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Abstract Background Hematopoietic stem progenitor cells (HSPCs) undergo phenotypical and functional changes during their emergence and development. Although the molecular programs governing the development of human hematopoietic stem cells (HSCs) have been investigated broadly, the relationships between dynamic metabolic alterations and their functions remain poorly characterized. Methods In this study, we comprehensively described the proteomics of HSPCs in the human fetal liver (FL), umbilical cord blood (UCB), and adult bone marrow (aBM). The metabolic state of human HSPCs was assessed via a Seahorse assay, RT‒PCR, and flow cytometry-based metabolic-related analysis. To investigate whether perturbing glutathione metabolism affects reactive oxygen species (ROS) production, the metabolic state, and the expansion of human HSPCs, HSPCs were treated with buthionine sulfoximine (BSO), an inhibitor of glutathione synthetase, and N-acetyl-L-cysteine (NAC). Results We investigated the metabolomic landscape of human HSPCs from the fetal, perinatal, and adult developmental stages by in-depth quantitative proteomics and predicted a metabolic switch from the oxidative state to the glycolytic state during human HSPC development. Seahorse assays, mitochondrial activity, ROS level, glucose uptake, and protein synthesis rate analysis supported our findings. In addition, immune-related pathways and antigen presentation were upregulated in UCB or aBM HSPCs, indicating their functional maturation upon development. Glutathione-related metabolic perturbations resulted in distinct responses in human HSPCs and progenitors. Furthermore, the molecular and immunophenotypic differences between human HSPCs at different developmental stages were revealed at the protein level for the first time. Conclusion The metabolic landscape of human HSPCs at three developmental stages (FL, UCB, and aBM), combined with proteomics and functional validations, substantially extends our understanding of HSC metabolic regulation. These findings provide valuable resources for understanding human HSC function and development during fetal and adult life.

Frictional sliding creates distinct microstructural and chemical discontinuities between the subsurface layer and base materials, which dictate the friction and wear properties. Traditional methods for lowering friction and wear in metals primarily rely on strategies that lower the interfacial shear strength between the contacting discontinuities. Contrary to conventional wisdom, we propose an alternative strategy: introducing tribo-induced or pre-designed heterostructures to suppress tribo-induced strain localization, thus yielding superior tribological properties unachievable with their conventional homogeneous counterparts. Citing recent experimental examples, this review explores the multiscale heterogeneities contributing low friction and wear, by interlinking surface deformation mechanisms and applied tribological conditions.

Abstract Background Growth differentiation factor‐15 (GDF‐15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF‐15 and pre‐eclampsia (PE). Method The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF‐15 were measured by using enzyme‐linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF‐15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs). Results MOM of GDF‐15 in PE participants was higher compared with controls (1.588 vs. 1.000, p 1) had a 4.74‐fold (95% CI = 2.23–10.08, p

Abstract Efficient and rapid auxiliary diagnosis of different grades of lung adenocarcinoma is conducive to helping doctors accelerate individualized diagnosis and treatment processes, thus improving patient prognosis. Currently, there is often a problem of large intra-class differences and small inter-class differences between pathological images of lung adenocarcinoma tissues under different grades. If attention mechanisms such as Coordinate Attention (CA) are directly used for lung adenocarcinoma grading tasks, it is prone to excessive compression of feature information and overlooking the issue of information dependency within the same dimension. Therefore, we propose a Dimension Information Embedding Attention Network (DIEANet) for the task of lung adenocarcinoma grading. Specifically, we combine different pooling methods to automatically select local regions of key growth patterns such as lung adenocarcinoma cells, enhancing the model's focus on local information. Additionally, we employ an interactive fusion approach to concentrate feature information within the same dimension and across dimensions, thereby improving model performance. Extensive experiments have shown that under the condition of maintaining equal computational expenses, the accuracy of DIEANet with ResNet34 as the backbone reaches 88.19%, with an AUC of 96.61%, MCC of 81.71%, and Kappa of 81.16%. Compared to seven other attention mechanisms, it achieves state-of-the-art objective metrics. Additionally, it aligns more closely with the visual attention of pathology experts under subjective visual assessment.

ObjectiveThe objective of this study is to assess the viability of utilizing radiomics for predicting the treatment response of lung cancer brain metastases (LCBM) to whole-brain radiotherapy (WBRT) combined with temozolomide (TMZ).MethodsFifty-three patients diagnosed with LCBM and undergoing WBRT combined with TMZ were enrolled. Patients were divided into responsive and non-responsive groups based on the RANO-BM criteria. Radiomic features were extracted from contrast-enhanced the whole brain tissue CT images. Feature selection was performed using t-tests, Pearson correlation coefficients, and Least Absolute Shrinkage And Selection (LASSO) regression. Logistic regression was employed to construct the radiomics model, which was then integrated with clinical data to develop the nomogram model. Model performance was evaluated using receiver operating characteristic (ROC) curves, and clinical utility was assessed using decision curve analysis (DCA).ResultsA total of 1834 radiomic features were extracted from each patient's images, and 3 features with predictive value were selected. Both the radiomics and nomogram models exhibited satisfactory predictive performance and clinical utility, with the nomogram model demonstrating superior predictive value. The ROC analysis revealed that the AUC of the radiomics model in the training and testing sets were 0.776 and 0.767, respectively, while the AUC of the nomogram model were 0.799 and 0.833, respectively. DCA curves demonstrated that both models provided benefits to patients across various thresholds.ConclusionRadiomic-defined image biomarkers can effectively predict the treatment response of WBRT combined with TMZ in patients with LCBM, offering potential to optimize treatment decisions for this condition.

Abstract Background Recent therapeutic-plasmid DNA vaccine strategies for rheumatoid arthritis (RA) have significantly improved. Our pcDNA-CCOL2A1 vaccine is the most prominent and the first antigen-specific tolerising DNA vaccine with potent therapeutic and prophylactic effects compared with methotrexate (MTX), the current “gold standard” treatment for collagen-induced arthritis (CIA). This study developed a highly efficient, cost-effective, and easy-to-operate system for the lab-scale production of endotoxin-free supercoiled plasmids with high quality and high yield. Based on optimised fermentation culture, we obtained a high yield of pcDNA-CCOL2A1 vaccine by PEG/MgCl2 precipitation and TRION-114. We then established a method for quality control of the pcDNA-CCOL2A1 vaccine. Collagen-induced arthritis (CIA) model rats were subjected to intramuscular injection of the pcDNA-CCOL2A1 vaccine (300 μg/kg) to test its biological activity. Results An average yield of 11.81 ± 1.03 mg purified supercoiled plasmid was obtained from 1 L of fermentation broth at 670.6 ± 57.42 mg/L, which was significantly higher than that obtained using anion exchange column chromatography and a commercial purification kit. Our supercoiled plasmid had high purity, biological activity, and yield, conforming to the international guidelines for DNA vaccines. Conclusion The proposed innovative downstream process for the pcDNA-CCOL2A1 vaccine can not only provide a large-scale high-quality supercoiled plasmid DNA for preclinical research but also facilitate further pilot-scale and even industrial-scale production of pcDNA-CCOL2A1 vaccine.

Abstract The use of attenuated bacteria for oral delivery of DNA vaccines is a recent innovation. We designed and constructed the naked plasmid DNA vaccine pcDNA-CCOL2A1, which effectively prevented and treated a rheumatoid arthritis model by inducing immunotolerance. We aimed to ensure a reliable, controllable dosage of this oral DNA vaccine preparation and establish its stability. We transformed pcDNA-CCOL2A1 via electroporation into attenuated Salmonella typhimurium SL7207. A resistant plate assay confirmed the successful construction of the transformed strain of the SL7207/pcDNA-CCOL2A1 oral DNA vaccine. We verified its identification and stability in vitro and in vivo. Significant differences were observed in the characteristics of the transformed and blank SL7207 strains. No electrophoretic restriction patterns or direct sequencing signals were observed in the original extract of the transformed strain. However, target gene bands and sequence signals were successfully detected after PCR amplification. CCOL2A1 expression was detected in the ilea of BALB/c mice that were orally administered SL7207/pcDNA-CCOL2A1. The pcDNA-CCOL2A1 plasmid of the transformed strain was retained under the resistant condition, and the transformed strain remained stable at 4 °C for 100 days. The concentration of the strain harboring the pcDNA-CCOL2A1 plasmid was stable at 109 CFU/mL after 6–8 h of incubation. The results demonstrated that the transformed strain SL7207/pcDNA-CCOL2A1 can be expressed in vivo, has good stability, and may be used to prepare the oral DNA vaccine pcDNA-CCOL2A1 with a stable, controllable dosage and the capacity to provide oral immunization. This vehicle can effectively combine both oral immunotolerance and DNA vaccination.

A tungsten carbide (WC) ceramic coating is fabricated by a new method of Fe-coating-mediated carburization, in which the tungsten substrate is carburized using a pre-electroplated Fe coating. In this carburization process, the electroplated Fe coating is transformed into a carbon steel coating, and a significant number of interstitial carbon atoms in the carbon steel coating diffuse into the tungsten substrate, forming a WC ceramic coating on it. The so-formed WC ceramic coating is nonporous, uniform in thickness, and has a microstructure with grain size gradient. The thickness of the electroplating Fe coating had no effect on the microstructure and growth rate of WC coating when the thickness of the electroplating iron coating was in the range of 5–20 μm. The hardness of the coating reached 2800 HV0.05, and the adhesion strength between the substrate and coating was greater than 100 N. Compared with conventional solid carburization, Fe-coating-mediated carburization can generate nonporous ceramic coatings over wider ranges of temperature and carbon potential at a higher growth rate. Accordingly, the microstructure and properties of the coating could be optimized further.

Abstract In 1917, Einstein considered stimulated photon emission of electron radiation, offering the theoretical foundation for laser, technically achieved in 1960. However, thermal phonons along with heat creation of non-radiative transition, are ineffective, even playing a detrimental role in lasing efficiency. Here, we realize a photon-phonon collaboratively pumped laser enhanced by heat in a counterintuitive way. We observe a laser transition from phonon-free 1064 nm lasing to phonon-pumped 1176 nm lasing in Nd:YVO4 crystal, associated with the phonon-pumped population inversion under high temperatures. Moreover, an additional temperature threshold (Tth) appears besides the photon-pump power threshold (Pth), and a two-dimensional lasing phase diagram is verified with a general relation ruled by Pth = C/Tth (constant C upon loss for a given crystal), similar to Curie’s Law. Our strategy will promote the study of laser physics via dimension extension, searching for highly efficient and low-threshold laser devices via this temperature degree of freedom.

The plant AT protein and zinc-binding protein (PLATZ) genes, a novel cluster of plant-specific zinc-finger-dependent DNA-binding proteins, play a crucial role in regulating stress response and plant development. However, there has been little study focus on the role of the cucumber PLATZ family in assimilating loading in leaves. (1) In this study, a total of 12 PLATZ genes were identified from the cucumber genome. The cucumber PLATZ genes were clustered into five groups, and unevenly distributed on five chromosomes. A single pair of cucumber PLATZ genes underwent segmental duplication. (2) The results of genome-wide expression analysis suggested that the cucumber PLATZ genes were widely expressed in a wide range of cucumber tissues, with three PLATZ (PLATZ2, PLATZ6, and PLATZ12) genes exhibiting high expression in the vascular tissues of cucumber leaves. PLATZ2, PLATZ6, and PLATZ12 proteins were primarily located in cytomembrane and nucleus. (3) In VIGS-PLATZ6 plants, the expression of Galactinol synthase 1 (GolS1) and STACHYOSE SYNTHASE (STS), two genes involved in the synthesis of raffinose family oligosaccharides (RFOs) were observed to be decreased in cucumber leaves. In conclusion, the comprehensive analysis of the cucumber PLATZ family and the preliminary functional verification of PLATZ6 lay the foundation for the molecular and physiological functions of cucumber PLATZ genes.

In the published article [...]

Global water scarcity has become a non-negligible problem that threatens the sustainable development of agriculture. In order to alleviate the contradiction between grain demand and water resource constraints, it is particularly important to explore appropriate irrigation strategy so as to synergistically increase grain yield and water use efficiency (WUE). The AquaCrop model were locally calibrated to simulate optimal irrigation amount for different hydrological years using a four-year field measurements (from 2017 to 2020) of maize with two irrigation levels (2400 m3/ha and 4800 m3/ha) in Shihezi, Xinjiang, China. On this basis, regulated deficit irrigation (RDI) strategies were optimized based on the variation of water consumption and soil water content (SWC) during the maize growth period. Results suggest that the optimal irrigation amount under static strategy (fixed proportion irrigation in growing season) in the wet, normal, and dry years was 4733 m3/ha, 5381 m3/ha, and 6090 m3/ha, respectively. In dynamic strategies, the optimized RDI4 (65% Ir (the amount of water required for each irrigation interval) at R2-R5 stage) and RDI5 strategy (85% Ir at V6-V12 stage and 85% Ir at R2-R5 stage) can save irrigation water while maintaining high yield. Under the premise of basically maintaining high yield (18Mg/ha), compared with each year's irrigation amount of 4800 m3/ha, the RDI4 strategy can reduce the irrigation amount by 4.33% in 2017; although the irrigation amount was slightly increased by 2.77% under the RDI5 strategy in 2018, the yield could be increased by 3.65%; in 2019, the RDI5 strategy can save 49.44% of irrigation water, and the RDI4 strategy will save 24.13% of irrigation water in 2020. From this study, it is recommended that a single irrigation amount of 65% Ir in R2 to R5 stages of maize growth or 85% Ir in V6 to V12 stages and 85% Ir in R2 to R5 stages can save irrigation water while maintaining high yield (18 Mg/ha).

Objective The association between haemoglobin-to-red blood cell distribution width ratio (HRR) and all-cause mortality remains poorly understood. This study aimed to examine the influence of HRR at the time of admission mortality over 1 year and 30 days in patients with sepsis.Design This was a secondary analysis.Setting This study was conducted in intensive care units (ICUs).Participants Adult patients with sepsis were identified and included from an intensive care database based on eligibility criteria.Primary outcome and measure The primary outcome was the rate of death within 1 year. The secondary outcome was the death rate within 30 days.Results A total of 4233 patients with sepsis who met the inclusion criteria were analysed, excluding those ineligible. These participants were divided into quartiles based on their HRR at admission. The overall mortality rates at 1 year and 30 days were 42.9% and 25.5%, respectively. A significant inverse association was observed between HRR quartiles and all-cause mortality (p

Background and purposePostinterventional rupture of intracranial aneurysms (IAs) remains a severe complication after flow diverter treatment. However, potential hemodynamic mechanisms underlying independent predictors for postinterventional rupture of IAs remain unclear. In this study, we employed arteriography-derived radiomic features to predict this complication.MethodsWe included 64 patients who underwent pipeline flow diversion for intracranial aneurysms, distinguishing between 16 patients who experienced postinterventional rupture and 48 who did not. We performed propensity score matching based on clinical and morphological factors to match these patients with 48 patients with postinterventional unruptured IAs at a 1:3 ratio. Postinterventional digital subtraction angiography were used to create five arteriography-derived perfusion parameter maps and then radiomics features were obtained from each map. Informative features were selected through the least absolute shrinkage and selection operator method with five-fold cross-validation. Subsequently, radiomics scores were formulated to predict the occurrence of postinterventional IA ruptures. Prediction performance was evaluated with the training and test datasets using area under the curve (AUC) and confusion matrix-derived metrics.ResultsOverall, 1,459 radiomics features were obtained, and six were selected. The resulting radiomics scores had high efficacy in distinguishing the postinterventional rupture group. The AUC and Youden index were 0.912 (95% confidence interval: 0.767–1.000) and 0.847 for the training dataset, respectively, and 0.938 (95% confidence interval, 0.806–1.000) and 0.800 for the testing dataset, respectively.ConclusionRadiomics scores generated using arteriography-derived radiomic features effectively predicted postinterventional IA ruptures and may aid in differentiating IAs at high risk of postinterventional rupture.

An attached cantilever scaffold, which mainly consists of a cantilever horizontal steel beam and a diagonal bar, is a new type of cantilever scaffold. The upper end of the diagonal bar is attached to an upper floor slab by a hinge, while the lower end is connected to a cantilever beam. Therefore, the position of the lower suspension point has a significant impact on the overall mechanical performance. However, current research on this topic is limited. Thus, in this study, we aim to optimize the mechanical behavior by changing the lower suspension point position. An optimization methodology based on the genetic algorithm is proposed. This methodology has been demonstrated to be efficient and accurate enough to determine the optimal lower suspension point position of a diagonal bar. The effects of different beam cross-sections, diagonal bar diameters, and upper suspension point positions are further investigated. The bearing capacity is shown to improve by more than 100% and 30% for hinged and rigidly connected cantilever beams when the proposed optimization methodology is adopted. The analysis in this study can serve as a reference for the optimal design of an attached cantilever scaffold and can provide a theoretical basis for developing related design software.

Abstract Since the first invention of the laser in 1960, direct lasing outside the fluorescence spectrum is deemed impossible owing to the “zero-gain” cross-section. However, when electron-phonon coupling meets laser oscillation, an energy modulation by the quantized phonon can tailor the electronic transitions, thus directly creating some unprecedented lasers with extended wavelengths by phonon engineering. Here, we demonstrate a broadband lasing (1000–1280 nm) in a Yb-doped La2CaB10O19 (Yb:LCB) crystal, far beyond its spontaneous fluorescence spectrum. Numerical calculations and in situ Raman verify that such a substantial laser emission is devoted to the multiphonon coupling to lattice vibrations of a dangling “quasi-free-oxygen” site, with the increasing phonon numbers step-by-step (n = 1–6). This new structural motif provides more alternative candidates with strong-coupling laser materials. Moreover, the quantitative relations between phonon density distribution and laser wavelength extension are discussed. These results give rise to the search for on-demand lasers in the darkness and pave a reliable guideline to study those intriguing electron-phonon-photon coupled systems for integrated photonic applications.

Abstract Background Breast cancer brain metastases (BCBM) are highly heterogenous with widely differing survival. The prognosis of the oligometastatic breast cancer (BC) patients with brain metastases (BM) has not been well studied. We aimed to investigate the prognosis of BCBM patients with limited intracranial and extracranial metastatic lesions. Methods Four hundred and forty-five BCBM patients treated between 1st January 2008 and 31st December 2018 at our institute were included. Clinical characteristics and treatment information were obtained from patient’s medical records. The updated breast Graded Prognostic Assessment (Breast GPA) was calculated. Results The median OS after diagnosis of BM were 15.9 months. Median OS for patients with GPA 0–1.0, 1.5–2, 2.5–3 and 3.5–4 were 6.9, 14.2, 21.8, 42.6 months respectively. The total number of intracranial and extracranial metastatic lesions, in addition to the Breast GPA, salvage local therapy and systemic therapy (anti-HER2 therapy, chemotherapy and endocrine therapy) were demonstrated to be associated with prognosis. One hundred and thirteen patients (25.4%) had 1–5 total metastatic lesions at BM diagnosis. Patients with 1–5 total metastatic lesions had a significantly longer median OS of 24.3 months compared to those with greater than 5 total metastatic lesions with a median OS of 12.2 months (P

Objectives: To investigate the health-related quality of life (HRQL) of long-term survivors of inoperable esophageal squamous cell carcinoma (ESCC) treated with definitive radiation therapy, the real-world trends in the use of advanced radiation techniques, and their impact on the survival outcomes of ESCC patients. Methods: In this multicenter retrospective observational study, the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed. A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up. The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon–Mann–Whitney test. Overall survival (OS) was estimated using the Kaplan–Meier method and the group differences were assessed by unstratified log-rank test. The Cox proportional hazards model with Efron's method of tie handling was used to calculate the risk factors for OS. Results: The data of a total of 3,308 patients were collected for this study, 248 were excluded because of missing data, and a final of 3,060 patients were included in the analysis. Most patients (2,901; 94.8%) received intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT)/tomotherapy (TOMO). The 5-year OS rate was 30%. Patients who received either two-dimensional radiotherapy (2DRT; HR, 2.43 [95% CI, 1.70–3.47]; P 80% patients did not experience weight loss. Nearly 80% patients found life very enjoyable or were fairly enjoying life. Conclusions: This large, multicenter retrospective study on ESCC patients who received definitive radiation therapy found that most ESCC survivors are satisfied with their quality of life. Most patients received advanced radiation technology. Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.

Abstract The application of drip irrigation has been paid more and more attention, but there was lack of systematic comparative analysis between drip irrigation and conventional border irrigation method for maize, currently. A 7-year field study from 2015 to 2021 evaluated the effects of drip irrigation (DI, 540 mm) or conventional border irrigation method (BI, 720 mm) on maize growth, water use efficiency (WUE) as well as profitability. The results showed the plant height, leaf area index, yield, WUE and economic benefit of maize with DI had significantly higher than BI. The dry matter translocation, the dry matter transfer efficiency and contribution of dry matter translocation to grain with DI showed significant increase of 27.44%, 13.97% and 7.85% compared to BI, respectively. In comparison to conventional border irrigation, the yield of drip irrigation increased by 14.39%, as well as WUE and irrigation water use efficiency (IWUE) increased by 53.77% and 57.89%. The net return and economic benefit of drip irrigation was 1998.87 and 756.58 USD$ hm−1 higher than that of BI. Drip irrigation increased net return and benefit/cost ratio by 60.90% and 22.88% compared with BI. These results demonstrate that the drip irrigation can effectively improve the growth, yield, WUE and economic benefit of maize in northwest China. Therefore, drip irrigation can be used for maize cultivation to increase crop yield and WUE in northwest China, which has cut down on irrigation water about 180 mm.

Thermomechanical fatigue (TMF) behaviour of 316L is investigated based on the internal stress and microstructural characterization at various cyclic stages. Results reveal that the cyclic stress response shows initial hardening followed by cyclic softening at a high strain amplitude, while presenting continuous cyclic hardening as the strain amplitude decreases. Among these, Out-of-phase TMF always shows cyclic softening irrespective of strain amplitude. It is important to note that the hardening of back stress and friction stress contribute to the initial and subsequent cyclic hardening. In contrast, the subsequent cyclic softening is mainly dominated by the reduced friction stress. It is observed that the proliferation of dislocations at grain boundaries and the enhanced dislocation interactions within the grains are primarily responsible for the hardening of back stress and friction stress, respectively. Specifically, the cyclic softening of friction stress is attributed to the annihilated dislocations as a result of cross-slip. It is also found from the hysteresis curves that the intensity of dynamic strain ageing is related to strain amplitude, loading history and phase angle, which correlates to the occurrence of cross-slip, the diffusion rate of the solute atom, the density of point defect and the mobility of vacancies. Finally, the effect of loading conditions on fracture behaviour is demonstrated from the point view of crack sources, secondary cracks, creep cavities and oxidation damage.

Abstract Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we report the efficacy and safety of combining toripalimab, lenvatinib, and gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine (1 g/m2) on Days 1 and 8 and oxaliplatin (85 mg/m2) Q3W for six cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing (WES) analysis. The primary endpoint was the objective response rate (ORR). Secondary outcomes included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DoR). As of July 1, 2022, the median follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients achieved partial response, and one achieved complete response. Patients (21/30) with DNA damage response (DDR)-related gene mutations showed a higher ORR, while patients (14/30) with tumor area positivity ≥1 (PD-L1 staining) showed a trend of high ORR, but without significant difference. The median OS, PFS, and DoR were 22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of patients experienced manageable grade ≥3 adverse events (AEs), commonly neutropenia (40.0%) and leukocytopenia (23.3%). In conclusion, toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC. A phase-III, multicenter, double-blinded, randomized study to validate our findings was approved by the National Medical Products Administration (NMPA, No. 2021LP01825). Trial registration Clinical trials: NCT03951597.

Mulching is a widely used agricultural water conservation measure in the semiarid regions of Northwest China. In order to explore the response process of different film mulching methods to soil microorganisms, we characterized the effect of different film mulching methods on soil microbial diversity and community structure characteristics in the root zone of drip-irrigated maize during the heading and maturity stages using high-throughput sequencing of 16SrDNA and ITS amplicons combined with bioinformatics analysis. Full mulching (FM) was contrasted to controls of no mulching (NM) and half-mulching (HM), yielding an order of microbial diversity, abundance, and evenness scores of HM > FM > NM. The HM and FM treatments reduced the relative abundance of Proteobacteria and Actinobacteria (the most abundant bacteria) in the bacterial community structure but increased that of Acidobacteria and Chloroflexi. In the fungal community structure, HM decreased the abundance of Sordariomycetes but increased that of Eurotiomycetes (the most abundant fungi). The abundance and community structure of bacteria were significantly correlated with soil temperature and those of fungi with pH. HM improved network complexity and competitive relationships among bacteria, while FM increased the relationship between fungal groups and the symbiosis of fungal communities. HM significantly increased maize yield (20.37% and 6.01% above NM and FM, respectively). In summary, full mulching was more favorable than no mulching for soil microbial diversity and community structure composition, but soil microbial diversity and yield responded better to half-mulching. These results provide a background for improving the yield of drip-irrigated maize and protecting the microbial ecosystems of farmland soils.

Summary: Background: Accurate tumour response prediction to targeted therapy allows for personalised conversion therapy for patients with unresectable colorectal cancer liver metastases (CRLM). In this study, we aimed to develop and validate a multi-modal deep learning model to predict the efficacy of bevacizumab in patients with initially unresectable CRLM using baseline PET/CT, clinical data, and colonoscopy biopsy specimens. Methods: In this multicentre cohort study, we retrospectively collected data of 307 patients with CRLM from the BECOME study (NCT01972490) (Zhongshan Hospital of Fudan University, Shanghai) and two independent Chinese cohorts (internal validation cohort from January 1, 2018 to December 31, 2018 at Zhongshan Hospital of Fudan University; external validation cohort from January 1, 2020 to December 31, 2020 at Zhongshan Hospital—Xiamen, Shanghai, and the First Hospital of Wenzhou Medical University, Wenzhou). The main inclusion criteria were that patients with CRLM had pre-treatment PET/CT images as well as colonoscopy specimens. After extracting PET/CT features with deep neural networks (DNN) and selecting related clinical factors using LASSO analysis, a random forest classifier was built as the Deep Radiomics Bevacizumab efficacy predicting model (DERBY). Furthermore, by combining histopathological biomarkers into DERBY, we established DERBY+. The performance of model was evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. Findings: DERBY achieved promising performance in predicting bevacizumab sensitivity with an AUC of 0.77 and 95% confidence interval (CI) [0.67–0.87]. After combining histopathological features, we developed DERBY+, which had more robust accuracy for predicting tumour response in external validation cohort (AUC 0.83 and 95% CI [0.75–0.92], sensitivity 80.4%, specificity 76.8%). DERBY+ also had prognostic value: the responders had longer progression-free survival (median progression-free survival: 9.6 vs 6.3 months, p = 0.002) and overall survival (median overall survival: 27.6 vs 18.5 months, p = 0.010) than non-responders. Interpretation: This multi-modal deep radiomics model, using PET/CT, clinical data and histopathological data, was able to identify patients with bevacizumab-sensitive CRLM, providing a favourable approach for precise patient treatment. To further validate and explore the clinical impact of this work, future prospective studies with larger patient cohorts are warranted. Funding: The National Natural Science Foundation of China; Fujian Provincial Health Commission Project; Xiamen Science and Technology Agency Program; Clinical Research Plan of SHDC; Shanghai Science and Technology Committee Project; Clinical Research Plan of SHDC; Zhejiang Provincial Natural Science Foundation of China; and National Science Foundation of Xiamen.

BackgroundLiver failure, including acute-on-chronic liver failure (ACLF), occurs mainly in young adults and is associated with high mortality and resource costs. The prognosis evaluation is a crucial part of the ACLF treatment process and should run through the entire diagnosis process. As a recently proposed novel algorithm, the quantitative difference (QD) algorithm holds promise for enhancing the prognosis evaluation of ACLF. ObjectiveThis study aims to examine whether the QD algorithm exhibits comparable or superior performance compared to the Model for End-Stage Liver Disease (MELD) in the context of prognosis evaluation. MethodsA total of 27 patients with ACLF were categorized into 2 groups based on their treatment preferences: the conventional treatment (n=12) and the double plasma molecular absorption system (DPMAS) with conventional treatment (n=15) groups. The prognosis evaluation was performed by the MELD and QD scoring systems. ResultsA significant reduction was observed in alanine aminotransferase (P=.02), aspartate aminotransferase (P1.69). A significant decrease in hemoglobin (P=.01), red blood cell count (P=.01), and total bilirubin (P=.02) was observed in the DPMAS group, but this decrease was not observed in QD (Lτ≤1.69). Furthermore, there was a significant association between MELD and QD values (P

Abstract Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy (trastuzumab), cancer stem cell (CSC)-like properties and multiple chemoresistance often concur and intersect in breast cancer, but molecular links that may serve as effective therapeutic targets remain largely unknown. Here, we identified the long noncoding RNA, LINC00589 as a key regulatory node for concurrent intervention of these processes in breast cancer cells in vitro and in vivo. We demonstrated that the expression of LINC00589 is clinically valuable as an independent prognostic factor for discriminating trastuzumab responders. Mechanistically, LINC00589 serves as a ceRNA platform that simultaneously sponges miR-100 and miR-452 and relieves their repression of tumor suppressors, including discs large homolog 5 (DLG5) and PR/SET domain 16 (PRDM16, a transcription suppressor of mucin4), thereby exerting multiple cancer inhibitory functions and counteracting drug resistance. Collectively, our results disclose two LINC00589-initiated ceRNA networks, the LINC00589-miR-100-DLG5 and LINC00589-miR-452-PRDM16- mucin4 axes, which regulate trastuzumab resistance, CSC-like properties and multiple chemoresistance of breast cancer, thus providing potential diagnostic and prognostic markers and therapeutic targets for HER2-positive breast cancer.

Web scraping is the process of extracting data from a website in an efficient and fast way. In such a scenario, python programming can offer useful set of methods that help web editors to improve the quality of the provided service. This scraper contains three steps 1) to understand the structure of web page, 2) design regular expression pattern and finally use that pattern to get certain data. In this paper, we also used Flask, Request, JSONify library to get the data, after processing, the data is transformed into the JSON form and ready for CSV with help of API. After generated all required regex patterns, the system uses these patterns as a set of rules, and with this, designed scraper tool works efficiently, and achieved outstanding results with help of support libraries to storing and extracting the news and web-based information. The proposed Web scraping tool eliminates the time and effort of manually collecting or copying data by automating the process. It is found that this designed scraper is easy and direct approach to extract the newspapers, websites, blogs, and images data.

Abstract Background Human apolipoprotein E (APOE) polymorphisms are attributable to the presence of three common alleles, namely, ε2, ε3, and ε4, which generate six genotypes, viz, E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4. APOE polymorphisms are associated with all types of tumors and cardiovascular diseases (CVD). However, the relationship between the type of APOE polymorphisms and tumorigenesis remains debatable. Therefore, we aimed to investigate the role of APOE polymorphisms on the tumor with or without CVD in southern China. Methods A total of 1438 participants were categorized into 4 groups: 409 patients with tumor, 369 patients with CVD, 338 patients with both tumor and CVD, and 322 controls. APOE polymorphisms were determined by genotyping assay. The factors influencing tumor patients with or without CVD were also analyzed by logistic regression analysis. Results The present study involved different types of solid tumors. Lung cancer was the most common cancer (20.2%, 151/747), followed by colorectal (17%, 127/747), esophageal (9.8%, 73/747), and liver (8.7%, 65/747) cancers. E3/E3 was the most frequent genotype, and ɛ3 was the greatest allele frequency in our study population. The frequencies of the E3/E3, E3/E4, E2/E3, E2/E4, E4/E4, and E2/E2 genotypes in tumor patients were 76.97% (575/747), 14.19% (106/747), 6.83% (51/747), 1.2% (9/747), 0.4% (3/747), and 0.4% (3/747), respectively. Tumor patients carrying ε3 with or without CVD showed higher levels of TG, TC, and LDL-C and lower levels of HDL-C compared to the controls carrying ε3. On the other hand, the tumor patients carrying ε4 with or without CVD showed higher levels of TG and LDL-C and lower levels of HDL-C (all P < 0.05). The frequency of APOE ε4 allele and the E3/E4 genotype was relatively greater in tumor or CVD patients (P < 0.001). In addition, ε4 allele acted as an independent risk factor for tumor patients group (P = 0.037, adjusted OR = 1.92, 95% CI 1.04–3.55) and tumor + CVD patients group (P = 0.012, adjusted OR = 2.53, 95% CI 1.22–5.23). Conclusions Individuals carrying ε4 are at a higher risk of tumor with or without CVD, and APOE polymorphisms affect the serum lipid profiles.

BackgroundPatients with untreated cerebral arteriovenous malformations (AVMs) are at risk of intracerebral hemorrhage. However, treatment to prevent AVM hemorrhage carries risks.ObjectiveThis study aimed to analyze the AVM nidus-related hemodynamic features and identify the risk factors for subsequent hemorrhage.MethodsWe retrospectively identified patients with untreated AVMs who were assessed at our institution between March 2010 and March 2021. Patients with ≥6 months of treatment-free and hemorrhage-free follow-up after diagnosed by digital subtraction angiography were included in subsequent examinations. The hemodynamic features were extracted from five contrast flow-related parameter maps. The Kaplan-Meier analyses and Cox proportional hazards regression models were used to find the potential risk factors for subsequent hemorrhage.ResultsOverall, 104 patients with a mean follow-up duration of 3.37 years (median, 2.42 years; range, 6–117 months) were included in study, and the annual risk of rupture was 3.7%. Previous rupture (hazard ratio [HR], 4.89; 95% confidence interval [CI], 1.16–20.72), deep AVM location (HR, 4.02; 95% CI, 1.01–15.99), higher cerebral blood volume (HR, 3.35; 95% CI, 1.15–9.74) in the nidus, and higher stasis index (HR, 1.54; 95% CI, 1.06–2.24) in the nidus were associated with subsequent hemorrhage in untreated AVMs.ConclusionHigher cerebral blood volume and stasis index in the nidus suggest increased blood inflow and stagnant blood drainage. The combination of these factors may cause subsequent hemorrhage of AVMs.

Electron–phonon‐coupling effect can generate the direct lasing beyond the fluorescence spectrum of the gain medium, but the laser efficiency is still low owing to weak multiphonon‐coupling intensity. Herein, associated with the three‐phonon‐assisted electron transitions beyond 1100 nm, the tunable laser generation from 1125 to 1155 nm and highly efficient continuous‐wave lasers at 1131 and 1140 nm in a ytterbium‐doped YCa4O(BO3)3 crystal are realized, by balancing the intracavity loss and phonon‐determined gain. The maximum output power reaches to 3.95 and 2.06 W at 1131 and 1140 nm, corresponding to a slope efficiency of 52.4% and 39.1%, respectively, which represents the highest efficiency in the solid‐state lasers in this spectral range. More impressively, this phonon‐assisted vibronic laser exhibits a wide‐spectral tunability and a good output power stability. Herein, a practical laser source in the underdeveloped spectral range is provided by the results, and they are helpful for the development of multiphonon‐assisted lasers beyond the inherent fluorescence spectrum.

Abstract Background Rapidly increasing health care costs are a widespread problem in the world. The cost-consciousness among Chinese medical staff is an important topic that needs further investigation. Our study aimed to focus on the cost-consciousness of Chinese medical staff and explore the factors related to their cost-consciousness. Differences regarding cost-consciousness between doctors and nurses were also reported. Methods Eight hospitals in Liaoning Province, China, were surveyed using a self-reporting questionnaire. A total of 1043 respondents, including 635 doctors and 408 nurses, participated in the study. A revised Chinese Cost-consciousness Scale was used to estimate cost-consciousness. Results The mean score of the Cost-consciousness Scale was 27.60 and 28.18 among doctors and nurses, respectively, and there were no significant differences in any personal characteristics. Most Chinese medical staff were aware of the treatment costs and considered cost control as their responsibility. Chinese doctors disliked adhering to guidelines more and preferred to remain independent in making or denying a treatment decision; thus, they like autonomously balancing the treatment and cost. Chinese nurses have similar attitudes, but nurses tended to deny costly services and interventions and were more sensitive to the health care costs by rationing decisions and uncertainty in their medical practice. Conclusion We reveal the attitudes regarding cost-consciousness among Chinese medical staff. Chinese medical staff was aware of their responsibility in health cost control. Chinese doctors and nurses had different tendencies with regard to health care cost containment. Our study highlights the importance of education and professional training on cost-consciousness.

Summary: Background: We assessed the safety and immunogenicity of a core–shell structured lipopolyplex (LPP) based COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults. Methods: We conducted an open-labeled, two-centered, and three-arm randomised phase 1 trial. Healthy adults, who had completed a two-dose of inactivated COVID-19 vaccine for more than six months, were enrolled and randomized to receive a booster dose of COVILO (inactivated vaccine) (n = 20) or SW-BIC-213-25μg (n = 20), or SW-BIC-213-45μg (n = 20). The primary study endpoint was adverse events within 30 days post-boosting. The secondary endpoint was the titers of binding antibodies and neutralizing antibodies against the wild-type (WT) of SARS-CoV-2 as well as variants of concern in serum. The exploratory endpoint was the cellular immune responses. This trial was registered with http://www.chictr.org.cn (ChiCTR2200060355). Findings: Between Jun 6 and Jun 22, 2022, 60 participants were enrolled and randomized to receive a booster dose of SW-BIC-213 (25 μg, n = 20, or 45 μg, n = 20) or COVILO (n = 20). The baseline demographic characteristics of the participants at enrollment were similar among the treatment groups. For the primary outcome, injection site pain and fever were more common in the SW-BIC-213 groups (25 μg and 45 μg). Grade 3 fever was reported in 25% (5/20) of participants in the SW-BIC-213-45μg group but was resolved within 48 h after onset. No fatal events or adverse events leading to study discontinuation were observed. For secondary and exploratory outcomes, SW-BIC-213 elicited higher and longer humoral and cellular immune responses than that in the COVILO group. Interpretation: SW-BIC-213, a core–shell structured lipopolyplex (LPP) based mRNA vaccine, was safe, tolerable, and immunogenic as a heterologous booster in healthy Chinese adults. Funding: Shanghai Municipal Government, the Science and Technology and Economic Commission of Shanghai Pudong New Area, and mRNA Innovation and Translation Center of Shanghai.

Abstract Background As a major reason for defensive medicine, the status and effect of “fear of malpractice” among Chinese medical staff is an important topic that needs to be studied. Our study investigated fear of malpractice among Chinese medical workers, assessed its association with burnout, and explored the mediating role of legal consciousness between these factors. Design A quantitative, cross-sectional study. Setting All respondents were investigated using a self-report questionnaire. Demographic characteristics and measurements including a fear of malpractice scale, and a burnout and legal consciousness scale were employed. The effect of fear of malpractice on burnout was examined by carrying out a binary regression analysis. A mediation model was used to test the mediating role of legal consciousness. Participants The study sample included 1031 doctors and nurses (297 male and 734 female; age = 36.3 ± 8.98). Results The average score of fear of malpractice was 20.97 ± 5.34. Respondents with higher levels of fear of malpractice were more prone to burnout ([OR] = 2.865; 95% CI 1.942–4.226). Legal consciousness partially and negatively mediated the effect of fear of malpractice on burnout. Conclusion High levels of fear of malpractice were found among Chinese medical workers, and this fear had a significant effect on burnout. Legal consciousness may be a resource that can alleviate burnout.

Abstract Background After traumatic brain injury (TBI), an acute, robust inflammatory cascade occurs that is characterized by the activation of resident cells such as microglia, the migration and recruitment of peripheral immune cells and the release of inflammatory mediators that induce secondary cell death and impede neurological recovery. In addition, neuroinflammation can alter blood–brain barrier (BBB) permeability. Controlling inflammatory responses is considered a promising therapeutic approach for TBI. Hydroxychloroquine (HCQ) has already been used clinically for decades, and it is still widely used to treat various autoimmune diseases. However, the effects of HCQ on inflammation and the potential mechanism after TBI remain to be defined. The aim of the current study was to elucidate whether HCQ could improve the neurological recovery of mice post-TBI by inhibiting the inflammatory response via the TLR4/NF-κB signaling pathway. Methods C57BL/6 mice were subjected to controlled cortical impact (CCI) and randomly divided into groups that received intraperitoneal HCQ or vehicle daily after TBI. TAK-242 (3.0 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h before TBI. Behavioral assessments were performed on days 1 and 3 post-TBI, and the gene expression levels of inflammatory cytokines were analyzed by qRT-PCR. The presence of infiltrated immune cells was examined by flow cytometry and immunostaining. In addition, BBB permeability, tight junction expression and brain edema were investigated. Results HCQ administration significantly ameliorated TBI-induced neurological deficits. HCQ alleviated neuroinflammation, the activation and accumulation of microglia and immune cell infiltration in the brain, attenuated BBB disruption and brain edema, and upregulated tight junction expression. Combined administration of HCQ and TAK-242 did not enhance the neuroprotective effects of HCQ. Conclusions HCQ reduced proinflammatory cytokine expression, and the underlying mechanism may involve suppressing the TLR4/NF-κB signaling pathway, suggesting that HCQ is a potential therapeutic agent for TBI treatment.

The bZIP (basic leucine zipper) proteins play crucial roles in various biological functions. Nitrogen (N) is an essential element for plant growth, especially in cucumber (Cucumis sativus) due to its shallow roots. However, the regulation of bZIP genes in cucumber nitrogen metabolism has not been studied yet. In this study, we identified a total of 72 bZIP genes (CsbZIPs) in the cucumber genome that could be classified into 13 groups. These genes were unevenly distributed on seven chromosomes, and synteny analysis showed that the CsbZIP genes were expanded in a segmentally duplicating manner. Furthermore, our genome-wide expression analysis suggested that CsbZIP genes had different patterns and that five CsbZIP genes were regulated by nitrogen treatment in both leaves and roots. Consistent with CsNPF, CsbZIP55 and CsbZIP65 were regulated by nitrogen treatment in leaves and roots. Moreover, the subcellular localization showed that CsbZIP55 and CsbZIP65 were specifically located in the nucleus, and the transcriptional activation assay showed that CsbZIP55 and CsbZIP65 have transcriptional activation activity. Additionally, in the CsbZIP55 and CsbZIP65 overexpression plants, most nitrogen-regulated CsNPF genes were downregulated. Taken together, our comprehensive analysis of the bZIP gene family lays a foundation for understanding the molecular and physiological functions of CsbZIPs.

A widely tunable phase-matched second harmonic generation (221–332 nm) covering almost the entire deep-UV spectral range is experimentally realized by angular engineering strategy of an additional periodic phase.

Abstract Background Cervical cancer (CC) is the fourth aggressive tumor affecting women worldwide. Circular RNA (circRNA) is enrolled in CC process. This study aims to unveil the profiles of circ_101119 (circCDK17) in cell proliferation, migration, invasion, apoptosis and glycolysis in CC. Methods The expression levels of circCDK17, microRNA-1294 (miR-1294) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). The protein expression levels of YWHAZ, recombinant glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) were determined by western blot. Cell proliferation, migratory and invasive abilities and apoptosis were illustrated by cell counting kit-8 (CCK-8) assay, transwell assay and flow cytometry analysis, respectively. Cell lactate production, glucose uptake and adenosine 5'-triphosphate (ATP) level were severally elucidated by lactate assay kit, glucose assay kit and ATP detection kit. Results CircCDK17 expression and the mRNA and protein expression levels of YWHAZ were dramatically upregulated, while miR-1294 expression was obviously downregulated in CC tissues or cells compared with control groups. CircCDK17 silencing suppressed cell proliferation, migration, invasion and glycolysis, and induced cell apoptosis in CC; however, miR-1294 inhibitor restrained these effects. Additionally, circCDK17 was a sponge of miR-1294 and miR-1294 bound to YWHAZ. Furthermore, circCDK17 knockdown inhibited tumor formation in vivo. Conclusion CircCDK17 knockdown repressed cell proliferation, migration, invasion and glycolysis, and promoted cell apoptosis via miR-1294/YWHAZ axis in CC. This finding provides a theoretical basis in studying circRNA-mediated therapy in CC.

An axially symmetric radial waveguide power divider, which utilizes a specific Cycloidal-Like tapered transition between a central coaxial launcher and a radial waveguide, is presented in this paper. In order to broad the operation band, the change of impedance of the coaxial to radial waveguide transition is investigated, and an analytic expression for the shape of the transition is obtained. A simple electromagnetic modeling for the stepped radial matching network is developed, and its characteristics are analyzed in detail using the circuit method. Eventually, a stepped-by-stepped design procedure for the power divider is established for the design of the radial waveguide power divider. A twenty-way radial waveguide divider is designed, fabricated, and measured to validate the proposed method. The measurements show that the return loss at the input port is better than 20 dB over almost the full ${Q}$ -band (33 to 48 GHz), while the amplitude/phase imbalance are within ±0.5 dB and ±3°, respectively. The simulated and measured results demonstrate a high degree of agreement.

ObjectivePediatric nonsaccular aneurysms are rare but challenging lesions; pipeline embolization devices (PEDs) are their potential treatment option. In this study, we aimed to evaluate the safety and efficacy of PEDs for treatment of these aneurysms.MethodsWe retrospectively selected pediatric patients with nonsaccular aneurysms treated using PEDs between June 2015 and July 2021 from our prospectively maintained database. For each patient, demographics, aneurysm characteristics, procedure details, and clinical and angiographic follow-up data were collected and summarized.ResultsThis study included 16 pediatric patients with 16 nonsaccular aneurysms treated with PEDs. A median clinical follow-up time of 1,376 days was achieved in 93.75% of the patients. The complication rate of the included patients was 25%, with two patients developing mass effect, one patient undergoing major ischemic stroke, and one patient experiencing stent foreshortening after the procedure. The complete occlusion rate of aneurysms without any neurologic sequelae was 93.33%, with a median angiographic follow-up period of 246 days. The mortality rate was 6.25%.ConclusionsThe use of PEDs to treat pediatric nonsaccular aneurysms is feasible, with a high rate of complete occlusion of the aneurysm and favorable follow-up outcomes.

The Yunkai Magmatic Arc (YKMA) is located southwest of the South China Block. It has experienced the amalgamation, splitting, and intracontinental orogeny caused by multistage tectonic thermal events. It is also a concentrated area of strong earthquakes in South China. On 12 October 2019, the Beiliu M5.2 earthquake occurred in the hinterland of the YKMA. To reveal the deep electrical structure of the YKMA and the seismogenic environment of the Beiliu earthquake, 101 high-quality data from the magnetotelluric (MT) survey points were acquired. The deep electrical structure images were obtained by three-dimensional electromagnetic inversion imaging. The results indicated that the deep part of the hinterland of the YKMA is characterized by a mushroom-shaped electrical structure composed of ultra-high resistance (R1, with a resistivity value exceeding 10,000 Ωm) and sub-high resistance (R2, with a resistivity value of about 1,000–10,000 Ωm) bodies. The epicenter of the Beiliu M5.2 earthquake was located in R1, close to the contact region between R1 and R2. There are broad low resistivity zones on the southeast and northwest sides of the YKMA. The low resistivity zones is considered to be correspond to the deep extension of the Wuchuan-Sihui and Hepu-Beiliu brittle-ductile shear zones, respectively. The brittle-ductile shearing of the boundary zones and the oblique upwelling of deep mantle-derived magma from the Leiqiong region are the main reasons for the activation of faults and the activity of moderate and strong earthquakes in the YKMA. In this geodynamic environment, local stress and strain accumulation easily occur in the brittle high resistivity body (R1). When the strain energy accumulation exceeded the threshold value that the rock could withstand, new fracture dislocations occurred in the weak region where R1 and R2 contact, which finally resulted in the 2019 Beiliu M5.2 earthquake.

ObjectiveGestational diabetes mellitus (GDM) is a common glucose metabolism disease occurs in pregnancy that affects both maternal and neonatal health. Recently, increasing studies have attached importance to the relationship between growth differentiation factor 15 (GDF-15) and GDM, but the results were inconclusive. Therefore, we conducted a meta-analysis to examine the association between GDF-15 and GDM.Materials and methodsA systematical search was performed in Gene Expression Omnibus (GEO), PubMed and Google Scholar till Oct 27, 2022. We first calculated the mean and standard deviation of GDF-15 expression levels from the included eligible datasets and articles. Then, a meta-analysis was conducted to depict the difference in GDF-15 mRNA or GDF-15 protein expression between case and control groups by using conservative random effect model. Moreover, the potential publication bias was checked with the aid of Begg’s test and Egger’s test. Finally, sensitivity analyses were performed by changing the inclusion criteria.ResultsIn summary, 12 GEO datasets and 5 articles were enrolled in our study, including 789 GDM patients and 1202 non-GDM pregnant women. It was found that the expression levels of GDF-15 mRNA and GDF-15 protein in late pregnancy were significantly higher in GDM patients compared with non-GDM pregnant women, with the standard mean difference (SMD) and 95% confidence interval (95% CI) of 0.48 (0.14, 0.83) and 0.82 (0.32-1.33), respectively. Meanwhile, a slightly weakened association between GDF-15 protein levels and GDM was also observed in the middle pregnancy, with SMD (95% CI) of 0.53 (0.04-1.02).ConclusionIn all, our results suggested that the expression levels of GDF-15 were significantly higher in GDM patients compared with non-GDM pregnant women, especially in the late pregnancy.

Background Insufficient low temperatures in winter and soil residues caused by paclobutrazol (PBZ) application pose a considerable challenge for mango floral induction (FI). Gibberellin inhibitors SPD (compound of mepiquat chloride, prohexadione-calcium and uniconazole) had a significant influence on enhancing the flowering rate and yield of mango for two consecutive years (2020–2021). Researchers have indicated that FI is regulated at the metabolic level; however, little is known about the metabolic changes during FI in response to SPD treatment. Methods Here, ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)-based widely targeted metabolomic analysis was carried out to assess the metabolic differences in the mango stem apex during different stage of mango FI (30, 80, 100 days after SPD/water treatment). Results A total of 582 compounds were annotated and 372 metabolites showed two-fold differences in abundance (variable importance in projection, VIP ≥ 1 and fold change, FC≥ 2 or≤ 0.5) between buds at 30, 80, 100 days after SPD/water treatment or between buds under different treatment. Lipids, phenolic acids, amino acids, carbohydrates, and vitamins were among metabolites showing significant differences over time after SPD treatment. Here, 18 out of 20 lipids, including the lysophosphatidylethanolamine (12, LPE), lysophosphatidylcholine (7, LPC), and free fatty acids (1, FA), were significantly upregulated from 80 to 100 days after SPD treatment comared to water treatment. Meanwhile, the dormancy release of mango buds from 80 to 100 days after SPD treatment was accompanied by the accumulation of proline, ascorbic acid, carbohydrates, and tannins. In addition, metabolites, such as L-homocysteine, L-histidine, and L-homomethionine, showed more than a ten-fold difference in relative abundance from 30 to 100 days after SPD treatment, however, there were no significant changes after water treatment. The present study reveals novel metabolites involved in mango FI in response to SPD, which would provide a theoretical basis for utilizing SPD to induce mango flowering.

Introduction: Lenvatinib plus an anti–PD-1 antibody has shown promising anti-tumor effects in patients with advanced hepatocellular carcinoma (HCC), but with clinical benefit limited to a subset of patients. We developed and validated a radiomic-based model to predict objective response to this combination therapy in advanced HCC patients. Methods: Patients (N = 170) who received first-line combination therapy with lenvatinib plus an anti–PD-1 antibody were retrospectively enrolled from 9 Chinese centers; 124 and 46 into the training and validation cohorts, respectively. Radiomic features were extracted from pretreatment contrast-enhanced MRI. After feature selection, clinicopathologic, radiomic, and clinicopathologic-radiomic models were built using a neural network. The performance of models, incremental predictive value of radiomic features compared with clinicopathologic features and relationship between radiomic features and survivals were assessed. Results: The clinicopathologic model modestly predicted objective response with an AUC of 0.748 (95% CI: 0.656–0.840) and 0.702 (95% CI: 0.547–0.884) in the training and validation cohorts, respectively. The radiomic model predicted response with an AUC of 0.886 (95% CI: 0.815–0.957) and 0.820 (95% CI: 0.648–0.984), respectively, with good calibration and clinical utility. The incremental predictive value of radiomic features to clinicopathologic features was confirmed with a net reclassification index of 47.9% (P < 0.001) and 41.5% (P = 0.025) in the training and validation cohorts, respectively. Furthermore, radiomic features were associated with overall survival and progression-free survival both in the training and validation cohorts, but modified albumin-bilirubin grade and neutrophil-to-lymphocyte ratio were not. Conclusion: Radiomic features extracted from pretreatment MRI can predict individualized objective response to combination therapy with lenvatinib plus an anti–PD-1 antibody in patients with unresectable or advanced HCC, and provide incremental predictive value over clinicopathologic features, and are associated with overall survival and progression-free survival after initiation of this combination regimen.

Objective To explore the association between dynamic changes in red blood cell distribution width to platelet count ratio (RPR) during hospitalisation and short-term mortality in patients with sepsis.Design A retrospective cohort study using propensity score matching.Setting Intensive care units (ICUs) of Beth Israel Deaconess Medical Center.Participants A total of 8731 adult patients with sepsis were included in the study. The patients were identified from the ICU of the Medical Information Mart for Intensive Care database. The observed group included patients who experienced an increase in RPR of more than 30% during the first week of ICU admission, whereas the control group included the rest.Main outcome and measure Using propensity score matching, a matched control group was created. The primary outcome was 28-day mortality, and the length of hospital stay and in-hospital mortality were the secondary outcomes.Results The difference was evident in 28-day mortality between the two groups (85.8% vs 74.5%, p

Evidence theory is widely used to deal with the fusion of uncertain information, but the fusion of conflicting evidence remains an open question. To solve the problem of conflicting evidence fusion in single target recognition, we proposed a novel evidence combination method based on an improved pignistic probability function. Firstly, the improved pignistic probability function could redistribute the probability of multi-subset proposition according to the weight of single subset propositions in a basic probability assignment (BPA), which reduces the computational complexity and information loss in the conversion process. The combination of the Manhattan distance and evidence angle measurements is proposed to extract evidence certainty and obtain mutual support information between each piece of evidence; then, entropy is used to calculate the uncertainty of the evidence and the weighted average method is used to correct and update the original evidence. Finally, the Dempster combination rule is used to fuse the updated evidence. Verified by the analysis results of single-subset proposition and multi-subset proposition highly conflicting evidence examples, compared to the Jousselme distance method, the Lance distance and reliability entropy combination method, and the Jousselme distance and uncertainty measure combination method, our approach achieved better convergence and the average accuracy was improved by 0.51% and 2.43%.

BackgroundFew studies have examined the association between reproductive history and the multidimensional health of older adults with more diverse reproductive histories and poorer health status in rural China. The purpose of this study is to explore the effect of parity, sex ratio of children and late childbearing on multidimensional health and its gender differences.MethodsThe analytical sample consisted of 3,377 older adults in rural China who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2018. Linear regression models were applied to estimate the relationship between reproductive history and multidimensional health, with separate models for each indicator of health outcomes.ResultsOlder adults in rural areas with greater parity were more likely to have better cognitive function (β = 0.409, 95% CI: 0.255–0.563), fewer Activities of Daily Living (ADL) limitations (β = −0.085, 95% CI: −0.137 to −0.034) and symptoms of depression (β = −0.396, 95% CI: −0.577 to −0.216). The social mechanism of intergenerational support from children later in life partly explained the positive effect of parity. Late childbearing had negative effects on cognitive function (β = −1.220, 95% CI: −1.895 to −0.545), ADL (β = 0.253, 95% CI: 0.028–0.478) and symptoms of depression (β = 1.025, 95% CI: 0.237–1.812). Women were more likely to be influenced by the positive effect of parity; the association between late childbearing and health was only significant in the male group.ConclusionsParity and late childbearing are associated with cognitive function, activities of daily living, and symptoms of depression in the older adults in rural China. Older adults with more children might be in better health, and this finding is especially significant in women. However, late childbearing had a negative effect on multidimensional health, especially for men. The social mechanism and gender differences between reproductive history and health need to be further explored.

The design theory of ceramic waveguide filter was introduced, and then the combination structure of coupling through slot with shallow or deep coupling blind hole was designed, which could meet the requirements of positive and negative coupling bandwidth.By adjusting the cross coupling between 3～6 cavities, the symmetry of the filter transmis-sion curve was improved, and the near and far end band suppression of the filter was realized.Finally, a six-cavity ce-ramic waveguide filter for 5G base station was designed.In the process of optimizing the filter, the influences of the rela-tive position offset of the cross-coupling through slot and the length of the cross-coupling through slot on the transmis-sion zero position, the near end and far end out of band suppression characteristics of the filter were discussed in detail, and the relevant change rules were given.The performance indexes of the optimized filter were as follows, center fre-quency was 3.5 GHz, working bandwidth was 200 MHz, insertion loss ≤ 1.2 dB, return loss ≥ 17 dB, near end out of band rejection ≥ 25 dB, far end out of band rejection ≥ 51 dB.According to the structural parameters of the simulation model, the performance test results of the samples are in good agreement with the simulation results.