavy metals in soils were evaluated using the species sensitivity distribution (SSD) model. The results showed that the soils of maize and rice were polluted by heavy metals. Cd was the primary pollutant, with an exceeding rate ranging from 87% to 445%. The contaminated level of maize fields was higher than those of rice fields. In contrast, only 3.51% and 13.4% of Cd content in maize kernels and rice grains exceeded the national threshold, and the Cd heavy metal accumulation ability of rice was higher than that of maize. The carcinogenic and non-carcinogenic risks of heavy metals for adults and children in the study area were at a low level. The carcinogenic risk of rice consumption was slightly higher than that of maize, and the health risk to children was higher than that to adults. The results derived from the SSD method showed that the 95% and 5% hazardous concentrations (HC5 and HC95) of maize fields were 0.67 for Cd, 771.99 for As, 40.85 for Pb and 609.88 for Cr mg·kg-1, and HC95were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg-1, respectively. The HC5 values of rice fields were 2.42 for Cd, 8.88 for As, 41.41 for Pb and 27.84 for Cr mg·kg-1, and the HC95 values were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg-1, respectively. The HC5 values of Cd, As, and Cr in maize fields and Cd in rice fields were significantly higher than the soil risk screening values in the current standard, and the HC95 values of the two fields were higher than the soil risk intervened values. The results indicated that the current standard would be too strict to evaluate the actual pollution level of soil heavy metals in this area.

Paeoniflorin Attenuates Dexamethasone-Induced Apoptosis of Osteoblast Cells and Promotes Bone Formation via Regulating AKT/mTOR/Autophagy Signaling Pathway.

Paeoniflorin, a natural product derived from Paeonia lactiflora, possesses diverse pharmacological activities such as anti-inflammatory, antitumor, and antidiabetic effects. It has been reported for promoting osteoblastogenesis and inhibiting osteoclastogenesis. This study investigates the therapeutic effects of paeoniflorin in glucocorticoid-induced osteoporosis (GIOP) in vitro and in vivo. MC3T3-E1 cells were incubated with dexamethasone (DEX; 200 µM) and/or paeoniflorin (10 µM), followed by the investigation of cell proliferation, differentiation, mineralization, apoptosis, and autophagy. The AKT activator SC79 was used for evaluating the involvement of the AKT/mTOR signaling pathway. After DEX pretreatments, paeoniflorin promoted osteoblast differentiation and mineralization characterized by increase in Runx2, ALP, beclin-1, and LC3-II/LC3-I ratio levels and a decrease in apoptosis. The autophagy-promoting effects of paeoniflorin were reversed by SC79. C57BL/6 mice were given DEX (1 mg/kg) once daily and paeoniflorin (15 mg/kg) 48 hours for a total of 8 weeks followed by the investigation of histological changes, the trabecular bone microarchitecture, and the levels of bone turnover markers. The results showed that paeoniflorin increased alkaline phosphatase (ALP) activity and upregulated the expression of osteocalcin and beclin-1 but reduced the levels of Bax and C-terminal telopeptide of type I collagen (CTX-1). Thus, paeoniflorin may alleviate DEX-induced osteoporosis by promoting osteogenic differentiation and autophagy via inhibition of the AKT/mTOR signaling pathway.

Emerging Roles and Potential Biological Value of CircRNA in Osteosarcoma.

Circular RNAs (circRNAs) are endogenous noncoding RNAs that are widely found in eukaryotic cells. They have been found to play a vital biological role in the development of human diseases. At present, circRNAs have been involved in the pathogenesis, diagnosis, and targeted treatment of multiple tumors. This article reviews the research progress of circRNAs in osteosarcoma (OSA) in recent years. The potential connection between circRNAs and OSA cell proliferation, apoptosis, metastasis, and chemotherapy sensitivity or resistance, as well as clinical values, is described in this review. Their categories and functions are generally summarized to facilitate a better understanding of OSA pathogenesis, and findings suggest novel circRNA-based methods may be used to investigate OSA and provide an outlook for viable biomarkers and therapeutic targets.