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ObjectiveTo determine the effect of adjuvant chemotherapy in patients with stage I mucinous ovarian cancer (MOC) undergoing fertility-preserving surgery.Patients and methodsThe clinicopathological characteristics and survival information of young women with stage I MOC from SEER databases between 2004 and 2019 were collected. The relationship between chemotherapy and the characteristics was examined by univariate and multivariate logistic regression analyses. Univariable and multivariate Cox proportional hazards survival analysis were employed for cancer-specific survival. Cox analysis was performed to build a nomogram model.ResultsAll 901 eligible patients with stage I MOC were screened from the SEER database. There were 321(35.6%) patients aged 9-30 years, 580(64.4%) aged 31-45 years, 645 (71.6%) patients with stage IA/IB, 256 (28.4%) with stage IC disease, 411(45.6%) who underwent fertility-sparing surgery, and276(30.6%) who received postoperative adjuvant chemotherapy. Multivariate logistic regression analyses showed that postoperative chemotherapy was often used in patients aged 31-45 relative to aged 9-30 (HR: 2.215, 95%CI 1.443-3.401, P < 0.001) or with grade 3 compared to grade 1 tumors (HR: 7.382, 95%CI 4.054-13.443, P < 0.001) or with stage IC compared to stage IA/IB (HR: 6.436, 95%CI 4.515-9.175, P < 0.001) or with non-fertility sparing surgery relative to fertility-sparing (HR:2.226, 95%CI 1.490-3.327, P < 0.001). Multivariate analysis for the special population with fertility preservation indicated that patients with chemotherapy (HR: 2.905, 95% CI: 0.938-6.030, P=0.068) or with grade 3 (HR: 4.750, 95% CI: 1.419-15.896, P=0.011) had a greater risk of mortality. Significant CSS differences were observed between the non-chemotherapy and chemotherapy groups in MOC when patients were stage IA/IB-grade 2 (P=0.004) (10-year CSS rates of chemotherapy=84%, non-chemotherapy = 100%), but not when they were stage IA/IB-grade 1, stage IA/IB-grade 3 or stage IC (both P>0.05). A prognostic prediction nomogram model was built for stage I MOC patient who underwent fertility-sparing and the C-index was 0.709.DiscussionThe patients aged 31-45 years, with grade 3, stage IC, and non-fertility-sparing surgery were more likely to receive adjuvant chemotherapy in the real world. For stage I MOC patient who underwent fertility-sparing surgery, the choice of chemotherapy may increase the risk of death, and it should be carefully selected in clinical practice.

Photodynamic therapy (PDT) is a new and rapidly developing treatment modality for clinical cancer therapy. Semiconductor polymer dots (Pdots) doped with photosensitizers have been successfully applied to PDT, and have made progress in the field of tumor therapy. However, the problems of severe photosensitivity and limited tissue penetration depth are needed to be solved during the implementation process of PDT. Here we developed the Pdots doped with photosensitizer molecule Chlorin e6 (Ce6) and photochromic molecule 1,2-bis(2,4-dimethyl-5-phenyl-3-thiophene)-3,3,4,5-hexafluoro-1-cyclopentene (BTE) to construct a photoswitchable nanoplatform for PDT. The Ce6-BTE-doped Pdots were in the green region, and the tissue penetration depth was increased compared with most Pdots in the blue region. The reversible conversion of BTE under different light irradiation was utilized to regulate the photodynamic effect and solve the problem of photosensitivity. The prepared Ce6-BTE-doped Pdots had small size, excellent optical property, efficient ROS generation and good photoswitchable ability. The cellular uptake, cytotoxicity, and photodynamic effect of the Pdots were detected in human colon tumor cells. The experiments in vitro indicated that Ce6-BTE-doped Pdots could exert excellent photodynamic effect in ON state and reduce photosensitivity in OFF state. These results demonstrated that this nanoplatform holds the potential to be used in clinical PDT.

The effects of ambient fine particles on male reproductive health have raised widespread concern. The particular underlying mechanisms of the damage remain largely unclear and demand more research in new directions. Previous research has revealed that DNA methylation plays an important role in male reproductive development and is also vulnerable to environmental influences. However, there hasn't been enough investigation into the involvement of DNA methylation in PM2.5-induced male reproductive toxicity. Here, we establish a real-time PM2.5 exposure model and revealed that PM2.5 exposure could lead to testicular dysfunction including spermatogenesis impairment and steroid hormone dysfunction. In particular, the decrease in the testicular global level of 5-methylcytosine (5mC) indicated a possible association of DNA methylation with testicular injury induced by PM2.5 exposure. Further genome-wide methylation analysis revealed genomic hypomethylation of testicular DNA and identified more than 1000 differentially methylated regions in both CAP and UA versus FA, indicating that PM2.5 exposure, even low-dose, could modulate the testicular methylome. Furthermore, integrated analysis of methylome and transcriptome identified some key methylated genes and networks, which may be involved in spermatogenesis and synthesis of steroid hormone. The testicular methylation levels of key genes especially Cyp11a1 and Pax8 raised, and their consequent reduced expression may impair the testosterone and sperm production process. Our research provides fundamental knowledge as well as novel insights into the possible involvement of DNA methylation in PM2.5-induced male reproductive harm.

ObjectiveTo compare the return to work (RTW) time between single-port laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for benign ovarian tumors.MethodsA cross-sectional cohort study was conducted, which consisted of 335 women of reproductive age with benign ovarian tumors and who were keen on returning to work as early as possible. Surgical outcomes, postoperative pain score, postoperative satisfaction with the cosmesis score (CS), and the RTW time of the SPLS group were compared with those of the MPLS group. Besides, the RTW time and CS were calculated from the questionnaire survey by a single specialized gynecologist.ResultsWomen who met the inclusion criteria were included in the SPLS (n = 106) and MPLS groups (n = 229). The RTW time in the SPLS group (22.13 ± 27. 06 days) was significantly shorter than that in the MPLS group (46.08 ± 57.86 days) (P < 0.001). The multivariate Cox analysis results showed that age (HR = 0.984, 95% CI, 0.971−0.997, P = 0.020), SPLS (HR = 3.491, 95% CI, 2.422−5. 032, P < 0.001), and return to normal activity time (HR = 0.980, 95% CI, 0.961−0.998, P = 0.029) were independent factors of the RTW time.ConclusionsSPLS may be advantageous in terms of shortening the RTW time for women with benign ovarian tumors.

Abstract Owing to the intrinsic advantages of spatiotemporal selectivity, photothermal theranostics have become the advancing edge of precision medicine for cancer. Developing photothermal transduction agents (PTAs) with near‐infrared (NIR) absorption, high photothermal conversion efficiency, robust photothermal stability, and good accumulation in tumors, is particularly valuable. Herein, we report a new concept, self‐assembly‐induced crystallization (SAIC), which can serve as a mechanism that dramatically boosts photothermal behaviors of PTA in NIR region. As a proof of concept, three heptamethine cyanine molecules with internal degrees of freedom (geometry and intramolecular interaction) are designed to fine‐tune their crystallinity. Notably, Cy7‐TCF‐EMBI molecules with rigid and planar skeletons self‐assemble into a crystalline state to maximize their packing density and improve the charge transfer, both of which contribute to nonradiative decay for energy dissipation as heat. The high packing density also renders an ideal scaffold for controlling intermolecular interactions to exhibit better photothermal stability, and endows an anisotropic three‐dimensional architecture for passive tumor targeting. This “SAIC” strategy may offer a conceptually novel, practically simple but effective approach to unveil the structure–property relationship that could provide some general rules in rational design of PTAs, and paves the way for a next generation of supramolecular medicine for photothermal theranostics.

Background Unintentional injuries (UIs) pose a threat to the health of children all over the world and are a major global health problem. The recurrence of UIs are influenced by the host itself or environmental factors. Children’s temperament and paternal parenting styles (PPS) are important potential factors for poor health outcomes, including recurrent unintentional injuries (recurrent UIs). Therefore, exploring the relationship among these variables may help reduce the likelihood of recurrent UIs in children. Purpose To elucidate the mediating effect of PPS in the relationship of children’s temperament characteristics and recurrent UIs among children. Methods By multistage random cluster sampling method, a total of 2,850 pupils in grades four and five from 10 different schools were included. The survey included the characteristics of UIs in the past year, parenting styles, and children’s temperament. Structural equation modeling (SEM) was used to examine the possible mediating effect of PPS between children’s temperament and recurrent UIs. Results In this study, the incidence rate of recurrent UIs was 3.8%. In temperament, children with recurrent UIs had higher mean scores than the non-recurrent UIs group (t = −3.40, −3.52, −3.45, respectively; p < 0.001) in the activity, predictability, persistence. Meanwhile, the scores of negative PPS (punishing, over-interference, rejection, and overprotection) were higher in the recurrent UIs group than in the non-recurrent UIs group (t = −5.78, −5.05, −5.56, and −3.29; p < 0.001, < 0.001, < 0.001, < 0.001, respectively). Using a stepwise binary logistic regression model, grade (OR = 0.23, 95% CI [0.12–0.41], p < 0.001), activity (OR = 1.61, 95% CI [1.14–2.26], p = 0.007) and over-interference (OR = 2.28, 95% CI [1.37–3.80], p = 0.002) had a significant independent relationship with recurrent UIs. The SEM results indicated that children’s temperament was significantly related to negative PPS (β = 0.26, p < 0.001) and recurrent UIs (β = 0.11, p = 0.029). The results of the bootstrap test confirmed the significance of the mediating effect of PPS (β = 0.06, p < 0.001) between children’s temperament and recurrent UIs. Conclusions These results suggest that negative PPS plays an important role in mediating children’s temperament and recurrent UIs. It is essential to consider PPS when creating tailored intervention programs to reduce children’s recurrent UIs.

K-Ras is a well-studied oncogene, and its mutation is frequently found in epithelial cancers like pancreas, lung, and colorectal cancers. Cancer cells harboring K-Ras mutations are difficult to treat due to the drug resistance and metastasis properties. Cancer stem cells (CSCs) are believed the major cause of chemotherapeutic resistance and responsible for tumor recurrence and metastasis. But how K-Ras mutation affects CSCs and inflammation is not clear. Here, we compared two colon cancer cell lines, HCT-116 and HT-29, with the former being K-RasG13D mutant and the latter being wildtype. We found that HCT-116 cells treated with a K-Ras mutation inhibitor S7333 formed significantly more tumor spheroids than the untreated control, while the wild type of HT-29 cells remained unchanged. However, the size of tumor spheroids was smaller than the untreated controls, indicating their proliferation was suppressed after S7333 treatment. Consistent with this, the expressions of stem genes Lgr5 and CD133 significantly increased and the expression of self-renewal gene TGF-β1 also increased. The flow cytometry analysis indicated that the expression of stem surface marker CD133 increased in the treated HCT-116 cells. To understand the pathway through which the G13D mutation induced the effects, we studied both RAS/ERK and PI3K/Akt pathways using specific inhibitors SCH772984 and BEZ235. The results indicated that RAS/ERK rather than PI3K/Akt pathway was involved. As CSCs play the initial role in cancer development and the inflammation is a vital step during tumor initiation, we analyzed the correlation between increased stemness and inflammation. We found a close correlation of increased Lgr5 and CD133 with proinflammatory factors like IL-17, IL-22, and IL-23. Together, our findings suggest that K-RasG13D mutation promotes cancer cell growth but decreases cancer stemness and inflammation thus tumorigenesis and metastasis potential in colon cancer. Inhibition of this mutation reverses the process. Therefore, care needs be taken when employing targeted therapies to K-RasG13D mutations in clinics.

Cervical cancer is a top lethal cancer for women worldwide. Although screening and vaccination programs are available in many countries, resulting in the decline of new cases, this is not true for developing countries where there are many new cases and related deaths. Cancer immunotherapy through adaptive cell therapy (ACT) has been applied in clinics, but now much attention is focused on autogenic tumor-infiltrating lymphocyte (TIL)-based therapy, which has shown more specificity and better ability to inhibit tumor growth. Data from melanoma and cervical cancers confirm that tumor-specific T cells in TILs can be expanded for more specific and effective ACT. Moreover, TILs are derived from individual patients and are ready to home back to kill tumor cells after patient infusion, aligning well with personalized and precision medicine. In addition to therapy, TIL cell types and numbers are good indicators of host immune response to the tumor, and thus they have significant values in prognosis. Because of the special relationship with human papillomavirus (HPV) infection, cervical cancer has some specialties in TIL-based prognosis and therapy. In this review, we summarize the recent advances in the prognostic significance of TILs and TIL-based therapy for cervical cancer and discuss related perspectives.

Abstract Background Astrocyte over-activation and extensive neuron loss are the main characteristic pathological features of spinal cord ischemia–reperfusion injury (SCII). Prior studies have placed substantial emphasis on the role of heat shock protein family A member 8 (HSPA8) on postischemic myocardial inflammation and cardiac dysfunction. However, it has never been determined whether HSPA8 participates in astrocyte activation and thus mediated neuroinflammation associated with SCII. Methods The left renal artery ligation-induced SCII rat models and oxygen–glucose deprivation and reoxygenation (OGD/R)-induced rat primary cultured astrocytes were established. The lentiviral vector encoding short hairpin RNA targeting HSPA8 was delivered to the spinal cord by intrathecal administration or to culture astrocytes. Then, the spinal neuron survival, gliosis, and nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and its related pro-inflammatory cytokines were analyzed. Results SCII significantly enhanced the GFAP and HSPA8 expression in the spinal cord, resulting in blood–brain barrier breakdown and the dramatical loss of spinal neuron and motor function. Moreover, injury also increased spinal nuclear factor-kappa B (NF-κB) p65 phosphorylation, NLRP3 inflammasome-mediated caspase-1 activation, and subsequent interleukin (IL)-1β as well as IL-18 secretion. Silencing the HSPA8 expression efficiently ameliorated the spinal cord tissue damage and promoted motor function recovery after SCII, through blockade of the astrocyte activation and levels of phosphorylated NF-κB, NLRP3, caspase-1, IL-1β, and IL-18. Further in vitro studies confirmed that HSPA8 knockdown protected astrocytes from OGD/R-induced injury via the blockade of NF-κB and NLRP3 inflammasome activation. Conclusion Our findings indicate that knockdown of HSPA8 inhibits spinal astrocytic damage after SCII, which may provide a promising therapeutic strategy for SCII treatment.

AIM:To investigate the protective effects of naringin(Nar)phospholipid complex(NPC)on oxidative injury in retinal pigment epithelium cells(ARPE-19 cells)induced by tert-butyl hydroperoxide(t-BHP)and elucidate the underlying mechanism.METHODS:The NPC was prepared by solvent method. Experimental cells are divided into seven groups: control group [cultured with dimethylsulfoxide(DMSO)], model group(intervention with 200μmol/L t-BHP), nuclear factor erythroid 2-related factor 2(Nrf2)-siRNA group(cell transfection for Nrf2 gene), naringin group(add 200μmol/L t-BHP after pretreatment with 200μmol/L naringin medium), NPC group(add 200μmol/L t-BHP after pretreatment with 200μmol/L NPC medium), Nrf2-siRNA+ naringin group(after 200μmol/L naringin pretreatment, Nrf2 gene interference, then add 200μmol/L t-BHP)and Nrf2-siRNA+ NPC group(after 200μmol/L NPC pretreatment, Nrf2 gene interference, then add 200μmol/L t-BHP). The intracellular levels of superoxide dismutase(SOD), malondialdehyde(MDA)and total antioxidant capacity(T-AOC)were detected, intracellular level of reactive oxygen species(ROS)was detected by DCFH-DA staining method. The mRNA and protein expressions of HO-1, NQO-1, GCL and Nrf2 were detected by real-time PCR and western blot, respectively. RESULTS:NPC more significantly increased the levels of SOD and T-AOC, reduced the contents of ROS and MDA than naringin in t-BHP-treated ARPE-19 cells. After naringin and NPC pre-protected ARPE-19 cells, the relative expression and protein expression of Nrf2, HO-1, NQO-1 and GCL mRNA were higher than those of the model group and Nrf2-siRNA group. There were statistically significant differences in the relative expression of 4 genes and the expression levels of 4 proteins in the naringin group and the NPC group, the Nrf2-siRNA+naringin group and the Nrf2-siRNA+NPC group. The expression of Nrf2, HO-1 and NQO-1 protein in the Nrf2-siRNA+naringin group was not significantly different than that in the Nrf2-siRNA group. Compared with the Nrf2-siRNA group, the expression of 4 proteins in the Nrf2-siRNA+NPC group was statistically significant, and the effect of NPC was significantly stronger than that of naringin.CONCLUSION: After naringin forms a phospholipid complex, it can significantly increase the antioxidant capacity in cells and reduce the oxidation level. It up-regulates the expression of Nrf2 and its downstream antioxidant enzymes and phase Ⅱ detoxification enzymes by activating the Nrf2/ARE antioxidative stress pathway to better protect ARPE-19 cells from oxidative damage.

Abstract Background Visual art training is a student-led approach using Western art pieces as the main teaching resources. It has been developed and applied in nursing and medical education in the United States. This study aimed to adapt visual art training to Chinese cultural context, then to compare the efficacy of the culturally-tailored visual art training versus traditional education on observational and diagnostic skills at 3-month follow-up among Chinese nursing students in master program. Methods This study included Phase 1 (cultural adaptation) and Phase 2 (3-month efficacy evaluation). It was conducted from June to September, 2019. In Phase 1, cultural barriers were identified and cultural adaptation strategy were made based on two focus group interviews. Phase 2 was a randomized controlled trial in a local museum. A total of 106 first-year nursing students in master program were randomized to the intervention group or the control group. Both groups received traditional education. In addition, intervention group received a visual art training (including a field-guided museum visit with observation and debriefing of Chinese oil paintings and clinical images, four teaching hours). Data were collected for both groups at baseline and 3-month follow-up on the observational and diagnostic skills measured by clinical image tests. Learning satisfaction with the visual art training was investigated among 53 intervention students and teaching satisfaction was done in 10 staff members by self-administered questionnaires. Results In phase 1, we adapted a culturally-tailored visual art training for nursing students in China. Observational skills of the intervention group increased significantly compared with the control group 3 months after the training (p .05). In general, all participants and staff were satisfied with the visual art training, especially the selected Chinese oil paintings and the student-led teaching process, but 34% (n = 18) were not satisfied with the long distance from the museum. Conclusions A culturally-tailored visual art training with great acceptability and feasibility was implemented in China. It had a sustained positive effect on improving the observational skills of Chinese nursing students. This study can be used for a reference to introduce visual art training to nursing students or nurses from other cultures. Trial registration Retrospectively registered in Chinese Clinical Trial Registry ( ChiCTR2000037956 ) on 4th September, 2020.

Studies have found that green practices can help organization create unique competitive advantages, such as enhancing the brand value. However, in the existing research, people did not know much about the exhibition audiences’ perceptions of green practices, or its impact on brand loyalty. This study explores the dimension of green practice perceptions of exhibition audiences, uses the trust-commitment theory to verify the relationship between green practice perceptions and exhibition brand loyalty. A total of 665 valid questionnaires were collected in the two exhibitions. The results show that four of the five types of green practices perceived by the audience will significantly affect green trust and then brand loyalty through commitment. Two of the five types of green practice perception can directly affect brand loyalty. And green self-identity will significantly adjust the relationship between green trust and affective commitment. Finally, suggestions are proposed for academic and practical reference.

BackgroundColorectal cancer (CRC) is a common gastrointestinal tumor with high morbidity and mortality. At the molecular level, patients at different stages present considerable heterogeneity. Although the miRNA in exosome is an effective biomarker to reveal tumor progression, studies based on stage-associated exosome miRNA regulatory network analysis still lacking. This study aims to identify CRC stage-associated exosome miRNAs and reveal their potential function in tumor progression.MethodsIn this study, serum and cellular exosome miRNA expression microarrays associated with CRC were downloaded from GEO database. Stage-common (SC) and stage-specific (SS) differentially expressed miRNAs were extracted and their targets were identified based on 11 databases. Furthermore, miRNA SC and SS regulatory function networks were built based on the CRC phenotypic relevance of miRNA targets, and the corresponding transcription factors were identified. Concurrently, the potential stage-associated miRNAs were identified by receiver-operating characteristic (ROC) curve analysis, survival analysis, drug response analysis, ceRNA analysis, pathway analysis and a comprehensive investigation of 159 publications.ResultsTen candidate stage-associated miRNAs were identified, with three SC (miR-146a-5p, miR-22-3p, miR-23b-3p) and seven SS (I: miR-301a-3p, miR-548i; IIIA: miR-23a-3p; IV: miR-194-3p, miR-33a-3p, miR-485-3p, miR-194-5p) miRNAs. Additionally, their targets were enriched in several vital cancer-associated pathways such as TGF-beta, p53, and hippo signaling pathways. Moreover, five key hotspot target genes (CCNA2, MAPK1, PTPRD, MET, and CDKN1A) were demonstrated to associated with better overall survival in CRC patients. Finally, miR-23b-3p, miR-301a-3p and miR-194-3p were validated being the most stably expressed stage-associated miRNAs in CRC serum exosomes, cell exosomes and tissues.ConclusionsThese CRC stage-associated exosome miRNAs aid to further mechanism research of tumor progression and provide support for better clinical management in patients with different stages.

Backgrounds and aimsPain is the main reason for hysteroscopy failure. In day-surgical settings, hysteroscopy procedures are commonly performed with the patient under sedation. Hypoxia is the most common adverse event during sedation and can lead to severe adverse events. This study aimed to compare the incidence of hypoxia when using high-flow nasal oxygen (HFNO) with that when using regular nasal oxygen in patients undergoing hysteroscopy with sedation.Materials and methodsIn this single-center, prospective, randomized, single-blinded study, 960 female patients undergoing elective diagnostic or operative hysteroscopy were randomly enrolled into the following two groups: the regular nasal group [O2 (3–6 L/min) covered by an HFNO] and the HFNO group [O2 (30–60 L/min)] from September 2021 to December 2021. All women were sedated with propofol (1.5 mg/kg) and remifentanil (1.5 μg/kg) in the operating room. The primary outcome was the incidence of hypoxia (75% ≤ SpO2 < 90%, < 60 s).ResultsHFNO decreased the incidence of hypoxia (75% ≤ SpO2 < 90%, < 60 s), subclinical respiratory depression (90% ≤ SpO2 < 95%) and severe hypoxia (SpO2 < 75% for any duration or 75% ≤ SpO2 < 90% for ≥ 60 s) from 24.38 to 0.83%, from 11.25 to 1.46% and from 3.75 to 0%, respectively (P < 0.001).ConclusionIn procedures conducted to treat female infertility, HFNO can reduce hypoxia during hysteroscopy in patients sedated with propofol, and it can prevent the occurrence of subclinical respiratory depression and severe hypoxia.

Sujiang pigs are a synthetic breed derived from Jiangquhai, Fengjing, and Duroc pigs. In this study, we sequenced the genome of 62 pigs with a coverage depth of 10× to 20×, including 27 Sujiang and 35 founder breed pigs, and we collected 360 global pigs’ genome sequence data from public databases including 39 Duroc pigs. We obtained a high-quality variant dataset of 365 Sujiang pigs by imputing the porcine 80 K single nucleotide polymorphism (SNP) Beadchip to the whole-genome scale with a total of 422 pigs as a reference panel. A dataset of 365 imputated Sujiang pigs was used to perform single-trait genome-wide association study (GWAS) and meta-analyses for growth and fatness traits. Single-trait GWAS identified 1 907, 18, and 14 SNPs surpassing the suggestively significant threshold for backfat thickness, chest circumference, and chest width, respectively. Meta-analyses identified 2 400 genome-wide significant SNPs and 520 suggestively significant SNPs for backfat thickness and chest circumference, and 719 genome-wide significant SNPs and 1 225 suggestively significant SNPs for all seven traits. According to the meta-analysis of backfat thickness and chest circumference, a remarkable region of 2.69 Mb on Sus scrofa chromosome 4 containing FAM110B, IMPAD1, LYN, MOS, PENK, PLAG1, SDR16C5 and XKR4 was identified as a candidate region. The haplotype heat map of the 2.69 Mb region verified that Sujiang pigs were derived from Duroc and Chinese indigenous pigs, especially Jiangquhai pigs. The Kruskal-Wallis test showed that haplotypes of the 2.69 Mb region significantly affected backfat thickness and chest circumference traits. We then focused on PLAG1, an important growth-related gene, and identified two synonymous SNPs with obvious differences among different breeds in the PLAG1 gene. We then performed genotyping of 365 Sujiang, 150 Duroc, 95 Jiangquhai, and 100 Fengjing pigs to confirm the above result and verified that the two variants significantly affected phenotypes of growth and fatness traits. Our findings not only provide insights into the genetic architecture of porcine growth and fatness traits but also provide potential markers for selective breeding of these traits in Sujiang pigs.

Background As the number of adults with congenital heart disease increases because of therapeutic advances, cardiac rehabilitation (CR) is increasingly being used in this population after cardiac procedures or for reduced exercise tolerance. We aim to describe the adherence and exercise capacity improvements of patients with adult congenital heart disease (ACHD) in CR. Methods and Results This retrospective study included patients with ACHD in CR at New York University Langone Rusk Rehabilitation from 2013 to 2020. We collected data on patient characteristics, number of sessions attended, and functional testing results. Pre‐CR and post‐CR metabolic equivalent task, exercise time, and maximal oxygen uptake were assessed. In total, 89 patients with ACHD (mean age, 39.0 years; 54.0% women) participated in CR. Referral indications were reduced exercise tolerance for 42.7% and post–cardiac procedure (transcatheter or surgical) for the remainder. Mean number of sessions attended was 24.2, and 42 participants (47.2%) completed all 36 CR sessions. Among participants who completed the program as well as pre‐CR and post‐CR functional testing, metabolic equivalent task increased by 1.3 (95% CI, 0.7–1.9; baseline mean, 8.1), exercise time increased by 66.4 seconds (95% CI, 21.4–111.4 seconds; baseline mean, 536.1 seconds), and maximal oxygen uptake increased by 2.5 mL/kg per minute (95% CI, 0.7–4.2 mL/kg per minute; baseline mean, 20.2 mL/kg per minute). Conclusions On average, patients with ACHD who completed CR experienced improvements in exercise capacity. Efforts to increase adherence would allow more patients with ACHD to benefit.

The alteration of glycometabolism is a characteristic of cancer cells. Long non-coding RNAs (lncRNAs) have been documented to occupy a considerable position in glycometabolism regulation. This research aims to construct an effective prediction model for the prognosis of bladder cancer (BC) based on glycometabolism-associated lncRNAs (glyco-lncRNAs). Pearson correlation analysis was applied to get glyco-lncRNAs, and then, univariate cox regression analysis was employed to further filtrate survival time-associated glyco-lncRNAs. Multivariate cox regression analysis was utilized to construct the prediction model to divide bladder cancer (BC) patients into high- and low-risk groups. The overall survival (OS) rates of these two groups were analyzed using the Kaplan–Meier method. Next, gene set enrichment analysis and Cibersortx were used to explore the enrichment and the difference in immune cell infiltration, respectively. pRRophetic algorithm was applied to explore the relation between chemotherapy sensitivity and the prediction model. Furthermore, reverse transcriptase quantitative polymerase chain reaction was adopted to detect the lncRNAs constituting the prediction signature in tissues and urine exosomal samples of BC patients. A powerful model including 6 glyco-lncRNAs was proposed, capable of suggesting a risk score for each BC patient to predict prognosis. Patients with high-risk scores demonstrated a shorter survival time both in the training cohort and testing cohort, and the risk score could predict the prognosis without depending on the traditional clinical traits. The area under the receiver operating characteristic curve of the risk score was higher than that of other clinical traits (0.755 > 0.640, 0.485, 0.644, or 0.568). The high- and low-risk groups demonstrated very distinct immune cells infiltration conditions and gene set enriched terms. Besides, the high-risk group was more sensitive to cisplatin, docetaxel, and sunitinib. The expression of lncRNA AL354919.2 featured with an increase in low-grade patients and a decrease in T3-4 and Stage III–IV patients. Based on the experiment results, lncRNA AL355353.1, AC011468.1, and AL354919.2 were significantly upregulated in tumor tissues. This research furnishes a novel reference for predicting the prognosis of BC patients, assisting clinicians with help in the choice of treatment.

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin–angiotensin–aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin–angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.

Neuroendocrine differentiation (NED) characterized by the expression of neuroendocrine markers, such as chromogranin A (CgA), is frequently observed in advanced prostate cancer (PCa), the prognostic significance of which is still controversial. Here we specifically addressed the issue of the potential prognostic value of CgA expression in advanced-stage PCa patients with distant metastases and its change over time from metastatic hormone-sensitive (mHSPC) to metastatic castration-resistant prostate cancer (mCRPC). CgA expression was assessed immunohistochemically in initial biopsies of mHSPC, as well as in second biopsies of mCRPC in sixty-eight patients, and its correlation with prognosis (together with conventional clinicopathologic parameters) was analyzed using the Kaplan–Meier method and Cox proportional hazard model. We found that CgA expression was an independent adverse prognostic factor for both mHSPC (CgA positivity ≥ 1%, HR = 2.16, 95% CI: 1.04–4.26, p = 0.031) and mCRPC (CgA ≥ 10%, HR = 20.19, 95% CI: 3.04–329.9, p = 0.008). CgA positivity generally increased from mHSPC to mCRPC and was a negative prognosticator. The assessment of CgA expression may help with the clinical evaluation of advanced-stage patients with distant metastases.

Semi-quantum cryptography communication stipulates that the quantum user has complete quantum capabilities, and the classical user has limited quantum capabilities, only being able to perform the following operations: (1) measuring and preparing qubits with a Z basis and (2) returning qubits without any processing. Secret sharing requires participants to work together to obtain complete secret information, which ensures the security of the secret information. In the semi-quantum secret sharing (SQSS) protocol, the quantum user Alice divides the secret information into two parts and gives them to two classical participants. Only when they cooperate can they obtain Alice’s original secret information. The quantum states with multiple degrees of freedom (DoFs) are defined as hyper-entangled states. Based on the hyper-entangled single-photon states, an efficient SQSS protocol is proposed. The security analysis proves that the protocol can effectively resist well-known attacks. Compared with the existing protocols, this protocol uses hyper-entangled states to expand the channel capacity. The transmission efficiency is 100% higher than that of single-degree-of-freedom (DoF) single-photon states, providing an innovative scheme for the design of the SQSS protocol in quantum communication networks. This research also provides a theoretical basis for the practical application of semi-quantum cryptography communication.

Based on Doppler radar observation and reanalysis data, the statistical characteristics of mesovortices (MVs) during the first rainy season (April–June) in Guangdong, South China, from 2017 to 2019 are studied, including their spatiotemporal distributions, structural features and favorable environmental conditions. The results show that the MVs usually exhibit short lifetimes; about 70% last for less than 30 min. The intensity and horizontal scale of the MVs are proportional to their lifetime. Long-lived MVs have larger horizontal scales and stronger intensities than short-lived ones. The MVs are mainly observed over the Pearl River Delta region, followed by western Guangdong Province, but relatively fewer in both eastern and northern Guangdong Province. The uneven spatial distribution of the MVs is closely related to the differences in the topographical features and the environment conditions over South China. MVs are prone to form over flat regions. The Pearl River Delta and eastern Guangdong regions are relatively flat compared to the more mountainous western and northern Guangdong regions. Moreover, the monsoonal south-westerlies, water vapor flux, atmospheric instability and vertical wind shear over southwest Guangdong are significantly larger than those in other regions and are favorable for the formation of MVs. The occurrence frequencies of MVs in central and southern parts of Guangdong display similar diurnal variations, reaching the peak during the late afternoon and early evening while dropping to the minimum overnight. However, the situation is opposite in northern Guangdong, with the peak overnight and the minimum during the late afternoon and early evening. The regional differences in diurnal variation are likely related to the moving direction of mesoscale convective systems (MCSs) in Guangdong.

Abstract Hyperalgesia, which often occurs in people suffering from alcohol use disorder, may drive excessive drinking and relapse. Emerging evidence suggests that the lateral habenula (LHb) may play a significant role in this condition. Previous research suggests that endocannabinoid signaling (eCBs) is involved in drug addiction and pain, and that the LHb contains core components of the eCBs machinery. We report here our findings in rats subjected to chronic ethanol vapor exposure. We detected a substantial increase in endocannabinoid-related genes, including Mgll and Daglb mRNA levels, as well as monoacylglycerol lipase (MAGL) protein levels, as well as a decrease in Cnr1 mRNA and type-1 cannabinoid receptor (CB1R) protein levels, in the LHb of ethanol-exposed rats. Also, rats withdrawing from ethanol exposure displayed hypersensitivity to mechanical and thermal nociceptive stimuli. Conversely, intra-LHb injection of the MAGL inhibitor JZL184, the fatty acid amide hydrolase inhibitor URB597, or the CB1R agonist WIN55,212-2 produced an analgesic effect, regardless of ethanol or air exposure history, implying that alcohol exposure does not change eCB pain responses. Intra-LHb infusion of the CB1R inverse agonist rimonabant eliminated the analgesic effect of these chemicals. Rimonabant alone elicited hyperalgesia in the air-, but not ethanol-exposed animals. Moreover, intra-LHb JZL184, URB597, or WIN55,212-2 reduced ethanol consumption in both homecages and operant chambers in rats exposed to ethanol vapor but not air. These findings suggest that LHb eCBs play a pivotal role in nociception and facilitating LHb eCBs may attenuate pain in drinkers.

IntroductionIn July 2021, Zhangjiajie City became the new epicenter of the COVID-19 outbreak. Aside from the physical manifestations of COVID-19, patients are also victims of severe social stigmatization. Stigma affects not only COVID-19 patients or survivors, but also individuals associated with them. This study aims to describe and assess the COVID-19-related stigma between patients, their relatives, and healthy local residents.MethodsThe study included 43 COVID-19 patients, 68 relatives, and 75 healthy residents from Zhangjiajie. Demographic data was collected, including gender, age, marital status, and educational level. Stigma attitudes toward COVID-19 were measured using the Stigma Scale and Social Distance Scale. Frequencies and percentages were described for each item of the scales, and differences among the three groups were examined using the chi-square test.ResultsWith regards to personal and perceived stigma, most participants agreed that patients with COVID-19 “could snap out of the problem” and that “they were dangerous.” For social distance, over 30% of participants from the three groups agreed with the item “unwillingness to marry into the family of someone with COVID-19.” In all groups, there were significant statistical differences in the belief that “the problem is not a real medical illness” and the desire to “spend the evening socializing.”ConclusionAlthough the outbreak was well-contained in Zhangjiajie, stigmatizing attitudes toward COVID-19 and desire for social distance to such patients were common among patients, their relatives and healthy local residents. Our study's results suggest that public education, anti-stigma interventions, and policies are necessary for people living in Zhangjiajie in order to effectively curtail the spread of COVID-19 and provide a useful strategy for a tourist city like Zhangjiajie to recover sooner from economic decline.

Sertoli cells play a pivotal role in the complex spermatogenesis process. This study aimed to investigate the effects of PM2.5 on Sertoli cells using the TM4 cell line and a real time whole-body PM2.5 exposure mouse model, and further explore the underlying mechanisms through the application of metabolomics and transcriptomics. The results in vivo and in vitro showed that PM2.5 reduced Sertoli cells number in seminiferous tubules and inhibited cell proliferation. PM2.5 exposure also induced Sertoli cell dysfunction by increasing androgen binding protein (ABP) concentration, reducing the blood-testis barrier (BTB)-related protein expression, and decreasing glycolysis capacity and lactate production. The results of transcriptomics, metabolomics, and integrative analysis of multi-omics in the TM4 Sertoli cells revealed the activation of xenobiotic metabolism, and the disturbance of glutathione and purine metabolism after PM2.5 exposure. Further tests verified the reduced GSH/GSSG ratio and the elevation of xanthine oxidase (XO) activity in the PM2.5-exposed TM4 cells, indicating that excessive reactive oxygen species (ROS) was generated via metabolic disorder caused by PM2.5. Moreover, the redox imbalance was proved by the increase in the mitochondrial ROS level, superoxide dismutase (SOD) and catalase (CAT) activity, as well as the activation of the Nrf2 antioxidative pathway. Further study found that the redox imbalance caused by PM2.5 induced DNA damage response and cell cycle arrest. Additionally, PM2.5 induced ferroptosis through iron overload and lipid peroxidation. Taken all together, our study provided new insights for understanding proliferation inhibition and dysfunction of TM4 Sertoli cells exposed to PM2.5 via metabolic disorder and redox imbalance-mediated DNA damage response and ferroptosis.

Background: Compliance with recommended pharmacological and non-pharmacological treatments to modify risk factors is associated with improved outcomes for patients with heart failure (HF). Methods: We conducted an analysis of the National Health and Nutrition Examination Survey (NHANES) years 1999–2018 to evaluate the adequacy of risk factor control and compliance with recommended lifestyle and medications according to the clinical guidelines for the management of HF. Demographic, clinical, and healthcare-access factors associated with having risk factors uncontrolled or not receiving recommended medications were determined using logistic regression analyses. Results: We collected 1906 participants aged 18 years or older with a self-reported history of HF. The majority were at target goals for blood pressure (45.07%), low-density lipoprotein cholesterol (22.04%), and glycated hemoglobin (72.15%), whereas only 19.09% and 27.38% were at targets for body mass index and waist circumference respectively. Besides, 79.49% and 67.23% of respondents reported smoking cessation and recommended alcohol consumption, whereas only 11.54% reported adequate physical activity. Proportion of taking beta blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and diuretics was 54.77%, 52.62% and 49.37%, respectively. Finally, the logistic regression analysis showed that metabolic syndrome and diabetes mellitus were associated with a higher likelihood of having risk factor uncontrolled, while metabolic syndrome, diabetes mellitus, and chronic kidney disease were predictors for not receiving recommended medications. Conclusions: Risk factor control and adherence to recommended lifestyle and medications are non-ideal among HF patients in the USA. A systematic approach for risk factor optimization in people with HF is urgently needed.

Patients with irritable bowel syndrome (IBS) experience not only enhanced visceral pain but also emotional comorbidities, such as anxiety and depression. Early life stress (ELS) is a high-risk for the development of IBS. Literatures have reported an important epigenetic modulation in sustaining extrinsic phenotypes. The amygdala is closely related to the regulation of visceral functions and emotional experiences. In this study, we hypothesized that ELS-induced reprogramming inappropriate adaptation of histone acetylation modification in the amygdala may result in visceral hypersensitivity and anxiety-like behaviors in ELS rats. To test this hypothesis, the model of ELS rats was established by neonatal colorectal dilatation (CRD). Visceral hypersensitivity was assessed based on the electromyography response of the abdominal external oblique muscle to CRD. Emotional comorbidities were examined using the elevated plus maze test, open field test, and sucrose preference test. Trichostatin A (TSA) and C646 were microinjected into the central amygdala (CeA) individually to investigate the effects of different levels of histone acetylation modification on visceral hypersensitivity and emotion. We found neonatal CRD resulted in visceral hypersensitivity and anxiety-like behaviors after adulthood. Inhibiting histone deacetylases (HDACs) in the CeA by TSA enhanced visceral sensitivity but did not affect anxiety-like behaviors, whereas inhibiting HAT by C646 attenuated visceral hypersensitivity in ELS rats. Interestingly, CeA treatment with TSA induced visceral sensitivity and anxiety-like behaviors in the control rats. Western blot showed that the expressions of acetylated 9 residue of Histone 3 (H3K9) and protein kinase C zeta type (PKMζ) were higher in the ELS rats compared to those of the controls. The administration of the PKMζ inhibitor ZIP into the CeA attenuated visceral hypersensitivity of ELS rats. Furthermore, the expression of amygdala PKMζ was enhanced by TSA treatment in control rats. Finally, western blot and immunofluorescence results indicated the decrease of HDAC1 and HDAC2 expressions, but not HDAC3 expression, contributed to the enhancement of histone acetylation in ELS rats. Our results support our hypothesis that amygdala-enhanced histone acetylation induced by stress in early life results in visceral hypersensitivity and anxiety-like behaviors in ELS rats, and reversing the abnormal epigenetic mechanisms may be crucial to relieve chronic symptoms in ELS rats.

Abstract Flexible perovskite solar cells (FPSCs) represent a promising technology in the development of next‐generation photovoltaic and optoelectronic devices. SnO2 electron transport layers (ETL) typically undergo significant cracking during the bending process of FPSCs, which can significantly compromise their charge transport properties. Herein, the semi‐planar non‐fullerene acceptor molecule Y6 (BT‐core‐based fused‐unit dithienothiophen [3,2‐b]‐pyrrolobenzothiadiazole derivative) is introduced as the buffer layer for SnO2‐based FPSCs. It is found that the Y6 buffer layer can enhance the ability of charge extraction and bending stability for SnO2 ETL. Moreover, the internal stress of perovskite films is also reduced. As a result, SnO2/Y6‐based FPSCs achieved a power conversion efficiency (PCE) of 20.09% and retained over 80% of their initial efficiency after 1000 bending cycles at a curvature radius of 8 mm, while SnO2‐based devices only retain 60% of their initial PCE (18.60%) upon the same bending cycles. In addition, the interfacial charge extraction is also effectively improved in conjunction with reduced defect density upon incorporation of Y6 on the SnO2 ETL, as revealed by femtosecond transient absorption (Fs‐TA) measurements.

Chinese fir (Cunninghamia lanceolata), which is an important coniferous tree species in China, is mainly planted in acidic soils with toxic aluminum (Al) levels. However, the consequences of Al toxicity and its resistance mechanism in Chinese fir remain largely uncharacterized. In this study, the Al-induced modification and possible role of cell wall in regulating Al tolerance in Chinese fir were investigated by using seedlings with contrasting Al tolerance, namely, Al-sensitive (YX02) and Al-resistant (YX01) genotypes. The results in present work showed that Al treatment resulted in a dose- and time-dependent inhibition of root growth and oxidative damage in both genotypes, but more in YX02 than in YX01. The severe oxidative damage observed in YX02 under Al stress was found to correlate with lower antioxidant enzyme activities as compared with YX01. The greater root growth inhibition observed in YX02 compared with YX01 was associated with a higher accumulation of Al in pectin and hemicllulose 1 (HC1) fraction because of the higher pectin and HC1 contents and the lower degree of pectin demethylation due to enhanced pectin methylesterase activity in YX02, which ultimately enhanced cell wall binding capacity for Al in YX02. Taken together, our results suggested that enhancement of antioxidant enzyme activities and cell wall modification-induced Al exclusion are the two mechanisms responsible for the Al tolerance of Chinese fir.

Despite the growing research interest in gaming disorder, risk screening tools developed specifically for the Chinese population are still lacking. This study aimed to construct a screening tool to evaluate the risk of gaming disorder (GD) development, by assessing the severity of GD symptoms among Chinese gamers, based on clinical expert interviews, structured interviews with GD patients, a background literature review, and IGD/GD criteria proposed by the DSM-5 and ICD-11. It introduced the Gaming Hazard Assessment Scale—a multidimensional GD risk screening tool—and evaluated the dimension structure, reliability, and validity of the scale among 959 Chinese gamers. A three-level structure, consisting of 18 items scored from 0 to 54, ultimately indicated satisfactory reliability, good validity, and acceptable model fit. The scale will help large-scale initial screening and early identification of patients with a high risk of GD. Further evaluation of the Gaming Hazard Assessment Scale in clinical settings is highly recommended.

Background: Ischemic stroke is a highly complex disorder. This study aims to identify novel methylation changes in ischemic stroke.Methods: We carried out an epigenome-wide study of ischemic stroke using an Infinium HumanMethylation 850K array (cases:controls = 4:4). 10 CpG sites in 8 candidate genes from gene ontology analytics top-ranked pathway were selected to validate 850K BeadChip results (cases:controls = 20:20). We further qualified the methylation level of promoter regions in 8 candidate genes (cases:controls = 188:188). Besides, we performed subgroup analysis, dose-response relationship and diagnostic prediction polygenic model of candidate genes.Results: In the discovery stage, we found 462 functional DNA methylation positions to be associated with ischemic stroke. Gene ontology analysis highlighted the “calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules” item, including 8 candidate genes (CDH2/PCDHB10/PCDHB11/PCDHB14/PCDHB16/PCDHB3/PCDHB6/PCDHB9). In the replication stage, we identified 5 differentially methylated loci in 20 paired samples and 7 differentially methylated genes (CDH2/PCDHB10/PCDHB11/PCDHB14/PCDHB16/PCDHB3/PCDHB9) in 188 paired samples. Subgroup analysis showed that the methylation level of above 7 genes remained significantly different in the male subgroup, large-artery atherosclerosis subgroup and right hemisphere subgroup. The methylation level of each gene was grouped into quartiles, and Q4 groups of the 7 genes were associated with higher risk of ischemic stroke than Q1 groups (p < 0.05). Besides, the polygenic model showed high diagnostic specificity (0.8723), sensitivity (0.883), and accuracy (0.8777).Conclusion: Our results demonstrate that DNA methylation plays a crucial part in ischemic stroke. The methylation of these 7 genes may be potential diagnostic biomarker for ischemic stroke.

BackgroundMelanoma is a highly aggressive skin cancer with a poor prognosis and mortality. Immune checkpoint blockade (ICB) therapy (e.g., anti-PD-1 therapy) has opened a new horizon in melanoma treatment, but some patients present a non-responsive state. Cancer-associated fibroblasts (CAFs) make up the majority of stromal cells in the tumor microenvironment (TME) and have an important impact on the response to immunotherapy. There is still a lack of identification of CAFs-related predictors for anti-PD-1 therapy, although the establishment of immunotherapy biomarkers is well underway. This study aims to explore the potential CAFs-related gene panel for predicting the response to anti-PD-1 therapy in melanoma patients and elucidating their potential effect on TME.MethodsThree gene expression datasets from melanoma patients without anti-PD-1 treatment, in a total of 87 samples, were downloaded from Gene Expression Omnibus (GEO) as the discovery sets (GSE91061) and validation sets (GSE78220 and GSE122220). The CAFs-related module genes were identified from the discovery sets by weighted gene co-expression network analysis (WGCNA). Concurrently, we utilized differential gene analysis on the discovery set to obtain differentially expressed genes (DEGs). Then, CAFs-related key genes were screened with the intersection of CAFs-related module genes and DEGs, succeeded by supervised machine learning-based identification. As a consequence of expression analysis, gene set enrichment analysis, survival analysis, staging analysis, TME analysis, and correlation analysis, the multidimensional systematic characterizations of the key genes were uncovered. The diagnostic performance of the CAFs-related gene panel was assessed by receiver operating characteristic (ROC) curves in the validation sets. Eventually, the CAFs-related gene panel was verified by the expression from the single-cell analysis.ResultsThe six-gene panel associated with CAFs were finally identified for predicting the response to anti-PD-1 therapy, including CDK14, SYNPO2, TCF4, GJA1, CPXM1, and TFPI. The multigene panel demonstrated excellent combined diagnostic performance with the area under the curve of ROC reaching 90.5 and 75.4% ~100% in the discovery and validation sets, respectively.ConclusionConfirmed by clinical treatment outcomes, the identified CAFs-related genes can be used as a promising biomarker panel for prediction to anti-PD-1 therapy response, which may serve as new immunotherapeutic targets to improve survival outcomes of melanoma patients.

Abstract Background Astrocytes participate in innate inflammatory responses within the mammalian central nervous system (CNS). HECT domain E3 ubiquitin protein ligase 1 (HECTD1) functions during microglial activation, suggesting a connection with neuroinflammation. However, the potential role of HECTD1 in astrocytes remains largely unknown. Results Here, we demonstrated that HECTD1 was upregulated in primary mouse astrocytes after 100 ng/ml lipopolysaccharide (LPS) treatment. Genetic knockdown of HECTD1 in vitro or astrocyte-specific knockdown of HECTD1 in vivo suppressed LPS-induced astrocyte activation, whereas overexpression of HECTD1 in vitro facilitated LPS-induced astrocyte activation. Mechanistically, we established that LPS activated σ-1R-JNK/p38 pathway, and σ-1R antagonist BD1047, JNK inhibitor SP600125, or p38 inhibitor SB203580 reversed LPS-induced expression of HECTD1, thus restored LPS-induced astrocyte activation. In addition, FOXJ2 functioned as a transcription factor of HECTD1, and pretreatment of primary mouse astrocytes with BD1047, SB203580, and SP600125 significantly inhibited LPS-mediated translocation of FOXJ2 into the nucleus. Conclusions Overall, our present findings suggest that HECTD1 participates in LPS-induced astrocyte activation by activation of σ-1R-JNK/p38-FOXJ2 pathway and provide a potential therapeutic strategy for neuroinflammation induced by LPS or any other neuroinflammatory disorders.

Abstract Background Acute kidney injury (AKI) occurs among patients with coronavirus disease-19 (COVID-19) and has also been indicated to be associated with in-hospital mortality. Remdesivir has been authorized for the treatment of COVID-19. We conducted a systematic review to evaluate the incidence of AKI in hospitalized COVID-19 patients. The incidence of AKI in different subgroups was also investigated. Methods A thorough search was performed to find relevant studies in PubMed, Web of Science, medRxiv and EMBASE from 1 Jan 2020 until 1 June 2020. The systematic review was performed using the meta package in R (4.0.1). Results A total of 16,199 COVID-19 patients were included in our systematic review. The pooled estimated incidence of AKI in all hospitalized COVID-19 patients was 10.0% (95% CI: 7.0–12.0%). The pooled estimated proportion of COVID-19 patients who needed continuous renal replacement therapy (CRRT) was 4% (95% CI: 3–6%). According to our subgroup analysis, the incidence of AKI could be associated with age, disease severity and ethnicity. The incidence of AKI in hospitalized COVID-19 patients being treated with remdesivir was 7% (95% CI: 3–13%) in a total of 5 studies. Conclusion We found that AKI was not rare in hospitalized COVID-19 patients. The incidence of AKI could be associated with age, disease severity and ethnicity. Remdesivir probably did not induce AKI in COVID-19 patients. Our systematic review provides evidence that AKI might be closely associated with SARS-CoV-2 infection, which should be investigated in future studies.

Abstract Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.

Understanding how cells discriminate between stimuli is an ongoing challenge. Here, the authors propose a mathematical framework for inferring the mutual information encoded in temporal signaling dynamics and use it to study how information is transmitted over time in response to different stimuli in NFκB, MAPK and p53 signaling pathways.

Abstract Background Due to tumor heterogeneity, the diagnosis, treatment, and prognosis of patients with lung squamous cell carcinoma (LUSC) are difficult. DNA methylation is an important regulator of gene expression, which may help the diagnosis and therapy of patients with LUSC. Methods In this study, we collected the clinical information of LUSC patients in the Cancer Genome Atlas (TCGA) database and the relevant methylated sequences of the University of California Santa Cruz (UCSC) database to construct methylated subtypes and performed prognostic analysis. Results Nine hundred sixty-five potential independent prognosis methylation sites were finally identified and the genes were identified. Based on consensus clustering analysis, seven subtypes were identified by using 965 CpG sites and corresponding survival curves were plotted. The prognostic analysis model was constructed according to the methylation sites’ information of the subtype with the best prognosis. Internal and external verifications were used to evaluate the prediction model. Conclusions Models based on differences in DNA methylation levels may help to classify the molecular subtypes of LUSC patients, and provide more individualized treatment recommendations and prognostic assessments for different clinical subtypes. GNAS, FZD2, FZD10 are the core three genes that may be related to the prognosis of LUSC patients.

Two novel garnet-type ceramics Ca3MZrGe3O12 (M = Co and Zn) with pure phase were prepared through a solid-state reaction method. Structure–property relationships were studied by the Rietveld refinement and Raman spectra. The appearance of two weak symmetric stretching vibrational peaks in Ca3ZnZrGe3O12 might be due to the lower ordering. Higher Q × f value in Co-analogue was related to the larger packing fraction and the lower FWHM of A1g mode. The smaller oxygen bond valence in Ca3CoZrGe3O12 indicates a smaller τf value. At the optimized sintering temperature of 1280 °C, Ca3CoZrGe3O12 shows desirable microwave dielectric properties with εr of 10.37, Q × f value of 60,100 GHz, and τf value of −28.5 ppm/oC. The Ca3ZnZrGe3O12 ceramic sintered at 1200 °C has the best microwave dielectric properties with εr of 10.48, Q × f value of 49,700 GHz, and τf value of −35.8 ppm/oC.

It is known that the magnetic field does not affect the free energy change for a driven classical system. Here, the author investigates the influence of the magnetic field on a driven quantum system, finding that the free energy change is amplified and that this quantum effect is reflected in an extended free energy equality.

Obesity is characterized by low-grade chronic inflammation, which underlies insulin resistance and non-alcoholic fatty liver disease (NAFLD). Swertiamarin is a secoiridoid glycoside that has been reported to ameliorate diabetes and NAFLD in animal models. However, the effects of swertiamarin on obesity-related inflammation and insulin resistance have not been fully elucidated. Thus, this study investigated the effects of swertiamarin on inflammation and insulin resistance in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed a HFD or HFD containing swertiamarin for 8 weeks. Obesity-induced insulin resistance and inflammation were assessed in the epididymal white adipose tissue (eWAT) and livers of the mice. Swertiamarin attenuated HFD-induced weight gain, glucose intolerance, oxidative stress, and insulin resistance, and enhanced insulin signalling in mice. Compared to HFD-fed mice, the swertiamarin-treated mice exhibited increased lipolysis and reduced adipocyte hypertrophy and macrophage infiltration in eWAT. Moreover, swertiamarin alleviated HFD-mediated hepatic steatosis and inflammation by suppressing activation of the p38 MAPK and NF-κB pathways within the eWAT and liver of obese mice. In conclusion, supplementation with swertiamarin attenuated weight gain and hepatic steatosis, and alleviated obesity-associated inflammation and insulin resistance, in obese mice.

Detecting community structure is an important problem in complex networks. Recently, the community detection method based on centers and neighbors (DCN) has been proposed, which is divided into two stages: community center point detection and label propagation. It has a better result on community detection of simple undirected graph than other algorithms. However, when there are two community centers connected directly, the method of DCN fails to find both centers. Based on the DCN algorithm, this paper proposes an optimization method based on visually-aided user interactions. By showing the local structure of the discovered center point through the force-directed layout, the potential community centers that are missing in DCN can be detected. We further propose the hierarchical visual clustering to assist users to detect more community centers easier. In addition, to make the propagation of labels more stable, we propose the multi-label propagation strategy based on importance which also preserves the labels proportion during propagation. The experimental results on both artificial and real-world networks demonstrate that our improved algorithm RefineDCN obtains better community detection results than the DCN algorithm.

Response surface methodology (RSM) and central composite design (CCD) were used to improve the preparation of carbon nanotube and graphene (CNT-GN)-sensing unit composite materials in this study. Four independent variable factors (CNT content, GN content, mixing time, and curing temperature) were controlled at five levels, and 30 samples were generated using the multivariate control analysis technique. On the basis of the experimental design, semi-empirical equations were developed and utilized to predict the sensitivity and compression modulus of the generated samples. The results reveal a strong correlation between the experimental and expected values of sensitivity and the compression modulus for the CNT-GN/RTV (room-temperature-vulcanized silicone rubber) polymer nanocomposites fabricated using different design strategies. The correlation coefficients for the sensitivity and compression modulus are R2 =0.9634 and R2=0.9115, respectively. The ideal preparation parameters of the composite in the experimental range include a CNT content of 1.1 g, a GN content of 1.0 g, a mixing time of 15 min, and a curing temperature of 68.6 °C, according to theoretical predictions and experimental findings. At 0~30 kPa, the CNT-GN/RTV-sensing unit composite materials may reach a sensitivity of 0.385 kPa−1 and a compressive modulus of 601.567 kPa. This provides a new idea for the preparation of flexible sensor cells and reduces the time and economic cost of experiments.

Background: We intended to explore the potential immunological functions and prognostic value of Myeloid Ecotropic Viral Integration Site 1 (MEIS1) across 33 cancer types. Methods: The data were acquired from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene expression omnibus (GEO) datasets. Bioinformatics was used to excavate the potential mechanisms of MEIS1 across different cancers. Results: MEIS1 was downregulated in most tumors, and it was linked to the immune infiltration level of cancer patients. MEIS1 expression was different in various immune subtypes including C2 (IFN-gamma dominant), C5 (immunologically quiet), C3 (inflammatory), C4 (lymphocyte depleted), C6 (TGF-b dominant) and C1 (wound healing) in various cancers. MEIS1 expression was correlated with Macrophages_M2, CD8+T cells, Macrophages_M1, Macrophages_M0 and neutrophils in many cancers. MEIS1 expression was negatively related to tumor mutational burden (TMB), microsatellite instability (MSI) and neoantigen (NEO) in several cancers. Low MEIS1 expression predicts poor overall survival (OS) in adrenocortical carcinoma (ACC), head and neck squamous cell carcinoma (HNSC), and kidney renal clear cell carcinoma (KIRC) patients, while high MEIS1 expression predicts poor OS in colon adenocarcinoma (COAD) and low grade glioma (LGG) patients. Conclusion: Our findings revealed that MEIS1 is likely to be a potential new target for immuno-oncology.

Polymer creep can significantly reduce the safety and dependability of composite applications, restricting their development and use in additional fields. In this study, single-factor and multi-factor analysis techniques were employed to systematically explore the impacts of nickel powder and graphene on the resistive creep of sensing units. The creep model between the rate of resistance changes and the pressure was established, and the material ratio was optimized to obtain a high creep resistance. The results demonstrated that the creep resistance was best when the filling particle was 10 wt.% and the ratio of nickel powder to graphene was 4:21, which was approximately 60% and 45% lower than the filling alone and the composite filling before optimization, respectively; the R2 of the theoretical value of the resistance creep model and the experimental value of the creep before and after optimization was 0.9736 and 0.9812, indicating that the resistance creep model was highly accurate. Consequently, the addition of filler particles with acceptable proportions, varied shapes, and different characteristics to polymers can effectively reduce polymer creep and has significant potential for the manufacture of sensing units for tactile sensors.

Pressure sensors urgently need high-performance sensing materials in order to be developed further. Sensitivity and creep are regarded as two key indices for assessing a sensor’s performance. For the design and optimization of sensing materials, an accurate estimation of the impact of several parameters on sensitivity and creep is essential. In this study, sensitivity and creep were predicted using the response surface methodology (RSM) and support vector regression (SVR), respectively. The input parameters were the concentrations of nickel (Ni) particles, multiwalled carbon nanotubes (MWCNTs), and multilayer graphene (MLG), as well as the magnetic field intensity (B). According to statistical measures, the SVR model exhibited a greater level of predictability and accuracy. The non-dominated sorting genetic-II algorithm (NSGA-II) was used to generate the Pareto-optimal fronts, and decision-making was used to determine the final optimal solution. With these conditions, the optimized results revealed an improved performance compared to the earlier study, with an average sensitivity of 0.059 kPa−1 in the pressure range of 0–16 kPa and a creep of 0.0325, which showed better sensitivity in a wider range compared to previous work. The theoretical sensitivity and creep were relatively similar to the actual values, with relative deviations of 0.317% and 0.307% after simulation and experimental verification. Future research for transducer performance optimization can make use of the provided methodology because it is representative.

Abstract Background The minimum clinical important differences (MCIDs) of resilience instruments in patients with cancer have not been comprehensively described. This study was designed to evaluate MCIDs of 10-item and 25-item resilience scales specific to cancer (RS-SC-10 and RS-SC-25). Methods From June 2015 to December 2018, RS-SCs were longitudinally measured in 765 patients with different cancer diagnoses at baseline (T0) and 3 months later (T1). The EORTC QLQ-C30, Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Allostatic Load Index were measured concurrently as anchors. Anchor-based methods (linear regression, within-group), distribution-based methods(within-group), and receiver operating characteristic curves (ROCs, within-subject) were performed to evaluate the MCIDs. Results 623 of 765 (84.1%) patients had paired RS-SCs scores. Moderate correlations were identified between the change in RS-SCs and change in anchors (r = 0.38–0.44, all p

16 Mg–Al–Zn–Bi quaternary alloys were utilized to measure the phase equilibria and transformation temperatures in the Mg-rich Mg–Al–Zn–Bi quaternary system by means of the X-ray diffraction, electron probe micro-analysis and differential scanning calorimetry techniques. The isothermal section at 400 °C and three vertical sections along Mg–8 wt%Al–0.75 wt%Zn–xBi, Mg–3.4 wt%Al–0.5 wt%Zn–xBi and Mg–6.9 wt%Al–2.3 wt%Zn–xBi in the Mg–Al–Zn–Bi quaternary system were constructed. Based on the literature data, the ternary Mg–Al–Bi and Mg–Bi–Zn systems were re-assessed using the CALculaiton of PHAse Diagram (CALPHAD) approach. The calculated phase equilibria agree well with the measured data. By directly extrapolating the constituent sub-ternary systems, the thermodynamic database for the Mg–Al–Zn–Bi quaternary system was developed. The remarkable consistency between the predicted phase equilibria and the presently measured data in Mg–Al–Zn–Bi quaternary system further demonstrated the accuracy and reliability of the established thermodynamic database. After that, by using the newly developed thermodynamic database, the growth restrict factors and the solidification curves in Bi-containing AZ series magnesium alloys were calculated and analyzed. It was confirmed that the grain size of AZ alloys can be refined with the addition of Bi, and the component Al had larger grain refinement effect than Bi. Besides, the amount of Bi had also noticeable effect on the solidification sequence of the AZ alloys.

Abstract Background The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC. Methods HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA). Results The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR = 2.62 for G3–4 vs. G1–2, p = 1.80E-05), clinical stage (OR = 1.74 for III-IV vs. I-II, p = 0.03), T (OR = 1.64 for T3–4 vs.T1–2, p = 0.04), tumor status (OR = 1.88 for with tumor vs. tumor free, p = 3.79E-03), plasma alpha fetoprotein (AFP) value (OR = 3.18 for AFP ≥ 400 vs AFP

ObjectiveCurrent pharmacological intervention for the cancer-related pain is still limited. The aim of this study was to explore whether repetitive transcranial magnetic stimulation (rTMS) could be an effective adjuvant therapy to reduce pain in patients with advanced non-small cell lung cancer (NSCLC).MethodsThis was a randomized, sham–controlled study. A total of 41 advanced NSCLC patients with uncontrolled pain (score≥4 on pain intensity assessed with an 11-point numeric rating scale) were randomized to receive active (10 Hz, 2000 stimuli) (n = 20) or sham rTMS (n = 20) for 3 weeks. Pain was the primary outcome and was assessed with the Numeric Rating Scale (NRS). Secondary outcomes were oral morphine equivalent (OME) daily dose, quality of life (WHO Quality of Life-BREF), and psychological distress (the Hospital Depression and Anxiety Scale). All outcomes were measured at baseline, 3 days, 1 week, 2 weeks, and 3 weeks.ResultsThe pain intensity in both groups decreased gradually from day 3 and decreased to the lowest at the week 3, with a decrease rate of 41.09% in the rTMS group and 23.23% in the sham group. The NRS score of the rTMS group was significantly lower than that of the sham group on the week 2 (p < 0.001, Cohen’s d =1.135) and week 3 (p=0.017, Cohen’s d = -0.822). The OME daily dose, physiology and psychology domains of WHOQOL-BREF scores, as well as the HAM-A and HAM-D scores all were significantly improved at week 3 in rTMS group.ConclusionAdvanced NSCL patients with cancer pain treated with rTMS showed better greater pain relief, lower dosage of opioid, and better mood states and quality of life. rTMS is expected to be a new effective adjuvant therapy for cancer pain in advanced NSCLC patients.

Tight sandstone reservoirs have complex pore throat structures and poor and large differences in petrophysical properties. In this study, taking the Chang 3 Member of Weibei Oilfield, Ordos Basin, China as an example, the microscopic mechanism of the differences in petrophysical properties of tight sandstone reservoirs was systematically studied by thin section observation, scanning electron microscope, whole-rock X-ray diffraction, and high-pressure mercury intrusion experiments. The research results show that the reservoir types of the Chang 3 Member are mainly feldspar lithic sandstone and lithic feldspar sandstone; the pore types include intergranular, intragranular dissolution pores, and a small amount of residual intergranular pores. Taking the permeability of 0.3 × 10−3 and 0.5 × 10−3 μm2 as the boundary, we divided the samples involved in high-pressure mercury intrusion into three categories according to the permeability from high to low: Type I, Type II, and Type III. Their proportions were 31.4, 20.0, and 48.6%, respectively. The study found that the smaller the sorting coefficient, the poorer the petrophysical properties of the samples; the pore throat distribution of different samples gradually changed to a uniform double peak–dominated type. The permeability of tight sandstone reservoirs is contributed by a small part of pore throats with a large radius, while the reservoir space is mainly contributed by a large number of pores connected with small throats. The porosity is negatively and positively correlated with the median pressure and mercury injection tortuosity, respectively. In addition, the pore throat radius corresponding to the maximum permeability contribution rate, maximum pore throat radius, and sorting coefficient are all positively correlated with the permeability. In general, the areas with larger pore throat radius, lower pore throat tortuosity, and larger pore throat sorting coefficient can be regarded as favorable areas for Chang 3 tight sandstone reservoirs.