WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.

What can we learn about stress and sleep from COVID-19 pandemic-perspective from the theory of preventive stress management.

Background: The COVID-19 pandemic has presented unique challenges to individuals worldwide, with a significant focus on the impact on sleep. However, the precise mechanisms through which emotional and cognitive variables mediate this relationship remain unclear. To expand our comprehensive understanding of variables, the present study utilizes the Preventive Stress Management theory, to test the relationship between perceived social support and sleep quality, as well as the effect of perceived COVID-19 stress, hope, negative emotions and coping styles. Methods: Data were collected in March 2022 from 1,034 college students in two universities located in Liaoning Province, China, using an online survey platform regarding perceived social support, perceived COVID-19 stress, sleep quality, hope, negative emotions and coping styles. The moderated mediation model were conducted using Process macro program (Model 6) and the syntax in SPSS. Results: The results revealed perceived COVID-19 stress and negative emotions sequentially mediated the negative relationship between perceived social support and sleep quality. Furthermore, hope and coping styles were found to moderate the sequential mediating effect. Conclusion: The present study sheds light on the pathways that affect sleep quality among college students during the COVID-19 pandemic. Findings highlight the protective roles played by positive social and personal resources, such as perceived social support, hope, and effective coping styles, against sleep problems. These insights have important implications for the development of targeted interventions to improve sleep outcomes during this challenging time.

Spatially Confined in Situ Formed Sodiophilic-Conductive Network for High-Performance Sodium Metal Batteries.

The sodium (Na) metal anode encounters issues such as volume expansion and dendrite growth during cycling. Herein, a novel three-dimensional flexible composite Na metal anode was constructed through the conversion-alloying reaction between Na and ultrafine Sb2S3 nanoparticles encapsulated within the electrospun carbon nanofibers (Sb2S3@CNFs). The formed sodiophilic Na3Sb sites and the high Na+-conducting Na2S matrix, coupled with CNFs, establish a spatially confined "sodiophilic-conductive" network, which effectively reduces the Na nucleation barrier, improves the Na+ diffusion kinetics, and suppresses the volume expansion, thereby inhibiting the Na dendrite growth. Consequently, the Na/Sb2S3@CNFs electrode exhibits a high Coulombic efficiency (99.94%), exceptional lifespan (up to 2800 h) at high current densities (up to 5 mA cm-2), and high areal capacities (up to 5 mAh cm-2) in symmetric cells. The coin-type full cells assembled with a Na3V2(PO4)3/C cathode demonstrate significant enhancement in electrochemical performance. The flexible pouch cell achieves an excellent energy density of 301 Wh kg-1.

Acoustohydrodynamic micromixers: Basic mixing principles, programmable mixing prospectives, and biomedical applications.

Acoustohydrodynamic micromixers offer excellent mixing efficiency, cost-effectiveness, and flexible controllability compared with conventional micromixers. There are two mechanisms in acoustic micromixers: indirect influence by induced streamlines, exemplified by sharp-edge micromixers, and direct influence by acoustic waves, represented by surface acoustic wave micromixers. The former utilizes sharp-edge structures, while the latter employs acoustic wave action to affect both the fluid and its particles. However, traditional micromixers with acoustic bubbles achieve significant mixing performance and numerous programmable mixing platforms provide excellent solutions with wide applicability. This review offers a comprehensive overview of various micromixers, elucidates their underlying principles, and explores their biomedical applications. In addition, advanced programmable micromixing with impressive versatility, convenience, and ability of cross-scale operations is introduced in detail. We believe this review will benefit the researchers in the biomedical field to know the micromixers and find a suitable micromixing method for their various applications.

CLCN3 in mediating the proliferation of human ovarian cancer cells.

Background: Chloride channel-3 (CLCN3), a crucial component of the voltage-gated chloride channel family, is implicated in numerous physiological and pathophysiological processes. This study aimed to investigate the characteristics of CLCN3 in pancancer and its influence on the immune response through the use of a range of databases. Concurrently, we assessed the impact of CLCN3 on the proliferation of ovarian cancer (OC) cells and explored its potential mechanisms. Methods: We employed the Tumor Immune Estimation Resource (TIMER) 2.0 and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases to examine the messenger RNA (mRNA) and the protein expression of CLCN3 across various cancers. The prognostic significance of CLCN3 was evaluated using the Gene Expression Profiling Interactive Analysis 2.0 (GEPIA 2.0) database. The University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) facilitated the analysis of CLCN3 promoter methylation levels. The association between CLCN3 expression and tumor-infiltrating immune cells was investigated using various algorithms. The cBioportal database facilitated the analysis of CLCN3 mutations and mutation sites across various cancers. The Tumor-Immune System Interactions Database (TISIDB) database was employed to explore the correlation between CLCN3 expression and immune or molecular subtypes across a variety of cancer types. We collected ovarian tissue samples, encompassing both normal ovarian and OC tissues. The human OC cell lines, SKOV3 cells and OVCAR433 cells, were cultured. CLCN3 expression was determined via reverse-transcription quantitative polymerase chain reaction (RT-qPCR), while phosphatidylinositol 3-kinase/Akt kinase (PI3K/AKT) expression was detected using Western blot. We utilized small interfering RNA (siRNA) technology to suppress CLCN3 expression. The proliferative capacity of SKOV3 and OVCAR433 cells was assessed using the Cell Counting Kit 8 (CCK-8) assay. Results: CLCN3 demonstrated an aberrant expression in a number of cancer types and was markedly reduced in OC tissues. Poor prognosis in cervical squamous cell cancer and myeloid leukemia was linked to excessive expression of CLCN3. The examination of immune cell infiltration, which included CD8+ T cells, B cells, T regulatory cells, and cancer-associated fibroblast cells, showed a strong association with aberrant CLCN3 expression. Following the use of siRNA technology, the ability of the ovarian carcinoma cell line SKOV3 and OVCAR433 to proliferate as well as the expression of PI3K/AKT both increased. Conclusions: CLCN3 is a possible biomarker for immune-related processes and the prognosis of cancer, and the PI3K/AKT signaling pathway may affect OC cells' ability to proliferate.

Long-term table tennis training alters dynamic functional connectivity and white matter microstructure in large scale brain regions.

Table tennis training has been employed as an exercise treatment to enhance cognitive brain functioning in patients with mental illnesses. However, research on its underlying mechanisms remains limited. In this study, we investigated functional and structural changes in large-scale brain regions between 20 table tennis players (TTPs) and 21 healthy controls (HCs) using 7-Tesla magnetic resonance imaging (MRI) techniques. Compared with those of HCs, TTPs exhibited significantly greater anisotropy fraction (FA) and axial diffusivity (AD) values in multiple fiber tracts. We used the locations with the most significant structural changes in white matter as the seed areas and then compared static and dynamic functional connectivity (sFC and dFC). Brodmann 11, located in the orbitofrontal cortex, showed altered dFC values to large-scale brain regions, such as the occipital lobe, thalamus, and cerebellar hemispheres, in TTPs. Brodmann 48, located in the temporal lobe, showed altered dFC to the parietal lobe, frontal lobe, cerebellum, and occipital lobe. Furthermore, the AD values of the forceps minor (Fmi) and right anterior thalamic radiations (ATRs) were negatively correlated with useful field of view (UFOV) test scores in TTPs. Our results suggest that table tennis players exhibit a unique pattern of dynamic neural activity; this provides evidence for potential mechanisms through which table tennis interventions can enhance attention and other cognitive functions.

Composite estimation to combine spatially overlapping environmental monitoring surveys.

Long-term environmental monitoring surveys are designed to achieve a desired precision (measured by variance) of resource conditions based on natural variability information. Over time, increases in resource variability and in data use to address issues focused on small areas with limited sample sizes require bolstering of attainable precision. It is often prohibitive to do this by increasing sampling effort. In cases with spatially overlapping monitoring surveys, composite estimation offers a statistical way to obtain a precision-weighted combination of survey estimates to provide improved population estimates (more accurate) with improved precisions (lower variances). We present a composite estimator for overlapping surveys, a summary of compositing procedures, and a case study to illustrate the procedures and benefits of composite estimation. The study uses the two terrestrial monitoring surveys administered by the Bureau of Land Management (BLM) that entirely overlap. Using 2015-18 data and 13 land-health indicators, we obtained and compared survey and composite indicator estimates of percent area meeting land-health standards for sagebrush communities in Wyoming's Greater Sage-Grouse (Centrocercus urophasianus) Core and NonCore conservation areas on BLM-managed lands. We statistically assessed differences in indicator estimates between the conservation areas using composite estimates and estimates of the two surveys individually. We found composite variance to be about six to 24 units lower than 37% of the survey variances and composite estimates to differ by about six to 10 percentage points from six survey estimates. The composite improvements resulted in finding 11 indicators to statistically differ (p <0.05) between the conservation areas compared to only six and seven indicators for the individual surveys. Overall, we found composite estimation to be an efficient and useful option for improving environmental monitoring information where two surveys entirely overlap and suggest how this estimation method could be beneficial where environmental surveys partially overlap and in small area applications.

The Significant Role of New Particle Composition and Morphology on the HNO3-Driven Growth of Particles down to Sub-10 nm.

New particle formation and growth greatly influence air quality and the global climate. Recent CERN Cosmics Leaving OUtdoor Droplets (CLOUD) chamber experiments proposed that in cold urban atmospheres with highly supersaturated HNO3 and NH3, newly formed sub-10 nm nanoparticles can grow rapidly (up to 1000 nm h-1). Here, we present direct observational evidence that in winter Beijing with persistent highly supersaturated HNO3 and NH3, nitrate contributed less than ∼14% of the 8-40 nm nanoparticle composition, and overall growth rates were only ∼0.8-5 nm h-1. To explain the observed growth rates and particulate nitrate fraction, the effective mass accommodation coefficient of HNO3 (αHNO3) on the nanoparticles in urban Beijing needs to be 2-4 orders of magnitude lower than those in the CLOUD chamber. We propose that the inefficient uptake of HNO3 on nanoparticles is mainly due to the much higher particulate organic fraction and lower relative humidity in urban Beijing. To quantitatively reproduce the observed growth, we show that an inhomogeneous "inorganic core-organic shell" nanoparticle morphology might exist for nanoparticles in Beijing. This study emphasized that growth for nanoparticles down to sub-10 nm was largely influenced by their composition, which was previously ignored and should be considered in future studies on nanoparticle growth.

Rhein against Staphylococcus xylosus by interfering with respiratory metabolism and inducing oxidative stress.

Currently, dairy mastitis caused by Staphylococcus xylosus poses a serious challenge for dairy farming. In this study, we explored the role and mechanism of rhein against S. xylosus with the hope of providing new research ideas to solve mastitis in dairy cows and ensure the source safety of dairy products. Through in vitro antimicrobial studies, we found that the minimum inhibitory concentration (MIC) of rhein was 64 µg/mL, and it significantly interfered with the formation of S. xylosus biofilm at sub-MIC. In experiments on mastitis in mice, rhein alleviated inflammation in mammary tissue, reduced the levels of TNF-α and IL-6, and decreased the number of S. xylosus. To explore the anti-S. xylosus mechanism of rhein, we identified the relevant proteins involved in carbon metabolism (Glycolysis/gluconeogenesis, TCA cycle, Fatty acid degradation) through proteomics. Additionally, proteins associated with the respiratory chain, oxidative stress (proteins of antioxidant and DNA repair), and nitrate respiration were also found to be upregulated. Thus, rhein may act as an antibacterial agent by interfering with the respiratory metabolism of S. xylosus and inducing the production of ROS, high levels of which alter the permeability of bacterial cell membranes and cause damage to them. We measured the concentrations of extracellular ß-galactosidase and nucleic acids. Additionally, SEM observation of S. xylosus morphology showed elevated membrane permeability and damage to the cell membrane. Finally, RT-PCR experiments showed that mRNAs of key proteins of the TCA cycle (odhA, mqo) and nitrate respiration (nreB, nreC, narG) were significantly up-regulated, consistent with proteomic results. In conclusion, rhein has good anti-S. xylosus effects in vitro and in vivo, by interfering with bacterial energy metabolism, inducing ROS production, and causing cell membrane and DNA damage, which may be one of the important mechanisms of its antimicrobial activity.

Effect of WeChat-Based Medication Guidance on Symptoms and Serological Parameters in Children with Mycoplasma Pneumoniae.

Objective: The aim of this study was to assess the effect of microsoft-based medication guidance on the level of symptoms and serological indicators in children receiving budesonide nebulisation combined with terbutaline for the treatment of Mycoplasma pneumoniae pneumoniae (MPP). Methods: A total of 109 children with MPP treated in The First Affiliated Hospital of Ningbo University of China between October 2022 and April 2023 were divided into the conventional group (n=54, with medication guidance by telephone follow-up) and the WeChat group (n=55, with medication guidance based on the WeChat platform) using a randomized number table. The time to resolution of symptoms, serological index levels, incidence of adverse drug events, medication adherence scores and satisfaction rate of family guidance were compared between the two groups. Results: The disappearance time of symptoms such as wheezing and cough in the WeChat group was shorter than that in the conventional group (P < .05). After treatment, the C-reactive protein (CRP), interleukin-6 (IL-6) and calcitoninogen (PCT) levels and the incidence of adverse drug events were lower in the WeChat group than in the conventional group (P < .05). After treatment, the levels of forceful spirometry (FVC), 1st-second expiratory volume (FEV1), peak expiratory flow rate (PEF), medication compliance score and family guidance satisfaction rate were higher in the WeChat group than in the conventional group (P < .05). Conclusion: WeChat-based medication guidance can optimize the therapeutic effect of MPP, improve children's medication compliance and satisfaction rate of family guidance, and reduce the occurrence of adverse drug events.

Sensitive Organic Photodetectors With Spectral Response up to 1.3 µm Using a Quinoidal Molecular Semiconductor.

Detecting short-wavelength infrared (SWIR) light has underpinned several emerging technologies. However, the development of highly sensitive organic photodetectors (OPDs) operating in the SWIR region is hindered by their poor external quantum efficiencies (EQEs) and high dark currents. Herein, the development of high-sensitivity SWIR-OPDs with an efficient photoelectric response extending up to 1.3 µm is reported. These OPDs utilize a new ultralow-bandgap molecular semiconductor featuring a quinoidal tricyclic electron-deficient central unit and multiple non-covalent conformation locks. The SWIR-OPD achieves an unprecedented EQE of 26% under zero bias and an even more impressive EQE of up to 41% under a -4 V bias at 1.10 µm, effectively pushing the detection limit of silicon photodetectors. Additionally, the low energetic disorder and trap density in the active layer lead to significant suppression of thermal-generation carriers and dark current, resulting in excellent detectivity (Dsh * ) exceeding 1013 Jones from 0.50 to 1.21 µm and surpassing 1012 Jones even at 1.30 µm under zero bias, marking the highest achievements for OPDs beyond the silicon limit to date. Validation with photoplethysmography measurements, a spectrometer prototype in the 0.35-1.25 µm range, and image capture under 1.20 µm irradiation demonstrate the extensive applications of this SWIR-OPD.

An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy.

BACKGROUND: The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting. OBJECTIVE: The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy. METHODS: The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells. RESULTS: The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 µg mL-1. CONCLUSION: This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

Hydrous ruthenium oxide triggers template-free and spontaneous growth of metal nanostructures.

Intrinsically conductive ruthenium oxide is an excellent material for energy storage and conversion. Herein, we present hydrous RuO2 (H-RuO2) as a potent reducing agent to achieve spontaneous growth of multiple noble metals at room temperature. Self-assembled gold and platinum, comprising small-sized nanoparticles, are generated on the surface of H-RuO2 without the need for additional templates. Structural analysis reveals that the disordered structure and the presence of oxygen vacancies trigger interfacial redox reactions between H-RuO2 and oxidative metal salts. The resulting integrated nanostructures, consisting of a metal oxide and different metals (H-RuO2@metal), are subsequently used to treat inflammatory bowel diseases. In addition to biomedical applications, our developed synthetic strategy, using reactive oxides to spontaneously generate multicomponent nanostructures, also holds great significance for other catalysis-based applications.

Injectable CNPs/DMP1-loaded self-assembly hydrogel regulating inflammation of dental pulp stem cells for dentin regeneration.

Vital pulp preservation, which is a clinical challenge of aseptic or iatrogenic accidental exposure of the pulp, in cases direct pulp capping is the main technology. Human dental pulp stem cells (hDPSCs) play a critical role in pulp tissue repair, but their differentiative ability could be inhibited by the potential infection and inflammatory response of the exposed pulp. Therefore, inflammatory regulation and differentiated promotion of hDPSCs are both essential for preserving living pulp teeth. In this study, we constructed a functional dental pulp-capping hydrogel by loading cerium oxide nanoparticles (CNPs) and dentin matrix protein-1 (DMP1) into an injectable Fmoc-triphenylalanine hydrogel (Fmoc-phe3 hydrogel) as CNPs/DMP1/Hydrogel for in situ drugs delivery. With a view to long-term storage and release of CNPs (anti-inflammatory and antioxidant) to regulate the local inflammatory environment and DMP1 to promote the regeneration of dentin. Results of CCK-8, LDH release, hemolysis, and Live/Dead assessment of cells demonstrated the good biocompatibility of CNPs/DMP1/Hydrogel. The levels of alkaline phosphatase activity, quantification of the mineralized nodules, expressions of osteogenic genes and proteins demonstrated CNPs/DMP1/Hydrogel could protect the activity of hDPSCs' osteogenic/dentinogenic differentiation by reducing the inflammation response via releasing CNPs. The therapy effects were further confirmed in rat models, CNPs/DMP1/Hydrogel reduced the necrosis rate of damaged pulp and promoted injured pulp repair and reparative dentin formation with preserved vital pulps. In summary, the CNPs/DMP1/Hydrogel composite is an up-and-coming pulp-capping material candidate to induce reparative dentin formation, as well as provide a theoretical and experimental basis for developing pulp-capping materials.

Spatial-temporal changes of landscape and habitat quality in typical ecologically fragile areas of western China over the past 40 years: A case study of the Ningxia Hui Autonomous Region.

In this paper, we use the InVEST model and five periods of land use data from 1980 to 2020 to assess the habitat quality of the Ningxia Hui Autonomous Region in Western China, which has characteristics of a typical fragile ecosystem. We further analyse the spatial and temporal characteristics of habitat quality evolution and its relationship with land use and landscape pattern indices to explore the close relationship between regional habitat quality changes and human natural resource conservation and utilization. The research results show that the overall habitat quality of Ningxia Hui Autonomous Region was stable and at a moderate level (0.57-0.60) during the 40 years from 1980 to 2020; Habitat patches (2020) with low (24.89%), high (22.45%) and very high (29.81%) quality occupy a larger proportion of the area, followed by very low (13.31%) and moderate levels (9.54%). Over the past 40 years, there have been 275 sample sites in Ningxia where habitat quality has deteriorated, 1593 sample sites where the habitat quality has remained stable, and 184 sample sites where the habitat quality has increased. From 1980 to 2020, the Mean Patch Area of landscape types in Ningxia decreased by 25.9 hm2. The Patch Density increased by 0.06 /hm2. The Largest Patch Index decreased by 15.69%. The Edge Density increased by 2.5 m/hm2. The Contagion Index decreased by 2.99%. The Area-Weighted Mean Patch Fractal Dimension remained basically unchanged (0.01). The Landscape Shape Index showed a trend of first increasing and then decreasing, increasing by 13.94. The Area-Weighted Mean Shape Index has been reduced by 9.45. The Shannon Diversity Index and Shannon Evenness Index both show an increasing trend, but the amplitude is relatively small, with 0.09 and 0.04, respectively. There was a significant spatial aggregation of high and low habitat quality in Ningxia, with high values usually distributed in the northern and southern areas with good natural conditions and low values distributed in areas with frequent human activities and poor natural conditions. The decrease in habitat quality in Ningxia was mainly due to the expansion of cultivated land and construction land, the increase in landscape fragmentation and the resulting decrease in connectivity. On the other hand, due to the implementation of ecological protection measures, such as the project of returning farmland to pasture and grass to forest, the quality of habitats in Ningxia increased. The conclusions of this study support the idea that the conservation of habitat quality in ecologically fragile areas should fully preserve the original natural habitats and reduce the interference of human activities to increase the habitat suitability of the landscape and the habitat connectivity between patches. At the same time, targeted ecological protection policies should be developed to restore the areas where the habitat quality has been damaged and ultimately maintain the stability of biodiversity and ecosystems in ecologically fragile areas. Meanwhile, for ecologically fragile areas with similar ecological characteristics to those of Ningxia, our research supports the idea of increasing the protection of the stability of the original habitats, increasing the proportion of ecological restoration projects, financial investment and seeking cooperation with local community managers and residents will help to improve the quality of the regional habitats and the enrichment of the biodiversity, and ultimately promote the harmonious coexistence of human beings and nature in the modernized sense of the word.

A comparative assessment of time-consuming and laborious diatom analysis：Brief experimentation with suggestion of automatic identification.

Diatom testing is considered a useful method for providing supportive evidence for the diagnosis of drowning in forensic pathology. However, various factors remain controversial for recognizing diatoms, such as being time-consuming and laborious and influencing the consistency of the results. Given the absence of precise and well-defined studies on this subject, this study aimed to determine the relationship between the ability to identify diatoms and researchers with different technical backgrounds. A total of 55 samples from 18 cases, including water, lungs, liver, and kidneys, were treated using the microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM), which was used to compare diatom analyses among three groups of well-trained forensic pathologists (FPs), trained junior employees (JEs), and new trainees (TEs). In addition to achieving similar accuracy of positive findings from drowning cases, counting efficiency was evaluated based on taxonomy records and counting time after viewing more than 5500 diatom images. In contrast to the higher counting efficiency of the JE group than that of the TE group, we observed a statistically significant difference (p < 0.05) in the diatom classification between these two groups. Based on our experiments, an efficient analysis for automatically identifying and classifying diatoms is urgently required.

Regulating pathway for bacterial diversities toward improved ecological benefits of thiencarbazone-methyl·isoxaflutole application: A field experiment.

Herbicide abuse has a significantly negative impact on soil microflora and further influences the ecological benefit. The regulating measures and corresponding mechanisms mitigating the decreased bacterial diversity due to herbicide use have rarely been studied. A field experiment containing the application gradient of an efficient maize herbicide thiencarbazone-methyl·isoxaflutole was performed. The relationship between soil bacterial community and thiencarbazone-methyl·isoxaflutole use was revealed. Modified attapulgite was added to explore its impacts on soil microflora under the thiencarbazone-methyl·isoxaflutole application. Based on the analytic network process-entropy weighting method-TOPSIS method model, the ecological benefit focusing on microbial responses was quantitatively estimated along with technical effectiveness and economic benefit. The results showed that the diversity indices of soil microflora, especially the Inv_Simpson index, were reduced at the recommended, 5 and 10 times the recommended dosages of thiencarbazone-methyl·isoxaflutole use. The Flavisolibacter bacteria was negatively correlated with the residues in soils based on the random forest model and correlation analysis, indicating a potential degrader of thiencarbazone-methyl·isoxaflutole residues. The structural equation model further confirmed that the high soil water content and soil pH promoted the function of Flavisolibacter bacteria, facilitated the dissipation of thiencarbazone-methyl·isoxaflutole residues and further improved the diversity of soil microflora. In addition, the presence of modified attapulgite was found to increase the soil pH, which may improve bacterial diversity through the regulating pathway. This explained the high ecological benefits of the treatment where the thiencarbazone-methyl·isoxaflutole was applied at the recommended dosage rates in conjunction with modified attapulgite addition. Therefore, the comprehensive benefits of thiencarbazone-methyl·isoxaflutole application with a focus on ecological benefits can be improved by regulating the soil pH with modified attapulgite.

Modeling the Formation of Organic Compounds across Full Volatility Ranges and Their Contribution to Nanoparticle Growth in a Polluted Atmosphere.

Nanoparticle growth influences atmospheric particles' climatic effects, and it is largely driven by low-volatility organic vapors. However, the magnitude and mechanism of organics' contribution to nanoparticle growth in polluted environments remain unclear because current observations and models cannot capture organics across full volatility ranges or track their formation chemistry. Here, we develop a mechanistic model that characterizes the full volatility spectrum of organic vapors and their contributions to nanoparticle growth by coupling advanced organic oxidation modeling and kinetic gas-particle partitioning. The model is applied to Nanjing, a typical polluted city, and it effectively captures the volatility distribution of low-volatility organics (with saturation vapor concentrations <0.3 µg/m3), thus accurately reproducing growth rates (GRs), with a 4.91% normalized mean bias. Simulations indicate that as particles grow from 4 to 40 nm, the relative fractions of GRs attributable to organics increase from 59 to 86%, with the remaining contribution from H2SO4 and its clusters. Aromatics contribute much to condensable organic vapors (∼37%), especially low-volatility vapors (∼61%), thus contributing the most to GRs (32-46%) as 4-40 nm particles grow. Alkanes also contribute 19-35% of GRs, while biogenic volatile organic compounds contribute minimally (<13%). Our model helps assess the climatic impacts of particles and predict future changes.

Identification of a small-molecule Tim-3 inhibitor to potentiate T cell-mediated antitumor immunotherapy in preclinical mouse models.

T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC' cleft of Tim-3, a highly conserved binding site of phosphatidylserine (PtdSer) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion in vitro and in vivo. In addition, ML-T7 promoted NK cells' killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3. ML-T7 strengthened DCs' functions through both Tim-3 and Tim-4, which is consistent with the fact that Tim-4 contains a similar FG-CC' loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to the Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wild-type and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti-PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.