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Liquid biopsy has the advantage of diagnosing diseases in a non-invasive manner. Seminal plasma contains secretions from the bilateral testes, epididymides, seminal vesicles, bulbourethral glands, and the prostate. These organs are relatively small and contain delicate tubes that are prone to damage by invasive diagnosis. Cell-free seminal nucleic acids are a newly emerged item in liquid biopsy. Here, we present a comprehensive overview of all known cell-free DNA and cell-free RNAs (mRNA, miRNA, lncRNA, circRNA, piRNA, YRNA, tsRNA, etc.) and discuss their roles as biomarker candidates in liquid biopsy. With great advantages, including high stability, sensitivity, representability, and non-invasiveness, cell-free DNA/RNAs may be developed as promising biomarkers for the screening, diagnosis, prognosis, and follow-up of diseases in semen-secreting organs. Moreover, RNAs in semen may participate in important processes, including sperm maturation, early embryo development, and transgenerational disease inheritance, which may be developed as potential treatment targets for future clinical use.

Objective. Investigate the influence of miR-107 on breast cancer cell growth and death through the PTEN/AKT signaling pathway. Method. As study subjects, the human breast cancer cell line MCF-7 and the normal breast cell line Hs 578Bst were chosen, and MCF-7 cells were, respectively, transfected with control miRNA and miR-107 inhibitor. CCK-8, flow cytometry, scratch assay, and Transwell assay were used to analyze the proliferation, apoptosis, and invasion, and in order to identify the proteins associated with apoptosis in each of the three categories, we used western blot analysis. Bcl-2, cleaved caspase-3, and cleaved caspase-9 expression, as well as PTEN/AKT signaling pathway-associated protein expression, are correlated. Result. The expression of miR-107 in MCF-7 cells was significantly greater than that in Hs 578Bst cells, with a P P P P > 0.05); the miR-107 inhibitor group had higher apoptosis (38.96) with P P > 0.05). There was no significant difference between the blank group and the miRNA control group with P > 0.05; compared with the blank group, the miR-107 inhibitor group had a lower expression of Bcl-2 protein (0.18), in addition to the degraded paradigms (0.73) and caspase-9 protein concentrations (0.79), respectively. Conclusion. The PTEN/AKT signaling pathway may be regulated by miR-107 to limit breast cancer cell growth and increase apoptosis, which suggests that miR-107 may be exploited as a tumor marker for therapeutic therapy.

A high-performance tire X-ray defect image classification method plays a key role in enhancing the automation level of tire defect detection. In industrial practice, however, a typical challenge is that the collected datasets of diverse tire defects are often imbalanced. To address this issue, a Wasserstein generative adversarial network (WGAN)–assisted image classification method is proposed for imbalanced tire X-ray defect detection. To expand the minority classes in original datasets, a WGAN model is established to generate high-quality X-ray defect images. Considering the feature similarity of different defect grades in the same type, the WGAN is trained based on a pre-trained model to extract deep features. An improved deep convolutional neural network model is restructured for performance improvement. Finally, the augmented balanced datasets are used to train the improved network for image classification of tire X-ray defects. The experiments validate that the proposed method is effective for type and grade classification of imbalanced tire X-ray defect detection, and shows better classification performance than existing popular models.

OBJECTIVE: To assess the safety and effectiveness of intravascular lithotripsy (IVL) treatment for de novo coronary lesion involving severely calcified vessels in a Chinese population. METHODS: The Clinical Trial of the ShOckwave Coronary IVL System Used to Treat CalcIfied Coronary ArtEries (SOLSTICE) was a prospective, single-arm, multicentre trial. According to the inclusion criteria, patients with severely calcified lesions were enrolled in the study. IVL was used to perform calcium modification prior to stent implantation. The primary safety endpoint was freedom from major adverse cardiac events (MACEs) at 30 days. The primary effectiveness endpoint was procedural success, defined as successful stent delivery with residual stenosis < 50% by core lab assessment without in-hospital MACEs. The morphological changes of calcium modification were assessed by optical coherence tomography (OCT) before and after IVL treatment. RESULTS: Patients (n = 20) were enrolled at three sites in China. Severe calcification by core lab assessment was present in all lesions, with a mean calcium angle and thickness of 300 ± 51° and 0.99 ± 0.12 mm (by OCT), respectively. The 30-day MACE rate was 5%. Both primary safety and effectiveness endpoints were achieved in 95% of patients. The final in-stent diameter stenosis was 13.1% ± 5.7% with no patient had a residual stenosis < 50% after stenting. No serious angiographic complications (severe dissection grade D or worse, perforation, abrupt closure, slow flow/no-reflow) observed at any time during the procedure. OCT imaging demonstrated visible multiplane calcium fracture in 80% of lesions with a mean stent expansion of 95.62% ± 13.33% at the site of maximum calcification and minimum stent area (MSA) of 5.34 ± 1.64 mm(2). CONCLUSIONS: The initial coronary IVL experience for Chinese operators resulted in high procedural success and low angiographic complications consistent with prior IVL studies, reflecting the relative ease of use of IVL technology.

Nitrogen self-doped hierarchical porous carbon for electrical double-layer capacitors was synthesized by direct carbonization of bean dregs-based tar with potassium acetate as the template agent. The pore structure parameters and chemical element composition were adjusted by varying the heating rate during the carbonization process. The electrochemical properties of the electrode materials were evaluated in a three electrode system with 6 M KOH as the electrolyte. The resultant bean dregs-based porous carbons (BDPCs) exhibited high specific surface area, unique hierarchical architecture (consisting of supermicro- and mesopores), and medium nitrogen content (0.66 to 0.78%). The BDPC-10 sample had the highest specific surface area of 1610 m2/g and reasonable pore size distribution, and consequently exhibited an excellent specific capacitance of 363.7 F/g at the current density of 1 A/g. Nevertheless, the capacitance was reduced to 280.5 F/g at 3 A/g, giving a capacitance retention ratio of 77.1%. This study suggests a facile and environmentally friendly template synthesis process for supercapacitor electrode materials preparation, but it also faces challenges to increase the rate capability.

While technology advancement and scientific innovation have created new topics and fields of inquiry in STEM education, external content experts such as university scientists/researchers have been increasingly involved to enhance K-12 teachers’ disciplinary understandings and professional development (PD). However, few studies have scrutinized scientist-facilitated PD programs regarding teacher epistemology, about how and in what ways the programs impact teachers’ epistemological understandings of disciplinary knowledge. To address the gap, this paper investigates the process by which teachers construct epistemological understandings and teaching practices in interacting with scientists. Informed by theories of epistemic cognition and social cognition, we conducted an interactional ethnography in a school-university partnered PD program with six primary teachers. Based on participant observation, teacher interviews, and classroom videos and artifacts, we identified three patterns of teacher-scientist negotiation: reciprocal negotiation of knowledge presentation, observation and interpretation of scientist practices, and inconsistency in knowledge translation. The teachers’ professional responsibility and knowledge served as a critical filter in their decisions of selecting, interpreting, and rejecting scientist inputs, leading to respective epistemological stances and pedagogical actions. The research uncovers the situated and multifaceted negotiation of teacher epistemology and offers implications for researching and supporting their epistemological development.

Ectomycorrhizal fungi (EMFs) form symbioses with plant roots to promote nutrient uptake by plants but it is controversial as to whether they induce disease resistance in plants. Here, we inoculated pine seedlings with Sphaeropsis sapinea, which was presymbiotic with the EMF Hymenochaete sp. Rl, and the mycorrhizal helper bacterium (MHB) Bacillus pumilus HR10, which promotes the formation of Pinus thunbergia–Hymenochaete sp. Rl mycorrhizae. The results showed that inoculation with Hymenochaete sp. Rl, B. pumilus HR10, and the consortium significantly reduced pine shoot blight disease caused by S. sapinea. After inoculation with pathogenic fungi, callose deposition was significantly increased in needles of pine seedlings inoculated with Hymenochaete sp. Rl, B. pumilus HR10, and the consortium, together with an increase in enzymatic and nonenzymatic systemic antioxidant activity as well as early priming for upregulated expression of PR3 and PR5 genes. Our findings suggest that ectomycorrhizal colonization enhances the resistance of pine seedlings to Sphaeropsis shoot blight by triggering a systemic defense response and that interactions between EMFs and MHBs are essential for mycorrhizal-induced disease resistance.

Higher education is poised at the precipice of the changes and challenges brought about by ChatGPT. This paper addresses some of the most fundamental questions about the role, position, and implications of ChatGPT and generative artificial intelligence (AI) tools amidst the evolving landscape of higher education and modern society. By linking technological affordances with educational needs, we conceptualize ChatGPT as a student-driven innovation with rich potential to empower students and enhance their educational experiences and resources. However, this empowerment comes at a price. It requires collaborative efforts among the stakeholders to address the new and emerging challenges regarding student training, higher education curricula and assessment, and technology development and governance. It also implies new directions for educational research and theories.

Interactions between the novel Chk1 inhibitor MK-8776 and the histone deacetylase (HDAC) inhibitor (HDACI) vorinostat were examined in human leukemia cells harboring wild-type (wt) or deficient p53. MK-8776 synergistically potentiated vorinostat-mediated apoptosis in various p53-wt or -deficient leukemia cell lines, whereas p53 knockdown by short hairpin RNA (shRNA) sensitized p53-wt cells to lethality of this regimen. Leukemia cell lines carrying FLT3-ITD were also sensitive to the MK-8776/vorinostat regimen. Synergistic interactions were associated with inhibition of Chk1 activity, interference with the intra-S-phase checkpoint, disruption of DNA replication, and downregulation of proteins involved in DNA replication (e.g., Cdt1) and repair (e.g., CtIP and BRCA1), resulting in sharp increases in DNA damage, reflected by enhanced γ-H2A.X formation, and apoptosis. Moreover, leukemia cells expressing kinase-dead Chk1 (D130A) or Chk1 shRNA were significantly more sensitive to HDACIs compared with their wt counterparts and displayed downregulation of CtIP and BRCA1 phosphorylation following HDACI exposure. Finally, the MK-8776/vorinostat regimen was active in primary acute myelogenous leukemia (AML) blasts, particularly against the CD34+/CD38−/CD123+ population enriched for leukemia-initiating cells. In contrast, identical regimens were relatively sparing toward normal cord blood CD34+ cells. Together, these findings indicate that the novel Chk1 inhibitor MK-8776 markedly potentiates HDACI lethality in leukemia cells displaying various genetic backgrounds through mechanisms involving disruption of the intra-S checkpoint, DNA replication, and DNA repair. They also argue that leukemic cells, including those bearing oncogenic mutations associated with poor prognosis, for example, p53 deletion/mutation or FLT3-ITD, may also be susceptible to this strategy. Mol Cancer Ther; 12(6); 878–89. ©2013 AACR.

PDF file - 1275K, Supplemental Table 1. Synergism between MK-8776 and SBHA or vorinostat in various human leukemia cell lines. Supplemental Figure S1. SBHA or vorinostat significantly potentiates lethality of MK-8776 in leukemia cell lines. Supplemental Figure S2. SBHA or vorinostat enhances Chk1 inhibition by MK-8776. Supplemental Figure S3. Disruption of Chk1 function increases S phase population and sensitizes cells to SBHA or vorinostat, in association with Cdt1 downregulation. Supplemental Figure S4. MK-8776/HDACIs abrogate intra-S-phase checkpoint and induce DNA damage in association with disruption of the CtIP/BRCA1 pathway that mediates DNA repair via HR. Supplemental Figure S5. Knock-down of p53 by shRNA sensitizes in p53-wt leukemia cells to the MK-8776/SBHA regimen, and this regimen is active against leukemia CD34+/CD38-/CD123+ primitive population. Supplemental Figure S6. The MK-8776/HDACI regimen is active against primary AML cells, while spare normal CD34+ cells.

Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that P. distasonis is decreased in patients with hepatic fibrosis, and that administration of P. distasonis to male mice improves thioacetamide (TAA)- and methionine and choline-deficient (MCD) diet-induced hepatic fibrosis. Administration of P. distasonis also leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal farnesoid X receptor (FXR) signaling and decreased taurochenodeoxycholic acid (TCDCA) levels in liver. TCDCA produces toxicity in mouse primary hepatic cells (HSCs) and induces mitochondrial permeability transition (MPT) and Caspase-11 pyroptosis in mice. The decrease of TCDCA by P. distasonis improves activation of HSCs through decreasing MPT-Caspase-11 pyroptosis in hepatocytes. Celastrol, a compound reported to increase P. distasonis abundance in mice, promotes the growth of P. distasonis with concomitant enhancement of bile acid excretion and improvement of hepatic fibrosis in male mice. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.

Purpose: The goal of this study was to characterize interactions between the proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors (HDACI) romidepsin or belinostat in chronic lymphocytic leukemia (CLL) cells.Experimental Design: Primary and cultured (JVM-3 and MEC-2) CLL cells were exposed to agents alone or in combination, after which cell death was determined by 7-aminoactinomycin D staining/flow cytometry. Acetylation of target proteins, activation of caspase cascades, and expression of apoptosis-regulatory proteins were monitored by Western blot analysis. Nuclear factor-κB (NF-κB) activity was determined by luciferase reporter assay. Cells were transiently transfected with wild-type and acetylation site-mutated (inactive) RelA(p65) (e.g., K221R, K310R, or K281/221/310R) and assessed for HDACI sensitivity.Results: Combined exposure to very low concentrations of romidepsin or belinostat (i.e., low nanomolar and submicromolar, respectively) in combination with low nanomolar concentrations of bortezomib synergistically induced cell death in primary and cultured CLL cells. These events were likely associated with prevention of HDACI-mediated RelA acetylation and NF-κB activation by bortezomib, down-regulation of antiapoptotic proteins (i.e., Bcl-xL, Mcl-1, and XIAP), as well as up-regulation of the proapoptotic protein Bim, resulting in activation of caspase cascade. Finally, CLL cells transfected with inactive RelA displayed a significant increase in HDACI lethality.Conclusions: Coadministration of the clinically relevant HDACIs romidepsin or belinostat with bortezomib synergistically induces cell death in CLL cells, likely through mechanisms involving, among other factors, NF-κB inactivation and perturbation in the expression of proapoptotic and antiapoptotic proteins. A strategy combining HDAC with proteasome inhibition warrants further attention in CLL.

Supplementary Figures S1-S4.

Purpose: The purpose of this study was to determine whether histone deacetylase (HDAC) inhibitors (HDACI) such as vorinostat or entinostat (SNDX-275) could increase the lethality of the dual Bcr/Abl-Aurora kinase inhibitor KW-2449 in various Bcr/Abl+ human leukemia cells, including those resistant to imatinib mesylate (IM).Experimental Design: Bcr/Abl+ chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cells, including those resistant to IM (T315I, E255K), were exposed to KW-2449 in the presence or absence of vorinostat or SNDX-275, after which apoptosis and effects on signaling pathways were examined. In vivo studies combining HDACIs and KW2449 were carried out by using a systemic IM-resistant ALL xenograft model.Results: Coadministration of HDACIs synergistically increased KW-2449 lethality in vitro in multiple CML and Ph+ ALL cell types including human IM resistant cells (e.g., BV-173/E255K and Adult/T315I). Combined treatment resulted in inactivation of Bcr/Abl and downstream targets (e.g., STAT5 and CRKL), as well as increased reactive oxygen species (ROS) generation and DNA damage (γH2A.X). The latter events and cell death were significantly attenuated by free radical scavengers (TBAP). Increased lethality was also observed in primary CD34+ cells from patients with CML, but not in normal CD34+ cells. Finally, minimally active vorinostat or SNDX275 doses markedly increased KW2449 antitumor effects and significantly prolonged the survival of murine xenografts bearing IM-resistant ALL cells (BV173/E255K).Conclusions: HDACIs increase KW-2449 lethality in Bcr/Abl+ cells in association with inhibition of Bcr/Abl, generation of ROS, and induction of DNA damage. This strategy preferentially targets primary Bcr/Abl+ hematopoietic cells and exhibits enhanced in vivo activity. Combining KW-2449 with HDACIs warrants attention in IM-resistant Bcr/Abl+ leukemias. Clin Cancer Res; 17(10); 3219–32. ©2011 AACR.

Supplementary Figures S1-S2 from Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells

PDF file - 140K, FP/obatoclax down-regulates Bcl-xL, but not Bcl-2, which plays a partial role in this regimen

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MOV file - 3MB, Video for the mice receiving both flavopiridol and obatolcax (day 120 after tumor cell injection via tail vein)

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PDF file - 104K, FP/obatoclax induces dose-dependent mitochondrial injury and cell death in MM cells, accompanied by down-regulation of Mcl-1 protein and mRNA

MOV file - 2.5MB, Video for the mice receiving vehicle (day 80 after tumor cell injection via tail vein)

MOV file - 9.5MB, Video for the mice receiving obatolcax (day 120 after tumor cell injection via tail vein)

Vernalization is a phenomenon in which plants must undergo a period of continuous low temperatures to change from the vegetative growth stage to the reproductive growth stage. Chinese cabbage is a heading vegetable, and flowering time is an essential developmental trait. Premature vernalization leads to premature bolting, which causes a loss of product value and yield. While research into vernalization has provided a wealth of information, a complete understanding of the molecular mechanism for controlling vernalization requirements has not yet been elucidated. In this study, using high-throughput RNA sequencing, we analyzed the plumule-vernalization response of mRNA and long noncoding RNA in the bolting-resistant Chinese cabbage double haploid (DH) line ‘Ju Hongxin’ (JHX). A total of 3382 lncRNAs were identified, of which 1553 differentially expressed (DE) lncRNAs were characterized as plumule-vernalization responses. The ceRNA network revealed that 280 ceRNA pairs participated in the plumule-vernalization reaction of Chinese cabbage. Through identifying DE lncRNAs in Chinese cabbage and analyzing anti-, cis-, and trans-functional analysis, some candidate lncRNAs related to vernalization promoting flowering of Chinese cabbage and their regulated mRNA genes were found. Moreover, the expression of several critical lncRNAs and their targets was verified using qRT-PCR. Furthermore, we identified the candidate plumule-vernalization-related long noncoding RNAs that regulate BrFLCs in Chinese cabbage, which was interesting and different from previous studies and was a new discovery. Our findings expand the knowledge of lncRNAs in the vernalization of Chinese cabbage, and the identified lncRNAs provide rich resources for future comparative and functional studies.

The nonuniform distribution of interference spectrum in wavenumber [Formula: see text]-space is a key issue to limit the imaging quality of Fourier-domain optical coherence tomography (FD-OCT). At present, the reconstruction quality at different depths among a variety of processing methods in [Formula: see text]-space is still uncertain. Using simulated and experimental interference spectra at different depths, the effects of common six processing methods including uniform resampling (linear interpolation (LI), cubic spline interpolation (CSI), time-domain interpolation (TDI), and K-B window convolution) and nonuniform sampling direct-reconstruction (Lomb periodogram (LP) and nonuniform discrete Fourier transform (NDFT)) on the reconstruction quality of FD-OCT were quantitatively analyzed and compared in this work. The results obtained by using simulated and experimental data were coincident. From the experimental results, the averaged peak intensity, axial resolution, and signal-to-noise ratio (SNR) of NDFT at depth from 0.5 to 3.0[Formula: see text]mm were improved by about 1.9[Formula: see text]dB, 1.4 times, and 11.8[Formula: see text]dB, respectively, compared to the averaged indices of all the uniform resampling methods at all depths. Similarly, the improvements of the above three indices of LP were 2.0[Formula: see text]dB, 1.4 times, and 11.7[Formula: see text]dB, respectively. The analysis method and the results obtained in this work are helpful to select an appropriate processing method in [Formula: see text]-space, so as to improve the imaging quality of FD-OCT.

Effects of motivation on cognition and performance have been found empirically in different fields. However, the relationship between motivation and performance seems complex and multi-faceted. While seemingly inconsistent or incompatible studies and theories of different disciplinary origins exist in this regard, we show that many of them can potentially be synthesized. Simulations within a unifying computational cognitive architecture account for empirical phenomena from different studies, which demonstrate that a mechanistic (computational) account can potentially unify the interpretations of these studies, largely based on utility calculation from intrinsic motives, and allow for further, more detailed explorations.

Background Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage. Methods C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing (scRNA-seq) was then carried out on TCS- or mock-treated mouse livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the molecular and cellular events after TCS exposure. To verify the TCS-induced liver fibrosis, the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red staining. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies. Results We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control group profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells (HSCs) were significantly increased in TCS-treated group. We found that TCS promoted fibrosis-associated proliferation of hepatocytes, in which Gata2 and Mef2c are the key driving TFs. Our data also suggested that TCS induced the proliferation and activation of HSCs, which was experimentally verified in both liver tissue and cell model. In addition, other changes including the dysfunction and capillarization of endothelial cells, an increase of fibrotic characteristics in B plasma cells, and M2 phenotype-skewing of macrophage cells, were also deduced from the scRNA-seq analysis, and these changes are likely to contribute to the progression of liver fibrosis. Lastly, the key differential ligand-receptor pairs involved in cellular communications were identified and we confirmed the role of GAS6_AXL interaction-mediated cellular communication in promoting liver fibrosis. Conclusions TCS modulates the cellular activities and fates of several specific cell types (including hepatocytes, HSCs, endothelial cells, B cells, Kupffer cells and liver capsular macrophages) in the liver, and regulates the ligand-receptor interactions between these cells, thereby promoting the proliferation and activation of HSCs, leading to liver fibrosis. Overall, we provide the first comprehensive single-cell atlas of mouse livers in response to TCS and delineate the key cellular and molecular processes involved in TCS-induced hepatotoxicity and fibrosis.

BackgroundRetinopathy of prematurity (ROP) is a retinal vascular disease with a high incidence in premature infants and is a leading cause of childhood blindness worldwide. The purpose of our study was to analyze the association between the use of probiotics and retinopathy of prematurity.MethodsThis study retrospectively collected clinical data of premature infants with gestational age ResultsA total of 443 preterm infants met the inclusion criteria, of which 264 didn't receive probiotics and 179 were supplemented with probiotics. There were 121 newborns with ROP in the included population. The results of univariate analysis showed that the preterm infants with and without probiotics were significantly different in the gestational age, the birth weight, the one-minute Apgar score, the oxygen inhalation time, the acceptance rate of invasive mechanical ventilation, the prevalence of bronchopulmonary dysplasia, ROP and severe intraventricular hemorrhage and periventricular leukomalacia (P P P ConclusionThis study showed that probiotic was associated with a reduced risk of ROP in preterm infants with gestational age of

Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.

PurposeThe efficacy of programmed cell death protein 1(PD-1)/Programmed cell death 1 ligand 1 (PD-L1) inhibitors for endometrial cancer remain controversial, and guidelines are unconsistent on which are preferred theropies for advanced disease, or who develop metastases and recurrence. Therefore we aimed to estimate the efficacy and safety of PD-1/PD-L1 inhibitors in endometrial cancer on a more complete database by adding multiple randomized trials. Methods:A systematic and comprehensive search was carried out in PD-1/PD-L1 inhibitors monotherapy. Results: The ORR of PD-1/PDL-1 inhibitors was 29%, and subgroup analysis showed that the pooled ORR of the proficient mismatch repair (pMMR) group was 4% and which was 45% of the deficient mismatch repair (dMMR) group. The DCR of PD-1/PD-L1 inhibitors was 48%, through subgroup analysis, we found that DCR of the pMMR group was 21% and which was 58% of the dMMR group. The proportion of patients occurring overall adverse events was 65% and grade three or higher adverse events was 14%. The proficient mismatch repair (pMMR) group and the deficient mismatch repair (dMMR) group showed different results. Conclusion: PD-1/PD-L1 inhibitors had shown little success in the pMMR population and better efficacy in the dMMR population.

The single crystal scintillating optical fibers acting as the scintillators and light conductors show potential application in scintillating fiber array detectors with high spatial resolution. In this paper we report the growth of 0.2 at% Ce:Y3Al5O12 single crystal fiber. The crystalline phase, surface morphology of the axial-section and cross-section, optical and scintillation properties of the as-grown fiber were investigated. The Ce:Y3Al5O12 single crystal fiber has a pure YAG phase, a uniform distribution of cerium in the axial-section and cross-section surface. Emission spectrum is composed of broad bands ranging from 440 to 700 nm. In addition, the single crystal fiber has a high light yield of 26115 ± 2000 photons/MeV, low energy resolution of 9.44% @662 keV and decay time of a fast component of 78 ns and a slow component of 301 ns. The intensity ratio of fast to slow components is roughly 8:1.

BACKGROUND: Hypertension is the most modifiable factor associated with cardiovascular events and complications. The conventional blood pressure (BP) meter method is simple but is limited in terms of real-time monitoring abnormal BP. Therefore, the development of a multifunction smartwatch (HUAWEI WATCH D) sphygmomanometer could significantly improve integrated BP monitoring. METHODS: We enrolled 361 subjects from Chinese PLA General Hospital, Beijing, China to validate the accuracy of the smartwatch versatile sphygmomanometer using ISO 81060-2:2018. Resting and ambulatory BP accuracy of the smartwatch were compared with gold standard clinical sphygmomanometers using ISO 81060-2:2018 guidelines, the accuracy of 24 h systolic blood pressure (SBP) circadian rhythm monitoring, and diurnal high SBP alert for this smartwatch were assessed using a confusion matrix approach. Additionally, we analyzed online users of different ages for compliance. RESULTS: Eighty-five subjects underwent resting BP measurements; the mean resting BP differences between two devices were −0.683 ± 6.203 mmHg (SBP) (P = 0.723) and 1.628 ± 5.028 mmHg (diastolic blood pressure, DBP) (P = 0.183). In 35 subjects’ ambulatory BP measurements, the mean differences of ambulatory BP were −1.943 ± 5.475 mmHg (SBP) (P = 0.923) and 3.195 ± 5.862 mmHg (DBP) (P = 0.065). All data complied with ISO 81060-2:2018 guidelines (mean ≤ ±5 mmHg and standard deviation ≤ ±8 mmHg) with no significant differences. Positive predictive values (PPV) of resting SBP and DBP were 0.635 and 0.671, respectively. The PPV of ambulatory SBP and DBP were 0.686. Also, 24 h SBP circadian rhythm monitoring was performed in 107 subjects: accuracy = 0.850, specificity = 0.864, precision/PPV = 0.833, sensitivity = 0.833, and F1-measure (F1) = 0.833. The accuracy, specificity, precision, sensitivity, and F1 values in 85 subjects undergoing diurnal high SBP alerting were 0.858, 0.876, 0.706, 0.809, and 0.754, respectively. CONCLUSIONS: When compared with the gold standard clinical sphygmomanometer, smartwatch results were consistent and accurate. Online user feedback showed that elderly individuals cared more about BP monitoring accuracy, with better compliance.