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Photodynamic therapy (PDT), employing photosensitizers to induce formation of reactive oxygen species (ROS) for tumor elimination, is emerging as a promising treatment modality in oncology due to its unique benefits. However, the PDT application in ovarian cancer, the most prevalent and lethal type of gynecological malignancy with a severe hypoxic microenvironment, remains unknown. This study revealed that photosensitizer TMPyP4 exhibited enhanced efficacy under H2O2 stimulation, with minimal change in cytotoxicity compared to TMPyP4 alone. The results showed that H2O2 increased ROS production induced by TMPyP4, leading to exacerbated mitochondrial dysfunction and DNA damage, ultimately inhibiting proliferation and inducing apoptosis in ovarian cancer cells. Mechanistically, H2O2 primarily enhanced the therapeutic efficacy of PDT with TMPyP4 against ovarian cancer cells by degrading HIF-1α, which subsequently modulated the HIF-1 signaling pathway, thereby alleviating the hypoxic environment in ovarian cancer cells. Our findings underscore the therapeutic potential of targeting HIF-1α within the hypoxic microenvironment for PDT in ovarian cancer and propose a novel integrated strategy for PDT treatment of this malignancy in vitro.

The proliferation of unverified or false information by irresponsible users can significantly amplify the spread of misinformation or fake news. Despite growing research on unverified information sharing, a comprehensive understanding of the varying influences of different factors and strategies to mitigate this issue remains under investigation. To address this research gap, this study, rooted in the theory of herd behavior, develops, and tests a model theorizing the reasons behind social media users' unverified information sharing. Data was collected from 510 respondents across six regions of China using a convenience sampling method. The collected data was analyzed using Mplus. The results from this study indicated that perceived severity, state uncertainty, and herding have a significant positive influence on unverified information sharing. These results enrich the understanding of unverified information-sharing behavior among Chinese social media users. Drawing from these results, we suggest platform administrators and policymakers mitigate herd behavior tendencies and stem the spread of misinformation by disseminating timely, accurate, and authoritative information. Since this action will reduce users' perceptions of severity and uncertainty. Social media users are also advised to stay vigilant over the implications of herd behavior and foster a more critical attitude towards information sharing.

ABSTRACT: Aflatoxin B1 (AFB1) is an unavoidable environmental toxin. The accumulation of AFB1 and its metabolites in the liver poses a threat to both human and animal health. Curcumin exhibits anti-oxidative, anti-tumor, and anti-inflammatory properties. There is no report on the mechanism regarding how curcumin relived liver necroptosis in chickens induced by AFB1 based on the regulatory network of ceRNA. To explore this, we performed transmission electron microscopy and sequenced lncRNA and mRNA in chicken livers treated with AFB1 and/or curcumin for 28 d in vivo. We observed substantial alterations in the lncRNA and mRNA expression profiles within the chicken liver, indicating that curcumin can mitigate AFB1-induced necroptosis both in vivo and in vitro. Further analysis, including the establishment of an lncRNA-miRNA-mRNA network and the utilization of a dual luciferase reporter assay, revealed that LOC769044 acts as a competing endogenous RNA (ceRNA) for miR-1679. In addition, STAT1 was identified as a direct target of miR-1679. Modulating miR-1679 levels through overexpression, and silencing LOC769044 and STAT1, effectively reversed the necroptotic effects induced by AFB1, a reversal that was also observed with curcumin supplementation. In conclusion, our data demonstrate that curcumin alleviates AFB1-induced liver necroptosis through the LOC769044/miR-1679/STAT1 signaling axis. This study suggests that LOC769044 may serve as a novel therapeutic target for managing AFB1-mediated liver toxicity.

Isoorientin (Iso) is a natural flavonoid present in the human diet, known for its anti-inflammatory, antioxidant, and antiviral properties. The purpose of this research was to illustrate the anti-inflammatory potential of Iso in ulcerative colitis (UC) mice and elucidate potential mechanisms. The mice model of UC was induced by cyclic intervention with Dextran Sulfate Sodium (DSS). We evaluated the efficacy of Iso in the treatment of UC, detected the expression of proteins related to the Galectin-3/NLRP3/IL-1β signaling pathway, and assessed the intestinal mucosa barrier function of colon tissue. Our findings demonstrated that Iso could improve colon length, the index of colonic weight, pathological damage to the colon, and serum cytokine secretion of UC mice. Most importantly, Iso could competitively bind Galectin-3, inhibit the interaction of Galectin-3 with NLRP3 and the expression of Galectin-3, NLRP3, ASC, caspase-1, IL-1β, and IL-18, increase the expression of MUC2, Occludin, and ZO-1. In summary, Iso had a therapeutic effect on UC mice, and its mechanism may be to inhibit the inflammatory response and improve the intestinal mucosa barrier by binding Galectin-3 and inhibiting the Galectin-3/NLRP3/IL-1β signaling pathway.

Plant synthetic biology research requires diverse bioparts that facilitate the redesign and construction of new-to-nature biological devices or systems in plants. Limited by few well-characterized bioparts for plant chassis, the development of plant synthetic biology lags behind that of its microbial counterpart. Here, we constructed a web-based Plant Synthetic BioDatabase (PSBD), which currently categorizes 1677 catalytic bioparts and 384 regulatory elements and provides information on 309 species and 850 chemicals. Online bioinformatics tools including local BLAST, chem similarity, phylogenetic analysis, and visual strength are provided to assist with the rational design of genetic circuits for manipulation of gene expression in planta. We demonstrated the utility of the PSBD by functionally characterizing taxadiene synthase 2 and its quantitative regulation in tobacco leaves. More powerful synthetic devices were then assembled to amplify the transcriptional signals, enabling enhanced expression of flavivirus non-structure 1 proteins in plants. The PSBD is expected to be an integrative and user-centered platform that provides a one-stop service for diverse applications in plant synthetic biology research.

Sphingolipids (SPLs) represent a highly diverse and structurally complex lipid class. The discussion of SPL metabolism-related issues is of importance in understanding the neuropathological progression of Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular deposits of the amyloid β-peptide (Aβ) and intraneuronal aggregates of the microtubule-associated protein tau. Critical roles of Aβ oligomer deposited and ganglioside GM1 could be formed as “seed” from insoluble GAβ polymer in initiating the pathogenic process, while tau might also mediate SPLs and their toxicity. The interaction between ceramide and α-Synuclein (α-Syn) accelerates the aggregation of ferroptosis and exacerbates the pathogenesis of AD. For instance, reducing the levels of SPLs can mitigate α-Syn accumulation and inhibit AD progression. Meanwhile, loss of SPLs may inhibit the expression of APOE4 and confer protection against AD, while the loss of APOE4 expression also disrupts SPLs homeostasis. Moreover, the heightened activation of sphingomyelinase promotes the ferroptosis signaling pathway, leading to exacerbated AD symptoms. Ferroptosis plays a vital role in the pathological progression of AD by influencing Aβ, tau, APOE, and α-Syn. Conversely, the development of AD also exacerbates the manifestation of ferroptosis and SPLs. We are compiling the emerging techniques (Derivatization and IM-MS) of sphingolipidomics, to overcome the challenges of AD diagnosis and treatment. In this review, we examined the intricate neuro-mechanistic interactions between SPLs and Aβ, tau, α-Syn, APOE, and ferroptosis, mediating the onset of AD. Furthermore, our findings highlight the potential of targeting SPLs as underexplored avenue for devising innovative therapeutic strategies against AD.

Summary: Plasma proteins are promising biomarkers and potential drug targets in lung cancer. To evaluate the causal association between plasma proteins and lung cancer, we performed proteome-wide Mendelian randomization meta-analysis (PW-MR-meta) based on lung cancer genome-wide association studies (GWASs), protein quantitative trait loci (pQTLs) of 4,719 plasma proteins in deCODE and 4,775 in Fenland. Further, causal-protein risk score (CPRS) was developed based on causal proteins and validated in the UK Biobank. 270 plasma proteins were identified using PW-MR meta-analysis, including 39 robust causal proteins (both FDR-q

Background: Toxoplasma gondii is an opportunistic parasitic protozoan that can cause highly fatal toxoplasmic encephalitis when the host immune system is compromised. However, the transition from chronic to acute infection remains poorly understood. In this study, we conducted a 180-day observation of tissue damage and inflammation in the brains of mice infected with T. gondii. Subsequently, we investigated the inflammatory factors that T. gondii infection may alter using two-sample Mendelian randomization (MR) analysis. Methods: We first established a mouse model of T. gondii infection. Subsequently, the mice were euthanized, the brain tissue collected, and immunohistochemistry and hematoxylin and eosin staining performed to observe tissue damage and inflammatory conditions at various time points. Our study also included a published large-scale genome-wide association study meta-analysis that encompassed the circulating concentrations of 41 cytokines. This dataset included 8293 individuals from three independent population cohorts in Finland. Genetic association data for T. gondii were sourced from the Integrative Epidemiology Unit and European Bioinformatics Institute datasets, which included 5010 and 559 individuals of European ancestry, respectively. To assess the causal relationship between T. gondii infection and inflammatory biomarkers, we applied a two-sample MR. Results: Inflammation and damage resulting from T. gondii infection varied among the distinct regions of the mouse brain. Based on the MR analysis results, three inflammatory biomarkers were chemically assigned to Chemokines and Others, including IP10 (interferon gamma inducible protein-10), MCP1 (monocyte chemoattractant protein-1), and TRAIL (TNF-related apoptosis-inducing ligand). Conclusion: Our study commenced with the assessment of tissue damage and progression of inflammation in distinct regions of the mouse brain after T. gondii infection. Subsequently, using MR analysis, we detected potential alterations in inflammatory factors associated with this infection. These findings offer valuable insights into the mechanisms underlying toxoplasmic encephalitis and suggest directions for the prevention and treatment of T. gondii infections.

Surfactants were proposed to be added into magnesium sulfate solution to improve the leaching process of weathered crust elution-deposited rare earth ores (WREOs). Effects of surfactants and their concentration on the seepage of leaching solutions and the leaching efficiency of rare earth (RE) and aluminum (Al) were investigated, and the leaching kinetics, the mass transfer process, the adhesion work and the adhesion work reduction factor were analyzed to reveal its strengthening leaching mechanism. The results show that cetyltrimethylammonium bromide (CTAB) has a better strengthening effect on the leaching process than dodecyl trimethyl ammonium bromide (DTAB), sodium dodecyl sulfate (SDS), sodium oleate and oleic acid. In the presence of 0.04% CTAB in 0.2 mol/L solution, the permeability coefficient of WREOs increases from 0.945×10−5 to 1.640×10−5 cm·s−1, and the leaching efficiency of RE increases from 80% to 90%, confirming the promotion of surfactants on the leaching process of WREOs. Kinetic analysis shows that the leaching process conforms to the inner diffusion control model, and the leaching kinetics equations of RE and Al related to CTAB content are obtained. Mass transfer discussion shows a smaller height equivalent to theoretical plate (HETP) of RE and Al at CTAB content of 0.04%, suggesting the higher mass transfer efficiency here. According to the interfacial properties of leaching solutions, the calculated adhesion work and the adhesion work reduction factor further demonstrate the strengthening leaching effect of CTAB on the leaching process of WREOs.

The progressive collapse of flat plate structures due to brittle punching shear failure of reinforced concrete (RC) slab-column connections is a major concern in structural engineering. This paper proposed an innovative star-shaped steel plates (SSPs) system to achieve an effective yet practical enhancement of the punching and post-punching performance of RC slab-column connections. SSPs were fabricated from thin steel plates, welded together, and placed in the centre of the joint. Engineering cementitious composite (ECC) was also adopted to replace the joint core concrete and work with the SSPs further to improve the punching shear behaviour of the joint. To evaluate the effectiveness of the proposed system, five large-scale RC slab-column connections with different SSPs configurations and concrete materials were tested under monotonic load. The results showed that the initial stiffness of the joint was minimally affected by the presence of SSPs, but the system significantly improved the punching shear strength, post-punching load-bearing capacity, and deformation capacity of the joint. Specimens with ECC and SSPs exhibited an even higher punching shear strength and more ductile post-punching behaviour. The study also found that the optimum enhancement of the punching shear behaviour of the slab-column joint can be realised when the SSPs yield just before the joint experiences punching shear damage. Finally, formulas were developed to reasonably predict the punching shear strength and post-punching load-carrying capacity of the SSPs reinforced slab-column connections.

Background: As an inevitable event after kidney transplantation, ischemia‒reperfusion injury (IRI) can lead to a decrease in kidney transplant success. The search for signature genes of renal ischemia‒reperfusion injury (RIRI) is helpful in improving the diagnosis and guiding clinical treatment. Methods: We first downloaded 3 datasets from the GEO database. Then, differentially expressed genes (DEGs) were identified and applied for functional enrichment analysis. After that, we performed three machine learning methods, including random forest (RF), Lasso regression analysis, and support vector machine recursive feature elimination (SVM-RFE), to further predict candidate genes. WGCNA was also executed to screen candidate genes from DEGs. Then, we took the intersection of candidate genes to obtain the signature genes of RIRI. Receiver operating characteristic (ROC) analysis was conducted to measure the predictive ability of the signature genes. Kaplan‒Meier analysis was used for association analysis between signature genes and graft survival. Verifying the expression of signature genes in the ischemia cell model. Results: A total of 117 DEGs were screened out. Subsequently, RF, Lasso regression analysis, SVM-RFE and WGCNA identified 17, 25, 18 and 74 candidate genes, respectively. Finally, 3 signature genes (DUSP1, FOS, JUN) were screened out through the intersection of candidate genes. ROC analysis suggested that the 3 signature genes could well diagnose and predict RIRI. Kaplan‒Meier analysis indicated that patients with low FOS or JUN expression had a longer OS than those with high FOS or JUN expression. Finally, we validated using the ischemia cell model that compared to the control group, the expression level of JUN increased under hypoxic conditions. Conclusions: Three signature genes (DUSP1, FOS, JUN) offer a good prediction for RIRI outcome and may serve as potential therapeutic targets for RIRI intervention, especially JUN. The prediction of graft survival by FOS and JUN may improve graft survival in patients with RIRI.

Objective: This study aimed to assess the role of leukocyte immunoglobulin-like receptor A2 (LILRA2) in ovarian carcinoma (OC) oncogenesis and prognosis. Materials and methods: Using the Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, the association between clinicopathological profiles and LILRA2 expression was investigated using logistic regression analysis. Kaplan–Meier analysis, Cox regression analysis, and column plots predicted the clinical outcomes of patients with OC and determine the predictive value of LILRA2. The biological functions of LILRA2 were assessed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. We used single-sample Gene Set Enrichment Analysis to investigate the relationship between immune cell infiltration and LILRA2 expression. Results: LILRA2 expression in OC tumors was significantly higher than in normal tissue (P

Aflatoxin B1 (AFB1) is extremely carcinogenic and can cause liver cancer in humans and animals with continued ingestion. As a natural compound, curcumin (Cur) exhibits excellent anti-inflammatory, and anti-cancer properties with few side effects. In this study, a total of 60 male mice (6-week-olds, 15 per group). After one week of acclimatization feeding, the mice were divided into control group (Con), AFB1 group, curcumin group (Cur), and AF+Cur group. The mice were gavaged with curcumin (Cur, 100 mg/kg) and/or AFB1 (0.75 mg/kg). To identify a new therapeutic target for AFB1-induced pyroptosis, we performed proteomic profiling for curcumin alleviating liver injury caused by AFB1 to further validate the targets through volcano plot analysis, Venn analysis, heatmap analysis, correlation, cluster analysis, GO and KEGG enrichment. AFB1 exposure resulted in the loss of hepatocyte membrane, swelling of the endoplasmic reticulum, and a significant increase in transaminase (ALT and AST) contents, while curcumin greatly improved these changes. We found that differentially expressed proteins are enriched in the endoplasmic reticulum membrane and identified ITPR2 as a target of curcumin that alleviates AFB1-induced liver injury by proteomics. Furthermore, ITPR2 expression was detected by immunofluorescence, and qRT-PCR for mRNA expression of genes downstream of ITPR2 (calpain1, calpain2, caspase-12, caspase-3). ITPR2-activated endoplasmic reticulum stress-related proteins (calpain1, calpaini2, bcl-2, BAX, cl-caspase-12, cl-caspase-3), apoptosis (PARP) and pyroptosis (DFNA5) related proteins were examined by western blotting. The analysis showed that it effectively prevents AFB1-induced pyroptosis by lowering endoplasmic reticulum stress via interfering with ITPR2 and its downstream proteins (calpain1, calpain2, bcl-2, Bax) and inhibiting caspase-12/caspase-3 pathway. Conclusively, this study applied proteomic profiling to elucidate ITPR2 as a new target, which might give a new perspective on the mechanism of curcumin alleviating AFB1-induced pyroptosis.

The purpose of this study was to investigate the role of epigenetic DNA methylation and CYPs expression in AFB1-exposed broiler liver and the protective effect of curcumin. Sixty-four one-day-old AA broilers were randomly divided into four groups, including control group, AFB1 group (1 mg/kg AFB1), curcumin + AFB1 group (1 mg/kg curcumin) and curcumin group (300 mg/kg curcumin). Histological observation, CYP450 enzyme activities, the expression levels of DNA methyltransferases and CYP450 enzymes, and the overall DNA methylation level in broiler liver were investigated. Dietary AFB1 was found to induce severe liver injury in broilers, upregulate the mRNA and protein expression of CYP450 enzymes (CYP1A1, CYP1A2 and CYP3A4) and the enzyme activities of CYP1A2 and CYP3A4. According to HPLC, qPCR and western blot analyses, the overall DNA methylation level and the mRNA and protein expression of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) in the liver were significantly increased after AFB1 exposure. Importantly, the Pearson test and correlation analysis data revealed that the overall DNA methylation level of broiler liver was positively correlated with DNMTs, while CYP1A1, CYP1A2 and CYP3A4 were negatively correlated. Surprisingly, curcumin supplementation strongly ameliorated AFB1-induced hepatotoxicity by restoring the histological changes, decreasing the expression and enzymatic activity of liver CYP450 enzymes (CYP1A1, CYP1A2, and CYP3A4), and increasing the overall DNA methylation level and the expression of DNMTs. Taken together, we concluded that curcumin could protect against AFB1-induced liver injury by mediating the effects of DNA methylation and CYPs expression.

Background: Brain abscess (BA) is a rare but life-threatening infection. Early identification of the pathogen is helpful to improve the outcomes. This study aimed to describe the clinical and radiological features of patients with BA caused by different organisms. Methods: A retrospective, observational study of patients with known etiologic diagnosis of BA in Huashan Hospital Affiliated to Fudan University in China between January 2015 and December 2020 was conducted. Data on patient demographics, clinical and radiological presenting features, microbiological results, surgical treatment, and outcomes were collected. Results: Sixty-five patients (49 male, 16 female) with primary BAs were included. Frequent clinical presentations included headache (64.6%), fever (49.2%) and confusion (27.3%). Streptococcus viridans was associated with thicker wall of abscesses (6.94 ± 8.43 mm for S. viridans versus 3.66 ± 1.74 mm for other organisms, P = 0.031) and larger oedema (89.40 ± 15.70 mm for S. viridans versus 74.72 ± 19.70 mm for other organisms, P = 0.023). The independent factor associated with poor outcome identified by multivariate analysis was confusion (Odds ratio 6.215, 95% confidence interval 1.406–27.466; P = 0.016). Conclusions: Patients with BAs caused by Streptococcus species had nonspecific clinical signs, but specific radiological features, which might be helpful for early diagnosis.

In this study, a skin gas detection system based on quartz enhanced photoacoustic spectroscopy (QEPAS) with a constant temperature collection chamber and an automatic frequency adjustment function was used to collect and monitor carbon dioxide (CO2) emissions from human skin. The detection element of the system is an on-beam structure assembled by a 30.72 kHz quartz tuning fork (QTF). A laser with a wavelength of 4991.26 cm−1 is emitted (with a wavelength adjustment range of 10 cm−1) to excite the QTF. When the integration time is 365 s, the system can achieve a minimum detection limit (MDL) of 2.6 ppmv. The sensitivity of the system is 636.9 ppmv/V. The gas detection system is used to monitor the concentration of CO2 emissions from different parts of the skin and the same part covered by different cosmetics. The CO2 emission rate is defined as the ratio of the skin gas monitoring time of 25 min to the CO2 concentration variable in the gas chamber (volume of 8 mL). The results were collected from three healthy volunteers. Among the six different parts, the cheeks emitted the fastest rate (the average rate was 365.5 ppmv/min) of CO2, and the thighs emitted the slowest rate (the average rate was 56.4 ppmv/min) of CO2. Comparing the experimental results of the six sites at different times, the order of the CO2 emission rate is identical for all six sites. In the experiments with the three cosmetic products (experimental site: forearm), comparing the CO2 emission rate from clean skin with the CO2 emission rate from cosmetic-covered skin shows that sunscreen is the most breathable, followed by barrier cream, and foundation is the least breathable.

Summary: Combination therapy is a promising approach in treating multiple complex diseases. However, the large search space of available drug combinations exacerbates challenge for experimental screening. To predict synergistic drug combinations in different cancer cell lines, we propose an improved deep forest-based method, ForSyn, and design two forest types embedded in ForSyn. ForSyn handles imbalanced and high-dimensional data in medium-/small-scale datasets, which are inherent characteristics of drug combination datasets. Compared with 12 state-of-the-art methods, ForSyn ranks first on four metrics for eight datasets with different feature combinations. We conduct a systematic analysis to identify the most appropriate configuration parameters. We validate the predictive value of ForSyn with cell-based experiments on several previously unexplored drug combinations. Finally, a systematic analysis of feature importance is performed on the top contributing features extracted by ForSyn. The resulting key genes may play key roles on corresponding cancers. Motivation: Combination therapy has shown promise as a treatment for complex diseases such as cancer. Synergistic drug combinations can offer increased therapeutic efficacy and reduce toxicity compared with single drugs. However, class imbalances in datasets have complicated the use of computational tools, such as deep learning, for synergistic drug prediction. We propose an improved deep forest-based model, ForSyn, to address the above problem on imbalanced, medium- or small-scale datasets with high dimensionality.

Heated tobacco products (HTPs) are a novel type of cigarette that have received extensive attention. The tobacco plug could be made from tobacco granules (TGs), which are heated but not burned during the inhalation process. Thermal conductivity is an important property to evaluate the speed of heating TGs to meet the critical temperature for generating aerosol. Nevertheless, thermal physics properties of TGs is rarely reported. In this study, the thermophysical performance for the tobacco granules is systematically studied. An effective strategy of raising the thermal conductivity of TGs by introducing a small amount of nanoparticles of high-thermal-conductivity-materials (HTCMs, copper, silver, and graphene) is proposed, which not only results in a 35% improvement in the thermal conductivity but also reduces the maximum temperature for generating aerosol. In addition, introducing Cu and Ag particles in the TGs are favorable for improving the antibacterial effect. This method is worth promoting for enhancing the thermal conductivity of other plant-derived heated products.

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe–/– mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

The fabrication of biphasic cartilage-bone integrated scaffolds is an attractive alternative for osteochondral repair but has proven to be extremely challenging. Existing three-dimensional (3D) scaffolds are insufficient to accurately biomimic the biphasic cartilage-bone integrated microenvironment. Currently, photo-crosslinkable hydrogels based on tissue-specific decellularized extracellular matrix (dECM) have been considered as an important technique to fabricate biomimetic scaffolds, but so far there has been no breakthrough in the photo-crosslinkable hydrogel scaffolds with biphasic cartilage-bone biomimetic microenvironment. Here, we report a novel strategy for the preparation of biomimetic cartilage-bone integrated scaffolds based on photo-crosslinkable cartilage/bone-derived dECM hydrogels, which are able to reconstruct biphasic cartilage-bone biomimetic microenvironment. The biphasic cartilage-bone integrated scaffolds provided a 3D microenvironment for osteochondral regeneration. The cartilage biomimetic scaffolds, consisting of cartilage-derived dECM hydrogels, efficiently regulated chondrogenesis of bone marrow mesenchymal stem cells (BMSCs). The bone biomimetic scaffolds, composed of cartilage/bone-derived dECM hydrogels, first regulated chondrogenesis of BMSCs, followed by endochondral ossification over time. Taken together, the biphasic cartilage-bone integrated tissue could be successfully reconstructed by subcutaneous culture based on cartilage-bone bilayered structural design. Furthermore, the biphasic cartilage-bone biomimetic scaffolds (cell-free) achieved satisfactory cartilage-bone integrated regeneration in the osteochondral defects of rabbits’ knee joints.

Nanomedicines, mainly consisting of liposome nanodrugs, polymer nanodrugs, protein nanodrugs, drug nanocrystals and inorganic nanodrugs, usually show higher efficiency than conventional small molecular drugs. Polymeric vesicles, owing to the advantages of good stability, easy functionalization, and large-scale production, have received extensive attention in drug loading and release. The hydrophilic cavity and hydrophobic vesicle wall can simultaneously encapsulate hydrophilic and hydrophobic drugs, which was beneficial to exert the synergistic therapeutic effect of drugs. In this review, we focused on the loading and release of nanodrugs in polymeric vesicles. The application of polymeric vesicles for single, multi-drug loading and co-assembly of polymers and nanoparticles were reviewed. The research progress of polymeric vesicles in the fields of targeted transport, drug release kinetics and stimuli-responsive controlled release of drugs was discussed.

Cotton (Gossypium spp.) is one of the most important cash crops worldwide. At present, new cotton varieties are mainly produced through conventional cross breeding, which is limited by available germplasm. Although the genome of cotton has been fully sequenced, research on the function of specific genes lags behind due to the lack of sufficient genetic material. Therefore, it is very important to create a cotton mutant library to create new, higher-quality varieties and identify genes associated with the regulation of key traits. Traditional mutagenic strategies, such as physical, chemical, and site-directed mutagenesis, are relatively costly, inefficient, and difficult to perform. In this study, we used a radiation mutation method based on linear electron acceleration to mutate cotton variety ‘TM-1’, for which a whole-genome sequence has previously been performed, to create a high throughput cotton mutant library. Abundant phenotypic variation was observed in the progeny population for three consecutive generations, including cotton fiber color variation, plant dwarfing, significant improvement of yield traits, and increased sensitivity to Verticillium wilt. These results show that radiation mutagenesis is an effective and feasible method to create plant mutant libraries.

Malignant melanoma is a highly aggressive, malignant, and drug-resistant tumor. It lacks an efficient treatment approach. In this study, we developed a novel anti-melanoma strategy by using anti-tapeworm drug niclosamide and anti-malarial drug quinacrine, and investigated the molecular mechanism by in vitro and in vivo assays. Meanwhile, other types of tumor cells, immortalized epithelial cells and bone marrow mesenchymal stem cells were used to evaluate the universal role of anti-cancer and safety of the strategy. The results showed, briefly, an exposure to niclosamide and quinacrine led to an increased apoptosis-related protein p53, cleaved caspase-3 and cleaved PARP and autophagy-related protein LC3B expression, and a decreased expression of autophagy-related protein p62, finally leading to cell apoptosis and autophage. After inhibiting autophagy by Baf-A1, flow cytometry and western blot showed that the expression of apoptosis-related proteins was down-regulated and the number of apoptotic cells decreased. Subsequently, in the siRNA-mediated p53 knockdown cells, the expression of apoptosis-related proteins and the number of apoptotic cells were also reduced, while the expression of autophagy-related proteins including LC3B, p62 did not change significantly. To sum up, we developed a new, safe strategy for melanoma treatment by using low doses of niclosamide and quinacrine to treat melanoma; and found a novel mechanism by which the combination application of low doses of niclosamide and quinacrine exerts an efficient anti-melanoma effect through activation of autophagy-mediated p53-dependent apoptosis. The novel strategy was verified to exert a universal anti-cancer role in other types of cancer.

This study aimed to investigate the association of miRNA-21 with mutant p53 expression, prognosis, interaction, and clinicopathological features of non-small cell lung cancer (NSCLC). Tissue specimens from 200 NSCLC patients were collected for qRT-PCR analysis of miR-21 and p53 expression, and p53 mutations were analyzed by Sanger sequencing. NSCLC cell lines were used to determine the effects of miR-21 knockdown on cell viability, cell cycle distribution, and p53 expression. We found that miR-21 expression was upregulated in NSCLC tissues, which was associated with an increase in p53 mRNA levels and with advanced tumor-node-metastasis (TNM) stages and lymph node metastasis. The most common mutant sites of p53 in NSCLC were R175H and R248Q. Moreover, elevated miR-21 and p53 expression levels were associated with shorter overall survival. Knockdown of miR-21 reduced NSCLC cell viability, arrested NSCLC cells at the G0-to-G1 phase of the cell cycle, and downregulated mutant p53 mRNA levels and phosphorylated p53 protein expression in A549 and H1650 cells compared to control cells. miR-21 is associated p53 at mutant sites R175H and R248Q, which seems not to be oncogenic, as it is being reported, since in a normal cell, without a mutated p53, it will probably have a protective role.

This study set out to assess the mitigative effects of curcumin on AFB1-induced necroptosis and inflammation in chicken liver. Ninety-six one-day-old AA broiler chickens were separated into four groups, including control group, AFB1 (1 mg/kg) group, curcumin (300 mg/kg) + AFB1 (1 mg/kg) group and curcumin (300 mg/kg) group. After 28 days treatment, livers were collected for different experimental analyses. The morphological observation results showed obvious necrotic characteristics, including cell swelling, rupture of cell and mitochondrial membranes and inflammation in chicken livers. AFB1 exposure increased oxidative stress index (ROS and MDA) and decreased the antioxidant activity markers (SOD, CAT and GSH) and ATPase activities in chickens’ liver. ELISA results showed that AFB1 exposure significantly induced the cytokines (TNF-α, iNOS, IL-6 and IL-1β) release from the liver tissues. While, western blot and qRT-PCR results showed that the protein and mRNA expressions of inflammatory (TLR4/myd88/NF-κB) and necroptosis (RIPK1/RIPK3/MLKL) genes were up-regulated by AFB1 exposure. We suspect that signal crosstalk between TLR4 and TNF-α triggers inflammation and RIPK1/RIPK3 mediating necroptosis in AFB1-induced chicken liver injury. Curcumin can regulate the TLR4/RIPK signaling pathway, reduced oxidative stress biomarkers and inflammatory cytokines levels and attenuated the expression of necroptosis and inflammation genes altered by AFB1 to reduce necroptosis of chicken liver tissue. In conclusion, curcumin can protect against AFB1-induced necroptosis and inflammation by TLR4/RIPK pathway in chicken liver.

Summary: Background: Maternal serum Lamin A (LMNA) was reported to have potential diagnostic value in the prenatal diagnosis of congenital heart disease (CHD). In this study, we aimed to further assess the prognostic value of maternal serum LMNA in predicting adverse pregnancy outcomes. Methods: A prospective screening study was performed on singleton pregnancies at 15–18 weeks of gestation. After a routine test for alpha fetoprotein (AFP), chorionic gonadotropin (hCG), and unconjugated estriol (uE3), serum LMNA levels were measured. Serum LMNA levels were then converted into multiples of the median (MoM). The median MoM values for adverse pregnancy outcomes were compared with those in normal pregnancies. For diseases with differential LMNA expression in the prospective study, another case-control cohort was recruited. The diagnostic value of LMNA in these diseases was further evaluated. Findings: Between January 1, 2017 and June 30, 2018, a total of 2906 singleton pregnancies were recruited. Of the 2,906 cases, 2711 had data available for analysis. Congenital structural abnormalities, chromosomal abnormalities, and obstetric complications were observed in 152 (5·6%), 15 (0·6%), and 278 (10·3%) patients, respectively. LMNA was downregulated in pregnancies with fetal CHD, fetal neural tube defects (NTD), and preeclampsia (PE). The case-control study cohort included 256 CHD, 60 NTD, 67 PE, and 400 normal pregnancies. The areas under the curve for the prenatal diagnoses of CHD, NTD, and PE were 0·875, 0·871, and 0·816, respectively. Interpretation: Maternal serum LMNA was found to be a potential biomarker for the prenatal diagnosis of fetal CHD, NTD, and PE. Funding: National Key Research and Development Program, National Natural Science Foundation of China, LiaoNing Revitalization Talents Program, National Natural Science Foundation of Liaoning, and 345 Talent Project of Shengjing Hospital.

Safranal (SFR) is the major constituent of saffron. The purpose of this study was to observe the effect of SFR on myocardial ischemia induced by isoprenaline (ISO) and to explore its possible mechanism. The myocardial ischemia rat model was established by subcutaneous injection of ISO (85 mg/kg/d) on the 8th and 9th day of the experiment. Serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured, as were changes in calcium concentration, reactive oxygen species (ROS) and cardiac morphology of the myocardial tissue. The effects of SFR on cell contraction, Ca2+ transient and L-type Ca2+ current (ICa-L) in isolated rat myocardial cells were measured using the Ion Optix detection system and the whole-cell patch-clamp technique. SFR can decrease the activity of serum CK, LDH and MDA, and increase the activity of serum SOD, reduce intracellular calcium concentration and the manufacture of ROS. In addition, SFR can improve changes in heart morphology. SFR can significantly inhibit contraction, Ca2+ transients and ICa-L in isolated ventricular myocytes. SFR has a cardioprotective role in ISO-induced MI rats, and the underling mechanism is related to the inhibition of oxidative stress, myocardial contractility, ICa-L and the regulation of Ca2+ homeostasis.

It has great significance to monitor the oil and gas pipeline leakage to reduce economic loss and environmental pollution. In this paper, we propose a method to recognize the leakage of oil and gas pipeline based on both vibration and temperature information according to the distributed optical fiber sensor’s measurement ability. After comparing various feature values and different classifier models, we choose six temperature feature values, five vibration feature values, and the random forest model as the optimum combination for the pipeline leakage recognition. The method can accurately recognize the states of leakage, interference, and normal operation. The average recognition accuracy is 98.57%, which is higher than the traditional single-parameter judgment method, and the recognition time is only 6.79 ms.

Aflatoxin B1 (AFB1) is a potent hepatotoxic and carcinogenic agent. Curcumin possesses potential anti-inflammatory, anti-oxidative and hepatoprotective effects. However, the role of LncRNAs in the protective mechanisms of curcumin against AFB1-induced liver damage is still elusive. Experimental broilers were randomly divided into 1) control group, 2) AFB1 group (1 mg/kg feed), 3) cur + AFB1 group (1 mg/kg AFB1 plus 300 mg/kg curcumin diet) and 4) curcumin group (300 mg/kg curcumin diet). Liver transcriptome analyses and qPCR were performed to identify shifts in genes expression. In addition, histopathological assessment and oxidant status were determined. Dietary AFB1 caused hepatic morphological injury, significantly increased the production of ROS, decreased liver antioxidant enzymes activities and induced inflammation and apoptosis. However, dietary curcumin partially attenuated the abnormal morphological changes, oxidative stress, and apoptosis in liver tissues. Transcriptional profiling results showed that 34 LncRNAs and 717 mRNAs were differentially expressed with AFB1 and curcumin co-treatment in livers of broilers. Analysis of the LncRNA-mRNA network, GO and KEGG enrichment data suggested that oxidative stress, inflammation and apoptosis pathway were crucial in curcumin’s alleviating AFB1-induced liver damage. In conclusion, curcumin prevented AFB1-induced oxidative stress, inflammation and apoptosis through LncRNAs. These results provide new insights for unveiling the protective mechanisms of curcumin against AFB1-induced liver damage.

Frozen waves have the good characteristic for resisting the diffraction and absorption in absorbing medium, which can solve the low transmittance of light waves in seawater. By the turbulence spectrum of seawater and the theory of frozen waves, we develop a frozen wave theory for random field and establish a transmittance model for finite energy frozen beams and analyze the diffracting- and absorption-resistance of finite energy frozen waves from the beam transmission wavelength, beam waist, beam orbital angular momentum quantum number, inner scale of turbulence, outer scale of turbulence, the “temperature structure” constant and the ratio of temperature and salinity. The transmittance of for finite energy frozen waves decreases as the propagation distance increases, and by designing longitudinal profile we can compensate the attenuation loss of the transmittance. We derive that the frozen wave has an optimal wavelength window in “seawater transmission window”. Our results theoretically provide a feasible basis for the establishment of underwater multipoint base station optical communication network. Keywords: Diffraction- and attenuation-resistant, Frozen beam, Transmittance, Oceanic turbulence

We extend the theory of detection probabilities of single-photon communication in turbulent atmosphere to the entangled case and derive analytical expressions for detection probabilities. We show that the rotational field correlation in the entangled case cannot be expressed as a straightforward extension from the disentangled case. By considering the orbital angular momentum (OAM) entangled Laguerre-Gaussian (LG) beams for illustration, we explore the effect of non-Kolmogorov atmospheric turbulence on the probabilities of both the biphoton detection and the single-photon detection. The entanglement of OAM LG beams contributes positively to the faithful detection probability. The change of maximal crosstalk probability in the detection process is also explored, which displays the non-linear dependence on the crosstalk quantum number. Keywords: Atmospheric turbulence, Orbital angular momentum, Entanglement, Optical communication

Germinal matrix hemorrhage is induced by stereotaxic injection of collagenase into the germinal matrix of P7 Sprague-Dawley rats. Hemoglobin assay, western blot, immunofluorescence and neurobehavioral tests were used to test the effects of BLVRA on hematoma resolution and anti-inflammatory response. We showed that BLVRA triggered a signaling cascade that ameliorated post-hemorrhagic neurological deficits in both short-term and long-term neurobehavioral tests in a GMH rat model. Specifically, BLVRA inhibited toll-like receptor 4 (TLR4) expression by translocating to the nucleus in an endothelial nitric oxide (eNOS)/nitric oxide (NO)-dependent manner. BLVRA also induced the upregulation of CD36 scavenger receptor level in microglia/microphages, of which the prominent role is to enhance hematoma resolution. However, the beneficial effects of BLVRA were abolished with the knockdown of eNOS, indicating that the eNOS/NO system is an important downstream factor of BLVRA. Our results demonstrate a mechanism of BLVRA modulating hematoma resolution and suppressing inflammation through eNOS/NO/TLR4 pathway in the GMH rat model.

Human brains are prone to neurodegeneration, given that endogenous neural stem/progenitor cells (NSPCs) fail to support neurogenesis. To investigate the molecular programs potentially mediating neurodegeneration-induced NSPC plasticity in regenerating organisms, we generated an Amyloid-β42 (Aβ42)-dependent neurotoxic model in adult zebrafish brain through cerebroventricular microinjection of cell-penetrating Aβ42 derivatives. Aβ42 deposits in neurons and causes phenotypes reminiscent of amyloid pathophysiology: apoptosis, microglial activation, synaptic degeneration, and learning deficits. Aβ42 also induces NSPC proliferation and enhanced neurogenesis. Interleukin-4 (IL4) is activated primarily in neurons and microglia/macrophages in response to Aβ42 and is sufficient to increase NSPC proliferation and neurogenesis via STAT6 phosphorylation through the IL4 receptor in NSPCs. Our results reveal a crosstalk between neurons and immune cells mediated by IL4/STAT6 signaling, which induces NSPC plasticity in zebrafish brains.

By analyzing the construction features of a Lommel Gaussian-Schell beam and the beam wander for Gaussian beams, we derive the closed-from approximations expression for the wander of Lommel Gaussian-Schell beam through unstable stratification and weak ocean-turbulence. Turbulence conditions with a smaller outer- and inner-scale of turbulence usually cause smaller beam wander. There is a extremum value βex of the beam paraxial coefficient corresponding to the maximum beam wander for given parameters of turbulence and beam. We can utilize larger beam waist, longer wavelength, higher quantum number of orbital angular momentum and larger asymmetry factor, meanwhile, avoid extremum value βex to reduce the beam wander. The influence of salinity fluctuations of turbulent ocean on beam wander is greater than temperature fluctuations. Under the assumption of unit diffusivity ratio, the beam wander is either underestimated or overestimated. Keywords: Beam wander, Lommel Gaussian-Schell, Turbulent ocean

We propose a model of the fiber coupling efficiency for a partially coherent collimating laser beam propagating through turbulent biological tissue to fiber. By studying the influence of link parameters on fiber coupling efficiency, we find that there are optimal focal length and transmitting beam radius for specific turbulent tissue. We also find that a larger characteristic length and small length-scale factor, or smaller fractal dimension and strength coefficient of refractive-index fluctuation will lead to larger fiber coupling efficiency. In order to improve the fiber coupling efficiency, we recommend select the optimum focal length, moderate transmitting beam radius, lower aperture diameter of the coupling lens, longer wavelength and higher coherent degree of light source. 2000 MSC: 41A05, 41A10, 65D05, Keywords: Fiber coupling efficiency, Biological tissue, Turbulence, Optimum parameter, Laser beam