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Abstract Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, −20.0; 160 mg, −19.9) vs. placebo (−14.6; p

Constipation is a prevalent gastrointestinal condition that significantly affects patients' physical and mental well-being, yet current treatments often lack safety and efficacy. Emerging evidence highlights the critical role of the microbiota-gut-brain axis (MBGA) in managing constipation, paving the way for probiotics as an adjuvant treatment to improve constipation symptoms. In this study, we isolated a gut probiotic strain, Lacticaseibacillus paracasei NCU-04, and investigated its improvement effects on loperamide-induced constipation in mice. We demonstrated that L. paracasei NCU-04 exhibited excellent probiotic properties, including robust growth, strong antibacterial and antioxidant capacities, and a lack of hemolytic activity in vitro. The administration of L. paracasei NCU-04 effectively improved the defecation-related indicators such as the fecal water content, time to the first black stool defecation, and intestine transit rate, suggesting enhanced gut immobility in constipated mice. Additionally, L. paracasei NCU-04 significantly reduced colon inflammation induced by loperamide. Further, L. paracasei NCU-04 increased levels of colonic motilin, 5-hydroxytryptamine (5-HT), and c-kit, while decreased that of aquaporin 3, vasoactive intestinal peptide, and peptide YY. Notably, L. paracasei NCU-04 effectively upregulated the expression of 5-HT and its receptor (i.e., 5-HT4R) in the brains of constipated mice. High-throughput sequencing revealed that L. paracasei NCU-04 restored the diversity and composition of the gut microbiota disturbed by loperamide, and significantly increased the relative abundance of Prevotella and Lactobacillus genera in the stool, while decreased that of Odoribacter, Rikenella, and Parabacteroides. Importantly, L. paracasei NCU-04 also effectively improved the depression-like behaviors associated with constipation, possibly through 5-HT mediated MGBA. These results suggest that L. paracasei NCU-04 may offer a promising approach for treating constipation and its related depressive symptoms, supporting its potential as a functional food or adjuvant therapy for human health.

Surface hydraulic fracturing is an important measure for increasing reservoir permeability, which has advantages such as engineering safety and a large impact range and can be implemented ahead of the mine’s underground engineering. However, its underground outburst reduction range and effect are rarely reported, and there is a lack of connection with underground fracturing wells. Taking coalbed methane wells in the Lu’an Mining Area as an example, underground observation, microseismic monitoring, and numerical simulation methods were used to study the fracturing range and outburst control effect of surface wells. The fracturing zone of coalbed methane wells is approximately elliptical in shape, with the main fractures extending along the direction of the maximum horizontal principal stress. It can be divided into five zones: sand laying zone (radius of 140~150 m), fracture propagation zone (radius of about 180 m), fracturing fluid permeability zone (width of about 1 m), gas surge zone (width of 2~3 m), and final desorption zone (width of about 2 m). The stress around the fracturing zone increases along the direction of maximum and minimum principal stresses, while the stress value within the zone decreases, with a range of approximately 5~20% of the original geostress. The outburst reduction index Δh2 in the fracturing zone significantly decreased after fracturing. The percent of Δh2 (

ObjectiveThis study aims to analyze the efficacy and safety of different electrical stimulation treatments for post-stroke motor dysfunction, and to quantitatively analyze the advantages between them and their possible benefits for patients.MethodsWe will systematically search seven databases. All of them will be retrieved from inception to 15, April 2024. Two reviewers will evaluation the risk of bias in all included studies with the version 2 of the Cochrane risk-of-bias assessment tool. Data synthesis will be performed using a random-effects model of network meta-analysis to compare the efficacy and safety of different electrical stimulation therapies. The surface under the cumulative ranking curve was used to indicate the possibility of the pros and cons of the intervention. The strength of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation framework.DiscussionThis study will provide evidence that electrical stimulation therapy can effectively improve motor function in stroke patients and will also provide some valuable references for clinical decision-making and treatment guidelines.Trial registrationPROSPERO registration number: CRD42023459102.

IntroductionMoral disengagement is an essential concept in organizational behavioral ethics, as it is strongly related to employee behaviors and attitudes. What is not clear, however, is which leader traits are directly associated with employees’ moral disengagement and which are indirectly associated with unethical behavior. This study draws on a social cognitive perspective that links leaders’ other-oriented perfectionism (LOOP) with unethical employee behavior. Specifically, we propose that LOOP provides employees with excuses and encouragement to engage in unethical pro-organizational behavior (UPB).MethodsWe analyzed data collected from 266 full-time employees at two-time points, and used mediated and moderated structural equation models to test the hypotheses, and the findings largely support our claims.ResultsThe results suggest that LOOP effectively promotes employees’ involvement in UPB. Moderated mediation tests suggest that the positive indirect impact of LOOP on employees’ unethical behavior via moral disengagement was attenuated by higher employees’ moral identity.DiscussionIn summary, the results indicate that when leaders emphasize only perfection and make unrealistic demands on their employees, the latter perceive that engaging in unethical behavior is demanded by the leader, that the responsibility is not theirs, and thus they are more willing to engage in unethical behavior. This study discusses the implications of these findings from both practical and theoretical perspectives.

Background: Sorafenib (Sor) represents a first-line therapy for hepatocellular carcinoma (HCC); however, its efficacy is constrained by secondary failure, which limits its clinical use. Recent studies have indicated that the suppression of Programmed cell death-Ligand 1 (PD-L1) may potentiate Sor's anti-liver cancer effects; furthermore, PD-L1 expression is known to be regulated by NF-κB. Previous research has demonstrated that paeoniflorin (PF) downregulates the NF-κB axis, nevertheless, current research has not yet determined whether PF can synergistically enhance the efficacy of Sor against HCC by modulating the NF-κB/PD-L1 pathway. Methods: The study employed a H22 hepatoma-bearing mouse model, which was treated with PF, Sor, and their combination over a period of 12 days. The impact of PF and Sor on tumor growth, proliferation, apoptosis, T-cell subsets, IL-2 and IFN-γ production, and NF-κB and PD-L1 expression was assessed. Moreover, Splenic lymphocyte from normal mice and tumor cells from model mice were co-cultured in vitro, and the tumor-specific cytotoxic T lymphocyte activity was analyzed. In the final phase of the study, Huh-7 cells were stimulated with PF in combination with an NF-κB activator or inhibitor, and the subsequent production of NF-κB and PD-L1 was investigated. Results: PF and Sor exhibit a synergistic anti-tumor effect, compared to the use of Sor alone, the combined use of PF and Sor significantly increased the number of CD4+ and CD8+ T cells in tumor tissue, markedly enhanced the cytotoxic activity of tumor-specific cytotoxic T lymphocytes, and reversed the depletion of interleukin-2 and the increase in PD-L1 expression following Sor intervention. This combination also further reduced the level of IFN-γ in peripheral blood and the expression of NF-κB and PD-L1 in tumor tissue. Additionally, in vitro experiments confirmed that PF reduces the expression of PD-L1 in Huh-7 liver cancer cells by inhibiting NF-κB. Conclusions: PF plays a synergistic role of Sor inhibiting HCC progression by regulating the NF-κB/PD-L1 pathway.

The effective collaboration between crop habitat adaptability evaluation and yield prediction is of great significance. Climate factors occupy an indispensable role, but the contributions of different climate factors to crop growth present spatiotemporal heterogeneity and confusion, amplifying the challenges associated with large-scale dynamic evaluations. Additionally, the mounting input parameters in yield prediction compound the uncertainty and intricacy of modeling. To address these challenges, a climate-driven dynamic habitat adaptability evaluation indicator (HAEI) was developed, capable of forecasting county-level winter wheat yields in China. First, the distribution characteristics and matching relationship between climate and yield variability were explored from multi-source data in the long time series, and a novel method of multiple-factor adaptive matching habitat membership degree was proposed. Second, considering the interaction and contribution differences between multiple-factor at different phenological periods, a comprehensive HAEI suitable for the entire growth period of winter wheat is constructed. The results showed that HAEI can integrate climate information that has a greater impact on yield variability and has a significant correlation with yield in various regions and periods, with an average correlation of 0.70. Remarkably, the predictive models incorporating HAEI consistently outperformed other yield prediction algorithms, demonstrating superior accuracy (R2 = 0.62–0.76, nRMSE = 0.1517–0.2031). Even in the least favorable scenario, involving a linear model with HAEI input, satisfactory results were achieved. This comprehensive framework effectively mitigates the adverse consequences of widespread agricultural climate heterogeneity and evaluates the habitat adaptability and yield status of wheat at the county level in China.

The intensive use of pesticides in the North China Plain (NCP) has resulted in widespread contamination of pesticides in the local atmosphere, posing risks to air quality and human health. However, the occurrence and distribution of atmospheric pesticides in the NCP as well as their risk assessment have not been well investigated. In this study, 300 monthly samples were collected using passive air samplers with polyurethane foam at ten rural sites with different crop systems in Quzhou county, the NCP, from June 2021 to May 2022. The pesticides were quantified using mass-spectrometric techniques. Our results revealed that chlorpyrifos, carbendazim, and atrazine were the most frequently found pesticides in the air samples, with detection frequencies of ≥ 87 % across the samples. The average concentrations of atmospheric pesticides during spring (7.47 pg m−3) and summer (16.05 pg m−3) were significantly higher than those during autumn (2.04 pg m−3) and winter (1.71 pg m−3), attributable to the intensified application of pesticides during the warmer seasons. Additionally, cash crop sites exhibited higher concentrations (10.26 pg m−3) of atmospheric pesticides compared to grain crop (5.59 pg m−3) and greenhouse sites (3.81 pg m−3), primarily due to more frequent pesticides spraying events in cash crop fields. These findings indicate a distinct spatial–temporal distribution pattern of atmospheric pesticides influenced by both seasons and crop systems. Furthermore, the model-based inhalation risk assessment indicates that inhalation exposure to atmospheric pesticides is unlikely to pose a significant public concern.

Photothermal immunochromatographic sensor is an emerging detection technology, and it is important to develop new sensing probes with excellent photothermal performance to improve its detection performance. In the present study, a novel photothermal sensing probe based on violet phosphorus nanosheets with satisfactory photothermal conversion efficiency (31.1 %) was reported for the first time. A photothermal immunochromatographic sensor using the above probe was applied for visual and photothermal detection of diethylstilbestrol. The diethylstilbestrol concentration was inversely proportional to photothermal sensing signal and showed a good linear correlation in the range of 0.75 ∼ 50 μg·L−1. After optimizing, the visual and photothermal detection limits were 6 μg·L−1 and 0.56 μg·L−1, respectively. The recovery rates in tap water, milk and pork samples ranged from 82.2 % to 115.2 %, with a coefficient of variation (CV) ranging from 2.0 % to 10.8 %. This work not only structured a new type of photothermal probe, but also expanded the application range of violet phosphorus.

Abstract In recent years, the rapid development of nanotechnology has made significant impacts on the industry. With the wide application of nanotechnology, nanoparticles (NPs) are inevitably released into the environment, and their fate, behavior and toxicity are indeterminate. Studies have indicated that NPs can be absorbed, transported and accumulated by terrestrial plants. The presence of NPs in certain edible plants may decrease harvests and threaten human health. Understanding the transport and toxicity of NPs in plants is the basis for risk assessment. In this review, we summarize the transportation of four types of NPs in terrestrial plants, and the phytotoxicity induced by NPs, including their impacts on plant growth and cell structure, and the underlying mechanisms such as inducing oxidative stress response, and causing genotoxic damage. We expect to provide reference for future research on the effects of NPs on plants. Graphical Abstract

Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by in vivo and in vitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15 weeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development.

Abstract Background The purpose of this meta-analysis was to compare the efficacy and outcomes of bifocal bone transport (BFT) and trifocal bone transport (TFT) for the treatment of tibial bone defects caused by fracture-related infection (FRI). Methods The literature searches of Cochrane Library, Embase, Google Scholar databases, PubMed/Medline, and Web of Science for literature published up to September 20, 2022, were performed. The quality of the included studies was evaluated according to the MINORS scale. Patients were divided into the BFT group and the TFT group, depending on the site of the osteotomy. The demographic data, defect size (DS), external fixation time (EFT), external fixation index (EFI), bone and functional results, complications, and autologous bone grafting (ABG) were extracted and analyzed using the Review Manager software (version 5.3). Results Five studies included 484 patients with tibial bone defects treated by bone transport investigated in this meta-analysis, with a mean bone defect of 9.3 cm. There were statistical differences in DS (MD = − 2.38, 95% CI − 3.45 to − 1.32, P

Abstract Background Brain microvascular endothelial cells (BMECs) play a major role in the blood–brain barrier (BBB), and are critical for establishing an in vitro BBB model. Currently, iPSC-derived BMECs (iBMECs) have been used to construct in vitro BBB models with physiological barrier functions, such as high trans-endothelial electrical resistance (TEER) and expression of transporter proteins. However, the relatively low p-glycoprotein (P-gp) level and a decrease in the efflux ratio of its substrates in iBMECs suggest their immature nature. Therefore, more mature iBMECs by optimizing the differentiation induction protocol is beneficial for establishing a more reliable in vitro BBB model for studying central nervous system (CNS) drug transport. Methods To identify human brain endothelial cell fate-inducing factors, HUVEC was transfected with Zic3A-, Zic3B-, and Sox18-expressing lentivirus vector. Since SOX18 was found to induce BMEC properties, we used a Dox-inducible Tet-on system to express SOX18 during iBMEC differentiation and explored the impact of SOX18 expression on iBMEC maturation. Results Sox18-mediated iBMECs achieved a higher TEER value than normal iBMECs (> 3000 Ω cm2). From day 6 to day 10 (d6–10 group), the iBMECs with SOX18 expression expressed a series of tight junction markers and showed upregulation of Mfsd2a, a specific marker of the BBB. The d6–10 group also expressed SLC2A1/Glut1 at levels as high as normal iBMECs, and upregulated ABCB1/P-gp and ABCC1/MRP1 expression. Moreover, Sox18-mediated iBMECs showed higher viability than normal iBMECs after puromycin treatment, indicating that SOX18 expression could upregulate P-gp activity in iBMECs. Conclusions Inducible SOX18 expression in iBMECs gained BBB phenotypes, including high TEER values and upregulation of tight junction-related genes, endothelial cell (EC) markers, BBB transporters, and higher cell viability after treatment with puromycin. Collectively, we provide a differentiation method for the maturation of human iPS cell-derived BMECs with SOX18 expression, describing its contribution to form an in vitro BBB model for CNS drug transport studies.

Drought is the most important factor limiting winter wheat yield in the North China Plain (NCP). Choosing high-yielding cultivars is an important measure to minimize the negative effects of drought stress. Field studies were conducted with 10 cultivars in the 2020–2022 seasons under three irrigation treatments (I0, without irrigation; I1, irrigated at jointing stage; I2, irrigated at jointing and anthesis stages) in the NCP to examine the water use strategies and root and shoot traits of high-yielding cultivars under different water supply conditions. The results showed that yield variation among cultivars was 21.2–24.6%, 23.7–25.9% and 11.6–15.3% for the I0, I1 and I2 treatments, respectively. Under water deficit conditions (I0 and I1), high-yielding cultivars reduced water use during vegetative stages and increased soil water use during reproductive stages, especially water use from deeper soil layers. Those cultivars with higher root length density (RLD) in deep soil layers exhibited higher water uptake. Each additional millimeter of water used after anthesis from the 100–200 cm soil layers increased grain yield by 23.6–29.6 kg/ha and 16.4–28.5 kg/ha under I0 and I1, respectively. This water use strategy enhanced dry matter accumulation after anthesis, decreased canopy temperature (CT) and increased relative leaf water contents (RLWC), which ultimately improved grain yield. For winter wheat grown under I2, cultivars that decreased water use after anthesis had higher water productivity (WP). Root length (RL), root weight (RW) and root:shoot ratio were each negatively correlated with grain yield, while above-ground biomass was positively correlated with grain yield. Therefore, higher dry matter accumulation and smaller root systems are two important traits of high-yielding cultivars under sufficient water supply conditions (I2) in the NCP.

Microbial degradation of feathers offers potential for bioremediation, yet the microbial response mechanisms warrant additional investigation. In prior work, Pseudomonas aeruginosa Gxun-7, which demonstrated robust degradation of feathers at elevated concentrations, was isolated. However, the molecular mechanism of this degradation remains only partially understood. To investigate this, we used RNA sequencing (RNA-seq) to examine the genes that were expressed differentially in P. aeruginosa Gxun-7 when exposed to 25 g/L of feather substrate. The RNA-seq analysis identified 5571 differentially expressed genes; of these, 795 were upregulated and 603 were downregulated. Upregulated genes primarily participated in proteolysis, amino acid, and pyruvate metabolism. Genes encoding proteases, as well as those involved in sulfur metabolism, phenazine synthesis, and type VI secretion systems, were notably elevated, highlighting their crucial function in feather decomposition. Integration of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) taxonomies, combined with a review of the literature, led us to propose that metabolic feather degradation involves environmental activation, reducing agent secretion, protease release, peptide/amino acid uptake, and metabolic processes. Sulfite has emerged as a critical activator of keratinase catalysis, while cysteine serves as a regulatory mediator. qRT–PCR assay results for 11 selected gene subset corroborated the RNA-seq findings. This study enhances our understanding of the transcriptomic responses of P. aeruginosa Gxun-7 to feather degradation and offers insights into potential degradation mechanisms, thereby aiding in the formulation of effective feather waste management strategies in poultry farming.

During the storage and transportation processes, the occurrence of core browning in ‘Yali’ pear fruit due to adversity injury can be easily mitigated by implementing different cooling methods, especially in advanced maturity fruits. In this study, ‘Yali’ pears at an advanced maturity stage were subjected to slow cooling and rapid cooling treatment. The quality-related physiological percentage and severity, and the rate of good fruits were determined, and RNA-seq was used to explore the effects of different cooling methods on pathways related to core browning in advanced-maturity pears at the transcriptional level. The results indicated that, compared with slow cooling treatment, rapid cooling significantly inhibited core browning in advanced-maturity ‘Yali’ pears. Measurements of quality-related physiological indexes suggested that rapid cooling treatment led to higher SSC content, firmness, L* value, and b* value, indicating better brightness, coloration, and higher soluble solid content, which are desirable for commercial sale. Rapid cooling effectively suppressed the physiological metabolism of ‘Yali’ pears, delaying fruit senescence compared with slow-cooling treatment. Furthermore, the RNA-Seq sequencing results revealed that pathways related to browning are involved in hormone signal transduction pathways, which are associated with resistance and aging processes of pear fruit. In summary, rapid cooling treatment delayed the core browning of advanced maturity of ‘Yali’ pears, indicating that the core browning of ‘Yali’ pears is related to the cooling method, and the mechanism of rapid cooling in reducing the core browning of advanced maturity of ‘Yali’ pears was by delaying the aging process of the fruit. This provides a new perspective for alleviating the core browning of advanced-maturity ‘Yali’ pears during storage and transportation, and provides a theoretical reference for studying the mechanism of core browning of ‘Yali’ pears.

Cinnamon (Cinnamomum sp.) essential oil microcapsules, oregano (Origanum sp.) essential oil microcapsules, and oregano–thyme (Thymus sp.) essential oil microcapsules are rarely used in the postharvest preservation treatment of okra (Abelmoschus esculentus L.). The mechanism of these three essential oil microcapsules on the postharvest preservation of okra is also not yet well understood. In this study, fresh okra was preserved by three kinds of essential oil microcapsules (cinnamon essential oil microcapsules, oregano essential oil microcapsules, and oregano–thyme essential oil microcapsules). The effect of essential oil microcapsules on the postharvest storage quality of okra was discussed. We also used RNA-Seq to preliminarily explore the mechanism of oregano–thyme essential oil microcapsules on the pre-harvest storage quality of okra. The results showed that the three kinds of essential oil microcapsules could maintain the high sensory evaluation quality and firmness of okra, slow down the increase in respiratory intensity, slow down the total number of colonies on the fruit surface, and slow down weight loss. Through analysis, it was found that the effect of oregano–thyme essential oil microcapsules was remarkably better than that of cinnamon essential oil microcapsules and oregano essential oil microcapsules. The preservation mechanism of oregano–thyme essential oil microcapsules on postharvest okra was preliminarily elucidated by RNA-Seq. This study provides a certain basis for a follow-up study of essential oil microcapsules in the preservation of okra.

ObjectiveTo explore the additional value of cardiac magnetic resonance (CMR) post-contrast T1 mapping in the detection of myocardial infarction, compared with late gadolinium enhancement (LGE).Materials and methodsA CMR database of consecutive patients with myocardial infarction was retrospectively analyzed. All patients were scanned at 3 T magnetic resonance; they underwent conventional CMR (including LGE) and post-contrast T1 mapping imaging. Two radiologists interpreted the CMR images using a 16-segment model. The first interpretation included only LGE images. After 30 days, the same radiologists performed a second analysis of random LGE images, with the addition of post-contrast T1 mapping images. Images were analyzed to diagnose myocardial scars, and the transmural extent of each scar was visually evaluated. Diagnoses retained after LGE were compared with diagnoses retained after the addition of post-contrast T1 mapping.ResultsIn total, 80 patients (1,280 myocardial segments) were included in the final analysis. After the addition of post-contrast T1 mapping, eight previously unidentified subendocardial scars were detected. Compared with LGE images, the percentage of infarcted segments was higher after the addition of post-contrast T1 mapping images (21.7% vs. 22.3%, P = 0.008), the percentage of uncertain segments was lower after the addition of post-contrast T1 mapping (0.8% vs. 0.1%, P = 0.004), and the percentage of uncertain transmural extent of scarring was lower after the addition of post-contrast T1 mapping (0.9% vs. 0.1%, P = 0.001).ConclusionThe addition of post-contrast T1 mapping after LGE helps to improve the detection of myocardial infarction, as well as the assessment of the transmural extent of scarring.

Salmonella causes most deaths from diarrheal disease worldwide. Therefore, Salmonella must be accurately and quickly detected, even in complex food matrices, which is difficult to achieve using conventional culture methods. Here we propose a novel photonic polymerase chain reaction (PCR) method based on ferroferric oxide (Fe3O4) for the detection of Salmonella typhimurium in complex samples. Owing to the great photothermal conversion performance of Fe3O4, rapid thermal cycling could be accomplished. Our optimized photonic PCR system specifically detected Salmonella typhimurium in complex food matrices within 50 min. Quantitative data showed a limit of detection up to 102 CFU/mL in food samples. This method is suitable for the detection of all pathogenic microorganisms and is universal.

Understanding the response characteristics and thresholds of grassland spring phenology (GSP) to different climatic factors in arid and semi-arid regions is of great significance to deal with global climate change. The Mongolian Plateau is one of the largest plateaus located in arid and semi-arid regions of eastern Asia, extremely sensitive to climate change. At present, the response characteristics and thresholds of the grassland spring phenology to climate factors in the Mongolian Plateau remain uncertain. Here, we used statistical analysis, random forest and geographical detector to explore these uncertainty. We found that 1) 76.67% of study area showed a significant advancing trend. GSP has significantly advanced by −0.656 days/decade (P 10 °C and TMN > −5 °C, and it delays as the FRS, WET and CLD increase. This study is of great significance to reveal the impact characteristics and threshold of climate change on the GSP, which could do help in understanding climate change.

Objective: To examine whether joint management of cancer pain by physicians and pharmacists in clinics provides economic advantages from the perspective of the Chinese healthcare system.Methods: From February 2018 to March 2020, 100 patients who visited the joint cancer pain clinic at the Xiangya Hospital of Central South University were included. These patients were randomly assigned to either the control or intervention groups. The control group received regular outpatient services from a physician, while the intervention group received regular outpatient services from a physician and medication education provided by a pharmacist. The study considered various direct costs, including drug expenses, physician-pharmacist outpatient services, adverse event management, consultations, examinations, and readmissions. The outcome indicators considered were the cancer pain control rate and the reduction in pain scores. Decision tree modeling, single-factor sensitivity analysis, and probabilistic sensitivity analysis were performed to evaluate the cost-effectiveness of joint physician-pharmacist outpatient services compared to physician-alone outpatient services.Results: The intervention group showed a significantly higher cancer pain control rate than the control group (0.69 vs. 0.39, p = 0.03). In the decision tree model, the intervention group had a significantly lower pain score than the control group (0.23 vs. 0.14). The cost per person in the intervention group was $165.39, while it was $191.1 per person in the control group. The univariate sensitivity analysis showed that the cost of self-management for patients in the control group was identified as the primary sensitivity factor. Probabilistic sensitivity analysis indicated that the joint clinic group had a favorable incremental cost-effectiveness compared to the physician clinic group. In addition, the probabilistic sensitivity analysis demonstrated an absolute advantage in the incremental cost-effectiveness of the joint clinic group over the outpatient physician group.Conclusion: The participation of pharmacists in joint cancer pain clinic services led to improved pain management for patients, demonstrating a clear advantage in terms of cost-effectiveness.

Diabetes mellitus (DM) is a metabolic disease characterized by high blood sugar. Due to its complex pathogenesis, no effective drugs have been found so far. Ophiopogonin D (OP-D) has anti-inflammatory, antioxidant, and anticancer activities, but its role in DM has not been studied so far. Hydrogen peroxide (H2O2) was used to induce INS-1 cells. INS-1 cells induced by H2O2 were treated with OP-D, and cell apoptosis, oxidative stress damage, and related indexes of mitochondrial function were respectively detected by cell counting kit-8, flow cytometry, western blot, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, JC-1 fluorescent probe, and related kits. Subsequently, molecular docking techniques were used to investigate the relationship between OP-D and Keap1 and to explore the regulation mechanism of OP-D on H2O2-induced oxidative stress and mitochondrial function in INS-1 cells. OP-D inhibited the apoptosis and oxidative stress level of H2O2-induced INS-1 cells, thereby inhibiting cell damage. Moreover, OP-D inhibited mitochondrial dysfunction in H2O2-induced INS-1 cells. At last, we found that Keap1/Nrf2 specific signaling pathway inhibitor ML385 was able to reverse the inhibitory effect of OP-D on H2O2-induced oxidative stress and mitochondrial dysfunction in INS-1 cells. In conclusion, OP-D improves oxidative stress and mitochondrial dysfunction in pancreatic β cells induced by H2O2 through activating Keap1/Nrf2/ARE pathway in DM.

Biological tissue information of the lung, such as cells and proteins, can be obtained from bronchoalveolar lavage fluid (BALF), through which it can be used as a complement to lung biopsy pathology. BALF cells can be confused with each other due to the similarity of their characteristics and differences in the way sections are handled or viewed. This poses a great challenge for cell detection. In this paper, An Improved Yolov5s Based on Transformer Backbone Network for Detection and Classification of BALF Cells is proposed, focusing on the detection of four types of cells in BALF: macrophages, lymphocytes, neutrophils and eosinophils. The network is mainly based on the Yolov5s network and uses Swin Transformer V2 technology in the backbone network to improve cell detection accuracy by obtaining global information; the C3Ghost module (a variant of the Convolutional Neural Network architecture) is used in the neck network to reduce the number of parameters during feature channel fusion and to improve feature expression performance. In addition, embedding intersection over union Loss (EIoU_Loss) was used as a bounding box regression loss function to speed up the bounding box regression rate, resulting in higher accuracy of the algorithm. The experiments showed that our model could achieve mAP of 81.29% and Recall of 80.47%. Compared to the original Yolov5s, the mAP has improved by 3.3% and Recall by 3.67%. We also compared it with Yolov7 and the newly launched Yolov8s. mAP improved by 0.02% and 2.36% over Yolov7 and Yolov8s respectively, while the FPS of our model was higher than both of them, achieving a balance of efficiency and accuracy, further demonstrating the superiority of our model.

Ganoderma lucidum possesses anti-inflammatory, antioxidant, and immunomodulatory properties. We evaluated the anti-inflammatory and anti-melanogenesis effects of G. lucidum alone (S1), G. lucidum and Polygonatum odoratum (S2), and G. lucidum and P. ginseng (S3) using an ultraviolet B-irradiated HaCaT cell model and a prostaglandin 2 (PGE2)-treated B16-F10 melanocyte model. S3 inhibited PGE-2 and LL-37 secretion in HaCaT cells and melanin and tyrosinase expression in B16-F10 cells. Furthermore, LC/MS/MS results revealed that the levels of 70 components were higher in S3 than in S1 and S2. These results demonstrate that G. lucidum and P. ginseng co-culture fermentation broth possess in vitro anti-inflammatory and anti-melanogenesis effects; it can be used in the skin care industry.

A decoction is the most common form of Chinese herbal medicine dosing. An Angelica sinensis decoction was qualitatively and semi-quantitatively analyzed for 15 highly toxic pesticide residues by thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS) with a triple quadrupole mass spectrometer in multiple reaction monitoring mode without pretreatment. The instrument response was optimal and sensitivity was highest with the following parameters: thermal desorption temperature, 300 °C; 0.1% formic acid aqueous solution-methanol (1:1,V:V) solvent; syringe pump flow rate, 150 μL/h; and sampler length, 5 cm. Good linearity was attained within the appropriate linear range with the detection limits ranging from 0.01–0.05 mg/L. The same positive sample was verified for QuEChERS pretreatment coupled with liquid chromatography tandem mass spectrometry, showing good agreement with TD-ESI/MS. The newly developed method was demonstrated to be a rapid, green, and efficient analytical method for screening 15 highly toxic pesticide residues in Angelica sinensis decoctions.

AbstractIn the present study, conditions for succinic acid (SA) production using xylose mother liquor (XML) as culture medium by Actinobacillus succinogenes GXAS137 were optimized. Firstly, single–factor experiments were performed to evaluate the basal culture medium for SA fermentation. Thereafter, the Plackett–Burman design was used to screen out three significant factors of XML, corn steep liquor powder (CSLP) and MgCO3 affecting the SA yields from the original nine factors. Subsequent use of steepest ascent experiment determined the center area of the three factors. Finally, the response surface methodology was used to further optimize the interactions between the three main factors and predict the maximum SA concentration through Box-Behnken design. The optimal conditions of SA fermentation were maximally documented in the XML (110 g/L), CSLP (18.86 g/L) and MgCO3 (69.12 g/L). The maximum production of SA was 58.06 ± 0.57 g/L after 60 h with a yield of 0.72 ± 0.06 g/g total sugar, approaching the predicted value (57.99 g/L). It was 1.63-fold of the SA production obtained with the basic medium (35.54 g/L). In addition, batch fermentations were carried out in a 1.3-L stirred bioreactor and SA reached 58.47 g/L. These results indicate that XML could be an alternative substrate for the economical production of SA by A. succinogenes GXAS137.

Abstract Background Esophageal carcinoma is the highly lethal cancer in the world, predominantly in some areas of East Asia. We previously reported that overexpression of cytoskeleton regulator Wiskott-Aldrich syndrome protein and SCAR Homolog (WASH) associates with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC). However, the molecular mechanism and clinical significance involved in WASH overexpression have not been fully elucidated. Methods Bioinformatics analysis and luciferase reporter assay were used to predict and validate miR-637 as a regulator of WASH in ESCC cell lines. qRT-PCR, Western blotting and ELISA assays were performed to examine RNA expression and protein levels, respectively. Next, the biological functions of miR-637 were explored by tumor sphere formation assay in vitro and nude mouse tumor xenograft in vivo. Finally, we evaluated the association of miR-637 levels with clinical features in ESCC patients. Results We identified miR-637 as a WASH-targeting miRNA. miR-637 mimic strongly attenuated the downstream IL-8 production and tumor sphere formation in esophageal cancer cells, whereas miR-637 inhibitor displayed an opposite effect. IL-8 could facilitate stem-like properties and partially rescue the phenotypes induced by miR-637 mimic. Furthermore, miR-637 inhibitor dramatically promoted IL-8 expression and cancer stemness properties in a WASH-dependent manner. Ectopic expression of miR-637 also inhibited tumor growth in a mouse model. Clinically, low expression of miR-637 was observed in tumor tissues and the low expression levels of miR-637 were correlated with poor survival of ESCC patients. In particular, plasma miR-637 could be used as a noninvasive biomarker for ESCC patients. Conclusions These results implicate the potential application of miR-637 for diagnosis and prognosis of esophageal cancer.

Abstract Background Insulin-like peptide 5 (INSL5) is involved in both reproductive and metabolic processes in polycystic ovary syndrome (PCOS). This study aimed to evaluate the relationship between INSL5 and anti-Müllerian hormone (AMH). Methods A retrospective case–control study was conducted in a university-based reproductive centre between December 2019 and January 2021. We included 117 women with PCOS and 100 healthy subjects from Zhejiang Province. All subjects were divided into four groups (1st–4th) based on quartiles of serum INSL5 levels. Serum INSL5 concentration was assayed using an enzyme-linked immunosorbent assay. Results A significant direct association was observed between serum INSL5 and AMH levels in women with PCOS. The mean AMH level in the 1st–4th INSL5 level quartiles were 4.64, 5.20, 6.46, and 9.48 ng/ml, respectively (P

As we all know, YOLOv4 can achieve excellent detection performance in object detection and has been effectively applied in many fields. However, the inconsistency of scale features affects the prediction accuracy of the path aggregation network (PANet) in YOLOv4 for small objects, resulting in low detection accuracy. This paper presents YOLOv4, which uses an adaptive recursive path aggregation network (AR-PANet) to improve the detection accuracy of small objects. First, the output characteristics of the PANet are fed back into the backbone network by using a recursive structure to enrich the characteristic information of the object. Second, an adaptive approach is developed to eliminate conflicting information in multi-scale feature space, thereby enhancing scale invariance and promoting feature extraction accuracy for small objects. Finally, the CBAM is used to map the multi-scale features obtained from the AR-PANet to independent channels and spatial dimensions to achieve feature refinement, thus improving the detection accuracy of small objects. Experimental results show that our proposed method can effectively improve the accuracy of small object detection in multiple datasets, addressing this challenging problem with impressive results. Thus, our proposed approach has great potential and valuable applications in the fields of remote sensing and intelligent transportation.

Due to the gradual adoption of WeChat by older adults in China and their interest in health information, Chinese older people started to acquire health information through WeChat. We explored the specific patterns and influencing factors of the elderly's health information acquisition behavior senior adults. The cross-sectional study collected self-reported data with survey (N = 336) in the southeast of China, Zhejiang province. The findings of this study extend the previous research by suggesting that elderly adults' health information acquisition behavior has three patterns (actively seeking, passively browsing, and long-term collecting). These findings contribute to a better understanding of digital literacy, three dimensions of health literacy and their relationship with three specific patterns of health acquisition behavior. This study also provides practical insights related to narrow the technological gap of the older adults, improve their e-Health literacy of the elderly, and purify the health information environment in the network.

The potential negative impacts of organochlorine pesticides on the environment and human health continue to receive attention. In order to study the spatial distribution characteristics of organochlorine pesticides in the inland alpine region, researchers collected soil and water samples in the Huangshui River Basin of the Qinghai–Tibetan Plateau and tested them for organochlorine pesticide residues represented by dichlorodiphenyltrichloroethane (DDT) and hexachlorohexane (HCH). The study identified the sources of OCPs by component analysis. We also constructed the LEVEL III model, applicable to the Huangshui River Basin, and used it to study the migration patterns of OCPs in various environmental media. OCPs were detected at low levels in the study area environment. The results of the OCPs source analysis show that there are both historical residuals and new sources in the region. Residual DDTs may originate from the mixture of technical DDTs and dicofol, and HCHs may originate from lindane or technical HCH. DDTs are mainly stored in soil, the input and output pathways are mainly atmospheric advection input and output, and its transport behavior in the environment is mainly air–soil exchange. Carcinogens in the study area pose little threat to people exposed to contaminated soil and contaminated water, but the cancer risk to children is greater than to adults. This study is helpful to managers of regional pesticide management and control.

Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years. A major challenge of cancer vaccine is to target cytosols of dendritic cells (DCs) in the lymph nodes (LNs) to enhance efficiency of antigen cross-presentation, which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells. Here, we address this issue by conjugating ovalbumin (OVA) to PEG-PCL using disulfide bond (-ss-), and the degradable pH-responsive polymer-PEI-PCL as delivery carrier. In addition, the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs. Subsequently, CpG ODN1826, a TLR-9 agonist, was further introduced into a mixed micelle of 30 nm or less as a unique tumor vaccine. Importantly, the results demonstrated the mixed micelles with 1:1 mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs, meanwhile, OVA was modified to the surface of mixed micelles via disulfide bonds (-ss-) for promotion efficiency of antigen cross-presentation. More surprisingly, combination of tumor vaccine with anti-PD-1, the therapy of ectopic melanoma (B16-OVA) and lung metastasis melanoma (B16-OVA) is excellent therapeutic effect. Taken together, our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.

Purpose – With increasing marine resource development, the rapid development of the marine economy, and the continuous decline of the marine natural resource system, the contradiction between marine resources and economic development is becoming increasingly acute. The study of marine resources and economic development has become a hot and challenging issue in marine resource economics research in recent years. The purpose of this study is to analyze the current situation of marine resources and to realize the sustainable use of marine resources. Design/methodology/approach – This study systematically reviews and analyzes the current status of research on marine resources and economic development issues in four main aspects: marine resource management, marine resources and economic growth, marine resources and economic security, and marine resource accounting in the field of marine resource economics. Findings – It is found that compared to the current status of research on land-based resources and economic development, there is a significant lag in both theoretical construction and methodological innovation in marine resources and economic development. Originality/value – The purpose of this study is to systematically grasp the current status of marine resources research, promote the coordinated development of marine resources and economic growth, and then realize the safe and sustainable development and utilization of marine resources.

As emerging pollutants of global concern, absorbed nanoplastics might have negative impacts on plant development and nutrient uptake, thereby decreasing yields. If nanoplastics are transferred to the edible parts of plants, they may pose a threat to human health when large quantities are ingested. While nanoplastic-induced phytotoxicity is attracting increasing attention, little is known about how to inhibit nanoplastic accumulation in plants and reduce the subsequent adverse effects. Here we investigated the absorption and accumulation of polystyrene nanoplastics (PS-NPs) in different plant species and the role of brassinosteroids in alleviating PS-NP toxicity. Brassinosteroids inhibited accumulation of PS-NPs in tomato fruit and reversed PS-NP-induced phytotoxicity to promote plant growth and increase fresh weight and plant height. Brassinosteroids also reversed the induction of aquaporin-related genes by PS-NPs including TIP2-1, TIP2-2, PIP2-6, PIP2-8, PIP2-9, SIP2-1, and NIP1-2, providing a potential stress mechanism by which PS-NPs accumulate in the edible parts and targets for inhibition. In transcriptomic analyses, brassinosteroids enhanced fatty acid and amino acid metabolism and synthesis. In conclusion, exogenous application of 50 nM brassinosteroids alleviated the adverse effects of PS-NPs on plants, and exogenous application of brassinosteroids might be an effective means to minimize PS-NP-induced phytotoxicity.

Cancer-associated fibroblasts (CAFs) are one of the most abundant stromal cells in the tumor microenvironment which mediate desmoplastic response and are the primary driver for an immunosuppressive microenvironment, leading to the failure of triple-negative breast cancer (TNBC) immunotherapy. Therefore, depleting CAFs may enhance the effect of immunotherapy (such as PD-L1 antibody). Relaxin (RLN) has been demonstrated to significantly improve transforming growth factor-β (TGF-β) induced CAFs activation and tumor immunosuppressive microenvironment. However, the short half-life and systemic vasodilation of RLN limit its in vivo efficacy. Here, plasmid encoding relaxin (pRLN) to locally express RLN was delivered with a new positively charged polymer named polymeric metformin (PolyMet), which could increase gene transfer efficiency significantly and have low toxicity that have been certified by our lab before. In order to improve the stability of pRLN in vivo, this complex was further formed lipid poly-γ-glutamic acid (PGA)/PolyMet-pRLN nanoparticle (LPPR). The particle size of LPPR was 205.5 ± 2.9 nm, and the zeta potential was +55.4 ± 1.6 mV. LPPR displayed excellent tumor penetrating efficacy and weaken proliferation of CAFs in 4T1luc/CAFs tumor spheres in vitro. In vivo, it could reverse aberrantly activated CAFs by decreasing the expression of profibrogenic cytokine and remove the physical barrier to reshape the tumor stromal microenvironment, which enabled a 2.2-fold increase in cytotoxic T cell infiltration within the tumor and a decrease in immunosuppressive cells infiltration. Thus, LPPR was observed retarded tumor growth by itself in the 4T1 tumor bearing-mouse, and the reshaped immune microenvironment further led to facilitate antitumor effect when it combined with PD-L1 antibody (aPD-L1). Altogether, this study presented a novel therapeutic approach against tumor stroma using LPPR to achieve a combination regimen with immune checkpoint blockade therapy against the desmoplastic TNBC model.

Nanoplastics (NPs) and acetaminophen (APAP) are thought to be common contaminants and are invariably detected in the environment. Despite the increasing awareness of their toxicity to humans and animals, the embryonic toxicity, skeletal development toxicity, and mechanism of action of their combined exposure have not been clarified. This study was performed to investigate whether combined exposure to NPs and APAP induces abnormal embryonic and skeletal development in zebrafish and to explore the potential toxicological mechanisms. All zebrafish juveniles in the high-concentration compound exposure group showed some abnormal phenomena such as pericardial edema, spinal curvature, cartilage developmental abnormality and melanin inhibition together with a significant downward trend in body length. Behavioral data also implicated that the exposure of APAP alone, as well as the co-exposure of NPs and APAP, caused a depression in the total distance, swimming speed and the maximum acceleration. Furthermore, real-time polymerase chain reaction analysis showed that compared with exposure alone, the expression level of genes related to osteogenesis, runx2a, runx2b, Sp7, bmp2b and shh was significantly reduced with compound exposure. These results suggest that the compound exposure of NPs and APAP has adverse impacts on zebrafish embryonic development and skeletal growth.

Knowledge on the distribution of rapeseed enables accurate yield forecasting and supports agricultural planning to assist global security in edible oil supply. Large-scale remotely sensed maps of rapeseed nevertheless are non-existent in China because of landscape fragmentation, cloudy weather conditions, and phenological variations. Existing rapeseed mapping methods based on spectral, phenological, and machine learning algorithms are challenging to accurately and seamlessly extract the planting distribution of rapeseed over a large spatial region. In view of this, the annual extent of rapeseed in the Yangtze River Economic Belt (YREB) of China from 2017 to 2021 was mapped. Multisource data including Sentinel-1/2, Google Earth very-high-resolution (GE-VHR) images, and Global Land Data Assimilation System (GLDAS) data were used to develop a systematic methodology. First, the ground reference dataset was collected from fieldwork and all available GE-VHR images to construct a rapeseed point collection (RPC). Second, RPC, Sentinel-1, and GLDAS data were used to estimate the annual rapeseed peak-flowering date maps (RPDMs) based on a random forest regression model. Third, a hybrid mapping strategy was implemented on Google Earth Engine leveraging the dense Sentinel-1/2 data to generate the annual seamless 10 m rapeseed extent maps (REMs). Accuracy assessment illustrates the reliability of the RPDM with an R2 of 0.86 (RMSE = 5.32 days). Comparisons with other rapeseed mapping methods and comprehensive validation attest to the high precision of the REMs, with an average F1 score of 0.93. Moreover, the rapeseed cultivation area decreased over the five study years. Rapeseed fields in the YREB are highly fragmented, averaging 18 per ha, but trend analysis suggests a potential for crop intensification. This study provides an essential reference and information service for rapeseed production and agricultural resource survey in China.

Steel strands have been widely used in industrial fields as a reliable load-bearing component. Under the influence of environmental erosion and fatigue stress, different types of damage, such as corrosion and fracture, will occur in the in-service steel strands, which will cause unpredictable loss of personnel and property. Ultrasonic nondestructive testing technology has become an ideal testing method for long-distance metal structures in recent years due to the advantages of long detection distance and high efficiency. The detection effect of ultrasonic nondestructive testing technology largely depends on the propagation characteristics of the selected guided wave modes. However, due to the influence of the helical structure of the steel strands and the contact between the wires, the propagation characteristics of the guided waves in the steel strands are very complicated. In this paper, a method for analyzing the dispersion characteristics of steel strands based on the Floquet boundary conditions (Floquet BCs) is proposed. The essence of this method is the mutual transformation principle of wave solution and vibration solution. To adapt to the helical structure of steel strands, this paper proposes a helical coordinate system and twisted coordinate system and deduces the corresponding wavenumber conversion formula. The results of Floquet BCs are consistent with the semi-analytical finite element method and sweep frequency finite element modeling method, which proves the correctness of the Floquet BC method from both theoretical and experimental perspectives. This paper provides a new idea for analyzing the dispersion characteristics of complex waveguides such as steel strands.

Structural variations (SVs) are a key type of cancer genomic alterations, contributing to oncogenesis and progression of many cancers, including colorectal cancer (CRC). However, SVs in CRC remain difficult to be reliably detected due to limited SV-detection capacity of the commonly used short-read sequencing. This study investigated the somatic SVs in 21 pairs of CRC samples by Nanopore whole-genome long-read sequencing. 5200 novel somatic SVs from 21 CRC patients (494 SVs / patient) were identified. A 4.9-Mbp long inversion that silences APC expression (confirmed by RNA-seq) and an 11.2-kbp inversion that structurally alters CFTR were identified. Two novel gene fusions that might functionally impact the oncogene RNF38 and the tumor-suppressor SMAD3 were detected. RNF38 fusion possesses metastasis-promoting ability confirmed by in vitro migration and invasion assay, and in vivo metastasis experiments. This work highlighted the various applications of long-read sequencing in cancer genome analysis, and shed new light on how somatic SVs structurally alter critical genes in CRC. The investigation on somatic SVs via nanopore sequencing revealed the potential of this genomic approach in facilitating precise diagnosis and personalized treatment of CRC.

Abstract Background Fusarium wilt of banana is a soil-borne disease caused by Fusarium oxysporum formea speciales (f.sp.) cubense with the Tropical Race 4 (FOC TR4), which seriously restricts the development of the banana industry. The utilization of antagonistic microorganisms to inhibit the propagation of pathogens has become a hot research topic in the field of biological prevention and control because of its green and efficient advantages. Results In this study, 60 siderophore strains from banana rhizosphere soil were screened. Three strains showing antifungal activity were screened out using FOC TR4 as the antagonistic pathogen. Among them, the strain Gxun-6 showed the highest antifungal activity, of up to 68.8%. It also showed significant inhibitory effect on the other 8 plant pathogens tested, thereby demonstrating broad-spectrum antifungal activity. Combined with colony morphology, physiological and biochemical analysis, and 16S rRNA evolutionary tree analysis, Gxun-6 was identified as Bacillus siamensis. Pot experiments showed that this strain had remarkable Fusarium wilt prevention and growth-promoting effect on banana. The control effect can reach 88.26%. The fresh weight increased by 25.36%. Conclusions The strain had strong Fusarium wilt control and growth promoting effects on banana and can be used as a strain resource for developing banana.

Abstract Background Feathers are the most abundant agricultural waste produced by poultry farms. The accumulation of a large number of feathers not only seriously pollutes the environment but also causes the waste of protein resources. The degradation of feather waste by keratinase-producing strains is currently a promising method. Therefore, screening high-producing keratinase strains from marine environment and studying the fermentation conditions, enzymatic properties and feather degradation mechanism are crucial for efficient degradation of feathers. Results A novel efficient feather-degrading bacteria, Gxun-17, isolated from the soil sample of a marine duck farm of Beibu Gulf in Guangxi, China, was identified as Bacillus tropicus. The optimum fermentation conditions were obtained by single factor and orthogonal tests as follows: feather concentration of 15 g/L, maltose concentration of 10.0 g/L, MgSO4 concentration of 0.1 g/L, initial pH of 7.0 and temperature of 32.5 °C. The strain completely degraded the feathers within 48 h, and the highest keratinase activity was 112.57 U/mL, which was 3.18-fold that obtained with the basic medium (35.37 U/mL). Detecting the keratinase activity and the content of sulphur-containing compounds in the fermentation products showed that the degradation of feathers by the strain might be a synergistic effect of the enzyme and sulphite. The keratinase showed optimal enzyme activity at pH 7.0 and temperature of 60 °C. The keratinase had the best performance on the casein substrate. When casein was used as the substrate, the Km and Vmax values were 15.24 mg/mL and 0.01 mg/(mL·min), respectively. Mg2+, Ca2+, K+, Co2+, Al3+, phenylmethylsulphonyl fluoride and isopropanol inhibited keratinase activity, which indicated that it was a serine keratinase. Conversely, the keratinase activity strongly increased with the addition of Mn2+ and β-mercaptoethanol. Conclusions A novel feather-degrading B. tropicus Gxun-17 was obtained from marine environment. The strain adapted the extreme conditions such as low temperature, high salt and high pressure. Thus, the keratinase had high activity, wide range of temperature and pH, salt tolerance and other characteristics, which had potential application value.

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8+ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

Complex networks have encouraged scholars to develop an effective method for abstracting and optimizing aviation networks. However, researchers often overlook the aviation network’s temporal attribute and treat it as a static network. Aviation networks have strong temporal characteristics and the dynamic connection cannot be realistically described by a static network. It is necessary to more accurately and realistically represent these connections during the operation of an aviation network. This study explored temporal structures of the Chinese aviation temporal network (CATN) based on flight schedules and actual operational time data. Temporal networks based on time windows were represented to analyze the temporal topology features and robustness of the CATN. The results demonstrated the following: (1) based on the spatial-temporal aviation network, there is a morning departure peak (7:00–8:00) and an evening arrival peak at the airline hub (20:00–21:00); (2) examining the centrality of each airport in the CATN at various time intervals exposed fluctuations in their rankings, which could not be identified by a static network, and (3) the robustness of the CATN was found to be unaffected by time windows, but it displayed poor resilience against deliberate attacks, particularly when subjected to betweenness and closeness attacks, which target the network’s shortest paths. For obtaining a greater understanding of the operating situation of civil aviation, displaying the topological features and robustness of the temporal network is of great importance.

Current toxicology research on nanoplastics (NPs) generally uses commercial spherical NPs. However, the physicochemical characteristics of commercial NPs are significantly different from those of NPs formed under natural conditions, possibly affecting the validity of the results. In analytical chemistry, a reference sample is selected such that its physicochemical properties are as similar as possible to the target. Therefore, a simulated “natural” NP synthesized in the laboratory that closely resembles naturally derived NPs would be used as an authentic standard. Here, we established the assay of scanning electron microscope (SEM)-particle size distribution analyzer (PSDA)-surface-enhanced Raman scattering (SERS) to detect NPs and prepared simulated “natural” NPs from polypropylene food packaging material using a method that mimics natural conditions. Nanofiltration was used to isolate three sets of simulated NPs with particle sizes ranging from 50–100 nm, 100–200 nm, and 200–400 nm. These simulated “natural” NPs were more similar to naturally occurring counterparts when compared with commercial NPs. These new standard NPs, which should be scalable for large-scale use, will improve the accuracy, reliability, and translatability of toxicological studies of NPs.

Atmospheric organic aerosol (OA) affects air quality and human health. However, compared with urban areas, the chemical composition and temporal distribution of OA in rural regions are still not well understood. In this study, one-year atmospheric particles with an aerodynamic equivalent diameter of ≤2.5 μm (PM2.5) were collected at a rural site in Quzhou County, the North China Plain (NCP), from August 2020 to July 2021. OA in PM2.5 samples were analyzed with an ultrahigh-performance liquid chromatograph (UHPLC) coupled to an ultrahigh-resolution Orbitrap mass spectrometer in negative mode (ESI−). The results show that the chemical composition and properties of OA varied in different seasons. According to the hierarchical cluster analysis, the molecular formulas of winter OA were close to those in spring, whereas the chemical composition of OA in summer and autumn was similar. The O/C ratio of summer OA was the highest at 1.21, followed by that in autumn (0.92) and spring (0.87), while the winter OA had the lowest O/C ratio of 0.64. It indicates that, compared to the other three seasons, OA underwent more intense oxidation processes in the summer. Moreover, winter OA contained more aromatic compounds with a relative peak abundance fraction of 40%, which may be related to anthropogenic sources (e.g., coal burning) in the winter in the NCP. In addition, biomass burning is considered an important source of OA in the rural region of Quzhou County, the NCP, in all seasons.

Configuration-controllable metamaterials are a kind of metamaterials whose bandgaps can be effectively adjusted through configuration control, but the configuration changes also produce initial stress. In this paper, the distribution of the initial stress of the configuration-controllable metamaterial under axial displacement and the influence of initial stress on the band gap characteristics of the structure were analyzed using numerical and experimental methods. The results show that initial stress has a significant influence on the bandgap characteristics, and the position and width of the bandgap change with the magnitude of the initial stress. The bandgap distribution of the structure after considering the initial stress is more consistent with the reported experimental results. The influence of initial stress on bandgap cannot be ignored. When the compressive loading displacement is 10 mm, the frequency range of the first bandgap is 262 Hz–310 Hz and that of the second bandgap is 394 Hz–405 Hz. And the frequency range of the first and second bandgaps will be converted into 254 Hz–291 Hz and 391 Hz–400 Hz when considering initial stress. The initial stress generated by compression deformation reduces the frequency of the structural bandgap. The beginning and ending frequencies of the first bandgap will move toward low frequencies, and the first bandgap will close when the compression displacement reaches 30 mm. The initial stress generated by tensile deformation increases the frequency of the structural bandgap. The beginning and ending frequencies of the first bandgap move toward high frequencies, and the bandgap will close when the tensile displacement is 30 mm.