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Abstract Accurately quantifying agricultural water use is essential for protecting agricultural systems from the risk of water scarcity and promoting sustainable water management. While previous studies have innovatively provided spatially explicit analyses or datasets, they tend to have relatively coarse resolution (~8.3 km), and inadequately considered precise localization parameters. Here, we produced annual blue and green water use for 15 main crops with a resolution of 1 km for the years 1991–2019 in China. Firstly, we estimated the yearly crop blue and green water use at the site scale by incorporating more localized input parameters using a dynamic water balance model. Then, the random forest model was combined with site-scale simulation results to generate spatial predictions of blue and green water for each crop from 1991 to 2019. The resulting maps showed a high correlation with locally observed values at field stations (R2 = 0.95), statistics (R2 = 0.77), and exhibited some strengths compared with existing datasets that covered various scales. This dataset can play a key role in devising sustainable water management strategies.

Abstract The Huang-Huai-Hai region accounts for 80% of China’s wheat production, leading to severe groundwater depletion and substantial environmental impacts. Here we present an optimization framework for wheat redistribution to reduce both water requirements and environmental impacts without compromising production. Our results show that environmental footprints can be reduced—blue water by 16%, grey water by 21%, and greenhouse gas emissions by 18%—while enhancing resource use efficiency, with irrigation water productivity improving by 21% and nitrogen use efficiency by 11%. Maintaining current production levels is achievable with these adjustments. Furthermore, allowing a 17–18% decrease in wheat production could result in a groundwater depth increase of 9.03–9.38 m by 2030, ensuring sustainable groundwater use. In regions experiencing groundwater depletion, blue water, grey water and greenhouse gas emissions could decrease by over one third. Our findings offer an alternative strategy for promoting sustainable agriculture in regions facing groundwater depletion worldwide.

Background and aimsThis study aimed to investigate the effect of iron overload on acetylcholinesterase activity in the frontal lobe tissue of rats with minimal hepatic encephalopathy (MHE) and its relation to cognitive ability. By elucidating the potential mechanisms of cognitive impairment, this study may offer insights into novel therapeutic targets for MHE.Materials and methodsTwelve Sprague-Dawley rats were purchased and randomly assigned to either the experimental or control group with six rats in each group. Following the induction of MHE, the Morris Water Maze (MWM) was utilized to assess spatial orientation and memory capacity. Subsequently, Magnetic Resonance Imaging (MRI) scans were performed to capture Quantitative Susceptibility Mapping (QSM) images of all rats' heads.ResultsCompared to the control group rats, the MHE model rats showed significantly reduced learning and memory capabilities as well as spatial orientation abilities (P < 0.05). Furthermore, the susceptibility values in the frontal lobe tissue of MHE model rats was significantly higher than that of the control group rats (P < 0.05), and the corresponding BuChE activity in the frontal lobe extract of model rats was significantly increased while BuChE activity in the peripheral blood serum was significantly decreased compared to the control group rats (P < 0.05). Meanwhile, our findings indicate a significant positive correlation between latency period and BuChE activity with susceptibility values in the MHE group.ConclusionThe changes in BuChE activity in frontal lobe extract may be related to changes in spatial orientation and behavioral changes in MHE, and iron overload in the frontal lobe tissue may regulate changes in BuChE activity, BuChE levels appear to be iron-dependent.

As a kind of protective material, Diamond-Like Carbon (DLC) film can effectively improve the mechanical and tribological properties of the substrate surface. In DLC family, tetrahedral amorphous carbon (ta-C) with ultra-high hardness and excellent protective properties has been widely concerned in the field of hard protective materials. It is well known that the structure and properties of ta-C are strongly dependent on carbon plasma characteristics in the plasma environment. Therefore, it is extremely crucial to obtain the optimal process window of ta-C described by plasma micro-parameters with general significance. This paper proposed the Langmuir probe was used to diagnose the carbon plasma of the afterglow generated by arc evaporation, aiming to investigate the characteristics of carbon plasma and sheath. The effect of ion energy and ion flux adjusted by the pulse bias voltage and arc current on the sp3 hybrid bonds and hardness of DLC films was studied, aiming to find out which conditions satisfied the formation of ta-C. The results showed the microstructure and properties of DLC films were co-adjusted by ion energy and ion flux. When the carbon ions met the appropriate ion energy range (50–300 eV) and low ion flux (

Objective: Physical activity-related interventions alleviate the severity of erectile dysfunction (ED), but it is unknown whether the recommended volume of physical activity (PA) or a higher level of physical activity reduces the likelihood of ED in adult males. We aimed to evaluate the association between the recommended volume of PA and ED among US male adults. Design: A nationally representative cross-sectional survey. Setting: National Health and Nutrition Examination Survey 2001–2004. Participants: A total of 2509 men aged ≥20 years were enrolled. Primary and secondary outcome measures: ED and PA were assessed by a standardised self-report questionnaire. Weighted logistic regression analysis and spline fitting were used to assess the relationship between PA volume and the odds of ED. Results: Among 2509 US adult males, the mean (standard error) age was 43.7 (0.46) years. A total of 61.1 % of men reached the recommended volume of aerobic PA. Compared with participants not meeting the PA guidelines, individuals who had recommended aerobic activities demonstrated a 34 % reduction in the odds of having ED (OR 0.66, 95 % CI 0.48–0.90; p = 0.011). Notably, according to the restricted cubic spline, we revealed a dose‒response pattern between PA volume and reduced odds of ED, even when exceeding the recommended PA levels. When compared to males with moderate-equivalent PA of less than 150 min/week, the odds of ED in those with moderate-equivalent PA levels of 150–300 min/week and >300 min/week decreased by 22 % and 39 %, respectively. Compared with participants who did not meet the PA guidelines, the multivariable-adjusted ORs (95 % CIs) of ED associated with adequate PA volumes were 0.37 (0.22–0.61) among non-smokers and 0.85 (0.57–1.25) among current smokers (p for interaction = 0.023). Conclusions and Relevance: Our findings supported the benefit of meeting the guideline-recommended PA equivalents or higher volumes for ED prevention. However, PA-related benefit might be significantly diminished by smoking.

Nitrogen (N) fertilizer is essential for agricultural production as it is the main nutrient driving crop growth. However, in China, only one-third of applied N fertilizer is effectively absorbed by crops, while the rest leads to significant environmental impacts. In this study, we introduced a nitrogen threshold boundary (NTB) approach to establish different thresholds for N use efficiency (NUE) and N surplus without affecting crop yield. We also developed an integrated assessment framework to systematically evaluate the potential for improving N utilization and reducing environmental impacts in the production of grain crops (rice, wheat, maize, and soybeans) and cash crops (tea, fruits, and vegetables) at the county level in Fujian Province. Three N management strategies were evaluated: a scenario with reduced N surplus (S1), a scenario with increased NUE (S2), and a combined scenario that simultaneously reduces N surplus and increases NUE (S3). The predictions indicate that, under the aforementioned scenarios, there will be a decrease of 66%, 58%, and 71% in N application without affecting crop yields, respectively. Correspondingly, N surplus will decrease by 65%, 56%, and 67%, while greenhouse gas (GHG) emissions will decrease by 54%, 48%, and 57%. In addition, NUE will increase by 23%, 17% and 25%, respectively. It is notable that scenario S3 demonstrated the greatest potential for improvement. For cash crops, N application will decrease by 65–78%, NUE will increase by 13–21%, N surplus will decrease by 63–74%, and GHG emissions will reduce by 66–78%. In contrast, for grain crops, N application will decrease by 27–38%, NUE will increase by 9–13%, N surplus will decrease by 26–37%, and GHG emissions will reduce by 24–28%. Overall, the potential for improvement is greater for cash crops compared to grain crops. The application of the assessment framework in this study demonstrates its effectiveness as a valuable tool for promoting green and sustainable development in conventional agricultural regions.

Sunitinib, the first-line targeted therapy for metastatic clear cell renal cell carcinoma (ccRCC), faces a significant challenge as most patients develop acquired resistance. Integrated genomic and proteomic analyses identified PYGL as a novel therapeutic target for ccRCC. PYGL knockdown inhibited cell proliferation, cloning capacity, migration, invasion, and tumorigenesis in ccRCC cell lines. PYGL expression was increased in sunitinib-resistant ccRCC cell lines, and CP-91149 targeting the PYGL could restore drug sensitivity in these cell lines. Moreover, chromatin immune-precipitation assays revealed that PYGL upregulation is induced by the transcription factor, hypoxia-inducible factor 1α. Overall, PYGL was identified as a novel diagnostic biomarker by combining genomic and proteomic approaches in ccRCC, and sunitinib resistance to ccRCC may be overcome by targeting PYGL.

Abstract Background Increasing evidence suggests that immunotherapy, especially immune checkpoint inhibitors (ICIs), has the potential to facilitate long-term survival in various cancer besides prostate cancer. Emerging evidence indicated that pyroptosis, an immunogenic form of cell death, could trigger an anti-tumor immune microenvironment and enhance the effectiveness of immunotherapy. Nevertheless, the mechanism underlying the regulation of pyroptosis signaling in prostate cancer remains unclear. Methods The differential expression of human E3 ligases in prostate cancer was integratedly analyzed from five independent public datasets. Moreover, the immunohistochemistry analysis of a tissue microarray derived from prostate cancer patients confirmed the results from the bioinformatic analysis. Furthermore, prostate cancer cell lines were evaluated via the next-generation RNA sequencing to assess transcriptomic profile upon CDC20 depletion. Next, qRT-PCR, Western blotting, cycloheximide assay, immunoprecipitation, and ubiquitination assay were employed to explore the correlation and interaction between CDC20 and GSDME. Both immune-deficient and immune-competent murine models were utilized to examine the anti-tumor efficacy of CDC20 inhibition with or without the anti-PD1 antibodies, respectively. To analyze the immune microenvironment of the xenografts, the tumor tissues were examined by immunohistochemistry and flow cytometry. Results The analysis of multiple prostate cancer cohorts suggested that CDC20 was the most significantly over-expressed E3 ligase. In addition, CDC20 exerted a negative regulatory effect on the pyroptosis pathway by targeting GSDME for ubiquitination-mediated proteolysis in a degron-dependent manner. Knockdown of CDC20 leads to increased GSDME abundance and a transition from apoptosis to pyroptosis in response to death signals. Furthermore, in our syngeneic murine models, we found that depletion of CDC20 significantly enhances the anti-tumor immunity by promoting the infiltration of CD8+ T lymphocytes dependent on the existence of GSDME, as well as reducing myeloid immune cells. More importantly, Apcin, a small molecular inhibitor that targets CDC20, exhibited synergistic effects with anti-PD1-based immunotherapy in murine models of prostate cancer. Conclusions Overall, these findings provide new insights into the upstream regulation of GSDME-mediated pyroptosis by CDC20, which specifically interacts with GSDME and facilitates its ubiquitination in a degron-dependent manner. Importantly, our data highlight novel molecular pathways for targeting cellular pyroptosis and enhancing the effectiveness of anti-PD1-based immunotherapy.

Background: The purpose of this study is to assess the effects of high serum estradiol (E2) levels on reproductive outcomes as well as to compare pregnancy outcomes of duration of vaginal E2 administration after the day of progesterone (P4) initiation in frozen-thawed embryo transfer (FET) hormonal replacement cycles. Methods: We performed a retrospective cohort study on 627 patients ≤40 years old that underwent a FET cycle. The patients were grouped based on the serum E2 level on the P4 initiation day as follows: E2 ≤600 pg/mL (n = 471); E2 ≥900 pg/mL (n = 151); the group of E2 600–900 pg/mL (n = 5) was not included in the analysis due to too small sample size. A total of 151 patients with E2 ≥900 pg/mL were grouped based on the duration of vaginal E2 administration after the day of P4 initiation: withdrawal before transfer (n = 53); constant administration (n = 98). Results: There was no significant difference in implantation rate, clinical pregnancy rate, spontaneous abortion rate, premature birth rate, live birth rate and multiple pregnancy rate between the two E2 level groups. The logistic regression analysis demonstrated that age was the only variable that significantly affected clinical pregnancy rate and live birth rate. There were no fetal malformations in either group. Baseline characteristics of patients with different duration of vaginal E2 administration were similar. The pregnancy outcomes showed no significant difference between the withdrawal before transfer group and the constant administration group. Conclusions: In FET cycles, high E2 level on the embryo transfer day did not reduce the clinical pregnancy and live birth rates. In addition, vaginal E2 could be stopped on the embryo transfer day since we found no benefit in continuing E2 until the pregnancy testing day.

BackgroundIn breast cancer, in the era of precision cancer therapy, different patterns of genetic mutations dictate different treatments options. However, it is not clear whether the genetic profiling of breast cancer patients undergoing breast-conserving surgery is related to the adverse reactions caused by radiotherapy.MethodsWe collected formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 54 breast cancer patients treated with radiation after breast-conserving surgery and identified comprehensive molecular information in hundreds of cancer-associated genes by FoundationOne CDx (F1CDx), a next-generation sequencing (NGS)-based assay.ResultsAmong our cohort of 54 breast cancer patients, we found high-frequency mutations in cancer-related genes such as TP53 (56%), RAD21 (39%), PIK3CA (35%), ERBB2 (24%), and MYC (22%). Strikingly, we detected that the WNT pathway appears to be a signaling pathway with specific high-frequency mutations in the HER2 subtype. We also compared the mutation frequencies of the two groups of patients with and without cutaneous radiation injury (CRI) after radiotherapy and found that the mutation frequencies of two genes, FGFR1 and KLHL6, were significantly higher in patients with CRI : No subgroup than in those with CRI : Yes.ConclusionDifferent breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.

Considering the environmental protection and infrastructure needs for solid waste recycling and improvement of soil engineering properties, a fiber–gangue composite soil consolidation material is proposed to improve the mechanical properties of expansive soils and the workability to resist freeze–thaw (FT) cycling effects. The unconfined compressive strength (UCS) of the expansive soil was measured at varying FT cycles. Then, thermal–mechanical field simulation using Advanced Simulation for Engineering and Sciences (ABAQUS) numerical simulation software was conducted to analyze the stress–strain behavior of the model and compared with the UCS test results obtained during the laboratory test. After that, the microstructural characteristics of modified soil systems after FT cycles were carried out using scanning electron microscope (SEM) mapping to obtain the reinforcement mechanism. The investigation results indicate that the UCS of the modified expansive soil (MES) not only increased after experiencing 12 FT cycles, but also demonstrated a 20.1% reduction in UCS inhibition by the improver compared to plain-expansive soil (PES). Therefore the addition of fiber–coal gangue composite effectively amends the effect of FT cycles on the UCS of expansive soil. UCS test results suggest that a reasonable 9 mm long 0.3% fiber and 20% coal gangue ratio of the composite modifier is advantageous to the soil’s mechanical properties. ABAQUS numerical simulations results the UCS strength of the specimens deteriorates gradually with the increase in the number of FT cycles, which is in agreement with the laboratory measured values. From the SEM observation, the PES samples were loose and the pores increased, while the coal gangue and the fibers of the incorporated expansive soil particles formed links between them, the structure was tight, the pores and cracks were reduced, and the compactness was improved.

Background and aims: Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. Materials and methods: Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. Results: MHE rats showed impaired spatial memory and exploratory behavior (P

Abstract Background Currently, due to synergy enhancement of anti‐tumor effects and potent stimulation of abscopal effects, combination therapy with irradiation and programmed cell death protein 1/programmed death‐ligand 1 (PD‐1/PD‐L1) immune checkpoint inhibition (immuno‐radiotherapy, iRT) has revolutionized the therapeutic guidelines. It has been demonstrated that tumor‐draining lymph nodes (TDLN) are essential for effective antitumor immunity induced by radiotherapy, immunotherapy, or iRT. Given that the function of TDLN in iRT remains unclear, this study aimed to investigate the function and mechanism of TDLN in iRT‐induced abscopal effects. Methods The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN. The flow cytometry, multiple immunofluorescence analysis, and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment. Additionally, we tempted to interrogate the possible mechanisms via RNA‐sequencing of tumor‐infiltrating lymphocytes and TDLN. Results TDLN deficiency impaired the control of tumor growth by monotherapy. Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT‐stimulated anti‐tumor and abscopal effects. Furthermore, in the absence of TDLN, the infiltration of CD45+ and CD8+ T cells was substantially reduced in both primary and abscopal tumors, and the anti‐tumor function of CD8+ T cells was attenuated as well. Additionally, the polarization of tumor‐associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN. RNA‐sequencing data indicated that impaired infiltration and anti‐tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment. Conclusions TDLN play a critical role in iRT by promoting the infiltration of CD8+ T cells and maintaining the M1/M2 macrophage ratio.

Background BANF1 is well known as a natural opponent of cyclic GMP-AMP synthase (cGAS) activity on genomic self-DNA. However, the roles of BANF1 in tumor immunity remain unclear. Here, we investigate the possible impact of BANF1 on antitumor immunity and response to immunotherapy.Methods The Cancer Genome Atlas public data were analyzed to evaluate the relevance of the expression of BANF1, patients’ survival and immune cell infiltration. We monitored tumor growth and explored the antitumor efficacy of targeting tumor-intrinsic BANF1 in combination with anti-programmed cell death protein-1 (PD-1) in MC38 or B16F10 tumor models in both immunocompetent and immunodeficient mice. Flow cytometry, immunofluorescence and T cells depletion experiments were used to validate the role of BANF1 in tumor immune microenvironment reprogramming. RNA sequencing was then used to interrogate the mechanisms how BANF1 regulated antitumor immunity.Results We show that upregulated expression of BANF1 in tumor tissues is significantly associated with poor survival and is negatively correlated with immune cell infiltration. Deficiency of BANF1 in tumor cells markedly antagonizes tumor growth in immunocompetent but not immunocompromised mice, and enhances the response to immunotherapy in murine models of melanoma and colon cancer. In the immunotherapy clinical cohort, patients with high BANF1 expression had a worse prognosis. Mechanistically, BANF1 knockout activates antitumor immune responses mediated by cGAS-synthase-stimulator of interferon genes (cGAS-STING) pathway, resulting in an immune-activating tumor microenvironment including increased CD8+ T cell infiltration and decreased myeloid-derived suppressor cell enrichment.Conclusions BANF1 is a key regulator of antitumor immunity mediated by cGAS-STING pathway. Therefore, our study provides a rational that targeting BANF1 is a potent strategy for enhancing immunotherapy for cancer with BANF1 upregulation.

Abstract Objectives Cystic echinococcosis (CE) is a neglected parasitic zoonotic disease caused by the larval stage of the tapeworm Echinococcus granulosus (E. granulosus). This study aimed to understand the clinical characteristics of human CE in Ningxia Hui Autonomous Region (NHAR) located in northwest China and to investigate the antibody profiles against the recombinant E. granulosus antigen P29 (rEg.P29) in plasma of CE patients. Methods A total of 37 human CE patients, along with 37 healthy donors enrolled in this study and demographic and clinical data were analyzed, including age, gender, laboratory data, symptoms, and cysts description. Plasma levels of cytokines, total IgG, and total IgE were determined by sandwich ELISA kits. Specific antibodies against rEg.P29 and hydatid cyst fluid (HCF) were assessed by indirect ELISA. Results The results revealed that females have a higher percentage of CE patients than males. The incidence of CE reached a peak in the 41–50 years-old group. The liver was the most frequent location, accounting for 91.9%. Based on the CT images, cysts of 34 patients who had liver involvement, were classified as 1 (2.9%) CE1, 12 (35.3%) CE2, 5 (14.7%) CE3a, 1 (2.9%) CE3b, and 15 (44.2%) CE5. Twenty-nine (78.4%) patients had a single cyst and 8 (21.6%) had at least two cysts. The most frequently reported symptom was upper abdominal pain. The plasma level of IL-6 and total IgE were significantly increased in CE patients compared with healthy donors. Additionally, IgG response to rEg.P29 in CE patients was significantly higher than in healthy donors, and the dominant IgG subclass was IgG4. Further analysis of different patient groups revealed that rEg.P29-specific IgG and IgG4 were only elevated in CE patients with CE2 type cysts. Conclusions This study systematically investigated the clinical characteristics of patients with CE and may provide a reference basis for the diagnosis and treatment of CE in NHAR. Furthermore, tests of specific IgG and IgG4 against rEg.P29 can be used as an assisted method for imaging techniques to identify cystic activity and determine the best therapeutic approach for CE.

Abstract Background The giant panda (Ailuropoda melanoleuca) is a threatened species endemic to China. Alopecia, characterized by thinning and broken hair, mostly occurs in breeding males. Alopecia significantly affects the health and public image of the giant panda and the cause of alopecia is unclear. Results Here, we researched gene expression profiles of four alopecia giant pandas and seven healthy giant pandas. All pandas were approximately ten years old and their blood samples collected during the breeding season. A total of 458 up-regulated DEGs and 211 down-regulated DEGs were identified. KEGG pathway enrichment identified that upregulated genes were enriched in the Notch signaling pathway and downregulated genes were enriched in ribosome, oxidative phosphorylation, and thermogenesis pathways. We obtained 28 hair growth-related DEGs, and identified three hub genes NOTCH1, SMAD3, and TGFB1 in PPI analysis. Five hair growth-related signaling pathways were identified with abnormal expression, these were Notch, Wnt, TGF-β, Mapk, and PI3K-Akt. The overexpression of NOTCH1 delays inner root sheath differentiation and results in hair shaft abnormalities. The delayed hair regression was associated with a significant decrease in the expression levels of TGFB1. Conclusions Our data confirmed the abnormal expression of several hair-related genes and pathways and identified alopecia candidate genes in the giant panda. Results of this study provide theoretical basis for the establishment of prevention and treatment strategies for giant pandas with alopecia.

BackgroundPostoperative radiotherapy (PORT) is a therapeutic strategy for patients with non-small cell lung cancer (NSCLC). Nevertheless, some studies suggesting PORT does not improve overall survival (OS) including Lung ART phase III trial. The role of PORT and high-risk groups need to be confirmed.MethodsPatients from the Surveillance, Epidemiology, and End Results program (SEER) from 2004 to 2015 were eligible. Aged ≥18 years with stage IIIA-N2 NSCLC, accepted PORT or not were considered for the study. Cox regression analyses and multivariate competing risk model were performed. Propensity score matching (PSM) was conducted. Data from a single-center study in China were used for validation.ResultsIn all patients with IIIA-N2 NSCLC, death from respiratory illness increased year by year, with right lung-related deaths accounting for the main proportion. In SEER database, PORT was detrimental for OS after PSM (hazard ratio [HR], 1.088; 95% CI, 1.088–1.174; P = 0.031), with a same trend for death from the lungs (HR, 1.13; 95% CI, 1.04–1.22; P = 0.005). Right tumor receiving PORT were prone to death from lung disease(HR, 1.14; 95% CI, 1.02–1.27; P = 0.018). In China single-center cohort, PORT was significantly correlated with deteriorated OS (HR 1.356; 95% CI 1.127–1.632; P

The Jurassic Da’anzhai Member in Sichuan Basin is an important target for shale oil exploration. Whole rock X-ray diffraction analysis, thin section, SEM and TOC testing, as well as major and trace element analysis are used to analyze the relationship of lithofacies and pore types with the sedimentary environment of the Da’anzhai Member in the Central Sichuan Basin. The results show the Da’anzhai Member in the Well Ren’an 1 (RA1) is divided into six types of lithofacies, based on a three-level division method of mineral composition-TOC-mineral structure— namely, massive mud-bearing shell limestone lithofacies (F), thick argillaceous shell limestone lithofacies (E), laminated clay silt shale lithofacies (D), thin shell calcareous shale lithofacies (C), laminated shell-bearing shale lithofacies (B), and thick clay shale lithofacies (A). The pore spaces include intergranular pores, intergranular dissolution pores, authigenic calcite intergranular pores, authigenic quartz intercrystalline pores, intergranular pores of clay minerals or pyrite nodules, as well as organic pores. The Da’anzhai Member was deposited in a semi-deep to shallow lake sedimentary environment, with relatively low salinity. This strata experienced moderate-to-strong chemical weathering as a result of the semi-arid, warm and humid paleoclimate environmental conditions that persisted during its deposition; low weathering and dry paleoclimate conditions occurred periodically. Paleoenvironment is an important influence on the lithofacies and pore types of the Da’anzhai Member. The persistence of arid climate conditions contributed to a decline in water depth, relatively high salinity, low organic productivity, and the deposition of carbonate rocks that characterize lithofacies E and F; mostly intercrystalline pores formed in these lithofacies in response to the prevailing arid climate conditions. Conversely, warm, and humid climate conditions increased the inflow of fresh water, terrigenous debris, and nutrients into the lacustrine basin that led to the deposition of fine-grained sedimentary rocks of lithofacies A, B, and C. These lithofacies are characterized by abundant nano pores, such as clay intercrystalline pores and organic pores.

BackgroundImmunotherapy has improved the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC). However, in patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, the superior efficacy of immunotherapy has not been elucidated and especially in real-world practice. Our study aimed to use real-world data to assess the efficacy of immunotherapy in KRAS-mutant NSCLC in a Chinese cohort.MethodsIn this retrospective cohort study, we extracted the clinical, molecular, and pathologic data from the electronic health records of patients with advanced KRAS-mutant NSCLC at Shandong Cancer Hospital between January 2018 and May 2022. Furthermore, we evaluated the progression-free survival (PFS) and overall survival (OS) of the included patients.ResultsBetween January 2018 and November 2020, 793 patients were identified with stage IIIB-IV NSCLC and a total of 122 patients with KRAS mutations were included in the analysis. The majority of patients were diagnosed with stage IV (82.0%) adenocarcinoma (93.4%), along with a history of smoking (57.4%). Of these, 42% of patients received anti-PD-(L)1 with or without chemotherapy (Immunotherapy-based regimens), while 58.2% of patients received chemotherapy (Chemotherapy-based regimens). The median overall survival (mOS) in this cohort was 22.9 months (95% CI: 14.1–31.7), while the median-progression-free survival (mPFS) was 9.4 months (95% CI: 6.6–12.1). Patients receiving immunotherapy-based regimens displayed better mOS than those receiving chemotherapy-based regimens (45.2 vs. 11.3 months; P=1.81E-05), with no statistical difference observed in the mPFS (10.5 vs. 8.2 months; P=0.706). Patients receiving immunotherapy-based regimens either in the first line (P=0.00038, P=0.010, respectively) or second-line setting (P=0.010, P=0.026, respectively) showed benefits in both PFS and OS. Subgroup analysis indicated that in patients having KRAS G12C or non-KRAS G12C mutant types, immunotherapy showed benefits of better OS (P=0.0037, P=0.020, respectively) than chemotherapy. Moreover, in advanced NSCLCs patients with or without KRAS/TP53 co-mutation the immunotherapy-based regimen achieved longer OS and PFS than chemotherapy-based regimens.ConclusionsIn the Chinese population of patients with KRAS-mutant advanced NSCLC, immunotherapy-based regimens achieved longer OS than chemotherapy-based regimens, which was independent of first or second-line setting, as well as KRAS mutational subtypes.

Sustainable generation is impacted by the adoption of renewable energy, the growth of energy markets, and economic strategies. This paper offers a sustainable strategy and a technoeconomic analysis of off-grid hybrid energy systems (HES) in remote islands of Iran, including Lavan, Larak, and Failaka, utilizing PV module, wind turbine, and hydrokinetic turbines. Hourly wind speed, solar irradiation, and hydrovelocity have been implemented under load following (LF) and cycle charging (CC) dispatch strategies in order to ascertain the most appropriate systems. Lavan Island achieves the winning HES with a CC dispatch strategy, which consists of 3 hydroelectric turbines, 1 wind turbine, 349 kW of solar power, 150 kW of generator power, 316 kWh of batteries, and 287 kW of the converter. This ideal HES, which generates a consistent generation profile and reasonable net present cost (NPC) and cost of energy (COE) of M0.160$ and $0.013 kWh, respectively, can be practically attained in these areas. LF-controlled optimal solutions use less fuel than CC-based ones, leading to a higher share of renewable energy. Compared to Larak and Lavan, the CC- and LF-controlled options on Failaka Island generate cleaner electricity with emissions that are 57% and 44% lower. Regarding the ability to recoup the project’s initial investment costs, long-term energy production would be more financially viable than short-term. Short-term projects with higher financial uncertainty due to the salvage cost should use the CC method.

Background and aimsPatients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE.Materials and methodsWe enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA.ResultsBuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05).ConclusionThe altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE.

Abstract Background The giant panda (Ailuropoda melanoleuca) is a threatened endemic Chinese species and a flagship species of national and global conservation concern. Life history theory proposes that reproduction and immunity can be mutually constraining and interrelated. Knowledge of immunity changes of male giant pandas during the breeding season is limited. Results Here, we researched peripheral blood gene expression profiles associated with immunity. Thirteen captive giant pandas, ranging from 9 to 11 years old, were divided into two groups based on their reproductive status. We identified 318 up-regulated DEGs and 43 down-regulated DEGs, which were enriched in 87 GO terms and 6 KEGG pathways. Additionally, we obtained 45 immune-related genes with altered expression, mostly up-regulated, and identified four hub genes HSPA4, SUGT1, SOD1, and IL1B in PPI analysis. These 45 genes were related to pattern recognition receptors, autophagy, peroxisome, proteasome, natural killer cell, antigen processing and presentation. SUGT1 and IL1B were related to pattern recognition receptors. HSP90AA1 was the most up-regulated gene and is a member of heat shock protein 90 family. HSP90 contributes to the translocation of extracellular antigen. KLRD1 encodes CD94, whose complex is an inhibitor of the cytotoxic activity of NK cells, was down-regulated. IGIP, which has the capability of inducing IgA production by B cells, was down-regulated, suggesting low concentration of IgA in male giant pandas. Our results suggest that most immune-related genes were up-regulated and more related to innate immune than adaptive immune. Conclusions Our results indicated that breeding male giant pandas presented an immunoenhancement in innate immunity, enhanced antigen presentation and processing in cellular immunity compared to non-breeding males. The humoral immunity of male giant pandas may show a tendency to decrease during the breeding season. This study will provide a foundation for further studies of immunity and reproduction in male giant pandas.

Background: Hepatitis B virus (HBV) infection is one of the health problems and has adverse effects on public health. However, the consequences of male HBV carriers for assisted reproductive techniques (ART) remain unclear.Objective: To examine whether men with HBV would impact sperm quality and the intrauterine insemination (IUI)/ in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) outcomes.Methods: We retrospectively analyzed data from 681 infertile couples for IUI/IVF/ICSI fresh cycle outcomes. Case group was 176 infertile couples with male HBV infection undergoing embryo transfer in our center (99 for IVF and 77 for ICSI) and 51 infertile couples for IUI. Negative control was 454 non-infected infertility couples, matched for female age, BMI and infertility duration (102 for IUI and 198 for IVF and 154 for ICSI).Results: Sperm viability among infertile men with HBV infection was significantly lower than control group (74.1 ± 13.7 vs. 77.0 ± 12.8, P < 0.01). Sperm motility was significantly decreased in HBV positive men in comparison to the control group (32.5 ± 14.6 vs. 35.5 ± 12.9, P < 0.05). In IVF/ICSI cycles, two groups had similar results in two pronuclear (2PN) fertilization rate, implantation rate, clinical pregnant rate and abortion rate (P > 0.05). There was also no difference in the clinical pregnant rate and abortion rate in IUI cycles (P > 0.05).Conclusion: Men with HBV infection will affect their sperm quality, but not affect the outcomes of ART.

The North China Plain (NCP) has the largest groundwater depletion in the world, and it is also the major production area of winter wheat in China. For sustainable food production and sustainable use of irrigated groundwater, it is necessary to optimize the irrigation amount for winter wheat in the NCP. Previous studies on the optimal irrigation amount have less consideration of the groundwater constraint, which may result in the theoretical amount of optimal-irrigation exceeding the amount of regional irrigation availability. Based on the meteorological data, soil data, crop variety data, and field management data from field experimental stations of Tangshan, Huanghua, Luancheng, Huimin, Nangong, Ganyu, Shangqiu, Zhumadian and Shouxian, we simulated the variation of yield and water use efficiency (WUE) under different irrigation levels by using the CERES-Wheat model, and investigated the optimal irrigation amount for high yield (OIy), water saving (OIWUE), and the trade-off between high yield and water saving (OIt) of winter wheat in the NCP. Based on the water balance theory, we then calculated the irrigation availability, which was taken as the constraint to explore the optimal irrigation amount for winter wheat in the NCP. The results indicated that the OIy ranged from 80 mm to 240 mm, and the OIWUE was 17% to 67% less than OIy, ranging from 0 mm to 200 mm. The OIt was between 80 mm and 240 mm, realizing the co-benefits of high yield and water saving. Finally, we determined the optimal irrigation amount (62–240 mm) by the constraint of irrigation availability. Our results can provide a realistic and scientific reference for the security of both grain production and groundwater use in the NCP.

Conventional crystal growth models assume crystals grow into a structure-less liquid, even though liquid metals have shown evidence of structural ordering. Here, the authors show crystal growth can be influenced by the presence of thermodynamically unstable local structural order in the liquid.

When theoretically studying the control method of LCL-type static synchronous compensator (STATCOM), we often ignore the influence of complex power grid on the stability and reactive compensation performance of STATCOM. Improving traditional current decoupling method with PI controller (PI decoupling) in synchronous (dq) reference frame, an original current decoupling method with active disturbance rejection controller (ADRC decoupling) is proposed in this paper. First, the influence of internal and external disturbances on STATCOM with PI decoupling method is analyzed. External disturbances include harmonic grid voltage and grid inductance variation. Internal disturbances come from coupled channels between d axis and q axis, and parameter perturbations of LCL filter. Second, the principle of ADRC decoupling method applied to LCL-type STATCOM is analyzed in detail. Taking advantage of ADRC's capability to estimate and compensate for the “total disturbances”, robustness of STATCOM is improved. Comparing with PI decoupling method, ADRC decoupling method can improve the disturbances rejection performance and stability of LCL-type STATCOM. Finally, results from STATCOM simulation model show the effectiveness and superiority of this original method.

Photoperiodic flowering, a plant response to seasonal photoperiod changes in the control of reproductive transition, is an important agronomic trait that has been a central target of crop domestication and modern breeding programs. However, our understanding about the molecular mechanisms of photoperiodic flowering regulation in crop species is lagging behind. To better understand the regulatory gene networks controlling photoperiodic flowering of soybeans, we elucidated global gene expression patterns under different photoperiod regimes using the near isogenic lines (NILs) of maturity loci (E loci). Transcriptome signatures identified the unique roles of the E loci in photoperiodic flowering and a set of genes controlled by these loci. To elucidate the regulatory gene networks underlying photoperiodic flowering regulation, we developed the network inference algorithmic package CausNet that integrates sparse linear regression and Granger causality heuristics, with Gaussian approximation of bootstrapping to provide reliability scores for predicted regulatory interactions. Using the transcriptome data, CausNet inferred regulatory interactions among soybean flowering genes. Published reports in the literature provided empirical verification for several of CausNet's inferred regulatory interactions. We further confirmed the inferred regulatory roles of the flowering suppressors GmCOL1a and GmCOL1b using GmCOL1 RNAi transgenic soybean plants. Combinations of the alleles of GmCOL1 and the major maturity locus E1 demonstrated positive interaction between these genes, leading to enhanced suppression of flowering transition. Our work provides novel insights and testable hypotheses in the complex molecular mechanisms of photoperiodic flowering control in soybean and lays a framework for de novo prediction of biological networks controlling important agronomic traits in crops.

Ge2Sb2Te5 (GST) is a technologically important phase-change material for data storage, where the fast reversible phase transition between crystalline and amorphous states is used for recording information. The effects of vacancies on crystal GST were investigated by ab initio calculations. Based on analysis of the vacancy formation energy, the GST structure with Ge vacancy (VGe) was found to be the most stable. Thereafter, the influence of VGe defects on crystal GST structure was deliberated by analyzing the band structure, electron density difference, total density of states (TDOS) and partial density of states (PDOS) of GST structure. The results reveal that VGe can promote the Fermi level enter into the valence band, which makes the GST material exhibit more pronounced properties of P-type semiconductors. Nevertheless, VGe shows a slight effect on the chemical bond characters. When VGe concentration maintained at 20% in the GST structure, the band gap is the widest about 0.45eV. Moreover, VGe can result in the electrons in s orbital of Ge, Sb and p, d orbitals of Te make a contribution to the valence band, while electrons in p and d orbitals of Ge, Sb are more favorable to conduction band.

With nuclear magnetic resonance (NMR) and micrometer-nanometer CT Scanning technology, quantitative research was carried out of the micro-existing state of tight oil in the Chang7 Member of the Triassic Yanchang Formation in the Ordos Basin. The total reserves of the tight oil in the reservoirs were determined using NMR technology. The initial oil saturation was measured as 63.99%. The 2-D slice images of the tight oil reservoirs were obtained using CT Scanning technology, and the 3-D images were acquired after digital synthesis processing. Accordingly, the existence states of the tight oil in the reservoirs are divided into six types, namely thin film form, cluster form, throat form, emulsion form, particle form and isolation form. It is found by quantitative calculation of the contents of tight oil in different existence states of tight oil that the emulsion form and thin film form are the main existence states, which account for 70% of the total amount of the tight oil in the reservoirs, followed by the cluster and particle forms. The contents of isolation form and throat form tight oil are low. The contents of tight oil in various existence states are related to initial water saturation, clay mineral content and pores structure of the reservoirs. Key words: tight oil, microscopic state, quantitative research, Ordos Basin, Triassic Yanchang Formation

Symmetric and asymmetric divisions are important for self-renewal and differentiation of stem cells during neurogenesis. Although cerebellar granule neurogenesis is controlled by sonic hedgehog (SHH) signaling, whether and how this process is mediated by regulation of cell division modes have not been determined. Here, using time-lapse imaging and cell culture from neuronal progenitor-specific and differentiated neuron-specific reporter mouse lines (Math1-GFP and Dcx-DsRed) and Patched+/− mice in which SHH signaling is activated, we find evidence for the existence of symmetric and asymmetric divisions that are closely associated with progenitor proliferation and differentiation. While activation of the SHH pathway enhances symmetric progenitor cell divisions, blockade of the SHH pathway reverses the cell division mode change in Math1-GFP;Dcx-DsRed;Patched+/− mice by promoting asymmetric divisions or terminal neuronal symmetric divisions. Thus, cell division mode change mediates the regulation of cerebellar granule neurogenesis controlled by SHH signaling.

Functional textiles with unique functions, including free cutting, embroidery and changeable shape, will be attractive for smart wear of human beings. Herein, we fabricated a sandwich-like humidity sensor made from silver coated one-dimensional magnetite nanowire (Fe3O4 NW) arrays which were in situ grown on the surface of modified polypropylene nonwoven fabric via simultaneous radiation induced graft polymerization and co-precipitation. The humidity sensor exhibits an obvious response to the relative humidity (RH) ranging from RH 11% to RH 95% and its response value reaches a maximum of 6600% (ΔI/I0) at 95% relative humidity (RH). The humidity sensor can be tailored into various shapes and embroidered on its surface without affecting its functionalities. More interesting, the intensity of its response is proportional to the size of the material. These features permit the sensor to be integrated into commercial textiles or a gas mask to accurately monitor a variety of important human activities including respiration, blowing, speaking and perspiration. Moreover, it also can distinguish different human physical conditions by recognizing respiration response patterns. The sandwich-like sensor can be readily integrated with textiles to fabricate promising smart electronics for human healthcare.

Nature has shaped the make up of proteins since their appearance, [Formula: see text]3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated folding times for the present-day catalog of protein domains directly from their size-modified contact order. These values were mapped onto an evolutionary timeline of domain appearance derived from a phylogenomic analysis of protein domains in 989 fully-sequenced genomes. Our results show a clear overall increase of folding speed during evolution, with known ultra-fast downhill folders appearing rather late in the timeline. Remarkably, folding optimization depends on secondary structure. While alpha-folds showed a tendency to fold faster throughout evolution, beta-folds exhibited a trend of folding time increase during the last [Formula: see text]1.5 billion years that began during the "big bang" of domain combinations. As a consequence, these domain structures are on average slow folders today. Our results suggest that fast and efficient folding of domains shaped the universe of protein structure. This finding supports the hypothesis that optimization of the kinetic and thermodynamic accessibility of the native fold reduces protein aggregation propensities that hamper cellular functions.

The genetic code shapes the genetic repository. Its origin has puzzled molecular scientists for over half a century and remains a long-standing mystery. Here we show that the origin of the genetic code is tightly coupled to the history of aminoacyl-tRNA synthetase enzymes and their interactions with tRNA. A timeline of evolutionary appearance of protein domain families derived from a structural census in hundreds of genomes reveals the early emergence of the 'operational' RNA code and the late implementation of the standard genetic code. The emergence of codon specificities and amino acid charging involved tight coevolution of aminoacyl-tRNA synthetases and tRNA structures as well as episodes of structural recruitment. Remarkably, amino acid and dipeptide compositions of single-domain proteins appearing before the standard code suggest archaic synthetases with structures homologous to catalytic domains of tyrosyl-tRNA and seryl-tRNA synthetases were capable of peptide bond formation and aminoacylation. Results reveal that genetics arose through coevolutionary interactions between polypeptides and nucleic acid cofactors as an exacting mechanism that favored flexibility and folding of the emergent proteins. These enhancements of phenotypic robustness were likely internalized into the emerging genetic system with the early rise of modern protein structure.