Effects of clonal fragmentation on Pyrrosia nuda depend on growth stages in a rubber plantation.

Introduction: Clonal fragmentation helps to assess clonal plants' growth resilience to human and environmental disturbance. Although clonal integration in epiphytes in tropical rubber plantations is important to understand their role in enhancing biodiversity and ecosystem services, research on this subject is limited. These plantations are typically monospecific economic forests that face increased anthropogenic disturbances. Methods: In this study, we selected the clonal fern Pyrrosia nuda to study its survival status, biomass, maximum quantum yield of photosystem II (Fv/Fm), and frond length in response to the level of clonal fragmentation in a tropical rubber plantation. Results and discussion: The results showed that (1) clonal fragmentation significantly negatively affected the survival rate, biomass, and frond length of clonal plants, but with minimal effects on Fv/Fm at different growth stages; (2) the performance of a ramet (e.g., biomass or frond length) increased with ramet developmental ages and decreased with the number of ramets in a clonal fragment. The age-dependent impacts of clonal fragmentation provide insights into the biodiversity conservation of epiphytes and forest management in man-made plantations. Therefore, to better conserve the biodiversity in tropical forests, especially in environment-friendly rubber plantations, there is a need to reduce anthropogenic disturbances and alleviate the level of fragmentation.

MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer.

Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. SIGNIFICANCE: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.

Arene-Arene Coupled Disulfamethazines (or Sulfadiazine)-Phenanthroline-Metal(II) Complexes were Synthesized by In Situ Reactions and Inhibited the Growth and Development of Triple-Negative Breast Cancer through the Synergistic Effect of Antiangiogenesis, Anti-Inflammation, Pro-Apoptosis, and Cuproptosis.

The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development. The molecular mechanism was confirmed that HA-Cu could downregulate the expression of key proteins in the VEGF/VEGFR2 signaling pathway and the expression of inflammatory cytokines, enhance the advantage of pro-apoptotic protein Bax, and enforce cuproptosis by weakening the expression of FDX1 and enhancing the expression of HSP70. Our research will provide a theoretical and practical reference for the development of metal-sulfamethazine and its derivatives as chemotherapy drugs for cancer treatment.

Trichostatin A relieves anxiety-and depression-like symptoms in APP/PS1 mice.

Background: Cognitive deficits and behavioral disorders such as anxiety and depression are common manifestations of Alzheimer's disease (AD). Our previous work demonstrated that Trichostatin A (TSA) could alleviate neuroinflammatory plaques and improve cognitive disorders. AD, anxiety, and depression are all associated with microglial inflammation. However, whether TSA could attenuate anxiety- and depression-like behaviors in APP/PS1 mice through anti-inflammatory signaling is still unclearly. Methods: In the present study, all mice were subjected to the open field, elevated plus maze, and forced swim tests to assess anxiety- and depression-related behaviors after TSA administration. To understand the possible mechanisms underlying the behavioral effects observed, CST7 was measured in the hippocampus of mice and LPS-treated BV2 microglia. Results: The results of this study indicated that TSA administration relieved the behaviors of depression and anxiety in APP/PS1 mice, and decreased CST7 levels in the hippocampus of APP/PS1 mice and LPS-induced BV2 cells. Conclusion: Overall, these findings support the idea that TSA might be beneficial for reducing neurobehavioral disorders in AD and this could be due to suppression of CST7-related microglial inflammation.

Positive association between chlorinated paraffins and the risk of allergic diseases in children and adolescents.

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.

Selective orexin 2 receptor blockade alleviates cognitive impairments and the pathological progression of Alzheimer's disease in 3xTg-AD mice.

The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid ß (Aß) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting and ELISA were used to detect Aß deposition, tau phosphorylation and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aß pathology, tau phosphorylation and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated.

Subspace Identification of Bridge Frequencies Based on the Dimensionless Response of a Two-Axle Vehicle.

As an essential reference to bridge dynamic characteristics, the identification of bridge frequencies has far-reaching consequences for the health monitoring and damage evaluation of bridges. This study proposes a uniform scheme to identify bridge frequencies with two different subspace-based methodologies, i.e., an improved Short-Time Stochastic Subspace Identification (ST-SSI) method and an improved Multivariable Output Error State Space (MOESP) method, by simply adjusting the signal inputs. One of the key features of the proposed scheme is the dimensionless description of the vehicle-bridge interaction system and the employment of the dimensionless response of a two-axle vehicle as the state input, which enhances the robustness of the vehicle properties and speed. Additionally, it establishes the equation of the vehicle biaxial response difference considering the time shift between the front and the rear wheels, theoretically eliminating the road roughness information in the state equation and output signal effectively. The numerical examples discuss the effects of vehicle speeds, road roughness conditions, and ongoing traffic on the bridge identification. According to the dimensionless speed parameter Sv1 of the vehicle, the ST-SSI (Sv1 < 0.1) or MOESP (Sv1 ≥ 0.1) algorithm is applied to extract the frequencies of a simply supported bridge from the dimensionless response of a two-axle vehicle on a single passage. In addition, the proposed methodology is applied to two types of long-span complex bridges. The results show that the proposed approaches exhibit good performance in identifying multi-order frequencies of the bridges, even considering high vehicle speeds, high levels of road surface roughness, and random traffic flows.

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer: A single-arm phase 2 clinical trial.

Background: Human epidermal growth factor receptor 2 (HER2)-targeted agents have significantly improved the outcomes of patients with HER2-positive breast cancer; however, a large proportion of patients still develop resistance to trastuzumab. In this study, we investigated the efficacy and safety of inetetamab, another anti-HER2 antibody, combined with pyrotinib and oral vinorelbine in patients with HER2-positive advanced breast cancer so as to provide new ideas for the treatment. Methods: In this prospective, single-arm, phase 2 trial, patients with HER2-positive advanced breast cancer with disease progression after trastuzumab were recruited. Patients received a combination of inetetamab (loading dose of 8 mg/kg and subsequent doses of 6 mg/kg intravenously once every 3 weeks), pyrotinib (400 mg orally once daily), and vinorelbine (60 mg/m2 orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), and safety. Results: Between February 13, 2022 and December 25, 2022, 30 patients were screened and enrolled in this study. The median age of the patients at enrollment was 54 years, 12 patients (40.0 %) had hormone-receptor-positive disease and 23 patients (76.7 %) had visceral metastasis. The median PFS was 8.63 months (95 % confidence interval [CI] 4.15-13.12 months). The median OS was not reached. The ORR was 53.3 % (16/30) and the DCR was 96.7 % (29/30). The most common Grade III/IV adverse events were leukopenia (n = 5, 16.7 %), neutropenia (n = 4, 13.3 %), and diarrhea (n = 3, 10 %). No treatment-related serious adverse events or deaths occurred. Conclusions: The combination regimen of inetetamab, pyrotinib, and oral vinorelbine showed encouraging efficacy and favorable safety in patients with HER2-positive advanced breast cancer and could be considered as an alternative treatment option for the patients. Trial registration: No.NCT05823623; https://www.clinicaltrials.gov/.

Toxicological evaluation and concentration of airborne PM0.1 in high air pollution period in Guangzhou, China.

The emissions and exposure limits for airborne PM0.1 are lacking, with limited scientific data for toxicity. Therefore, we continuously monitored and calculated the number and mass concentrations of airborne PM0.1 in December 2017, January 2018 and March 2018 during the high pollution period in Guangzhou. We collected PM0.1 from the same period and analyzed their chemical components. A549, THP-1 and A549/THP-1 co-cultured cells were selected for exposure to PM0.1, and evaluated for toxicological responses. Our aims are to 1) measure and analyze the number and mass concentrations, and chemical components of PM0.1; 2) evaluate and compare PM0.1 toxicity to different airway cells models at different time points. Guangzhou had the highest mass concentration of PM0.1 in December 2017, while the number concentration was the lowest. Chemical components in PM0.1 vary significantly at different time periods, and the correlation between the chemical composition or source of PM0.1 and the mass and number concentration of PM0.1 was dissimilar. Exposure to PM0.1 disrupted cell membranes, impaired mitochondrial function, promoted the expression of inflammatory mediators, and interfered with DNA replication in the cell cycle. The damage caused by exposure to PM0.1 at different times exhibited variations across different types of cells. PM0.1 in March 2018 stimulated co-cultured cells to secrete more inflammatory mediators, and CMA was significantly related to the expression of them. Our study indicates that it is essential to monitor both the mass and number concentrations of PM0.1 throughout all seasons annually, as conventional toxicological experiments and the internal components of PM0.1 may not effectively reveal the health damages caused by elevated number levels of PM0.1.

Vertical variation in leaf functional traits of Parashorea chinensis with different canopy layers.

Introduction: Canopy species need to shift their ecological adaptation to improve light and water resources utilization, and the study of intraspecific variations in plant leaf functional traits based at individual scale is of great significance for evaluating plant adaptability to climate change. Methods: In this study, we evaluate how leaf functional traits of giant trees relate to spatial niche specialization along a vertical gradient. We sampled the tropical flagship species of Parashorea chinensis around 60 meters tall and divided their crowns into three vertical layers. Fourteen key leaf functional traits including leaf morphology, photosynthetic, hydraulic and chemical physiology were measured at each canopy layer to investigate the intraspecific variation of leaf traits and the interrelationships between different functional traits. Additionally, due to the potential impact of different measurement methods (in-situ and ex-situ branch) on photosynthetic physiological parameters, we also compared the effects of these two gas exchange measurements. Results and discussion: In-situ measurements revealed that most leaf functional traits of individual-to-individual P. chinensis varied significantly at different canopy heights. Leaf hydraulic traits such as midday leaf water potential (MWP) and leaf osmotic potential (OP) were insignificantly correlated with leaf photosynthetic physiological traits such as maximal net assimilation rate per mass (A mass). In addition, great discrepancies were found between in-situ and ex-situ measurements of photosynthetic parameters. The ex-situ measurements caused a decrease by 53.63%, 27.86%, and 38.05% in A mass, and a decrease of 50.00%, 19.21%, and 27.90% in light saturation point compared to the in-situ measurements. These findings provided insights into our understanding of the response mechanisms of P. chinensis to micro-habitat in Xishuangbanna tropical seasonal rainforests and the fine scale adaption of different resultant of decoupled traits, which have implications for understanding ecological adaption strategies of P. chinensis under environmental changes.

[Study on the Effect and Mechanism of Tetrandrine on Bone Marrow Mesenchymal Stem Cell-Mediated Drug Resistance in Leukemia].

OBJECTIVE: To explore the role of bone marrow mesenchymal stem cells (BMSC)，an essential element of the bone marrow microenvironment, in multidrug resistance(MDR) of K562 cells, as well as the reversal effect of tetrandrine (TET) on BMSC-mediated MDR and its potential mechanism. METHODS: A mixed co-culture system and a transwell co-culture system for BMSC and K562 cells were established, and the cells were divided into different groups and treated with daunorubicin (DNR) alone or combined with TET and DNR. The CCK-8 assay was used to detect the proliferation of K562 cells in each group, and the cell inhibition rate was calculated. Cytometric bead array (CBA) was used to detect the expression levels of IFN, IL-2, IL-6 and IL-10 in the supernatant of different groups. RT-qPCR and Western blot were used to detected the expression of STAT3 at mRNA and protein levels, respectively. RESULTS: Compared with K562+DNR group, the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR group was significantly decreased (P < 0.05), while the levels of IL-6 in the culture supernatant and phosphorylated STAT3 in K562 cells were significantly increased (P < 0.05). Compared with K562+BMSC+DNR group, the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR+TET group was significantly increased (P < 0.05), while the level of IL-6 and phosphorylated STAT3 was significantly decreased (P < 0.05). CONCLUSION: BMSC can promote the drug resistance of leukemia cells, and TET may reverse the BMSC-mediated drug resistance via inhibiting IL-6/STAT3 signaling pathway.

Association between occupational stress, occupational burnout, and depressive symptoms among medical staff during COVID-19: A cross-sectional study in Chongqing, China.

BACKGROUND: Studies have extensively examined the factors contributing to the onset of occupational stress, burnout, and depression. However, the relationship between these variables is limited. OBJECTIVE: This study aimed to explore the association between occupational stress, burnout, and depressive symptoms and to investigate the mediating effect of burnout between occupational stress and depressive symptoms in medical staff. METHODS: A cross-sectional survey was conducted among medical staff in Chongqing, China. The Core Occupational Stress Scale (COSS), Maslach Burnout Inventory: General Survey (MBI-GS), and Patient Health Questionnaire-9 (PHQ-9) were used to assess the status of occupational stress, burnout, and depressive symptoms, respectively. The bootstrapping analyses using SPSS PROCESS macros version 3 were conducted to examine mediating effects. RESULTS: The study conducted on medical staff in Chongqing revealed that the detection rates of occupational stress, occupational burnout, and depressive symptoms were 31.8%, 23.3%, and 30.3%, respectively. Hierarchical regression analysis revealed that occupational stress and burnout accounted for 19.3% (p <  0.001) and 18.8% (p <  0.001) of the variance in depressive symptoms, respectively. Mediation analysis showed that occupational stress indirectly affected depressive symptoms through the mediating effect of occupational burnout, with a mediation effect value of 0.13 (bootstrap 95% CI: 0.116-0.144) and the mediation effect accounting for 44.8% of the total effect. CONCLUSION: Our results indicated that occupational stress and burnout were predictors of depressive symptoms. Occupational stress had a significant indirect effect on depressive symptoms via burnout. These results suggest that reducing occupational stress and burnout could be effective strategies for preventing depression among medical staff.

Inhibition of Xanthine Oxidase by 4-nitrocinnamic Acid: In Vitro and In Vivo Investigations and Docking Simulations.

Background: Cinnamic acid and its derivatives have gained significant attention in recent medicinal research due to their broad spectrum of pharmacological properties. However, the effects of these compounds on xanthine oxidase (XO) have not been systematically investigated, and the inhibitory mechanism remains unclear.

Objectives: The objective of this study was to screen 18 compounds and identify the XO inhibitor with the strongest inhibitory effect. Furthermore, we aimed to study the inhibitory mechanism of the identified compound.

Methods: The effects of the inhibitors on XO were evaluated using kinetic analysis, docking simulations, and in vivo study. Among the compounds tested, 4-NA was discovered as the first XO inhibitor and exhibited the most potent inhibitory effects, with an IC50 value of 23.02 ± 0.12 µmol/L. The presence of the nitro group in 4-NA was found to be essential for enhancing XO inhibition. The kinetic study revealed that 4-NA inhibited XO in a reversible and noncompetitive manner. Moreover, fluorescence spectra analysis demonstrated that 4-NA could spontaneously form complexes with XO, referred to as 4-NA-XO complexes, with the negative values of △H and ΔS.

Results: This suggests that hydrogen bonds and van der Waals forces play crucial roles in the binding process. Molecular docking studies further supported the kinetic analysis and provided insight into the optimal binding conformation, indicating that 4-NA is located at the bottom outside the catalytic center through the formation of three hydrogen bonds. Furthermore, animal studies confirmed that the inhibitory effects of 4-NA on XO resulted in a significant reduction of serum uric acid level in hyperuricemia mice.

Conclusion: This work elucidates the mechanism of 4-NA inhibiting XO, paving the way for the development of new XO inhibitors.

Construction of Nomogram prediction model of myopia risk and lifestyle among primary school students in Tianjin City / 中国学校卫生

Objective@#To explore the relationship between lifestyle and myopia and construct Nomogram model to predict myopia risk among primary school students in Tianjin, so as to provide a scientific basis for precision myopia prevention and control.@*Methods@#From April to July of 2022, a census method was used to conduct vision testing and lifestyle related questionnaires among 373 180 primary school students in 15 districts of Tianjin. The relationship between lifestyle and myopia was analyzed by the multivariate Logistic regression, and a nomogram prediction model was constructed to predict myopia risk.@*Results@#The detection rate of myopia among primary school students in Tianjin was 37.6%. The results of the multivariate Logistic regression showed that daily outdoor activity time of 1-2 h ( OR =0.94) and >2 h ( OR =0.84), time of using daily electronic devices of >2 h ( OR =1.03), daily paper materials reading and writing time of 1-2 h ( OR =1.02) and >2 h ( OR =1.09), weekly fresh vegetable intake of 2-6 times ( OR =0.93) and ≥7 times ( OR =0.88) were statistically correlated with myopia ( P <0.01). The Nomogram prediction model showed that the factors associated with myopia were grade, family history of myopia, gender, daily outdoor activity time, weekly frequency of fresh vegetable intake, daily paper materials reading and writing time, and time of using daily electronic devices time.@*Conclusions@#The lifestyle of primary school students in Tianjin is associated with myopia. The constructed nomogram model could provide a scientific basis for identifying key intervention populations for myopia prevention and taking targeted prevention and control measures.

[Differences and mechanisms on water use of Pinus sylvestris var mongolica forests with different origins]. / 不同起源樟子松林水分利用的差异及机制.

Determining the differences of water use characteristics of a tree species with different origins (natural forests and introduced plantations) is significantly important for forest sustainable management. Pinus sylvestris var. mongolica is an important tree species of afforestation in the 'Three North' project in China. In this study, with Pinus sylvestris var. mongolica from two origins, we monitored the sap flow velocity of sapwood (Js) of trees by thermal dissipation sap flow probes, and analyzed the relationship between water transportation and the environmental factors during the growing season. The results showed that under the typical sunny day, daily sap flow velocity (Js-daily) of trees from plantations was significantly higher than that from natural forests. The mean value of Js-daily was 132.98 and 114.86 cm·d-1 for the two origins, respectively. Trees from plantations showed higher water transportation potential than natural forests. Vapor pressure deficit (VPD) mainly showed the driving effect on the water use process of trees from natural forests. In the plantations, there was an obvious threshold effect, and the inflection point of VPD was about 1.91 kPa, with the boundary function of Js-hour increased to the maximum of 17.88 cm·h-1. Atmospheric driven transpiration potential (Js-hour/VPD) of P. sylvestris var. mongolica trees with two origins decreased with the aggravation of soil drought, but sensitivity to drought was higher in the plantations than in the natural forests, suggesting the strong ability of Pinus sylvestris var. mongolica to regulate water use process.

Effectiveness and Safety of Palbociclib Plus Endocrine Therapy in Patients with Advanced Breast Cancer: A Multi-Center Study in China.

BACKGROUND: Palbociclib has been approved for marketing in China. However, its effectiveness, safety, and latent variables in the Chinese population require further investigation. METHODS: Information was retrieved from 397 patients with metastatic breast cancer (mBC) who received at least two cycles of palbociclib plus endocrine therapy (PAL plus ET) at eight clinical sites in China. The patients' demographic characteristics, treatment patterns, and adverse events (AEs) were analyzed. RESULTS: The objective response rate (ORR) and clinical benefit rate (CBR) for PAL plus ET were 28.97% and 66.25%, respectively. The median PFS was 14.2 months in the whole population. In addition to protein Ki-67 status and sensitivity to ETs, no liver metastases, fewer metastatic sites, an earlier line of therapy, and treatment combined with AI instead of FUL were also considered as independent prognostic factors for PAL treatment. Administration of PAL was generally well tolerated in patients with hormone-receptor-positive and human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) advanced breast cancer (ABC). The therapy was safe in the elderly population, which is consistent with the outcomes of the whole population and previous reports. CONCLUSIONS: In this most widely distributed study in China to date, palbociclib combined with ET proved its effectiveness for HR+/HER2- ABC treatment, and adverse events were manageable. Here, we identified some independent prognosis factors, but the mechanism by which these factors influence effectiveness requires further verification.

Estimation of forest canopy closure in northwest Yunnan based on multi-source remote sensing data colla-boration.

Forest canopy closure (FCC) is an important parameter to evaluate forest resources and biodiversity. Using multi-source remote sensing collaborative means to achieve regional forest canopy closure inversion with low cost and high-precision is a research hotspot. Taking ICESat-2/ATLAS data as the main information source and combined with data of 54 measured plots, we estimated FCC value by the Bayesian optimization (BO) algorithm improved random forest (RF), K-nearest neighbor (KNN), and gradient boosting regression tree (GBRT) model at footprint-scale. Combined with multi-source remote sensing image Sentinel-1/2 and terrain factors, we estimated the regional-scale FCC value of Shangri-La in the northwest Yunnan based on deep neural network (DNN) optimized by BO algorithm. The results showed that six characteristic parameters (percentage of tree canopy, standard deviation of relative height of photons at the top of the canopy, minimum canopy height, difference between 98% canopy height and median canopy height in the segment, number of top canopy photons, apparent surface reflectance) out of the 50 parameters that were extracted from ATLAS lidar footprint had higher contribution rate after RF characteristic variable optimization, which could be used as model variable for footprint-scale remote sensing estimation. Among BO-RF, BO-KNN, and BO-GBRT models, the FCC results estimated by the BO-GBRT model were the best at footprint-scale. The coefficient of determination (R2) was 0.65, the root mean square error (RMSE) was 0.10, the mean absolute residual (RS) was 0.079, and the prediction accuracy (P) was 0.792 for leave-one-out cross validation. It could be used as the FCC estimation model of 74808 ATLAS footprints for forest in the study area. We used the ATLAS footprint-scale FCC value of forest as the large sample data of the regional-scale BO-DNN model and combined with multi-source remote sensing factors to estimate FCC in the study area, the accuracy of the 10-fold cross-validation BO-DNN model was R2=0.47, RMSE=0.22, P=0.558. The mean values of FCC in the study area estimated by BO-DNN model and ordinary Kriging (OK) interpolation were 0.46 and 0.52, respectively, and the values mainly distributed in 0.3-0.6, accounting for 77.8% and 81.4%, respectively. The FCC efficiency obtained directly by the OK interpolation method was higher (R2=0.26), but the prediction accuracy was significantly lower than the BO-DNN model (R2=0.49). The FCC high value was distributed from northwest to southeast in the study area, and the northern and southeastern regions were the main distribution areas of high and low FCC values, respectively. It had certain advantages to estimate mountain area FCC based on ICESat-2/ATLAS high-density footprint, and the estimation results of small sample data at footprint-scale could be used as large sample data of deep learning model at region-scale, which would provide a reference for the low-cost and high-precision to FCC estimation on the footprint-scale up to the extrapolated regional-scale.

One-dimensional consolidation of highly saturated abandoned-soil under time-dependent stress: An analytical study.

A thorough knowledge of the consolidation behavior of highly saturated soil under time-dependent stress is essential for the design and construction of abandoned-soil dump sites in the soft soil regions of China. In this study, one-dimensional consolidation analytical solutions are derived for such soil under one-way and two-way drainage conditions, accommodating the time-dependent stress created by various dumping protocols. Representative soil samples are obtained, and consolidation tests are conducted with various saturation degrees (one-way drainage) and loading protocols (two-way drainage), to verify the consolidation equation and determine its range of applicability to various saturation degrees. The effects of layer thickness, dumping type, and compaction degree on the consolidation behaviors of highly saturated abandoned-soil dumps are investigated. The one-dimensional consolidation equation is applicable to soil with saturation degree not lower than 75% under instantaneous stress, stepped stress, and linear stress. The pore pressure distribution with depth is not symmetrical; the eccentric distance of consolidation degree increases with increasing layer thickness in the stress application stage and is approximately zero in the stress keeping stage. The pore pressure at middle of the soil layer increases with increasing layer thickness and decreases with increasing dumping rate from the completion of soil dumping. With increasing compaction degree, the middle pore pressure increases, while the surface settlement decreases. In the premise of the stability of an abandoned-soil dump, where the goals are to reduce post-construction settlement and to shorten the consolidation process of the entire soil layer, the important factors are smaller layer thickness, higher dumping rate, and larger compaction degree.

Differences in the pharmacokinetics and steady-state blood concentrations of orally administered lenvatinib in adult and juvenile rats.

Objective: The aim of this study was to compare the pharmacokinetics and steady-state serum concentrations of lenvatinib in adult and juvenile rats. Experimental study: An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method was developed to quantify lenvatinib in the serum and liver of rats. Six juvenile and six adult rats in each group were orally administered with a single dose of 7.0 mg/kg lenvatinib suspension for pharmacokinetics. Another 12 juvenile and adult rats were subjected to oral gavage with 7.0 mg/kg lenvatinib once daily for 5 days. Biofluild samples were pre-treated by protein precipitation and sorafenib was used as the internal standard for UPLC-MS analysis. The pharmacokinetic parameters were estimated by compartment and statistical model. The mRNA expression of CYP3A2 and SLC22A1 in liver of adult and juvenile rats was measured by real-time fluorescence quantitative PCR (RT-qPCR). Results: The UPLC-MS method met the requirements for quantitative analysis of lenvatinib in serum and liver. The pharmacokinetic results showed that the mean retention time (MRT(0-∞)) was 19.64 ± 7.64 h and 126.38 ± 130.18 h, with AUC(0-∞) values of 3.97 ± 0.73 µg‧mL-1 h and 5.95 ± 2.27 µg mL-1 h in adult and juvenile rats, respectively. When comparing adult rats (0.35 ± 0.15 µg/mL) to juvenile rats, no significant differences were observed in steady-state serum lenvatinib (0.32 ± 0.11 µg/mL), but a noteworthy decrease to one-third of steady-state liver lenvatinib was observed after multiple oral doses of lenvatinib in juvenile rats. Additional findings revealed that the mRNA expression of CYP3A2 and SLC22A1 was notably increased by 6.86 and 14.67 times, respectively, in juvenile rats compared to adult rats. Conclusion: Juvenile rats exhibit lower levels of lenvatinib in the liver's steady-state, potentially due to the disparity in CYP3A2 mRNA expression. These results imply that the dosage of lenvatinib for pediatric patients may need to be augmented in order to attain the desired clinical outcome.