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Abstract Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.

The structure of vascular bundles and the mechanical properties of fibers are crucial factors determining the utilization of bamboo. This study investigated the structure of vascular bundles and evaluated the morphological and micromechanical properties of the fibers in Oligostachyum sulcatum. The results showed that the fiber length and width of O. sulcatum meet the requirements of raw materials for the papermaking process. However, the fiber content in O. sulcatum is relatively low, which may increase the cost of papermaking. The vascular bundle growth exhibited non-uniformity, especially at the top part, with no discernible pattern in bundle area changes. The nanoindentation testing demonstrated that the bamboo's indentation modulus of elasticity (IMOE) and hardness values were comparable to those of moso bamboo (Phyllostachys edulis), suggesting its potential as a substitute in engineering applications.

Abstract Most of the adversarial attacks against speech recognition systems focus on specific adversarial perturbations, which are generated by adversaries for each normal example to achieve the attack. Universal adversarial perturbations (UAPs), which are independent of the examples, have recently received wide attention for their enhanced real-time applicability and expanded threat range. However, most of the UAP research concentrates on the image domain, and less on speech. In this paper, we propose a staged perturbation generation method that constructs CommanderUAP, which achieves a high success rate of universal adversarial attack against speech recognition models. Moreover, we apply some methods from model training to improve the generalization in attack and we control the imperceptibility of the perturbation in both time and frequency domains. In specific scenarios, CommanderUAP can also transfer attack some commercial speech recognition APIs.

Hydrological changes in groundwater coupled with earthquakes had been documented in previous studies by global researchers. Although few reports investigate multiple geochemical parameters that respond to earthquakes, trace elements received less attention, whereas they were suggested to be more sensitive to small earthquakes than the commonly used geochemical parameters. Beijing is located in the Zhangjiakou-Bohai (Zhang-Bo) seismic belt of North China, and although the occurrence of small earthquakes is frequent, the great historic earthquake in the Sanhe-Pinggu area M8 in 1679 in the adjoining southeast of Beijing gained widespread public attention. To find effective precursors that are significant for operational earthquake forecasting of the Beijing area, we carried out a one year test research project through weekly collection of groundwater samples during June 2021 to June 2022 from the seismic monitoring well of Wuliying in northwest Beijing. The 41 trace elements chemical compositions were analyzed for each sample. During the project ongoing period, the biggest earthquake with a magnitude of ML3.3 occurred in the Chaoyang District of Beijing on 3 February 2022. The content changes in these trace elements were systematically monitored before and after the earthquake. Through retrospective research, it was found that a few sensitive trace elements were anomalous to be coupled to the earthquake, including Li, Sc, Rb, Mo, Cs, Ba, W, U, Sr, Mn, Ni, and Zn. In addition to trace elements, we examined stable isotopes of hydrogen and oxygen and the existing hydrological data on groundwater level, temperature, major ions, and gases to assess the validity of geochemistry as a monitoring and predictive tool. We only found that F- (fluorine) ions and He (helium) gas had apparent shifts related to the earthquakes, while no shifts in the groundwater level were observed. Such characteristics of multiple geochemical parameters indicate that trace elements are likely to be more sensitive to crustal strain than the groundwater level and major ions. We assumed a most likely mechanism of the combination of mixing and water–rock interactions to explain the phenomenon. The probable scenario was that minor stresses caused by the earthquakes might create micro-cracks in bedrocks, thereby leading to a small volume of chemically distinct water mixing with the original water of the aquifer, and finally, the earthquake-induced rock fractures enhance the water–rock interactions, resulting in the post-seismic recovery of trace elements and δ18O value migration to the GWML. More testing works to find other sensitive sites to investigate multiple geochemical characteristics aiming at long-term to short-term earthquake prediction in the Beijing area and Zhang-Bo seismic belt are in progress.

Joint toxicity of organic-metal co-contamination can vary depending on organisms, toxicants, and even the sequence of exposure. This study examines how the combined toxicity of aniline (An) and cadmium (Cd) to soil bacteria in microcosms changes when the order of contaminant introduction is altered. Through analyzing biodiversity, molecular ecological network, functional redundancy, functional genes and pathways, we find the treatment of Cd followed by An brings about the strongest adverse impact to the bacterial consortium, followed by the reverse-ordered exposure and the simple mixture of the two chemicals. On the level of individual organisms, exposure sequence also affects the bacteria that are otherwise resistant to the standalone toxicity of both An and Cd. The dynamic behavior of aniline-cadmium composite is interpreted by considering the tolerance of organisms to individual chemicals, the interactions of the two toxicants, the recovery time, as well as the priority effect. The overall effect of the composite contamination is conceptualized by treating the chemicals as environmental filters screening the growth of the community.

Corona virus disease 2019(COVID-19) is one of the most serious respiratory pandemic diseases threatening human health for centuries. Alopecia areata (AA) is a sudden patchy hair loss, an autoimmune disease, which seriously affects the image and mental health of patients. Evidence shows that the risk of autoimmune diseases significantly increases after COVID-19, and is positively correlated with the severity, with a significant increase in the risk of alopecia in those over 40 years old. The relationship between COVID-19 and AA has become a hot topic of current research. Strengthening the research on the correlation between COVID-19 and AA can help to identify and protect susceptible populations at an early stage. This article reviews the research progress on the epidemiological background of COVID-19 and AA, the situation and possible mechanisms of AA induced by COVID-19 or COVID-19 vaccination, and potential treatment methods.

Abstract Background Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. Methods We employed LC–MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. Results There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p

Water pollution caused by textile dyes is considered a major and growing issue. To address this challenge, in this research, water-stable Cu-MOFs/GO composite catalysts were produced using the hydrothermal synthesis method as an efficient persulfate (PDS) activator for methyl orange (MO) degradation. We also explored the changes in surface morphology, crystal structure, surface functional groups, and valence states of the materials before and after the introduction of GO by Cu-MOFs. It was shown that Cu-MOFs/GO demonstrates a more stable surface structure, and the unique folded structure of GO provides a better hydrophobic environment for Cu metal cluster hence making MOF easier to grow. The Cu-MOFs/GO-PDS system showed a high activation performance on persulfate in a wide pH range (3–11), meanwhile, was less affected by the presence of natural anions in the environment and more inhibited by natural organic matter citric acid. Furthermore, the Cu-MOFs/GO had excellent stability, reusability and structural integrity, and the removal rate of MO was maintained after five cycles. In terms of oxidation mechanism, in addition to the generation of ·SO4− and OH· radicals, there were also singlet oxygen 1O2 and active Cu(III) in the system, and all of these active substances contributed to the removal of pollutant MO.

Abstract Background Many researchers have examined the impact of social insurance on health in elderly. However, in most cases, they have only demonstrated correlational results and have not been able to determine causal effects, possibly because confounding biases have not been fully addressed. In this study, we investigated the health effects of the New Rural Pension Scheme (NRPS) on the elderly (age≥60 years old) with chronic diseases in rural areas, and to explore the causal relationship and effects of NRPS and health status. Methods This paper used data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) and applied Bayesian networks and fuzzy regression discontinuity design to conduct causal analysis. Bayesian networks were used to explore the causal directed acyclic graphs of factors related to NRPS and health status. Based on the results of Bayesian network, a fuzzy regression discontinuity design was employed to estimate the causal effect of NRPS on health status. Results Among rural elderly with chronic diseases, Bayesian network mapping of causal relationships among NRPS, health status and covariates showed that age was a common cause of NRPS receipt and satisfaction with health. The results of the fuzzy regression discontinuity analysis showed that the effect of receiving NRPS on the health status was positive, but there was no statistically significant difference concerning the interval estimates. The results of the subgroup analysis with chronic obstructive pulmonary disease (COPD) and asthma indicated that the effect of NRPS receipt on the health status of elderly people with COPD was positive. There was a statistically significant effect of receiving NRPS on self-rated health description ( $${\beta }_{1}=3.653,P=0.032$$ β 1 = 3.653 , P = 0.032 ) and health satisfaction ( $${\beta }_{1}=4.204,P=0.033$$ β 1 = 4.204 , P = 0.033 ) in COPD population and a statistically significant effect of receiving NRPS on health satisfaction in asthma population ( $${\beta }_{1}=9.844,P=0.008$$ β 1 = 9.844 , P = 0.008 ). Conclusion This paper has confirmed the contribution and positive causal effect of NRPS on health status in a subgroup of older adults with COPD and asthma, using the CHARLS database as evidence. Thus, Chinese government should increase the take-up rate of the NRPS to enhance their positive impact on health status of elderly people with chronic diseases in rural areas.

Abstract In recent years, deep learning (DL) models have achieved significant progress in many domains, such as autonomous driving, facial recognition, and speech recognition. However, the vulnerability of deep learning models to adversarial attacks has raised serious concerns in the community because of their insufficient robustness and generalization. Also, transferable attacks have become a prominent method for black-box attacks. In this work, we explore the potential factors that impact adversarial examples (AEs) transferability in DL-based speech recognition. We also discuss the vulnerability of different DL systems and the irregular nature of decision boundaries. Our results show a remarkable difference in the transferability of AEs between speech and images, with the data relevance being low in images but opposite in speech recognition. Motivated by dropout-based ensemble approaches, we propose random gradient ensembles and dynamic gradient-weighted ensembles, and we evaluate the impact of ensembles on the transferability of AEs. The results show that the AEs created by both approaches are valid for transfer to the black box API.

In this work, the initial-boundary value problem for the global dynamical properties of solutions to a class of finite degenerate fourth-order parabolic equations with mean curvature nonlinearity is studied. With the help of the Nehari flow and Levine's concavity method, we establish some sharp-like threshold classifications of the initial data under sub-critical, critical and supercritical initial energy levels, that is, we describe the size of an initial data set. It requires the presumption that the initial data starting from one region of phase space have uniform global dynamical behavior, which means that the solution exists globally and decays via energy estimates that ultimately result in the solution tending to zero in the forward time. For the case in which the initial data corresponds to another region, we prove that the solutions related to these initial data are subject to blow-up phenomena in a finite time. In addition, we estimate the corresponding upper bound of the lifespan of the blow-up solution.

Background: Understanding undergraduates’ dietary literacy, including dietary knowledge, attitude and practice (KAP), is important for future health promotion policies. Therefore, this study aimed to investigate the current status and influencing factors of dietary literacy in Chinese college undergraduates and explore whether a nutritional lecture could improve their dietary literacy. Methods: This study included two parts: a cross-sectional study (n = 1026) conducted by a dietary literacy questionnaire, and a randomized controlled trail (RCT) that enrolled 99 college undergraduates who were randomized to a control group or a nutritional lecture group. Data from the questionnaire and 72 h food records were obtained on day 0, day 3 and day 100 before and after intervention. Results: This cross-sectional study showed that the mean scores of dietary KAP were respectively 100.0 (33.3), 59.1 (13.6) and 71.7 (11.7), with an excellent rate of 36.6%, 1.9% and 3.4%. Female upper-grade undergraduates and those with medicine-related majors illustrated higher dietary knowledge scores (p < 0.001). Dietary attitude rather than dietary knowledge had a significant impact on dietary practice (p < 0.001). This finding was in line with the results in the RCT study. Compared with the control group, dietary knowledge was significantly improved in the nutritional lecture group on both day 3 (p = 0.002) and day 100 (p = 0.023) after intervention. However, dietary behavior was improved only on day 3 post nutritional lecture (p = 0.029) but decreased to the original level 100 days later (p < 0.001). Conclusions: This study discovered the unsatisfying status and discrepancy between dietary literacy among college undergraduates of different sex, majors and college years. Dietary attitude instead of dietary knowledge was discovered as a determining role in dietary practice. One nutritional lecture could improve undergraduates’ dietary literacy but the effect was not long-lasting. Further studies with more reinforced and durable interventions are warranted.

Quantum interference (QI) has been widely studied in advanced materials and can be exploited to control the nonlinear response by varying the relative phase between the incident optical pulses. However, the contribution of the coherent injected photocurrent by QI from the indirect gap materials is still unclear because of the much weaker phonon-assisted absorption compared with that from the direct gap materials. Here, we investigate the coherent injected photocurrent in mono- and multilayer MoS2 with thickness at the nanometer scale under 2-color light excitation by detecting the generated coherent terahertz (THz) wave. We observe that the THz radiation can be controlled by the relative phase. Besides, we obtain similar experimental results of the THz wave generation from mono- and multilayer MoS2 when we change the relative polarization angle between 𝜔 and 2𝜔 pulses, in comparison to the case of direct gap materials. Thus, these experimental results further verify that, in multilayer MoS2 with an indirect gap, QI in the direct gap region is the dominant process for the THz wave generation. Furthermore, we demonstrate that QI can be a more effective mechanism to induce THz radiation than optical rectification under single-color light excitation. This study enhances the understanding of QI in indirect gap materials and highlights the potential of 2-color light excitation for investigating third-order nonlinear processes in advanced materials.

The swelling agent is a plant growth regulator that alters the composition and content of nutrients and volatile gases in the fruit. To identify whether grape fruit had been treated with swelling agent, the odor information and quality indexes of grape berries treated with different concentrations of swelling agent were examined by using electronic nose technology and traditional methods. The contents of soluble sugars, soluble solids, soluble proteins and vitamin C were significantly increased in N-(2-chloro-4-pyridyl)-N’-phenylurea (CPPU) treated fruit. The contents of hexanal, (E)-2-hexenal, and nonanal aldehydes decreased significantly. Similarly, the levels of phenyl ethanol, 1-octanol, ethanol, and ethyl acetate alcohols and esters also decreased noticeably. Additionally, the levels of damascenone, linalool, and geraniol ketones and terpenoids decreased. However, the contents of benzaldehyde, D-limonene, acetic acid and hexanoic acid increased. In addition, the electrical signals generated by the electronic nose (e-nose) were analyzed by linear discriminant analysis (LDA), support vector machine (SVM) and random forest (RF). The average recognition rate of SVM was 94.4%. The results showed that electronic nose technology can be used to detect whether grapes have been treated with swelling agent, and it is an economical and efficient detection method.

Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype-Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)-regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (CHPF2, PYGL, GALNT13, EXT2, and COLGALT2) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy.

Abstract Introduction Multidisciplinary team meetings (MDMs), also known as tumor conferences, are a cornerstone of cancer treatments. However, barriers such as incomplete patient information or logistical challenges can postpone tumor board decisions and delay patient treatment, potentially affecting clinical outcomes. Therapeutic Assistance and Decision algorithms for hepatobiliary tumor Boards (ADBoard) aims to reduce this delay by providing automated data extraction and high-quality, evidence-based treatment recommendations. Methods and analysis With the help of natural language processing, relevant patient information will be automatically extracted from electronic medical records and used to complete a classic tumor conference protocol. A machine learning model is trained on retrospective MDM data and clinical guidelines to recommend treatment options for patients in our inclusion criteria. Study participants will be randomized to either MDM with ADBoard (Arm A: MDM-AB) or conventional MDM (Arm B: MDM-C). The concordance of recommendations of both groups will be compared using interrater reliability. We hypothesize that the therapy recommendations of ADBoard would be in high agreement with those of the MDM-C, with a Cohen’s kappa value of ≥ 0.75. Furthermore, our secondary hypotheses state that the completeness of patient information presented in MDM is higher when using ADBoard than without, and the explainability of tumor board protocols in MDM-AB is higher compared to MDM-C as measured by the System Causability Scale. Discussion The implementation of ADBoard aims to improve the quality and completeness of the data required for MDM decision-making and to propose therapeutic recommendations that consider current medical evidence and guidelines in a transparent and reproducible manner. Ethics and dissemination The project was approved by the Ethics Committee of the Charité – Universitätsmedizin Berlin. Registration details The study was registered on ClinicalTrials.gov (trial identifying number: NCT05681949; https://clinicaltrials.gov/study/NCT05681949 ) on 12 January 2023.

Abstract Recently, studies show that deep learning-based automatic speech recognition (ASR) systems are vulnerable to adversarial examples (AEs), which add a small amount of noise to the original audio examples. These AE attacks pose new challenges to deep learning security and have raised significant concerns about deploying ASR systems and devices. The existing defense methods are either limited in application or only defend on results, but not on process. In this work, we propose a novel method to infer the adversary intent and discover audio adversarial examples based on the AEs generation process. The insight of this method is based on the observation: many existing audio AE attacks utilize query-based methods, which means the adversary must send continuous and similar queries to target ASR models during the audio AE generation process. Inspired by this observation, We propose a memory mechanism by adopting audio fingerprint technology to analyze the similarity of the current query with a certain length of memory query. Thus, we can identify when a sequence of queries appears to be suspectable to generate audio AEs. Through extensive evaluation on four state-of-the-art audio AE attacks, we demonstrate that on average our defense identify the adversary’s intent with over $$90\%$$ 90 % accuracy. With careful regard for robustness evaluations, we also analyze our proposed defense and its strength to withstand two adaptive attacks. Finally, our scheme is available out-of-the-box and directly compatible with any ensemble of ASR defense models to uncover audio AE attacks effectively without model retraining.

Abstract Background Intervertebral disc degeneration (IVDD) is closely associated with the structural damage in the annulus fibrosus (AF). Aberrant mechanical loading is an important inducement of annulus fibrosus cells (AFCs) apoptosis, which contributes to the AF structural damage and aggravates IVDD, but the underlying mechanism is still unclear. This study aims to investigate the mechanism of a mechanosensitive ion channel protein Piezo1 in aberrant mechanical loading-induced AFCs apoptosis and IVDD. Methods Rats were subjected to lumbar instability surgery to induce the unbalanced dynamic and static forces to establish the lumbar instability model. MRI and histological staining were used to evaluate the IVDD degree. A cyclic mechanical stretch (CMS)-stimulated AFCs apoptosis model was established by a Flexcell system in vitro. Tunel staining, mitochondrial membrane potential (MMP) detection, and flow cytometry were used to evaluate the apoptosis level. The activation of Piezo1 was detected using western blot and calcium fluorescent probes. Chemical activator Yoda1, chemical inhibitor GSMTx4, and a lentiviral shRNA-Piezo1 system (Lv-Piezo1) were utilized to regulate the function of Piezo1. High-throughput RNA sequencing (RNA-seq) was used to explore the mechanism of Piezo1-induced AFCs apoptosis. The Calpain activity and the activation of Calpain2/Bax/Caspase3 axis were evaluated by the Calpain activity kit and western blot with the siRNA-mediated Calapin1 or Calpain2 knockdown. Intradiscal administration of Lv-Piezo1 was utilized to evaluate the therapeutic effect of Piezo1 silencing in IVDD rats. Results Lumbar instability surgery promoted the expression of Piezo1 in AFCs and stimulated IVDD in rats 4 weeks after surgery. CMS elicited distinct apoptosis of AFCs, with enhanced Piezo1 activation. Yoda1 further promoted CMS-induced apoptosis of AFCs, while GSMTx4 and Lv-Piezo1 exhibited opposite effects. RNA-seq showed that knocking down Piezo1 inhibited the calcium signaling pathway. CMS enhanced Calpain activity and elevated the expression of BAX and cleaved-Caspase3. Calpain2, but not Calpain1 knockdown, inhibited the expression of BAX and cleaved-Caspase3 and alleviated AFCs apoptosis. Lv-Piezo1 significantly alleviated the progress of IVDD in rats after lumbar instability surgery. Conclusions Aberrant mechanical loading induces AFCs apoptosis to promote IVDD by activating Piezo1 and downstream Calpain2/BAX/Caspase3 pathway. Piezo1 is expected to be a potential therapeutic target in treating IVDD.

Fly ash was used as raw material to prepare zeolites through silicate gels, assisted by the hydrothermal method. The silicate gels could be effectively formed in a few minutes in a molten alkali environment. The zeolites could be prepared by using these silicate gels through the hydrothermal method, which realizes the transformation from useless materials to highly valuable materials. The obtained zeolites were applied to the removal of ammonium in water, achieving the highvalue utilization of fly ash. The synthesized zeolites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectrum (EDS), thermogravimetric (TG), and Fourier transform infrared (FTIR) spectroscopy. The study on the adsorption and removal of ammonium in water shows that the adsorption of ammonium is more in line with pseudo first-order kinetics, and the adsorption mainly occurs in the first 20 min. The adsorption can reach equilibrium in 30 min, and the maximum adsorption capacity can reach 49.1 mg/g. The adsorption capacity of ammonium has the best performance at pH = 5. Furthermore, within a certain range, an increase in temperature is beneficial for the removal of ammonium.

The timing, location, intensity, and drivers of forest disturbance and recovery are crucial for developing effective management strategies and policies for forest conservation and ecosystem resilience. Although many algorithms and improvement methods have been developed, it is still difficult to guarantee the detection accuracy for forest disturbance and recovery patterns in southern China due to the complex climate and topography, faster forest recovery after disturbance, and the low availability of noise-free Landsat images. Here, we improved the LandTrendr parameters for different provinces to detect forest disturbances and recovery trajectories based on the LandTrendr change detection algorithm and time-series Landsat images on the GEE platform, and then applied the secondary random forest classifier to classify the forest disturbance and recovery patterns in southern China during 1990–2020. The accuracy evaluation indicated that our approach and improved parameters of the LandTrendr algorithm can increase the detection accuracy for both the spatiotemporal patterns and multiple events of forest disturbance and recovery, with an overall accuracy greater than 86% and a Kappa coefficient greater than 0.91 for different provinces. The total forest loss area was 1.54 × 105 km2 during 1990–2020 (4931 km2/year); however, most of these disturbed forests were recovered and only 6.39 × 104 km2 was a net loss area (converted to other land cover types). The area with two or more times of disturbance events accounted for 11.50% of the total forest loss area. The total forest gain area (including gain after loss and the afforestation area) was 5.44 × 105 km2, among which, the forest gain area after loss was 8.94 × 104 km2, and the net gain area from afforestation was 4.55 × 105 km2. The timing of the implementation of forestry policies significantly affected the interannual variations in forest disturbance and recovery, with large variations among different provinces. The detected forest loss and gain area was further compared against with inventory and other geospatial products, and proved the effectiveness of our method. Our study suggests that parameter optimization in the LandTrendr algorithm could greatly increase the accuracy for detecting the multiple and lower rate disturbance/recovery events in the fast-regrowing forested areas. Our findings also offer a long-term, moderate spatial resolution, and precise forest dynamic data for achieving sustainable forest management and the carbon neutrality goal in southern China.

Bamboo is a naturally occurring composite material, which exhibits a decomposable structure with varying composition. The distinct structural features of bamboo contribute to its exceptional strength and flexibility, making it an excellent choice for construction purposes. However, only a limited portion of bamboo species has been studied for its mechanical properties, and research on Bambusa arundinaceae has primarily focused on its pharmaceutical values. Therefore, we investigated the relationship between the structural characteristics of B. arundinaceae and its mechanical properties using axial compression experiments and tangential bending experiments. The results showed that the distribution density of vascular bundles (VBs) of B. arundinaceae ranged from 1.98 to 4.34 pcs/mm2,while the volume fraction of fiber sheaths (FSs) ranged from 35.82 to 42.58%. The average compressive strength, flexural strength, and flexural elasticity modulus were 113.99 MPa, 239.07 MPa, and 17.39 GPa, which were 97.56%, 64.07%, and 66.09% higher than those of moso bamboo (Phyllostachys edulis), respectively. The compressive strength, flexural strengths, and elasticity modulus of B. arundinaceae were positively correlated with both the distribution density of VBs and the volume fraction of FSs. These insights are crucial for the advancement of durable and efficient materials in diverse sectors including construction and manufacturing.

In the paper, the modulation effect of rotor-stator interaction subjected to fluctuating rotation speed is investigated numerically. A quasi-bivariate variable mode decomposition method for analyzing non-stationary flow fields is proposed for the first time. Different from the previous studies, this paper emphasizes the local features of the transient flow field at fluctuating rotation speed. The results show that the impact of fluctuating rotation speed on the impeller force is limited, but it significantly impacts the pressure pulsation at fluctuating frequency. The correlation between amplitude and fluctuation ratio is positive. Meanwhile, the fluctuating rotation speed also induces sidebands centered on the blade passing frequency and its harmonics. The periodic changes in rotational speed lead to frequency and amplitude modulation of pressure pulsations. The magnitude of the instantaneous frequency and amplitude increases as the fluctuation ratio grows. The change in pressure field is well synchronized with the rotational speed, while the change in velocity field lags behind the rotational speed. The variation of pressure field with rotational speed is mainly attributed to two aspects. One is the flow structure at the fluctuating frequency, and the other is the instantaneous component of the flow structure at blade passing frequency.

Mental health problems of various populations during the COVID-19 pandemic have received high attention, but there is little research on the mental health of Chinese civil servants. The present study investigated occupational stress, mental health problems (i.e., anxiety, depression, and insomnia), social support, and work-family conflict in Chinese civil servants during the COVID-19 pandemic. A total of 327 civil servants in Wenzhou city, China, participated in an online survey, which collected data on socio-demographic characteristics, occupational stress, mental health problems (i.e., anxiety, depression, and insomnia), social support, and work-family conflict. Data were analyzed using non-parametric tests and a multiple mediation model. Self-reported risk at work and support from mental health workers were relatively low. Anxiety, depression, and insomnia prevalence were 49.24 %, 47.1 %, and 20.48 %, respectively. Those who held higher ranks at work had lower levels of anxiety and depression. In addition, those who felt bad about their health status had more mental health problems. Social support and work-family conflict mediated the relationship between occupational stress and mental health problems significantly. Stress management training, organizational-level improvement in work arrangements, and professional mental health services are warranted for Chinese civil servants during the pandemic.

Cadmium (Cd) and aniline frequently co-occur in industrial settings but have rarely been addressed as composite toxicants in terms of the overall toxicity despite extensive knowledge of the environmental impact of each individual pollutant. In this study, we attempt to assess the relation of individual and combined toxic effects of Cd and aniline using a bacterial consortium cultured from soils as a model system. Results showed that the consortial bacteria exhibited drastically stronger tolerance to stand-alone Cd and aniline in comparison to literature data acquired from single species studies. When occurring simultaneously, the joint toxicity displayed a concentration-dependent behavior that wasn't anticipated based on individual chemical tests. Specifically, additive effects manifested with Cd and aniline at their IC10s, but changed to synergistic when the concentrations increased to IC20, and finally transitioned into antagonistic at IC30s and beyond. In addition, co-occurring aniline appeared to have retarded the cellular accumulation of Cd while increasing the enzymatic activities of superoxide dismutase and catalase relative to that in Cd-alone treatments. Finally, the bacterial community experienced distinct compositional changes under solo and combined toxicities with several genera exhibiting inconsistent behavior between treatments of single and composite toxicants. Findings from this study highlight the complexity of bacterial response to composite pollutions and point to the need for more comprehensive references in risk and toxicology assessment at multi-chemical contamination sites.

Abstract Background Bone regeneration is a complex procedure that involves an interaction between osteogenesis and inflammation. Macrophages in the microenvironment are instrumental in bone metabolism. Amount evidence have revealed that exosomes transmitting lncRNA is crucial nanocarriers for cellular interactions in various biotic procedures, especially, osteogenesis. However, the underlying mechanisms of the regulatory relationship between the exosomes and macrophages are awaiting clarification. In the present time study, we aimed to explore the roles of human umbilical vein endothelial cells (HUVECs)-derived exosomes carrying nuclear enrichment enriched transcript 1 (NEAT1) in the osteogenesis mediated by M2 polarized macrophages and elucidate the underlying mechanisms. Results We demonstrated HUVECs-derived exosomes expressing NEAT1 significantly enhanced M2 polarization and attenuated LPS-induced inflammation in vitro. Besides, the conditioned medium from macrophages induced by the exosomes indirectly facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Mechanically, Exos carrying NEAT1 decreased remarkably both expression of dead-box helicase 3X-linked (DDX3X) and nod-like receptor protein 3 (NLRP3). The level of NLRP3 protein increased significantly after RAW264.7 cells transfected with DDX3X overexpression plasmid. Additionally, the knockdown of NEAT1 in exosomes partially counteracted the aforementioned effect of Exos. The results of air pouch rat model demonstrated that HUVECs-derived exosomes increased anti-inflammatory cytokines (IL-10) and decreased pro-inflammatory cytokines (IL-1β and IL-6) significantly in vivo, contributing to amelioration of LPS-induced inflammation. Afterwards, we further confirmed that the HUVECs-derived exosomes encapsulated in alginate/gelatin methacrylate (GelMA) interpenetrating polymer network (IPN) hydrogels could promote the bone regeneration, facilitate the angiogenesis, increase the infiltration of M2 polarized macrophages as well as decrease NLRP3 expression in the rat calvarial defect model. Conclusions HUVECs-derived exosomes enable transmitting NEAT1 to alleviate inflammation by inducing M2 polarization of macrophages through DDX3X/NLRP3 regulatory axis, which finally contributes to osteogenesis with the aid of alginate/GelMA IPN hydrogels in vivo. Thus, our study provides insights in bone healing with the aid of HUVECs-derived exosomes-encapsulated composite hydrogels, which exhibited potential towards the use of bone tissue engineering in the foreseeable future.

Metalens can achieve more challenging functions especially dynamic regulation than traditional lens due to its unprecedented ability to manipulate light. In this paper, an approach to realizing switchable bidirectional metalens is proposed based on phase change material GST. Two geometric parameters of nanopillars were designed to demonstrate full phase modulation due to the Pancharatnam-Berry phase. According to the phase distribution, we realize the flexible control of the metalens through the transition of states. These special designs of unit structures make multi-focal point focus and two-dimensional focus also realized. In addition, the bidirectional switchable metalens have been realized through the transformation of states on a bilayer metasurface substrate. Its unique phase transition properties which are not available to previous metasurface can be applied in high quality imaging cameras, optical microscopes, lidar scanning systems, etc.

As a new concept for systematically evaluating ecosystem services, Gross Ecosystem Product (GEP) provides an effective means to comprehensively reveal the overall status of the ecosystem, the impact of economic activities on the ecological environment, and the effectiveness of ecological protection efforts. GEP accounting has been conducted in various regions; however, GEP’s application in natural reserves still requires further exploration. Taking the Qinling Mountains as the research area, this paper aims to assess the relationship between GEP and economic development on the basis of the GEP accounting system. The results indicated that: (1) From 2010 to 2020, GEP tended to increase continuously and exhibited a distribution pattern with high value regions in the east and west, and low value regions in the north and south. (2) Over the years, the coupling coordination degree between GEP and GDP was in a consistent upward trend. In 2020, a good coupling coordination state between GEP and GDP was achieved in most districts and counties. (3) With the relative development between GEP and GDP, the social economy of most districts and counties lagged behind GEP in 2010. The number of districts and counties lagging in GEP in 2020 increased, while the number of regions with a balanced development of GEP and GDP was still relatively discouraging. (4) In general, elevation, contagion, temperature, population density, and precipitation were the main drivers of coupling coordination degree between GEP and GDP. If the relationship between economic development and ecological environmental protection can be reasonably balanced, it will further promote the sustainable development of nature reserves, and provide a scientific basis for sustainable policy-making in other similar areas.

The energy inside the Earth can not only be released outward through earthquakes and volcanoes but also can be used by humans in the form of geothermal energy. Is there a correlation between different forms of energy release? In this contribution, we perform detailed seismic and geothermal research in the Beijing area. The results show that the geothermal resources in Beijing belong to typical medium-low temperature geothermal resources of the sedimentary basin, and some areas are controlled by deep fault activities (e.g., Xiji geothermal well (No. 17)). The heat sources are upper mantle heat, radioactive heat in granite, and residual heat from magma cooling. The high overlap of earthquakes and geothermal field locations and the positive correlation between the injection water and earthquakes indicate that the exploitation and injection water will promote the release of the earth’s energy. The energy releases are partitioned into multiple microearthquakes, avoiding damaging earthquakes (ML ≥ 5) due to excessive energy accumulation. Therefore, the exploitation of geothermal resources may be one way to reduce destructive earthquakes. Furthermore, the use of geothermal resources can also reduce the burning of fossil energy, which is of great significance in dealing with global warming.

Geochemical composition changes in groundwater related to earthquakes have been documented in previous studies, and most such studies focused on the changes in major ions, hydrogen, oxygen isotopes, and geochemical gases. Changes in trace elements were suggested to be more sensitive to small earthquakes than the commonly used chemical constituents such as major ions, yet they received less attention. Beijing is located in the Zhangjiakou-Bohai seismic belt and experiences frequent occurrences of small earthquakes. In this paper, we collected groundwater samples from a hot spring in Yanqing district of Beijing weekly from August 2021 to August 2022. Each water sample contained 41 trace chemical compositions. During the sampling, an earthquake with a magnitude of ML3.3 occurred in the Chaoyang district of Beijing on 3 February 2022, so these trace elements changes were systematically monitored before and after the earthquake: Li, Sc, Ti, and Pb elements had upward changes before the earthquake, while Cu, Nb, Th, Zn, Tl, and U elements had downward changes before the earthquake. Eu (rare earth elements) had upward changes after the earthquake. At the same time, the earthquake caused no significant changes in the groundwater level in the seismic monitoring well near the Songshan spring. Such responses indicate that trace elements are likely to be more sensitive to crustal strain than groundwater level. We considered that the earthquake-induced rock cracks before or after the earthquake caused enhancing water-rock interaction and led to the migration of trace elements between the water column and rocks, which is the mechanism to explain the trace elemental changes. This study probably provides a comprehensive assessment of the sensitivity of trace element constituents to the earthquake. Furthermore, we suggest that more long-term continuous monitoring and research of trace elements in Beijing and Zhangjiakou-Bohai Fault Zone should be considered to explore the response mechanism of groundwater geochemistry to earthquakes in the future.

Jianpi Yangzheng Xiaozheng decoction (JPYZXZ) is an empirical traditional Chinese medicine formula that has been reported to significantly prolong the survival of patients with advanced gastric cancer (GC). However, its underlying mechanism have not been fully elucidated. The present work aims to explore the possible mechanism of JPYZXZ on regulating GC progression. We firstly confirmed the inhibitory effect of JPYZXZ in GC MKN74 cells and 615-strain mice, which was possibly mediated with IL-6/JAK2/STAT3 pathway dependent PD-L1 expression. Moreover, we showed that JPYZXZ diminished the expression levels of GC-derived exosomal PD-L1 in MFC murine cells and xenograft GC model, as well as stage IIA-IIIB GC patients. We further found that in different types of tumor-infiltrating immune cells, PD-L1 expression was most positively correlated with myeloid-derived suppressor cells (MDSCs) in GC in the TISIDB database. We isolated exosomes derived from supernatants of MFC cells and co-cultured with bone marrow cells derived from C57BL/6 mice, and further revealed that the expansion of MDSCs was mediated by GC-derived exosomal PD-L1. Meanwhile, our results indicated that JPYZXZ inhibited the delivery of exosomal PD-L1 from GC cells to bone marrow cells, thereby alleviating exosomal PD-L1-induced differentiation and expansion of MDSCs in the tumor microenvironment. This led to a decrease in the levels of several immunosuppressive factors, including iNOS, Arg-1, TGF-β, IL-10, and IL-6, in 615-strain mice. Moreover, clinical data also revealed a significant positive relationship between exosomal PD-L1 and polymorphonuclear MDSCs under the JPYZXZ treatment in stage IIA-IIIB GC patients. In conclusion, our study confirmed that exosomal PD-L1 could be a key factor in controlling MDSCs differentiation in GC. JPYZXZ alleviated GC progression via suppressing exosomal PD-L1 mediated expansion of MDSCs, thereby remodeling the immunosuppressive tumor microenvironment, which provided the experimental evidence for the clinical application of JPYZXZ in the treatment of GC via PD-L1.

Abstract Microneedles, especially hollow microneedles (HMNs), play an important role in drug delivery, but most of the current HMNs are manufactured based on silicon microfabrication (lithography, etching, etc.), which are slightly conservative due to the lack of low‐cost, batch‐scale and customized preparation approach, especially for the HMNs with flexible substrate. For the first time, we propose the use of a high‐precision 3D printed master mold followed by a dual‐molding process for the preparation of HMNs with different shapes, heights, and inner and outer diameters to satisfy different drug delivery needs. The 3D printed master mold and negative mold can be reused, thereby significantly reducing the cost. HMNs are based on biocompatible materials, such as heat‐curing polymers or light‐curing resins. The thickness and rigidity/flexibility characteristics of the substrate can be customized for different applications. The drug delivery efficiency of the fabricated HMNs was verified by the in situ treatment of psoriasis on the backs of mice, which required only a 0.1‐fold oral dose to achieve similar efficacy, and the associated side effects and drug toxicity were reduced. Thus, this dual‐molding process can reinvigorate HMNs development.

Abstract High-quality-factor (high-Q-factor) electromagnetic resonance plays an important role in sensor applications. Previously proposed gas refractive index sensors are often limited by the large cavity length or microscale fabrication process in practical applications. Recently, ultra-high Q factor resonance based on the bound state in the continuum (BIC) has provided a feasible approach to solve these problems. In this paper, we propose a metasurface structure consisting of a single size tetramer cylinder. It supports dual band toroidal dipole (TD) resonances driven by BIC. The physical mechanism of double TD resonances is clarified by the multipole decomposition of the metasurface band structure and far-field scattering power. The sensor structure based on this achieves a sensitivity of 518.3 MHz/RIU, and the maximum line width does not exceed 680 kHz. The high-Q-factor electromagnetic resonance has the advantages of polarization independence and simplicity to manufacture. These findings will open up an avenue to develop the ultrasensitive sensor in the gigahertz regime.

Abstract Metasurface can use artificial microstructures to manipulate electromagnetic waves more accurately and flexibly. All-dielectric metalens have a wide range of materials and low cost so it has a wide application prospect. Herein, we propose a all-dielectric achromatic metalens built with Si as the structural unit that can operate over a broadband of wavelengths in the visible region. It controls the wavefront of light through the Pancharatnam–Berry phase and propagation phase to eliminate the chromatic aberration. Meanwhile, we also use Gerchberg–Saxton algorithm and its improved algorithm to iterate over multiple design wavelengths and obtain holographic phases suitable for broadband. Thus, both the metalenses and holographic metasurfaces can achieve achromatic broadband in the visible light range, which provides a new method for the development of meta-optical imaging devices.

Abstract Background Flap transplantation is commonly used in reconstructive surgery. A prerequisite for skin flap survival is sufficient blood supply. However, such approaches remain unclear. This study aimed to explore the underlying mechanisms of exosomes derived from human umbilical vascular endothelial cells (HUVECs) exposed to oxidative stress on endothelial progenitor cells (EPCs) and their subsequent influence on the survival of skin flaps. Methods HUVECs were treated with various concentrations of H2O2 to establish an oxidative stress model. To investigate the effects of H2O2-HUVEC-Exos and HUVEC-Exos, Cell Counting Kit-8, tube formation, invasion assays, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed in EPCs. Microarray analysis was used to reveal the differentially expressed long non-coding RNAs (lncRNAs) in the H2O2-HUVEC-Exos and HUVEC-Exos. In addition, gene silencing and western blotting were employed to determine the mechanism behind lncRNA nuclear enrichment enriched transcript 1 (Lnc NEAT1) in EPCs. Further, a rat skin flap model was used to determine the role of the exosomes in skin flap survival in vivo. Results HUVECs were stimulated with 100 μmol/L H2O2 for 12 h to establish an oxidative stress model. H2O2-HUVEC-Exos promoted the proliferation, tube formation, and invasion of EPCs and remarkably increased skin flap survival compared to the HUVEC-Exos and control groups. Sequencing of exosome RNAs revealed that the Lnc NEAT1 level was dramatically increased in the H2O2-HUVEC-Exos, leading to activation of the Wnt/β-catenin signaling pathway. Comparatively, knockdown of Lnc NEAT1 in HUVEC-Exos and H2O2-HUVEC-Exos significantly inhibits the angiogenic capacity of EPCs, reduced the survival area of skin flap and downregulated the expression levels of Wnt/β-catenin signaling pathway proteins, whereas Wnt agonist partly reversed the negative effect of NEAT1 downregulation on EPCs through the Wnt/β-catenin signaling pathway. Conclusions Exosomes derived from HUVECs stimulated by oxidative stress significantly promoted the pro-angiogenic ability of EPCs through the Wnt/β-catenin signaling pathway mediated by Lnc NEAT1 and hence enhanced random flap survival in vivo. Therefore, the application of H2O2-HUVEC-Exos may serve as an alternative therapy for improving random skin flap survival.

ABSTRACT The interactions between soil microbiomes at various trophic levels are essential for restoring soil functions. Legumes are considered as “pioneer crops” in degraded or contaminated soils because they can fix nitrogen through symbiotic relationships with rhizobacteria, which promotes soil fertility. However, little is known about the abilities of legumes to contribute to the health of soil contaminated with cadmium (Cd). In this research, we applied a soil amendment (commercial Mg–Ca–Si conditioner, CMC) at two rates (1,500 and 3,000 kg/ha) in a Cd-contaminated soybean field. Bulk and rhizosphere soil samples were collected to assess the amendment-induced effects on four microbial lineages (bacteria, fungi, arbuscular mycorrhizal fungi [AMF], and nematodes) and their functions including Cd stabilization, nutrient cycling, and pathogen control. Compared with the control, both CMC application rates increased the pH and reduced labile Cd fraction in the bulk and rhizosphere soils. Although the total Cd concentrations in the soil were similar, the Cd accumulation in the grains was significantly reduced in treatments of soil amendments. It was observed that the application of CMC can significantly reduce the AMF diversity but increased the diversity of the other three communities. Moreover, the biodiversity within keystone modules (identified by co-occurrence network analysis) played key roles in driving soil multifunctionality. Specifically, key beneficial groups in module 2 such as Aggregicoccus (bacteria), Sordariomycetes (fungi), Glomus (AMF), and Bursaphelenchus (nematode) were strongly associated with soil multifunctionality. By co-culturing bacterial suspensions with the soybean root rot pathogen Fusarium solani in the in vitro assays, we experimentally validated that the application of CMC promoted the suppression of soil bacterial community on pathogens by inhibiting the mycelium growth and spore germination. Also, the bacterial community was more resistant to Cd stress in soils receiving CMC amendment. Our findings provide valuable theoretical references for enhancing soil functions and health via applying a soil amendment (CMC) during Cd-contaminated soil remediation. IMPORTANCE Restoration of microbiome-driven soil functions and health is of great importance during Cd-contaminated soil remediation via soil amendment. Soybean and its symbiotic mutualism can provide abundant nitrogen and phosphorus to relieve the nutrient deficiency of Cd-contaminated soil. This study provides a novel perspective on the potential role of applying a soil amendment (CMC) in enhancing the functions and health of Cd-contaminated soils. Our results showed the distinct differences in soil microbial community responding to amendment-induced changes in edaphic properties. The biodiversity within keystone modules had major contributions to the maintenance of the soil’s multifunctionality and health. Additionally, a higher CMC application rate showed more beneficial effects. Collectively, our results enhance our understanding about the effects of applying CMC, together with soybean rotation, to enhance and maintain soil functions and health during the field Cd stabilization process.

IntroductionThe continuous application of cow manure in soil for many years leads to the accumulation of heavy metals, pathogenic microorganisms, and antibiotic resistance genes. Therefore, in recent years, cow manure has often been mixed with botanical oil meal as organic fertilizer applied to farmland to improve soil and crop quality. However, the effects of various botanical oil meal and cow manure mixed organic fertilizers on soil microbial composition, community structure, and function, tobacco yield, and quality remain unclear.MethodsTherefore, we prepared organic manure via solid fermentation by mixing cow manure with different oil meals (soybean meal, rape meal, peanut bran, sesame meal). Then, we studied its effects on soil microbial community structure and function, physicochemical properties, enzyme activities, tobacco yield and quality; then we analyzed the correlations between these factors.Results and discussionCompared with cow manure alone, the four kinds of mixed botanical oil meal and cow manure improved the yield and quality of flue-cured tobacco to different degrees. Peanut bran, which significantly improved the soil available phosphorus, available potassium, and NO3–-N, was the best addition. Compared with cow manure alone, soil fungal diversity was significantly decreased when rape meal or peanut bran was combined with cow manure, while soil bacterial and fungal abundance was significantly increased when rape meal was added compared with soybean meal or peanut bran. The addition of different botanical oil meals significantly enriched the subgroup_7 and Spingomonas bacteria and Chaetomium and Penicillium fungi in the soil. The relative abundances of functional genes of xenobiotics biodegradation and metabolism, soil endophytic fungi, and wood saprotroph functional groups increased. In addition, alkaline phosphatase had the greatest effect on soil microorganisms, while NO3–-N had the least effect on soil microorganisms. In conclusion, the mixed application of cow manure and botanical oil meal increased the available phosphorus and potassium contents in soil; enriched beneficial microorganisms; promoted the metabolic function of soil microorganisms; increased the yield and quality of tobacco; and improved the soil microecology.

Calamus caesius is one of the most well-known commercial climbing palm species across the world. A comprehensive understanding of the growth-dependent variation in microstructure and polymer distribution can provide fundamental information to guide its end-use applications. In this study, we investigated the age-wise characteristics of rattan stems and the ultrastructure of fibers using electron microscopy, light microscopy, and FTIR. The results showed that the frequency of vascular bundles with a diameter of 0.55∼0.62 mm in C. caesius was 3.49∼3.97 pieces/mm2. The diameter and length of the metaxylem vessel were 0.32∼0.34 mm and 2.86∼3.00 mm, respectively. Cellulose, lignin, xylan, and HCA are mainly concentrated in the fiber sheath of vascular bundles. The distribution of major polymers in positions other than the top was relatively stable. The tissue proportion of parenchyma, xylem, and phloem did not differ significantly at different positions. The proportion of fibers from 22.27%∼25.33% showed significant differences. The fiber length was 1.43∼1.76 mm, and the diameter was 10.78∼12.63 μm. During the growth process of the rattan stem, the secondary wall of fiber cells continued to accumulate inward towards the cell cavity from 2 to 6 layers. The unique fiber properties and stable vascular bundle composition of C. caesius may have potential in fields such as composite materials or renewable energy.

In longitudinal surveys, repeated measurements are collected from the same sample units over time to measure gross change (i.e., change at the level of individual sample members). Longitudinal samples are sometimes supplemented by fresh sample to measure net change (i.e., change at the aggregate level). That is, in each measurement wave, while one part of the sample is newly recruited (fresh), another part overlaps with previously interviewed sample (repeated interviews). Many aspects of survey design of longitudinal surveys have been studied extensively, such as definition of target population, sample design, survey weighting, intervals between interviews, nonresponse, and panel attrition. Although the impact of the overlap between samples on the statistical power has been studied, sample size determination lacks a formulation that takes account of these factors in longitudinal surveys that aim to measure net and gross changes simultaneously. In this study, we propose a framework for sample size calculation to measure net and gross changes in estimated means or proportions concurrently in longitudinal surveys. We present a framework to compute panel and fresh sample sizes for varying levels of net and gross change. Finally, we illustrate the framework using nchange, an R package we developed to execute the algorithm of the proposed framework. The framework and the R package will support researchers to determine sample sizes targeting specific power of analysis with respect to measuring net and gross changes in rotating- or split-panel surveys.

IntroductionSoil fumigant dazomet is a broad-spectrum nematicide and fungicide that can kill non-target microbes. Fungicides or organic fertilizers are often added after fumigation to improve the recovery of soil microbes. However, the effect of adding microbial organic fertilizers (MOF) after fumigation on the structure and function of rhizosphere soil microbial communities of crops is unclear.MethodsTherefore, we investigated the effects of adding Junweinong and Junlisu MOFs after dazomet fumigation on the structure and function of rhizosphere microbial communities and its relationship with soil properties and enzyme activities.Results and discussionThe results showed that the addition of these two MOFs after dazomet fumigation significantly reduced the rhizosphere soil available phosphorus, available potassium, organic matter content, and urease, alkaline phosphatase, and catalase activities, but increased the soil pH compared with the fumigation treatment. The application of MOFs after fumigation resulted in significant enrichment of bacteria such as Gaiella, norank_f_Vicinamibacteraceae, and Flavisolibacter and fungi such as Peroneutypa, Olpidium, and Microascus in the rhizosphere soil of the crop and increased the relative abundance of functional genes of 13 kinds of amino acids metabolism, pyruvate metabolism, TCA cycle, and pentose phosphate pathway as well as endophytic and epiphytic functional groups in the rhizosphere soil. In particular, NH4+-N, pH, and AK had the greatest effect on rhizosphere microorganisms. Overall, the addition of MOFs after fumigation promoted crop root nutrient uptake, enhanced rhizosphere soil microbial metabolism, allowed more beneficial communities to colonize the roots, and promoted soil microbiological health.

PurposeThe hallmark of non-arteritic anterior ischemic optic neuropathy (NAION) is vascular compromise to the anterior optic nerve and thinning of the retinal nerve fiber layer (RNFL) and secondary degeneration of the retinal ganglion cell body or thinning of the ganglion cell complex (GCC). This study investigates optical coherence tomography (OCT) and OCT Angiography (OCTA) changes in chronic NAION and identifies imaging biomarkers that best predict disease.MethodsWe performed a retrospective case-control study of 24 chronic NAION eyes (18 patients) and 70 control eyes (45 patients) to compare both whole-eye and regional OCT, OCTA, static perimetry measurements. OCT measurements were quantified automatically using commercial software, and OCTA was analyzed using custom MATLAB script with large vessel removal to measure 154 total parameters per eye.ResultsWe confirmed that static perimetry mean deviation (MD) was significantly worse in chronic NAION (–13.53 ± 2.36) than control (–0.47 ± 0.72; P < 0.001) eyes, and NAION eyes had 31 μm thinner RNFL (control: 95.9 ± 25.8 μm; NAION: 64.5 ± 18.0, P < 0.001), and 21.8 μm thinner GCC compared with controls (control: 81.5 ± 4.4 μm; NAION: 59.7 ± 10.5, P < 0.001). Spearman correlation analysis of OCTA parameters reveal that vessel area density (VAD) and flux are highly correlated with visual field MD and OCT measurements. Hierarchical clustering two distinct groups (NAION and control), where standardized measurements of NAION eyes were generally lower than controls. Two-way mixed ANOVAs showed significant interaction between patient status (control and chronic NAION) and structure (optic disk and macula) for annulus VAD and flux values and mean RNFL and GCC thickness. Post-hoc tests showed this effect stems from lower peripapillary values in NAION compared to controls. Separate logistic regression models with LASSO regularization identified VAD and flux are one of the best OCTA parameters for predicting NAION.ConclusionIschemic insult to the optic disk is more severe likely from primary degeneration of the affected peripapillary region while macula is affected by secondary retrograde degeneration and loss of retinal ganglion cells. In addition to OCT measurements, peripapillary and macular vascular parameters such as VAD and flux are good predictors of optic nerve and retinal changes in NAION.

Abstract Background Melanoma is a highly heterogeneous and aggressive cutaneous malignancy. Ferroptosis, a new pathway of cell death depending on the intracellar iron, has been shown to be significantly associated with apoptosis of a number of tumors, including melanoma. Nevertheless, the relationship between ferroptosis-related genes (FRGs) and the melanoma patients’ prognosis needs to be explored. Methods Download expression profiles of FRGs and clinical data from The Cancer Genome Atlas (TCGA) database. 70% data were randomly selected from the TCGA database and utilized the univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model to create a prognostic model, and the remaining 30% was used to validate the predictive power of the model. In addition, GSE65904 and GSE22153 date sets as the verification cohort to testify the predictive ability of the signature. Results We identified nine FRGs relating with melanoma patients’ overall survival (OS) and established a prognostic model based on their expression. During the research, patients were divided into group of high-risk and low-risk according to the results of LASSO regression analysis. Survival time was significantly longer in the low-risk group than that of in the high-risk group (P < 0.001). Enrichment analysis of different risk groups demonstrated that the reasons for the difference were related to immune-related pathways, and the degree of immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. Conclusions The FRG prognostic model we established can predict the prognosis of melanoma patients and may further guide subsequent treatment.

Abstract Prostate cancer (PCa) is the fifth leading cause of death from cancer in men worldwide. Its treatment remains challenging due to the heterogeneity of the tumor, mainly because of the lack of effective and targeted prognostic markers at the system biology level. First, the data were retrieved from TCGA dataset, and valid samples were obtained by consistent clustering and principal component analysis; next, key genes were analyzed for prognosis of PCa using WGCNA, MEGENA, and LASSO Cox regression model analysis, while key genes were screened based on disease-free survival significance. Finally, TIMER data were selected to explore the relationship between genes and tumor immune infiltration, and GSCAlite was used to explore the small-molecule targeted drugs that act with them. Here, we used tumor subtype analysis and an energetic co-expression network algorithm of WGCNA and MEGENA to identify a signal dominated by the ROMO1 to predict PCa prognosis. Cox regression analysis of ROMO1 was an independent influence, and the prognostic value of this biomarker was validated in the training set, the validated data itself, and external data, respectively. This biomarker correlates with tumor immune infiltration and has a high degree of infiltration, poor prognosis, and strong correlation with CD8+T cells. Gene function annotation and other analyses also implied a potential molecular mechanism for ROMO1. In conclusion, we putative ROMO1 as a portal key prognostic gene for the diagnosis and prognosis of PCa, which provides new insights into the diagnosis and treatment of PCa.

Shale oil and gas are currently the major fields of unconventional hydrocarbon exploration and development. The Fengcheng Formation (FF) shale in the Mahu Sag of the Junggar Basin is an alkaline lacustrine organic-rich shale with an extremely prospective shale oil potential. However, its strong heterogeneity and complex pore structure greatly influence the development of shale oil. It is significant to investigate the pore and geochemical characteristics of shale reservoirs for shale oil extraction. In this study, the pore structure and geochemical characteristics of FF have been investigated using core analysis, Rock-Eval pyrolysis, X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), mercury injection capillary pressure (MICP), low-temperature gas adsorption (LTGA), and X-ray computed tomography (X-ray CT). The results show that the shale of FF has moderate organic matter abundance, and the kerogen is mainly of Type II, which is now at the peak of oil generation. Shale minerals are mainly composed of carbonate (dolomite and calcite) and siliceous (quartz and feldspar) minerals, with extremely low clay mineral content. The pore types are mainly intergranular pores (inter-P), intragranular pores (intra-P), and microfractures associated with mineral particles. The pore space is contributed predominantly by micropores of 0.5–1.2 nm and mesopores of 10–50 nm, whereas macropores are underdeveloped. The pores are mostly ink bottle- and slit-shaped, and the pore connectivity is relatively poor. The pore development of shale in the FF is influenced by organic matter abundance, thermal maturity, mineral composition, etc. Organic matter content (TOC), thermal maturity (Ro), and carbonate minerals have a positive effect on pore development, and the pore volume (PV) increases with TOC, Ro, and carbonate minerals. While clay minerals show a negative effect, the PV decreases with clay minerals. Additionally, the influence of the clay mineral content on the pore morphology of shale should not be ignored. This study investigates the pore structure and geochemical characteristics of the alkaline lacustrine shale of FF in Mahu Sag, which is significant to deepen the understanding of alkaline lacustrine shale and to improve the production of shale oil.

AlGaN-based materials have exhibited considerable potential for fabricating ultraviolet (UV) light-emitting diodes (LEDs) owing to their direct, wide, and adjustable energy bandgap. AlGaN-based devices have extensive applicability owing to their stable physico-chemical properties. With decades of research effort, significant progress has been achieved in enhancing the working efficiency of AlGaN-based LEDs by optimizing the crystalline quality, doping efficiency, and device design. In this review, methods to obtain high-quality AlGaN-based materials, achieve high doping efficiency, and design UV-LED structures are summarized and discussed. Finally, the issues that need to be addressed in AlGaN-based UV-LED devices are highlighted.

Abstract Background Ovarian Carcinoma (OCa) is a high-mortality malignancy derived from female reproductive system. Increasing evidence has identified long non-coding RNAs (lncRNAs) as important regulators in OCa chemoresistance. In this study, we intended to explore the role of LINC01503 in OCa resistance to carboplatin (CBP). Methods Gene expression was measured by reverse transcription-quantitative PCR (RT-qPCR) in OCa cells. Western blot was adopted to detect protein levels of GATA1, PD-L1, E-cadherin, N-cadherin, Vimentin, Bcl-2, Bax, cleaved caspase-3. To assess the effects of LINC01503 on the resistance of OCa cells to CBP, Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry experiments were performed to evaluate half-maximal inhibitory concentration (IC50), cell viability, migrative and invasive ability, as well as cell apoptosis. Dual-luciferase reporter assay was employed to assess the associations between the genes. Results LINC01503 was upregulated in CBP-resistant OCa cells. LINC01503 knockdown reduced CBP resistance in OCa cells. Besides, GATA-binding protein 1 (GATA1) activated LINC01503 transcription in CBP-resistant OCa cells. MiR-766-5p was lowly expressed in CBP-resistant cells and confirmed as a target for LINC01503. In addition, miR-766-5p overexpression increased CBP sensitivity in OCa cells. PD-L1 was verified as the target of miR-766-5p. Besides, LINC01503 upregulated PD-L1 level by regulating miR-766-5p. Furthermore, rescue experiments showed that PD-L1 overexpression abrogated the inhibited impacts of blocking LINC01503 on CBP resistance in OCa cells. Conclusion GATA1-induced LINC01503 expedited CBP resistance in OCa cells via the miR-766-5p/PD-L1 axis, providing a new target for improving the efficacy of OCa chemotherapy. Graphical Abstract

Abstract Background Muscular invasive bladder cancer (MIBC) is a common malignant tumor in the world. Because of their heterogeneity in prognosis and response to treatment, biomarkers that can predict survival or help make treatment decisions in patients with MIBC are essential for individualized treatment. Aim We aimed to integrate bioinformatics research methods to identify a set of effective biomarkers capable of predicting, diagnosing, and treating MIBC. To provide a new theoretical basis for the diagnosis and treatment of bladder cancer. Methods and results Gene expression profiles and clinical data of MIBC were obtained by downloading from the Cancer Genome Atlas database. A dataset of 129 MIBC cases and controls was included. 2084 up‐regulated genes and 2961 down‐regulated genes were identified by differentially expressed gene (DEG) analysis. Then, gene ontology analysis was performed to explore the biological functions of DEGs, respectively. The up‐regulated DEGs are mainly enriched in epidermal cell differentiation, mitotic nuclear division, and so forth. They are also involved in the cell cycle, p53 signaling pathway, PPAR signaling pathway, and so forth. The weighted gene co‐expression network analysis yielded five modules related to pathological stages and grading, of which blue and turquoise were the most relevant modules for MIBC. Next, Using Kaplan–Meier survival analysis to identify further hub genes, the screening criteria at p ≤ .05, we found CNKSR1, HIP1R, CFL2, TPM1, CSRP1, SYNM, POPDC2, PJA2, and RBBP8NL genes associated with the progression and prognosis of MIBC patients. Finally, immunohistochemistry experiments further confirmed that CNKSR1 plays a vital role in the tumorigenic context of MIBC. Conclusion The research suggests that CNKSR1, POPDC2, and PJA2 may be novel biomarkers as therapeutic targets for MIBC, especially we used immunohistochemical further to validate CNKSR1 as a therapeutic target for MIBC which may help to improve the prognosis for MIBC.

Porcine parvovirus (PPV) is the primary cause of reproductive disorders in pigs. The porcine parvovirus 7 (PPV7) subtype was first identified in the United States in 2016. In this study, PPV7 was detected in different porcine samples, including serum, feces, saliva, and milk, from 69 pig farms in the Fujian and Guangdong regions of South China, and its coinfection with porcine circovirus 2 (PCV2), porcine circovirus 3 (PCV3), and porcine reproductive and respiratory syndrome virus (PRRSV) was determined. Whole-genome sequencing, phylogenetic analysis, and recombination analysis were performed on seven isolates, with each selected isolate originating from a different farm. There was a high rate of PPV7 positivity in blood, stool, and saliva but PPV7 DNA was absent from breast milk. The findings also showed that PPV7-positive samples had a high rate of coinfection with PCV2, PCV3, and PRRSV. Real-time PCR was used to determine the viral copy numbers of PCV2, PCV3, PRRSV, and PPV7 in serum samples and to assess whether PPV7 affected PCV2, PCV3, and PRRSV viral loads. Phylogenetic analysis showed that PPV7e and PPV7f were the most prevalent and widespread subtypes in the Fujian and Guangdong regions, respectively. While the PPV7a, PPV7b, PPV7c, and PPV7f subtypes were most prevalent in Fujian Province, PPV7a-e subtypes were prevalent in Guangdong, indicating that PPV7 has rich genetic diversity in these regions. A putative recombinant strain, 21FJ09, was identified using SimPlot and the Recombination Detection Program 4 software.

Two-color laser field-induced plasma filaments are efficient broadband terahertz (THz) sources with intense THz waves emitted mainly in the forward direction, and they have been investigated intensively. However, investigations on the backward emission from such THz sources are rather rare. In this paper, we theoretically and experimentally investigate the backward THz wave radiation from a two-color laser field-induced plasma filament. In theory, a linear dipole array model predicts that the proportion of the backward emitted THz wave decreases with the length of the plasma filament. In our experiment, we obtain the typical waveform and spectrum of the backward THz radiation from a plasma with a length of about 5 mm. The dependence of the peak THz electric field on the pump laser pulse energy indicates that the THz generation processes of the forward and backward THz waves are essentially the same. As the laser pulse energy changes, there is a peak timing shift in the THz waveform, implying a plasma position change caused by the nonlinear-focusing effect. Our demonstration may find applications in THz imaging and remote sensing. This work also contributes to a better understanding of the THz emission process from two-color laser-induced plasma filaments.

Abstract Under adverse conditions, such as sustained or chronic hyperglycemia or hyperlipidemia, ROS (reactive oxygen species) or/and ER-stress (endoplasmic reticulum stress) will be induced in pancreatic β cells. ROS or ER-stress damages β-cells even leads to apoptosis. Previously we found ROS or ER-stress resulted in JNK activation in β cells and overexpressing NR4A1 in MIN6 cells reduced JNK activation via modulating cbl-b expression and subsequent degrading the upstream JNK kinase (MKK4). To search other possible mechanisms, we found the mRNA level and protein level of MKP7 (a phosphatase for phospho-JNK) were dramatic reduced in pancreatic β cells in the islets from NR4A1 KO mice compared with that from wild type mice. To confirm what we found in animals, we applied pancreatic β cells (MIN6 cells) and found that the expression of MKP7 was increased in NR4A1-overexpression MIN6 cells. We further found that knocking down the expression of MKP7 increased the p-JNK level in pancreatic β cells upon treatment with TG or H2O2. After that, we figured out that NR4A1 did enhance the transactivation of the MKP7 promoter by physical association with two putative binding sites. In sum, NR4A1 attenuates JNK phosphorylation incurred by ER-stress or ROS partially via enhancing MKP7 expression, potentially decreases pancreatic β cell apoptosis induced by ROS or ER-stress. Our finding provides a clue for diabetes prevention.

Recent studies have emphasized the changes in large-scale brain networks related to healthy aging, with the ultimate purpose to aid in differentiating normal neurocognitive aging from neurodegenerative disorders that also arise with age. Emerging evidence from functional Magnetic Resonance Imaging (fMRI) indicates that connectivity patterns within specific brain networks, especially the Default Mode Network (DMN), distinguish those with Alzheimer's disease from healthy individuals. In addition, disruptive alterations in the large-scale brain systems that support high-level cognition are shown to accompany cognitive decline at the behavioral level, which is commonly observed in the aging populations, even in the absence of disease. Although fMRI is useful for assessing functional changes in brain networks, its high costs and limited accessibility discourage studies that need large populations. In this study, we investigated the aging-effect on large-scale networks of the human brain using high-density electroencephalography and electrophysiological source imaging, which is a less costly and more accessible alternative to fMRI. In particular, our study examined a group of healthy subjects in the age range from middle- to older-aged adults, which is an under-studied range in the literature. Employing a high-resolution computation model, our results revealed age associations in the connectivity pattern of DMN in a consistent manner with previous fMRI findings. Particularly, in combination with a standard battery of cognitive tests, our data showed that in the posterior cingulate / precuneus area of DMN higher brain connectivity was associated with lower performance on an episodic memory task. The findings demonstrate the feasibility of using electrophysiological imaging to characterize large-scale brain networks and suggest that changes in network connectivity are associated with normal aging.