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Abstract Background To a large extent, the ovarian reserve determines a woman’s reproductive potential. The etiological and pathological mechanisms of diminished ovarian reserve (DOR) remain unclear, and no reliable treatment is currently available for DOR. Adipokines and cytokines in follicular fluid (FF) play pivotal roles in follicular development and maturation. The concentrations of adipokines and cytokines in FF from individual follicles of women with DOR undergoing in vitro fertilization (IVF) were studied. In particular, we investigated the associations between the levels of adipokines and cytokines in individual FFs from women with different ovarian reserves and between the follicular levels of adipokines and cytokines and IVF outcomes in individual follicles. Methods A total of 115 women who underwent IVF were recruited. Patients diagnosed with DOR, defined as a basal antral follicle count

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective β-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

IntroductionThis study explores how graduate students’ mentorship homegate (or team) support (GSMTS) and challenging-hindering pressures impact their intrinsic motivation for research, identification with research roles, and innovative behaviors.MethodsData from 548 graduate students were collected using convenience sampling and analyzed using Amos and SPSS statistical software package via questionnaires distributed to universities in SiChuan province of China.ResultThe findings reveal that (1) research stress can not directly and positively predict innovative behaviors among graduate students, while intrinsic research motivation and research role identification mediate the relationship between research stress and graduate students’ innovative behavior; (2) hindering research pressure negatively impacts the intrinsic motivation for research, whereas challenging research pressure has a positive effect; (3) GSMTS directly fosters innovative behaviors among graduate students, with intrinsic motivation and roles’ identification for research as sequential mediators; and (4) GSMTS positively moderates the relationship between challenging research pressure and both the intrinsic motivation for research and role identity.DiscussionThis suggests that higher education institutions should cultivate an optimal research and innovation environment for graduate students by increasing challenging research pressure and reducing hindering pressure. They should also emphasize the development of graduate students’ intrinsic motivation for research and identification with research roles. Concurrently, the role of GSMTS should be highlighted to facilitate both the direct and indirect development of graduate students’ innovative behaviors.

In order to explore the water bleeding characteristics of gangue powder-based cemented filling materials, the influence of four factors: gangue powder-based mass concentration (A), cement content (B), fly ash content (C) and high water material content (D) on the water bleeding rate of cemented materials was studied by using range analysis and analysis of variance; the fitting formula of the influence of various factors on the water bleeding characteristics of gangue powder-based cementation filling materials was obtained. The results showed that the degree of influence on the water bleeding rate of gangue powder-based cemented filling materials based on range analysis was D>A>B>C, and showed that the influence on the water bleeding rate of materials based on variance analysis was D>B>A>C, and the water bleeding rate showed a downward with the increase of the mass concentration of gangue slurry, with the increase of cement content, it showed a trend of first decreasing and then increasing and then decreasing; with the increase of fly ash quality, it showed a trend of first decreasing and then stable; with the increase of high water, it showed a downward trend. High water content had the greatest influence on the water bleeding rate of materials, the mass concentration of gangue powder and cement quality had comparable effects on the water bleeding rate of materials, and fly ash content had little effect on the water bleeding rate of materials.

Cotyledon color is one of the important indices for identifying faba bean variety purity and measuring processing quality. Therefore, an in-depth study of the genetic mechanism of cotyledon color is vital for promoting faba bean industry development. We used the yellow cotyledon variety Qingcan 16 and the green cotyledon variety Qingcan 17 as parent plants to construct hybrid combinations. F1-, F2-, BC1F1-, and BC2F1-generation single-plant cotyledon colors were counted to clarify cotyledon color inheritance. F2-generation individuals were genotyped using ddRAD-Seq to construct a genetic linkage map and identify QTLs for cotyledon color. Green cotyledons were controlled by one pair of recessive nuclear genes. Using the screened 1991 SNP markers, a high-density linkage map was constructed, with a coverage length of 1476.95 cM and an average map distance of 0.96 cM. The green cotyledon trait was located using WinQTL Cart, and a vfGC candidate interval explaining 34.30 to 49.40% of the phenotypic variation was identified at LG02 (101.952 cM to 115.493 cM) and at LOD = 16.0, corresponding to chr1L 1,077,051,302 bp to 1,636,400,339 bp (559.35 Mb). The above interval contained 2021 genes, 20 of which were involved in photosynthesis, but no SGR or genes with similar functions were identified. However, the published faba bean vfSGR was located within the vfGC candidate interval, confirming that our localization interval was reliable. The above findings provided further clues for the fine localization of genes regulating green cotyledons and the development of molecular linked markers in faba bean.

Candidate genes related to first pod height (FPH) traits in faba bean plants are crucial for mechanised breeding. However, reports on quantitative trait locus (QTL) mapping related to the FPH of faba bean are few, thus limiting the high-quality development of the faba bean industry to a certain extent. The identification and screening of candidate genes related to FPH is extremely urgent for the advancement of mechanised breeding for faba bean. In this study, a high-density genetic linkage map was constructed using genotyping-by-sequencing (GBS) of an F3 population and QTLs (genes) related to FPH were identified. The genetic linkage map contained seven linkage groups with 3012 SNP markers with an overall length of 4089.13 centimorgan (cM) and an average marker density of 1.36 cM. Thirty-eight QTLs for the first pod node (FPN) and FPH were identified (19 each for FPN and FPH). The 19 QTLs associated with FPN were located on chromosomes 1L, 1S, 2, 3, 4, 5, and 6; the 19 QTLs associated with FPH were located on chromosomes 1L, 1S, 2, 3, 5, and 6. There was a co-localisation interval of qFPN6-1 and qFPH6-1 on chromosome 6. By annotating the QTL qFPH6-1 interval, 36 genes that may be related to FPH were identified, these genes are related to plant growth and development. The results provide a basis for the precise location of QTLs related to FPH and could accelerate the breeding of faba bean varieties adapted to mechanised harvesting.

The ceRNA network, consisting of both noncoding RNA and protein-coding RNA, governs the occurrence, progression, metastasis, and infiltration of lung adenocarcinoma. Signatures comprising multiple genes can effectively determine survival stratification and prognosis of patients with lung adenocarcinoma. To explore the mechanisms of lung adenocarcinoma progression and identify potential biological targets, we carried out systematic bioinformatics analyses of the genetic profiles of lung adenocarcinoma, such as weighted gene co-expression network analysis (WGCNA), differential expression (DE) assessment, univariate and multivariate Cox proportional hazard regression models, ceRNA modulatory networks generated using the ENCORI and miRcode databases, nomogram models, ROC curve assessment, and Kaplan-Meier survival curve analysis. The ceRNA network encompassed 37 nodes, comprising 12 mRNAs, 22 lncRNAs, and three miRNAs. Simultaneously, we performed integration analysis using the 12 genes from the ceRNA network. Our findings revealed that the signature established by these 12 genes serves as an adverse element in lung adenocarcinoma, contributing to unfavorable patient prognosis. To ensure the credibility of our results, we used in vitro experiments for further verification. In conclusion, our study delved into the potential mechanisms underlying lung adenocarcinoma via the ceRNA regulatory network, specifically focusing on the PIF1 and has-miR-125a-5p axis. Additionally, a signature comprising 12 genes was identified as a biomarker related to the prognosis of lung adenocarcinoma.

Abstract Introduction Acute lung injury (ALI) is a common and rapidly developing critical inflammatory lung disease in clinic. This study investigated the predictive value of lncRNA UCA1, extravascular lung water index (EVLWI), and lung ultrasound score (LUS) in predicting the overall outcome of patients with ALI. Methods Patients with ALI were recruited for detecting the content of UCA1, EVLWI, and LUS. All patients were cataloged into the survival group and death group according to the prognosis. The discrepancy of UCA1, EVLWI, and LUS was compared in the two groups. The prognostic significance of UCA1, EVLWI, LUS, and their combination was estimated by logistic regression and the receiver operating characteristic (ROC) curve. Results The levels of UCA1, LUS, and EVLWI were elevated in the death group compared with the survival group. The content of UCA1 was positively correlated with LUS scores and EVLWI scores. UCA1, LUS, and EVLWI were independent indicators of predicting the prognosis of patients with ALI. The ROC curve reflected that UCA1, LUS, and EVLWI could forecast the endpoint events of patients with ALI whereas their combined approach had the highest accuracy. Conclusion Highly expressed UCA1 is a biomarker in forecasting the outcome of patients with ALI. It had high accuracy in predicting the endpoint of patients with ALI when combined with LUS and EVLWI.

BackgroundWhile an elevated risk of second primary cancers (SPCs) has been observed in many other cancers, risk of SPCs has not been quantified in patients with rectal neuroendocrine neoplasms (NENs).MethodsSurvivors of primary rectal NENs diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER)-18 registries. Relative risk of SPCs was estimated as the standardized incidence ratio (SIR), which was calculated using SEER*Stat software.ResultsBetween 2000 and 2018, a total of 15836 patients diagnosed with rectal NENs, of whom 1436 (9.1%) received diagnosis of SPCs (SIR: 1.19, 95%CI: 1.13-1.26). The majority of patients were aged 50-69 and had their first cancer diagnosed at the localized stage. Male survivors had a higher propensity for developing SPCs overall, while female survivors exhibited higher risks of specific SPCs. Age at diagnosis of rectal NENs influenced the risk of SPCs, with younger patients having greater risks. A statistically significant increase in the incidence of SPCs was observed among patients aged 30-64 years. Black patients had higher relative risks of certain SPCs, while White patients had a lower risk of subsequent melanoma. Trend analysis revealed that the highest excess burden of SPCs was observed in the years 2000 to 2002. Risk of SPCs remained elevated within the first four years post-diagnosis for survivors of rectal NENs, but diminished thereafter.ConclusionThe study revealed that individuals who survived rectal NENs were at an elevated risk of developing SPCs compared to the general population. Our results hold important implications for the formulation of lifelong surveillance recommendations for cancer survivors.

Abstract Unrestricted reproduction and spread of pest had caused great damage to the quality and yield of crops in recent years. Besides the use of traditional chemical pesticides, natural products also make a huge contribution against pests. Chasmanthinine, a diterpenoid alkaloid isolated from Aconitum franchetii var. villosulum, shown extremely antifeedant activity against Spodoptera exigua. Therefore, a series of novel Chasmanthinine derivatives were synthesized and their biological activity was studied in this work. Compound 33 showed the strongest antifeedant activity (EC50 = 0.10 mg/cm2) among all the test compounds. The mechanism research of 33 revealed that its antifeedant effect was related to the inhibition of carboxylesterase (CES), and proved the thiophene acyl group could form a strong binding effect with CES by molecular docking. Moreover, compound 10 exhibited the strongest cytotoxicity (IC50 = 12.87 μM) against Sf9 cell line and moderate contact toxicity. The mechanism research indicated that compound 10 could induce Sf9 cells apoptosis. In summary, the results lay a foundation for the application of diterpene alkaloids in plant protection.

Because the new energy is intermittent and uncertain, it has an influence on the system’s output power stability. A hydrogen energy storage system is added to the system to create a wind, light, and hydrogen integrated energy system, which increases the utilization rate of renewable energy while encouraging the consumption of renewable energy and lowering the rate of abandoning wind and light. Considering the system’s comprehensive operation cost economy, power fluctuation, and power shortage as the goal, considering the relationship between power generation and load, assigning charging and discharging commands to storage batteries and hydrogen energy storage, and constructing a model for optimal capacity allocation of wind–hydrogen microgrid system. The optimal configuration model of the wind, solar, and hydrogen microgrid system capacity is constructed. A particle swarm optimization with dynamic adjustment of inertial weight (IDW-PSO) is proposed to solve the optimal allocation scheme of the model in order to achieve the optimal allocation of energy storage capacity in a wind–hydrogen storage microgrid. Finally, a microgrid system in Beijing is taken as an example for simulation and solution, and the results demonstrate that the proposed approach has the characteristics to optimize the economy and improve the capacity of renewable energy consumption, realize the inhibition of the fluctuations of power, reduce system power shortage, and accelerate the convergence speed.

Abstract The existence of inadequate ablation remains an important cause of treatment failure for loco‐regional ablation therapies. Here, using a preclinical model, it is reported that inadequate microwave ablation (iMWA) induces immunosuppressive niche predominated by myeloid cells. The gene signature of ablated tumor presented by transcriptome analyses is highly correlated with immune checkpoint blocking (ICB) resistance. Thus, an in situ scaffold with synergistic delivery of IPI549 and anti‐programmed death‐ligand 1 blocking antibody (aPDL1) for postablative cancer immunotherapy is designed and engineered, in which IPI549 capable of targeting myeloid cells could disrupt the immunosuppressive niche and subsequently improve ICB‐mediated antitumor immune response. Based on five mouse cancer models, it is demonstrated that this biomaterial system (aPDL1&IPI549@Gel) could mimic a “hot” tumor‐immunity niche to inhibit tumor progression and metastasis, and protect cured mice against tumor rechallenge. This work enables a new standard‐of‐care paradigm for the immunotherapy of myeloid cells‐mediated “cold” tumors after loco‐regional inadequate practices.

PurposesTo establish a predictive model incorporating clinical features and contrast enhanced ultrasound liver imaging and reporting and data system (CEUS LI-RADS) for estimation of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients.MethodsIn the retrospective study, 127 HCC patients from two hospitals were allocated as training cohort (n=98) and test cohorts (n=29) based on cutoff time-point, June 2020. Multivariate regression analysis was performed to identify independent indicators for developing predictive nomogram models. The area under receiver operating characteristic (AUC) curve was also determined to establish the diagnostic performance of different predictive models. Corresponding sensitivities and specificities of different models at the cutoff nomogram value were compared.ResultsIn the training cohort, clinical information (larger tumor size, higher AFP level) and CEUS LR-M were significantly correlated with the presence of MVI (all p

Abstract Background Polycystic kidney disease (PKD) is an inherited disease that is life‐threatening. Multiple cysts are present in the bilateral kidneys of PKD patients. The progressively enlarged cysts cause structural damage and loss of kidney function. Methods This study examined and analyzed 12 families with polycystic kidney disease. Whole exome sequencing (WES) or whole genome sequencing (WGS) of the probands was performed to detect the pathogenic genes. The candidate gene segments for lineal consanguinity in the family were amplified by the nest PCR followed by Sanger sequencing. The variants were assessed by pathogenic and conservational property prediction analysis and interpreted according to the American College of Medical Genetics and Genomics. Results Nine of the 12 pedigrees were identified the disease causing variants. Among them, four novel variants in PKD1, c.6930delG:p.C2311Vfs*3, c.1216T>C:p.C406R, c.8548T>C:p.S2850P, and c.3865G>A:p.V1289M (NM_001009944.2) were detected. After assessment, the four novel variants were considered to be pathogenic variants and cause autosomal dominant polycystic kidney disease in family. The detected variants were interpreted. Conclusion The four novel variants in PKD1, c.6930delG:p.C2311Vfs*3, c.1216T>C:p.C406R, c.8548T>C:p.S2850P, and c.3865G>A:p.V1289M (NM_001009944.2) are pathogenic variants and cause autosomal dominant polycystic kidney disease in family.

Objective Needlestick injuries caused by insulin pen injection are a serious occupational hazard for health care workers in China. We evaluated the prevalence of stick injuries with insulin pen injection and identified associated risk factors. Methods This cross-sectional survey was conducted from 1 October to 30 November 2018 in two tier three hospitals in Chongqing, China. Self-administered questionnaires were developed by the Chinese Nursing Association Diabetes Care Special Committee. We analyzed associations between potential risk factors and injuries at different operational steps. Results A total 233 of 302 (77%) participants (mean age 28.5±5.3 years) reported a needlestick incident. Most respondents (49%) had 3 to 10 years’ working experience and had received injection safety training. Most needlestick injuries occurred while recapping needles after injection. The risk of injury was significantly associated with department and job position. The injury rate increased with increased number of years worked. Respondents with ≥10 years working experience reported the highest needle-capping injury rate (88%): odds ratio 1.93, 95% confidence interval, 1.01 to 3.69. Conclusion Recapping needles after injection showed the highest risk for stick injury with an insulin pen. Nurses in the surgery department and those with longer work histories were more likely to be injured.

In high efficiency and high-frequency applications, the soft-start methods for DC-DC converter with fast output voltage settling speed have attracted widespread attention. A novel soft-start circuit with controllable start-up time, high start-up speed, high stability, and no off-chip capacitor for a current mode DC-DC is proposed in this paper. The proposed soft-start circuit introduces a current-limiting feedback technique so that the inductor current during soft-start is controllable. The stability of the soft-start technique is verified theoretically in this paper. A Boost converter using this novel soft-start technique is fabricated in 0.35 μm BCD process. The soft-start time of the Boost converter is only 380 μs at the conditions of 45 V output voltage, 20 μF load capacitance, and 500 mA load current.