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Abstract Colorectal cancer (CRC) is one of the most prevalent and lethal malignant tumors globally, posing significant health risks and societal burdens. Recently, advancements in next-generation sequencing technology have identified CRC intratumoral microbiota, thereby opening up novel avenues for further research. This review synthesizes the current advancements in CRC intratumoral microbiota and their impact on CRC progression and discusses the disparities in the relative abundance and community composition of CRC intratumoral microbiota across various colorectal tumors based on their anatomical location and molecular subtypes, as well as the tumor stages, and spatial tumor distribution. Intratumoral microbiota predominantly influence CRC development by modulating colonic epithelial cells, tumor cells, and the tumor microenvironment. Mechanistically, they can cause DNA damage, apoptosis and epithelial-mesenchymal transition. The effects of different intratumoral microbiota on CRC have been shown to be two-fold. In the future, to address the limitations of existing studies, it is important to develop comprehensive experimental protocols and suitable in vitro models for elucidating more mechanisms of intratumoral microbiota on CRC, which will facilitate the clinical application of microbe-related therapeutic strategies in CRC and potentially other tumors.

Background: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. Methods: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. Results: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = −4.74, p

Abstract Background Excessive alcohol consumption has been consistently linked to serious adverse health effects, particularly affecting the liver. One natural defense against the detrimental impacts of alcohol is provided by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), which detoxify harmful alcohol metabolites. Recent studies have shown that certain probiotic strains, notably Lactobacillus spp., possess alcohol resistance and can produce these critical enzymes. Incorporating these probiotics into alcoholic beverages represents a pioneering approach that can potentially mitigate the negative health effects of alcohol while meeting evolving consumer preferences for functional and health-centric products. Results Five lactic acid bacteria (LAB) isolates were identified: Lactobacillus paracasei Alc1, Lacticaseibacillus rhamnosus AA, Pediococcus acidilactici Alc3, Lactobacillus paracasei Alc4, and Pediococcus acidilactici Alc5. Assessment of their alcohol tolerance, safety, adhesion ability, and immunomodulatory effects identified L. rhamnosus AA as the most promising alcohol-tolerant probiotic strain. This strain also showed high production of ADH and ALDH. Whole genome sequencing analysis revealed that the L. rhamnosus AA genome contained both the adh (encoding for ADH) and the adhE (encoding for ALDH) genes. Conclusions L. rhamnosus AA, a novel probiotic candidate, showed notable alcohol resistance and the capability to produce enzymes essential for alcohol metabolism. This strain is a highly promising candidate for integration into commercial alcoholic beverages upon completion of comprehensive safety and functionality evaluations.

Abstract Background Expansion and contraction of inverted repeats can cause considerable variation of plastid genomes (plastomes) in angiosperms. However, little is known about whether structural variations of plastomes are associated with adaptation to or occupancy of new environments. Moreover, adaptive evolution of angiosperm plastid genes remains poorly understood. Here, we sequenced the complete plastomes for four species of xerophytic Ceratocephala and hydrophytic Myosurus, as well as Ficaria verna. By an integration of phylogenomic, comparative genomic, and selection pressure analyses, we investigated evolutionary patterns of plastomes in Ranunculeae and their relationships with adaptation to dry and aquatic habitats. Results Owing to the significant contraction of the boundary of IRA/LSC towards the IRA, plastome sizes and IR lengths of Myosurus and Ceratocephala are smaller within Ranunculeae. Compared to other Ranunculeae, the Myosurus plastome lost clpP and rps16, one copy of rpl2 and rpl23, and one intron of rpoC1 and rpl16, and the Ceratocephala plastome added an infA gene and lost one copy of rpl2 and two introns of clpP. A total of 11 plastid genes (14%) showed positive selection, two genes common to Myosurus and Ceratocephala, seven in Ceratocephala only, and two in Myosurus only. Four genes showed strong signals of episodic positive selection. The rps7 gene of Ceratocephala and the rpl32 and ycf4 genes of Myosurus showed an increase in the rate of variation close to 3.3 Ma. Conclusions The plastomic structure variations as well as the positive selection of two plastid genes might be related to the colonization of new environments by the common ancestor of Ceratocephala and Myosurus. The seven and two genes under positive selection might be related to the adaptation to dry and aquatic habitats in Ceratocephala and Myosurus, respectively. Moreover, intensified aridity and frequent sea-level fluctuations, as well as global cooling, might have favored an increased rate of change in some genes at about 3.3 Ma, associated with adaptation to dry and aquatic environments, respectively. These findings suggest that changing environments might have influenced structural variations of plastomes and fixed new mutations arising on some plastid genes owing to adaptation to specific habitats.

Abstract Colorectal cancer (CRC) is a significant public health concern, and its development is associated with mitochondrial dysfunction. Mitochondria can adapt to the high metabolic demands of cancer cells owing to their plasticity and dynamic nature. The fusion–fission dynamics of mitochondria play a crucial role in signal transduction and metabolic functions of CRC cells. Enhanced mitochondrial fission promotes the metabolic reprogramming of CRC cells, leading to cell proliferation, metastasis, and chemoresistance. Excessive fission can also trigger mitochondria-mediated apoptosis. In contrast, excessive mitochondrial fusion leads to adenosine triphosphate (ATP) overproduction and abnormal tumor proliferation, whereas moderate fusion protects intestinal epithelial cells from oxidative stress-induced mitochondrial damage, thus preventing colitis-associated cancer (CAC). Therefore, an imbalance in mitochondrial dynamics can either promote or inhibit CRC progression. This review provides an overview of the mechanism underlying mitochondrial fusion–fission dynamics and their impact on CRC biology. This revealed the dual role of mitochondrial fusion–fission dynamics in CRC development and identified potential drug targets. Additionally, this study partially explored mitochondrial dynamics in immune and vascular endothelial cells in the tumor microenvironment, suggesting promising prospects for targeting key fusion/fission effector proteins against CRC. Graphical Abstract

Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant’s biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.

Abstract Potassium‐ion batteries (PIBs) have garnered significant attention as a promising alternative to commercial lithium‐ion batteries (LIBs) due to abundant and cost‐efficient potassium reserves. However, the large size of potassium ions and the resulting sluggish reaction kinetics present major obstacles to the widespread use of PIBs. Herein, we present a simple method to ingeniously encapsulate SnS2 nanoparticles within sulfurized polyacrylonitrile (SPAN) fibers (SnS2@SPAN) for serving as a high‐performance PIB anode. The large interlayer spacing of SnS2 provides a fast transport channel for potassium ions during charge–discharge cycles, while the one‐dimensional SPAN skeleton offers massive binding sites and shortens the diffusion path for potassium ions, facilitating faster reaction kinetics. Additionally, the excellent ductility of SPAN can effectively accommodate the large volume changes that occur in SnS2 upon potassium‐ion insertion, thereby enhancing the cyclic stability of SnS2. Benefiting from the above advantages, the SnS2@SPAN composites exhibit impressive cyclability over 500 cycles at 4 A g−1, with a capacity retention rate close to 100%. This study provides an effective approach for stabilizing high‐capacity PIB anode materials with large volume variations.

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

Abstract The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid‐co‐glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2 polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid‐associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K‐AKT signaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.

Type 2 diabetes (T2DM) is characterized by insulin secretion deficiencies and systemic insulin resistance (IR) in adipose tissue, skeletal muscle, and the liver. Although the mechanism of T2DM is not yet fully known, inflammation and insulin resistance play a central role in the pathogenesis of T2DM. G protein‐coupled receptors (GPCRs) are involved in endocrine and metabolic processes as well as many other physiological processes. GPR50 (G protein‐coupled receptor 50) is an orphan GPCR that shares the highest sequence homology with melatonin receptors. The aim of this study was to investigate the effect of GPR50 on inflammation and insulin resistance in 3T3‐L1 preadipocytes. GPR50 expression was observed to be significantly increased in the adipose tissue of obese T2DM mice, while GPR50 deficiency increased inflammation in 3T3‐L1 cells and induced the phosphorylation of AKT and insulin receptor substrate (IRS) 1. Furthermore, GPR50 knockout in the 3T3‐L1 cell line suppressed PPAR‐γ expression. These data suggest that GPR50 can attenuate inflammatory levels and regulate insulin signaling in adipocytes. Furthermore, the effects are mediated through the regulation of the IRS1/AKT signaling pathway and PPAR‐γ expression.

Abstract Background CARs are engineered receptors comprising an immunoglobulin single‐chain variable fragment (scFv) that identifies and binds to the target antigen, a transmembrane domain, and an intracellular T‐cell signaling domain. CD19 is a B lineage‐specific transmembrane glycoprotein and is expressed in more than 95% of B‐cell malignancies. Streptavidin (SA) is a homo‐tetrameric protein derived from Streptomyces avidinii, which can bind four biotin molecules with an extremely high affinity at a Kd value of 10‐15 M. Aims The aim of the study is to generate a novel soluble multimeric fusion protein, sCD19‐streptavidin (sCD19‐SA) for functional detection and selective expansion of CD19‐targeted CAR‐T cells. Methods The fusion proteins CD19‐SA was expressed in CHO cells and purified by use of Ni‐nitrilotriacetic acid agarose beads. Results A novel fusion protein (sCD19‐SA) was generated, consisting of the extracellular domain of human CD19 and the core region of SA, and could be used to functionally detect CD19‐targeted CAR‐T cells. Furthermore, this protein was demonstrated to form multimers to activate CAR‐T cells to induce their selective expansion. Importantly, sCD19‐SA‐stimulated CD19‐targeted CAR‐T cells could improve antitumor effects in vivo. Conclusions Our study has highlighted the potential of utilizing antigen‐SA fusion proteins such as sCD19‐SA for CAR‐T therapy for the functional detection of CAR expression and selective expansion of CAR‐T cells.

Apoptosis is a complex and highly self-regulating form of cell death, which is an important cause of the continuous decline in ventricular function and is widely involved in the occurrence and development of heart failure, myocardial infarction, and myocarditis. Endoplasmic reticulum stress plays a crucial role in apoptosis-inducing. Accumulation of misfolded or unfolded proteins causes cells to undergo a stress response called unfolded protein response (UPR). UPR initially has a cardioprotective effect. Nevertheless, prolonged and severe ER stress will lead up to apoptosis of stressed cells. Non-coding RNA is a type of RNA that does not code proteins. An ever-increasing number of studies have shown that non-coding RNAs are involved in regulating endoplasmic reticulum stress-induced cardiomyocyte injury and apoptosis. In this study, the effects of miRNA and LncRNA on endoplasmic reticulum stress in various heart diseases were mainly discussed to clarify their protective effects and potential therapeutic strategies for apoptosis.

Objective: To describe the clinical spectrum of severe Chlamydia psittaci pneumonia in order to understand the disease better.Methods: Retrospective analysis was made on 31 patients with severe Chlamydia psittaci pneumonia diagnosed in ICU by next-generation sequencing of metagenome Metagenomic next-generation sequencing(mNGS) from January 2019–November 2022, including clinical characteristics, laboratory examination results, imaging characteristics, treatment, and prognosis.Results: We included 31 patients with severe Chlamydia psittaci pneumonia, 15 of whom had a history of virus exposure. There were 12 cases with multiple bacterial infections, and the common symptoms included fever (31/31,100%), dyspnea (31/31, 100%), cough (22/31, 71.0%), and myalgia (20/31, 64.5%). Laboratory data showed that white blood cells were average or slightly increased, but the levels of C-reactive protein and neutrophils were high. CT findings of the lung were consolidation (19/31, 61.3%) and pleural effusion (11/31, 35.5%). Only one lobe was involved in 11 patients (35.5%). Before diagnosis, 22 patients (71.0%) did not have atypical pathogens in their antimicrobial regimen. After diagnosis, 19 patients (61.3%) received single drug treatment, of which doxycycline or moxifloxacin were the most commonly used drugs. Among 31 patients, three died, nine improved, and nineteen were cured.Conclusion: The clinical manifestations of severe Chlamydia psittaci pneumonia are non-specific. The application of mNGS can improve the diagnostic accuracy of Chlamydia psittaci pneumonia, reduce the unnecessary use of antibiotics, and shorten the course of the disease. Doxycycline-based treatment is effective for severe chlamydia psittaci pneumonia, but it is necessary to understand the secondary bacterial infection and other complications in the course of the disease.

Numerous studies have suggested the possibility of explaining the etiology of metabolic syndrome through DNA methylation. DNA methyltransferase 3B (DNMT3B) plays an important role in de novo DNA methylation. There was an alteration in maternal (F0) endometrial function, which might lead to growth and developmental disorder in offspring (F1). In this study, we investigated the effect of maternal endometrial DNMT3B deficiency on the metabolism in offspring. We constructed endometrial DNMT3B conditional knockout female mice (cKO) which were mated with normal C57BL/6 male mice to obtain the F1 generation. Further, to study the development of these offspring, we observed them at three different life stages which included the 6-week-old juvenile, 9-week-old sub-adult and 12-week-old adult. Follow the detection of a range of metabolism-related indicators, we found that in the cKO F1 generation, liver triglyceride level was significantly elevated in 9-week-old female mice, lipid droplet deposition was significantly increased in 9-week-old and 12-week-old mice, and the expression of lipid metabolism key factors in the liver was markedly decreased except of 6-week-old male mice. These results indicate that maternal endometrial DNMT3B conditional knockout leads to imbalance in hepatic metabolism in F1 generation, the mechanism of which requires further discussion.

BackgroundKidney cancer (KC) is one of the most challenging cancers due to its delayed diagnosis and high metastasis rate. The 5-year survival rate of KC patients is less than 11.2%. Therefore, identifying suitable biomarkers to accurately predict KC outcomes is important and urgent.MethodsCorresponding data for KC patients were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. Systems biology/bioinformatics/computational approaches were used to identify suitable biomarkers for predicting the outcome and immune landscapes of KC patients.ResultsWe found two ferroptosis- and immune-related differentially expressed genes (FI-DEGs) (Klotho (KL) and Sortilin 1 (SORT1)) independently correlated with the overall survival of KC patients. The area under the curve (AUC) values of the prognosis model using these two FI-DEGs exceeded 0.60 in the training, validation, and entire groups. The AUC value of the 1-year receiver operating characteristic (ROC) curve reached 0.70 in all the groups.ConclusionsOur present study indicated that KL and SORT1 could be prognostic biomarkers for KC patients. Whether this model can be used in clinical settings requires further validation.

Chimeric antigen receptor (CAR)-T cell therapy has been shown to have considerable therapeutic effects in hematological malignancies, and NKG2D(z) CAR-T cell therapy has been verified to be safe based on clinical trials. However, due to the poor persistence of NKG2D(z) CAR-T cells, their therapeutic effect is not obvious. Here, we constructed NKG2D(bbz) CAR-T cells that can simultaneously activate 4-1BB and DAP10 costimulatory signaling. They were found to be cytotoxic to the target cells in vitro and in vivo. They exhibited low differentiation, low exhaustion, and good proliferation. Importantly, the proportions of central memory T (Tcm) and stem cell-like memory T (Tscm) cell subsets were strikingly increased. After long-term incubation with the target cells, they displayed reduced exhaustion compared to NKG2D(z) CAR-T cells. Further, in the presence of the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, they exhibited reduced exhaustion and apoptosis, upregulated Bcl2 expression, and an increased proportion of Tcm cell subsets. Finally, NKG2D(bbz) CAR-T cells had better antitumor effects in vivo. In summary, the results showed that NKG2D(bbz) CAR-T cells may be valuable for cellular immunotherapy of cancer.

Increased maternal glucocorticoid levels have been implicated as a risk factor for preeclampsia (PE) development. We found that pregnant rats exposed to dexamethasone (DEX) showed hallmarks of PE features, impaired spiral artery (SA) remodeling, and elevated circulatory levels of sFlt1, sEng IL-1β, and TNFα. Abnormal mitochondrial morphology and mitochondrial dysfunction in placentas occurred in DEX rats. Omics showed that a large spectrum of placental signaling pathways, including oxidative phosphorylation (OXPHOS), energy metabolism, inflammation, and insulin-like growth factor (IGF) system were affected in DEX rats. MitoTEMPO, a mitochondria-targeted antioxidant, alleviated maternal hypertension and renal damage, and improved SA remodeling, uteroplacental blood flow, and the placental vasculature network. It reversed several pathways, including OXPHOS and glutathione pathways. Moreover, DEX-induced impaired functions of human extravillous trophoblasts were associated with excess ROS caused by mitochondrial dysfunction. However, scavenging excess ROS did not improve intrauterine growth retardation (IUGR), and elevated circulatory sFlt1, sEng, IL-1β, and TNFα levels in DEX rats. Our data indicate that excess mitochondrial ROS contributes to trophoblast dysfunction, impaired SA remodeling, reduced uteroplacental blood flow, and maternal hypertension in the DEX-induced PE model, while increased sFlt1 and sEng levels and IUGR might be associated with inflammation and an impaired energy metabolism and IGF system.

Hypoxic pulmonary hypertension (HPH) is a fatal disease with limited therapeutic strategies. Combination therapy is regarded as the standard of care in PH and becoming widely used in clinical practice. However, many PH patients treated with combinations of available clinical drugs still have a poor prognosis. Therefore, identifying innovative therapeutic strategies is essential for PH. This study is designed to examine the effects of combined prevention with resveratrol and SR1001 on HPH in rats. The effects of combined prevention with resveratrol and SR1001 and each mono-prevention on the development of HPH, Th17 cells differentiation, expression of guanine nucleotide exchange factor-H1 (GEF-H1), Ras homolog gene family member A (RhoA) and Phosphorylated myosin phosphatase target subunit (MYPT1) were examined. HPH and RV hypertrophy occurred in rats exposed to hypoxia. Compared with normoxia group, the hypoxia group showed significantly increased ratio of Th17 cells. After treatment with resveratrol, HPH rats showed an obvious reduction of Th17 cells. SR1001 significantly reduced the increased p-MYPY1, RhoA, and GEF-H1 expression in the hypoxic rats. The mono-prevention with resveratrol or SR1001 significantly inhibited the Th17 cells differentiation, p-STAT3, p-MYPY1, RhoA, and GEF-H1 protein expression, which was further inhibited by their combination prevention. The combination of resveratrol and SR1001 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to exert further beneficial effects on HPH.

Abstract Background Fyn has been documented to have oncogenic features in multiple tumors, which might be a potential therapeutic target, however, few studies on the function role of Fyn and its specific inhibitors in melanoma. Methods We investigated the impacts of Fyn and its inhibitor Lj-1-60 on melanoma through bioinformatics analysis, western blot, cell viability, cell cycle and apoptosis and xenograft tumor model as well as immunohistochemical staining. Pull-down and in vitro kinase assay were used to demonstrate Lj-1-60 targeting Fyn. Transcriptome sequencing and RT-PCR were adopted to confirm the potential mechanisms of Lj-1-60 in melanoma. Results Our findings showed that Fyn was overexpressed in melanoma cells and knocked down of Fyn suppressed the proliferation of melanoma cells. To identify the potential inhibitors of Fyn, our in-house library including total of 111,277 chemicals was conducted to vitro screening, among those compounds, 83 inhibitors were further detected to explore the effect on melanoma cells growth and discovered a novel chalcone derivative Lj-1-60 that exhibited low cellular toxicity and high anti-tumor efficacy. Lj-1-60 directly was associated with Fyn and inhibited the Fyn kinase activity with Stat3 as substrate. What’s more, Lj-1-60 suppressed the proliferation of melanoma in vitro and in vivo through inducing cell cycle arrest and apoptosis. Moreover, the activation of Stat3 had also been abrogated both in Lj-1-60 treated melanoma cells or Fyn knocked down cells. Conclusion Our study revealed a novel Fyn inhibitor that could significantly suppress melanoma growth, which is a promising potential inhibitor for melanoma treatment.

Abstract Objective To establish nomogram based on inflammatory indices for differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). Methods A cohort of 422 patients with HCC or ICC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent differential factors. Through combining these independent differential factors, a nomogram was established for differential diagnosis between ICC and HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). The results were validated using a prospective study on 98 consecutive patients operated on from January 2019 to November 2019 at the same institution. Results Sex (OR = 9.001, 95% CI: 3.268‐24.792, P

Abstract Background Melanoma is one of the most aggressive tumors with the remarkable characteristic of resistance to traditional chemotherapy and radiotherapy. Although targeted therapy and immunotherapy benefit advanced melanoma patient treatment, BRAFi (BRAF inhibitor) resistance and the lower response rates or severe side effects of immunotherapy have been observed, therefore, it is necessary to develop novel inhibitors for melanoma treatment. Methods We detected the cell proliferation of lj-1-59 in different melanoma cells by CCK 8 and colony formation assay. To further explore the mechanisms of lj-1-59 in melanoma, we performed RNA sequencing to discover the pathway of differential gene enrichment. Western blot and Q-RT-PCR were confirmed to study the function of lj-1-59 in melanoma. Results We found that lj-1-59 inhibits melanoma cell proliferation in vitro and in vivo, induces cell cycle arrest at the G2/M phase and promotes apoptosis in melanoma cell lines. Furthermore, RNA-Seq was performed to study alterations in gene expression profiles after treatment with lj-1-59 in melanoma cells, revealing that this compound regulates various pathways, such as DNA replication, P53, apoptosis and the cell cycle. Additionally, we validated the effect of lj-1-59 on key gene expression alterations by Q-RT-PCR. Our findings showed that lj-1-59 significantly increases ROS (reactive oxygen species) products, leading to DNA toxicity in melanoma cell lines. Moreover, lj-1-59 increases ROS levels in BRAFi -resistant melanoma cells, leading to DNA damage, which caused G2/M phase arrest and apoptosis. Conclusions Taken together, we found that lj-1-59 treatment inhibits melanoma cell growth by inducing apoptosis and DNA damage through increased ROS levels, suggesting that this compound is a potential therapeutic drug for melanoma treatment.

Abstract Background Compared with open gastrectomy (OG), laparoscopic gastrectomy (LG) for gastric cancer has achieved rapid development and popularities in the past decades. However, lack of comprehensive analysis in long-term oncological outcomes such as recurrence and mortality hinder its full support as a valid procedure. Therefore, there are still debates on whether one of these options is superior. Aim To evaluate the primary and secondary outcomes of laparoscopic versus open gastrectomy for gastric cancer patients Methods Two authors independently extracted study data. Risk ratio (RR) with 95% confidence interval (CI) was calculated for binary outcomes, mean difference (MD) or the standardized mean difference (SMD) with 95% CI for continuous outcomes, and the hazard ratio (HR) for time-to-event outcomes. Review Manager 5.3 and STATA software were used for the meta-analysis. Results Seventeen randomized controlled trials (RCTs) involving 5204 participants were included in this meta-analysis. There were no differences in the primary outcomes including the number of lymph nodes harvested during operation, severe complications, short-term and long-term recurrence, and mortality. As for secondary outcomes, compared with the OG group, longer operative time was required for patients in the LG group (MD = 58.80 min, 95% CI = [45.80, 71.81], P

Previous contract protocols in blockchains ensure their fairness and traceability by utilizing centralized credible nodes. If credible nodes are dishonest or conspire with the signatory, then other nodes are compromised. Meanwhile, the leakage of sensitive information of participant nodes poses a serious threat to the privacy security of data access in blockchains. To address this issue, this study proposes a secure control method of digital certificate-based data access in blockchains. The proposed method combines blockchain and digital certificate technologies and designs a secure authentication protocol for privacy data in blockchains without verifying the encrypted identity signature of the third-party participant. The high-efficiency network forwarding protocol proposed in this work can support the fair contract signing of multiple signers via blockchain. This protocol can protect the privacy of contracts and identities of participants. Experimental results show that the proposed scheme is superior in terms of communication overhead, storage overhead, and detection rate.

Inflammation in gestational tissues plays critical role in parturition initiation. We sought to investigate the leukocyte infiltration and cytokine profile in uterine tissues to understand the inflammation during term and preterm labor in the mouse model. Preterm birth was induced by the administration of lipopolysaccharide (LPS) or RU38486. The populations of leukocytes were determined by flow cytometry. Macrophages were the largest population in the myometrium and decidua in late gestation. The macrophage population was significantly changed in the myometrium and decidua from late pregnancy to term labor and significantly changed at LPS- and RU386-induced preterm labor. Neutrophils, T cells, and NKT cells were increased in LPS- and RU38486-induced preterm labor. The above changes were accompanied by the increased expression of cytokines and chemokines. In late gestation, M2 macrophages were the predominant phenotype in gestational tissues. M1 macrophages significantly increased in these tissues at term and preterm labor. IL-6 and NLRP3 expression was significantly increased in macrophages at labor, supporting that macrophages exhibit proinflammatory phenotypes. NLRP3 inflammasome inhibitor MCC950 mainly suppressed macrophage infiltration in the myometrium at term labor and preterm labor. Our data suggest that the M1 polarization of macrophages contributes to inflammation linked to term and preterm labor initiation in gestational tissues.

Taking Baidu search index as the data source, this research collects yoga-related data in various provinces in China, analyzes the public’s attention to yoga on the Internet from the perspective of the complex network theory, so as to dig out characteristics of those who are interested in yoga as well as the temporal and spatial change of yoga attention from 2011 to 2020. Then, by transforming the time series into a network through the VG model and HVG model, the paper analyzes the network characteristics and predicts the popularity of yoga. Furthermore, the publicity of yoga and the public’s attention to it are analyzed, considering the policy, national education level, the influence of TV, mobile phone and other communication equipment, so as to help the market to provide corresponding products and services in a targeted manner and to promote the healthy development of the yoga industry.

According to the social exchange theory, this study analyzed how a bottom-line mentality (BLM) among leaders affects teachers' innovative behavior and how this relationship is mediated by relative deprivation and psychological safety and moderated by person-organization values fit. Using two stages of data collection, 491 responses from teachers were obtained and analyzed. The results revealed that leader BLM significantly negatively affected teachers' innovative behavior, and relative deprivation and psychological safety both partially mediated this influence of leader BLM. Person-organization values fit negatively moderated the positive effect of leader BLM on teachers' relative deprivation and the negative effect of leader BLM on teachers' psychological safety. This study enriches the current literature about BLM and tests the influence of leader BLM on teacher's innovation in the Chinese education and training institutions, and provides insights into favorable educational management practices.

How to motivate employees to break through the role constraints and show more initiative determines the success or failure of a company’s future development. Taking charge behavior refers to the behavior where individuals influence the change of organizational function through voluntary and constructive efforts, which is a challenging organizational citizenship behavior. This study investigates the underlying mechanism and boundary condition of authentic leadership (AL) on employees’ taking charge behavior based on the role identity theory and literature concerning perspective taking. Matched data were collected from a multi-source sample that included 146 direct supervisors and 328 subordinates in mainland, China. The empirical results indicate that AL has a positive influence on the employees’ taking charge behavior, and subordinates’ moqi mediates the relationship between them. In addition, the employees’ perspective taking positively moderated the positive relationship between AL and subordinates’ moqi, as well as the mediating effect of subordinates’ moqi in the relationship between AL and employees’ taking charge behavior. Compared with the low levels of perspective taking, high levels of that made the influence of AL on subordinates’ moqi stronger, so is the whole indirect effect. This study is the first to explore the influencing mechanism of AL on employees’ taking charge behavior from the perspective of the role identity theory, thereby enriching the relevant studies and providing practical insights for organizational leaders regarding on how to foster employees to take charge.

With rapid advances in edge computing and the Internet of Things, the security of low-layer hardware devices attract more and more attention. As an ideal hardware solution, field programmable gate array (FPGA) becomes a mainstream technology to design a complex system. The designed modules are named as intellectual property (IP) cores. In this paper, we consider both misappropriation of hardware devices and software IPs in edge computing and propose a PUF-based IP copyright anonymous authentication scheme. The scheme utilizes the double physical unclonable function (PUF) authentication model. Both the parties generate the challenge jointly in authentication to avoid replay attack and modeling attack on PUF circuit. The complexity of authentication is greatly reduced. Besides, the server of FPGA vendor is unnecessary to store all the challenge response pairs (CRPs) of each PUF-based chip due to the use of the double PUF authentication model. It saves the system resource and achieves better security. To protect software IP, IP core vendor inserts copyright information and anonymous buyer identity information into the design before trading. The anonymity of the buyer ensures the benefits of the buyer. With the participation of trustable device vendor, infringement behavior can be traced according to extracted fingerprints. The experiments show that the resource overhead of the proposed scheme is reduced by 61.96% and 31.61% by comparing with 2-1 DAPUF and built-in self-adjustable PUF. Besides, PUF stability is 99.54%. It demonstrates the good performance of the proposed scheme.

Background: The repair of large bone defects remains challenging for orthopaedic surgeons. Bone grafting remains the method of choice; such grafts fill spaces and enhance bone repair. Therapeutic agents also aid bone healing. The objective of this study is to develop a composite bioactive scaffold composed of polylactide-coglycolide (PLGA) and tricalcium phosphate (TCP) (the basic carrier) incorporating osteogenic, bioactive magnesium metal powder (Mg). Method: Porous PLGA/TCP scaffolds incorporating Mg were fabricated using a low-temperature rapid-prototyping process. We term the PLGA/TCP/Mg porous scaffold (hereafter, PPS). PLGA/TCP lacking Mg served as the control material when evaluating the efficacy of PPS. A total of 36 New Zealand white rabbits were randomly divided into blank, PLGA/TCP (P/T) and PPS group, with 12 rabbits in each group. We established bone defects 15 mm in length in rabbit radii to evaluate the in vivo osteogenic potential of the bioactive scaffold in terms of the direct controlled release of osteogenic Mg ion during in vivo scaffold degradation. Radiographs of the operated radii were taken immediately after implantation and then at 2, 4, 8 and 12 weeks. Micro-computed tomography of new bone formation and remaining scaffold and histological analysis were performed at 4, 8, 12 weeks after operation. Results: X-ray imaging performed at weeks 4, 8 and 12 post-surgery revealed more newly formed bone within defects implanted with PPS and PLGA/TCP scaffolds than blank group (p < 0.05). And micro-computed tomography performed at weeks 4 and 8 after surgery revealed more newly formed bone within defects implanted with PPS scaffolds than PLGA/TCP scaffolds (p

We have previously demonstrated that placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) dysfunction contributes to PE pathogenesis. We sought to elucidate molecular mechanisms underlying 11β-HSD2 dysfunction-induced PE and to seek potential therapeutic targets using a 11β-HSD2 dysfunction-induced PE-like rat model as well as cultured extravillous trophoblasts (EVTs) since PE begins with impaired function of EVTs. In 11β-HSD2 dysfunction-induced PE-like rat model, we revealed that placental mitochondrial dysfunction occurred, which was associated with mitDNA instability and impaired mitochondrial dynamics, such as decreased optic atrophy 1 (OPA1) expression. MitoTEMPO treatment significantly alleviated the hallmark of PE-like features and improved mitDNA stability and mitochondrial dynamics in the placentas of rat PE-like model. In cultured human EVTs, we found that 11β-HSD2 dysfunction led to mitochondrial dysfunction and disrupted mtDNA stability. MitoTEMPO treatment improved impaired invasion and migration induced by 11β-HSD2 dysfunction in cultured EVTs. Further, we revealed that OPA1 was one of the key factors that mediated 11β-HSD2 dysfunction-induced excess ROS production, mitochondrial dysfunction and mtDNA reduction. Our data indicates that 11β-HSD2 dysfunction causes mitochondrial dysfunctions, which impairs trophoblast function and subsequently results in PE development. Our study immediately highlights that excess ROS is a potential therapeutic target for PE.

Chimeric antigen receptor (CAR) technology has revolutionized cancer treatment, particularly in malignant hematological tumors. Currently, the BCMA-targeted second-generation CAR-T cells have showed impressive efficacy in the treatment of refractory/relapsed multiple myeloma (R/R MM), but up to 50% relapse remains to be addressed urgently. Here we constructed the BCMA-targeted fourth-generation CAR-T cells expressing IL-7 and CCL19 (i.e., BCMA-7 × 19 CAR-T cells), and demonstrated that BCMA-7 × 19 CAR-T cells exhibited superior expansion, differentiation, migration and cytotoxicity. Furthermore, we have been carrying out the first-in-human clinical trial for therapy of R/R MM by use of BCMA-7 × 19 CAR-T cells (ClinicalTrials.gov Identifier: NCT03778346), which preliminarily showed promising safety and efficacy in first two enrolled patients. The two patients achieved a CR and VGPR with Grade 1 cytokine release syndrome only 1 month after one dose of CAR-T cell infusion, and the responses lasted more than 12-month. Taken together, BCMA-7 × 19 CAR-T cells were safe and effective against refractory/relapsed multiple myeloma and thus warranted further clinical study.

Hyperglycemia exposure results in the dysfunction of endothelial cells (ECs) and the development of diabetic complications. Circular RNAs (circRNAs) have been demonstrated to play critical roles in EC dysfunction. The current study aimed to explore the role and mechanism of circRNA CLIP–associating protein 2 (circ_CLASP2, hsa_circ_0064772) on HG-induced dysfunction in human umbilical vein endothelial cells (HUVECs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the levels of circ_CLASP2, miR-140-5p and F-box, and WD repeat domain-containing 7 (FBXW7). The stability of circ_CLASP2 was identified by the actinomycin D and ribonuclease (RNase) R assays. Cell colony formation, proliferation, and apoptosis were measured by a standard colony formation assay, colorimetric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay, and flow cytometry, respectively. Western blot analysis was performed to determine the expression of related proteins. Targeted correlations among circ_CLASP2, miR-140-5p, and FBXW7 were confirmed by dual-luciferase reporter assay. High glucose (HG) exposure downregulated the expression of circ_CLASP2 in HUVECs. Circ_CLASP2 overexpression or miR-140-5p knockdown promoted proliferation and inhibited apoptosis of HUVECs under HG conditions. Circ_CLASP2 directly interacted with miR-140-5p via pairing to miR-140-5p. The regulation of circ_CLASP2 overexpression on HG-induced HUVEC dysfunction was mediated by miR-140-5p. Moreover, FBXW7 was a direct target of miR-140-5p, and miR-140-5p regulated HG-induced HUVEC dysfunction via FBXW7. Furthermore, circ_CLASP2 mediated FBXW7 expression through sponging miR-140-5p. Our current study suggested that the overexpression of circ_CLASP2 protected HUVEC from HG-induced dysfunction at least partly through the regulation of the miR-140-5p/FBXW7 axis, highlighting a novel therapeutic approach for the treatment of diabetic-associated vascular injury.

Colon cancer commonly develops from long-term chronic inflammation in the intestine and seriously threatens human health. Natural polyphenols have been valued as a crucial regulator of nutrient metabolism and metabolic diseases, owing to their anti-inflammatory and antioxidant functions and the ability to maintain a balance between gut microbes and their hosts. Notably, experimental and clinical evidence has shown that natural polyphenols could act as a targeted modulator to play a key role in the prevention or treatment of colon cancer. Thus, in this review, we summarized recent advances in the possible regulatory mechanism and the potential application of natural polyphenols in colon cancer, which might be regarded as a novel platform for the colon cancer management.

Aiming at the uncertainty in the existing tunnel surrounding rock stability evaluation methods and the inability to make scientific explanations in the process of determining the weights of multiple evaluation indicators, this paper combines subjective weighting based on the nonlinear characteristics of the surrounding rock stability evaluation criteria. Based on the advantages of the method AHP and the objective weighting method CRITIC, a comprehensive weighting method with multiple evaluation indicators is proposed, which is integrated with the multidimensional normal cloud model to establish a surrounding rock stability evaluation method for the improved weighted multidimensional cloud model and accurately obtain the safety level of tunnel surrounding rock construction. The multidimensional cloud model based on improved weighting not only solves the two major problems of randomness and ambiguity in surrounding rock stability evaluation but also fully considers the influence of the information contained in each evaluation factor on the results. The surrounding rock stability evaluation method in this paper is applied to the tunnel construction of the Beijing-Shanghai Expressway and Jinan Expressway connecting line construction project, and the evaluation results have a scientific guiding role for construction risk control.

Background: Scarce literature has yet to characterize the tactile discrimination capability as well as the underlying mechanism of tactile deficits in psychotic disorder. In particular, very little is known regarding the tactile perception acuity in schizophrenia.Methods: A total of 131 clinically stable patients with schizophrenia (SCZ) and 79 healthy control (HC) volunteers were enrolled in the study. All the participants were tested on a tactile stimulus device which could quantify the tactile discrimination capability with right index finger scanned over the angles via the passive finger-movement apparatus. The MATRICS Consensus Cognitive Battery (MCCB) was adapted to assess the neurocognition of the participants. Correlation analysis and multivariate linear regression analysis were performed to investigate the relationship between tactile perception performance and neurocognitive function.Results: It was discovered that there existed a significant deficits in the tactile passive perception acuity (i.e., tactile angle discrimination threshold) in patients with schizophrenia compared with their healthy controls (F (3, 206) = 11.458, P = 0.001,partial η2 = 0.053). The MCCB total score and its six domains were significantly lower in SCZ patients than those in HCs (all p < 0.001). In the SCZ group, the composite score of the MCCB (r = −0.312, P < 0.001) and domains of neurocognition including speed of processing (r = −0.191, P = 0.031), attention/vigilance (r = −0.177, P = 0.047), working memory (r = −0.316, P < 0.001), verbal learning (r = − 0.332, P < 0.001), visual learning (r = −0.260, P = 0.004), and reasoning and problem solving (r = −0.209, P = 0.018) showed significant negative correlations with the tactile angle discrimination threshold. Multivariate linear regression analysis revealed that neurocognition impairment, especially the decline of working memory (B = −0.312, P < 0.001),underpin the tactile perception discrimination deficits in patients with SCZ.Conclusion: To the best of our knowledge, this is the first study to unravel the deficits of tactile passive perception acuity and its underlying neurocognition basis in patients with SCZ. This finding adds novel evidence to the subtle variation in haptic discrimination skills in schizophrenia which contributes to a more comprehensive understanding of the sensory profiles of this disorder.

Abstract Background Human telomerase reverse transcriptase (hTERT) is highly expressed in over 80% of tumors, including human epithelial ovarian cancer (EOC). However, the mechanisms through which hTERT is up-regulated in EOC and promotes tumor progression remain unclear. The aim of this study is to identify RIF1 as a novel molecular target that modulate hTERT signaling and EOC growth. Methods RIF1 expression in ovarian cancer, benign and normal ovarian tissues was examined by immunohistochemistry. The biological role of RIF1 was revealed by MTS, colony formation and sphere formation assays. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify RIF1 as a novel hTERT promoter-binding protein in EOC cells. The role of RIF1 on tumorigenesis in vivo was detected by the xenograft model. Results RIF1 expression is upregulated in EOC tissues and is closely correlated with FIGO stage and prognosis of EOC patients. Functionally, RIF1 knockdown suppressed the expression and promoter activity of hTERT and consequently inhibited the growth and CSC-like traits of EOC cells. RIF1 knockdown also inhibited tumorigenesis in xenograft model. RIF1 overexpression had the opposite effect. Luciferase reporter assay and ChIP assay verified RIF1 directly bound to hTERT promoter to upregulate its expression. The rescue experiments suggested hTERT overexpression rescued the inhibition of EOC cell growth and CSC-like traits mediated by RIF1 knockdown. Consistently, hTERT knockdown abrogated the RIF1-induced promotion of EOC cell growth and CSC-like traits. Conclusions RIF1 promotes EOC progression by activating hTERT and the RIF1/hTERT pathway may be a potential therapeutic target for EOC patients.

Summary: Background/Objective: A novel porous scaffold poly (lactide-co-glycolide) and tricalcium phosphate (PLGA/TCP) was developed by three-dimensional printing technology for bone defect repair. As a Class 2 solvent with less severe toxicity, content of residual 1,4-dioxane in this newly developed scaffold should be rigorously controlled when it is translated to clinical use. In this study, a headspace gas chromatography-mass spectrometric (HS-GC-MS) method and related testing protocol were developed for quantitative determination of 1,4-dioxane in the PLGA/TCP composite scaffolds. Methods: Matrix effect analysis was used to optimise the pretreatment method of the scaffolds. Then, the procedure for testing 1,4-dioxane using HS-GC-MS was set up. The accuracy, precision, and robustness of this newly developed quantitative method were also validated before quantification of 1,4-dioxane in the scaffolds with different drying procedures. Results: Dimethyl formamide (DMF) was the optimal solvent for dissolving scaffolds for GC-MS with proper sensitivity and without matrix effect. Then, the optimised procedure was determined as: the scaffolds were dissolved in DMF and kept at 90°C for 40 minutes, separated on a HP-5MS column, and detected by mass spectroscopy. Recovery experiments gave 97.9–100.7% recovery for 1,4-dioxane. The linear range for 1,4-dioxane was determined as 1–40 ppm with linear correlation coefficient ≥ 0.9999. Intraday and interday precision was determined as being within relative standard deviation of below 0.68%. The passable drying procedure was related to lyophilising (−50°C, 50 Pa) the scaffolds for 2 days and drying in vacuum (50 Pa) for 7 days. Conclusion: This is the first quantitative method established to test 1,4-dixoane in a novel scaffold. This method was validated with good accuracy and reproducibility, and met the methodological requirements of the Guideline 9101 documented in the Chinese Pharmacopoeia 2015 Edition. The translational potential of this article: This quantitative method for determination of residual 1,4-dioxane in the novel scaffolds is a key technical method during its translation into clinical use because this method is an important and indispensable file in the enterprise standard when the porous scaffold is registered as a Class III implanted medical device for bone defect repair, which is used to guarantee the safety of the scaffolds. It is also applied to optimise the drying process of scaffolds and to monitor the quality of scaffolds in the industrialisation process. Further, this method provides references for other solvents quantitative determination in porous scaffolds or materials. Keywords: headspace gas chromatography mass spectrometry, three-dimensional printing porous scaffold, 1,4-dioxane

Background/Aims: Rap1 interacting factor 1 (RIF1) was deemed to be involved in replication timing regulation and DNA damage response. However, little is known about the role of RIF1 in malignancies. Thus, this study aimed to investigate whether the expression of RIF1 is relevant to the response of epithelial ovarian cancer (EOC) patients to cisplatin chemotherapy and its underlying mechanism. Methods: Immunohistochemistry was used for detecting the expression of RIF1 in 72 human ovarian cancer tissues followed by association analysis of RIF1 expression with patients’ responses to platinum-based chemotherapy. The survival analysis of ovarian patients based on platinum chemotherapy was analyzed using online databases. RNA interference of RIF1 was carried out in OVCAR3 and A2780 cell lines, to determine the effect of lacking RIF1 expression on cellular responses to cisplatin by using MTS assay. The nucleotide excision repair (NER) capacity of these cells was assessed by using host-cell reactivation and UV sensitivity assay. Western Blot analysis was carried out to determine the effect of RIF1 on the proteins of NER and apoptosis signaling pathway by using RIF1 knockdown cells. BALB/c nude mice model was used for detection of response to cisplatin in vivo. Results: RIF1 expression was significantly associated with the response of ovarian patients to platinum-based chemotherapy (P< 0.01). In cohorts from online databases, high expression of RIF1 was associated with higher mortality of EOC patients based on platinum chemotherapy (P < 0.01). RIF1 knockdown increased sensitivity to cisplatin in EOC in vitro and in vivo. Deletion of RIF1 impaired the NER activity by inhibiting the NER proteins in ovarian cancer cells. Besides, knockdown of RIF1 enhanced cisplatin-induced apoptosis. Conclusions: RIF1 plays an important role in regulating the expression of NER proteins, which in turn contributes to cellular response to cisplatin and EOC patients’ response to platinum-based chemotherapy. RIF1 knockdown also promotes cisplatin-induced apoptosis. RIF1 may serve as a novel biomarker for predicting platinum-based chemosensitivity and the prognosis of EOC patients.

Rapid fabricating and harnessing stimuli-responsive behaviors of microscale bio-compatible hydrogels are of great interest to the emerging micro-mechanics, drug delivery, artificial scaffolds, nano-robotics, and lab chips. Herein, we demonstrate a novel femtosecond laser additive manufacturing process with smart materials for soft interactive hydrogel micro-machines. Bio-compatible hyaluronic acid methacryloyl was polymerized with hydrophilic diacrylate into an absorbent hydrogel matrix under a tight topological control through a 532 nm green femtosecond laser beam. The proposed hetero-scanning strategy modifies the hierarchical polymeric degrees inside the hydrogel matrix, leading to a controllable surface tension mismatch. Strikingly, these programmable stimuli-responsive matrices mechanized hydrogels into robotic applications at the micro/nanoscale (3). Reverse high-freedom shape mutations of diversified microstructures were created from simple initial shapes and identified without evident fatigue. We further confirmed the biocompatibility, cell adhesion, and tunable mechanics of the as-prepared hydrogels. Benefiting from the high-efficiency two-photon polymerization (TPP), nanometer feature size (

Background: Recent evidence has indicated that long non-coding RNA (lncRNA) is involved in the pathogenesis of type 2 diabetes, but nothing is known about lncRNA expression changes of lymphatic endothelial cells in response to type 2 diabetes. Methods: The GSE38396 dataset was downloaded from the Gene Expression Omnibus database and the probe sets of Human Gnome U133 Plus2.0 microarray were annotated for lncRNA. Differentially expressed lncRNAs between diabetic and non-diabetic lymphatic endothelial cells were calculated. Results: Compared with lymphatic endothelial cells in non-diabetic patients, 31 lncRNAs were down-regulated and 79 lncRNAs were up-regualted in lymphatic endothelial cells of type 2 diabetic patients. Several known lncRNAs were found, such as H19, GAS5, UCA1, CRNDE, GAS5, and LINC00312. Co-expression network of differentially expressed lncRNAs and mRNAs were constructed. Based on genomic regions of these lncRNAs, we found that binding sites of MAF and TCF3 were enriched and these lncRNAs may be related to insulin reporter signaling pathway and response to insulin stimulus. Conclusions: In a word, we found a set of lncRNAs were differentially expressed in lymphatic endothelial cells in response to type 2 diabetes and these lncRNAs may be involved in the pathogenesis of diabetes-related complications.

Except the network attacks, the industrial networked devices in Internet of things are also threatened by intellectual property infringement. Watermarking technique is a prevalent way to avoid this threat. Previous work on authenticating a watermark in industrial intellectual properties easily discloses sensitive information of real embedded watermarks. In this case, the evidence of identifying the ownership of industrial intellectual property may be attacked by the illegal verifiers. Although several watermark detection techniques can address the disclosure of sensitive information in detection procedure, the efficiency of detection is relatively low. Besides, it may yield large communication overhead of multiple authentication rounds. Motivated by the needs of robustness and efficiency, this work proposed a zero-knowledge approach to authenticate ownership of field-programmable gate array intellectual property design in industrial environment, named NIWAS . The prover can convince the verifier that he knows a secret in the suspected intellectual property design via only one interaction. Real locations of watermarks are concealed through location obfuscation. With the received authentication package from the prover, the verifier cannot obtain other useful information about the watermarks. The experiments show that NIWAS achieves high efficiency and robustness of watermark detection.