Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages.

Immunosuppressive tumor microenvironment (TME) contributes to tumor progression and causes major obstacles for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism while its role in remodeling TME remains unclear. In this study, we reported that PGAM1 suppression in breast cancer (BC) cells led to a decrease in M2 polarization, migration, and interleukin-10 (IL-10) production of macrophages. PGAM1 regulation on CCL2 expression was essential to macrophage recruitment, which further mediated by activating JAK-STAT pathway. Additionally, the CCL2/CCR2 axis was observed to participate in PGAM1-mediated immunosuppression via regulating PD-1 expression in macrophages. Combined targeting of PGAM1 and the CCL2/CCR2 axis led to a reduction in tumor growth in vivo. Furthermore, clinical validation in BC tissues indicated a positive correlation between PGAM1, CCL2 and macrophage infiltration. Our study provides novel insights into the induction of immunosuppressive TME by PGAM1 and propose a new strategy for combination therapies targeting PGAM1 and macrophages in BC.

Isotopic insights and integrated analysis for heavy metal levels, ecological risks, and source apportionment in river sediments of the Qinghai-Tibet Plateau.

The research was carried out to examine the pollution characteristics, ecological risk, and origins of seven heavy metals (Hg, As, Pb, Cu, Cd, Zn, and Ni) in 51 sediment samples gathered from 8 rivers located on the Qinghai-Tibet Plateau (QTP) in China. The contents of Hg and Cd were 5.0 and 1.1 times higher than their background values, respectively. The mean levels of other measured heavy metals were below those found naturally in the local soil. The enrichment factor showed that the study area exhibited significantly enriched Hg with 70.6% sampling sites. The Cd contents at 19.6% of sampling sites were moderately enriched. The other sampling sites were at a less enriched level. The sediments of all the rivers had a medium level of potential ecological risk. Hg was the major ecological risk factor in all sampling sites, followed by Cd. The findings from the positive matrix factorization (PMF) analysis shown agricultural activities, industrial activities, traffic emissions, and parent material were the major sources. The upper, middle, and low reaches of the Quanji river had different Hg isotope compositions, while sediments near the middle reaches were similar to the δ202Hg of the industrial source. At the upstream sampling sites, the Hg isotope content was very close to the background level. The results of this research can establish a strong scientific sound to improve the safety of the natural circumstances of rivers on the QTP.

Microbial difference and its influencing factors in ice-covered lakes on the three poles.

Most lakes in the world are permanently or seasonally covered with ice. However, little is known about the distribution of microbes and their influencing factors in ice-covered lakes worldwide. Here we analyzed the microbial community composition in the waters of 14 ice-covered lakes in the Hoh Xil region of northern Qing-Tibetan Plateau (QTP), and conducted a meta-analysis by integrating published microbial community data of ice-covered lakes in the tripolar regions (the Arctic, Antarctica and QTP). The results showed that there were significant differences in microbial diversity, community composition and distribution patterns in the ice-covered tripolar lakes. Microbial diversity and richness were lower in the ice-covered QTP lakes (including the studied lakes in the Hoh Xil region) than those in the Arctic and Antarctica. In the ice-covered lakes of Hoh Xil, prokaryotes are mainly involved in S-metabolic processes, making them more adaptable to extreme environmental conditions. In contrast, prokaryotes in the ice-covered lakes of the Arctic and Antarctica were predominantly involved in carbon/nitrogen metabolic processes. Deterministic (salinity and nutrients) and stochastic processes (dispersal limitation, homogenizing dispersal and drift) jointly determine the geographical distribution patterns of microorganisms in ice-covered lakes, with stochastic processes dominating. These results expand the understanding of microbial diversity, distribution patterns, and metabolic processes in polar ice-covered lakes.

Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer.

Background: Immune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC). Methods: Fifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively. Results: A comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival. Conclusions: These results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.

Effects of immunogenic cell death-inducing chemotherapeutics on the immune cell activation and tertiary lymphoid structure formation in melanoma.

Background: The infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas. Methods: Doxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining. Results: Doxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8+ T cells and tissue-resident memory T cells (TRM) and an increase in the secretion of interferon-γ, granzyme B, and perforin in CD8+ T subsets and activation of B cells and dendritic cells. Doxorubicin alone and in combination with gemcitabine decreased regulatory T cells in the TIME. Moreover, doxorubicin treatment promoted the formation of HEV and TLS. Doxorubicin treatment also upregulated the expression of programmed cell death protein (PD)-1 in CD8+ T cells and programmed cell death protein ligand (PD-L)1 in tumor cells. Conclusions: These results indicate that doxorubicin with an ICD reaction promotes TLS formation and increases PD-1/PD-L1 expression in tumor tissues. The results demonstrate the development of a therapeutic avenue using combined immune checkpoint therapy.

The spatial landscape of T cells in the microenvironment of stage III lung adenocarcinoma.

This study aimed to provide more information for prognostic stratification for patients through an analysis of the T-cell spatial landscape. It involved analyzing stained tissue sections of 80 patients with stage III lung adenocarcinoma (LUAD) using multiplex immunofluorescence and exploring the spatial landscape of T cells and their relationship with prognosis in the center of the tumor (CT) and invasive margin (IM). In this study, multivariate regression suggested that the relative clustering of CT CD4+ conventional T cell (Tconv) to inducible Treg (iTreg), natural regulatory T cell (nTreg) to Tconv, terminal CD8+ T cell (tCD8) to helper T cell (Th), and IM Treg to tCD8 and the relative dispersion of CT nTreg to iTreg, IM nTreg to nTreg were independent risk factors for DFS. Finally, we constructed a spatial immunological score named the GT score, which had stronger prognostic correlation than IMMUNOSCORE® based on CD3/CD8 cell densities. The spatial layout of T cells in the tumor microenvironment and the proposed GT score can reflect the prognosis of patients with stage III LUAD more effectively than T-cell density. The exploration of the T-cell spatial landscape may suggest potential cell-cell interactions and therapeutic targets and better guide clinical decision-making. © 2024 The Pathological Society of Great Britain and Ireland.

Mesonia profundi sp. nov., isolated from deep-sea sediment of the Mariana Trench.

A Gram-stain-negative, aerobic, rod-shaped, non-flagellated, non-gliding bacterial strain, designated MT50T, was isolated from a deep-sea sediment sample collected from the Mariana Trench. Optimal growth of strain MT50T was observed at 25 °C, pH 7.0-7.5 and in the presence of 3-5 % (w/v) NaCl. The strain was positive for oxidase and catalase. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain MT50T is affiliated with the genus Mesonia, showing the highest sequence similarity (98.5 %) to the type strain of Mesonia ostreae. The digital DNA-DNA hybridization and average nucleotide identity values between strain MT50T and four closely related type strains of known Mesonia species (14.1-54.8 % and 72.7-86.8 %, respectively) were all below the threshold values to discriminate bacterial species, indicating that strain MT50T is affiliated with a novel species within the genus. The genomic G+C content deduced from the genome of strain MT50T was 36.2 mol%. The major fatty acids of strain MT50T were iso-C15 : 0, iso-C17 : 0 3-OH and anteiso-C15 : 0. The predominant respiratory quinone of the strain was MK-6. The polar lipids of strain MT50T included phosphatidylethanolamine and two unidentified lipids. Based on the polyphasic data presented in this study, strain MT50T represents a novel species of the genus Mesonia, for which the name Mesonia profundi sp. nov. is proposed. The type strain is MT50T (=MCCC 1K07833T=KCTC 92380T).

The complete mitochondrial genome of the tropical sea urchin Tripneustes gratilla (Linnaeus, 1758) with two spine colors.

The complete mitochondrial genomes of two spine-color individuals, red and white, of the tropical sea urchin species Tripneustes gratilla (Linnaeus, 1758) were sequenced on Illumina system platform. The red-spined species had a genome size of 15,774 bp, while the white-spined species had a genome size of 15,723 bp. Both genomes contained 13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. The GC composition in both species was above 40%. In order to investigate the phylogenetic relationships of two different spine-color individuals, a comprehensive analysis was conducted using eight complete mitochondrial genomic sequences of the genus Tripneustes on the software MEGA X. It was observed that the two spine color types of T. gratilla species showed a high similarity of 98.91%. However, different color-spined species of T. gratilla were found in separate branches of the phylogenetic tree of the same sea urchin species.

Ecological function and interaction of different bacterial groups during alginate processing in coastal seawater community.

The degradation of high molecular weight organic matter (HMWOM) is a core process of oceanic carbon cycle, which is determined by the activity of microbial communities harboring hundreds of different species. Illustrating the active microbes and their interactions during HMWOM processing can provide key information for revealing the relationship between community composition and its ecological functions. In this study, the genomic and transcriptional responses of microbial communities to the availability of alginate, an abundant HMWOM in coastal ecosystem, were elucidated. The main degraders transcribing alginate lyase (Aly) genes came from genera Alteromonas, Psychrosphaera and Colwellia. Meanwhile, some strains, mainly from the Rhodobacteraceae family, did not transcribe Aly gene but could utilize monosaccharides to grow. The co-culture experiment showed that the activity of Aly-producing strain could promote the growth of Aly-non-producing strain when alginate was the sole carbon source. Interestingly, this interaction did not reduce the alginate degradation rate, possibly due to the easily degradable nature of alginate. This study can improve our understanding of the relationship between microbial community activity and alginate metabolism function as well as further manipulation of microbial community structure for alginate processing.

SAR92 clade bacteria are potentially important DMSP degraders and sources of climate-active gases in marine environments.

Dimethylsulfoniopropionate (DMSP) is one of Earth's most abundant organosulfur molecules, which can be catabolized by marine bacteria to release climate-active gases through the cleavage and/or demethylation pathways. The marine SAR92 clade is an abundant oligotrophic group of Gammaproteobacteria in coastal seawater, but their ability to catabolize DMSP is untested. Three SAR92 clade strains isolated from coastal seawater in this study and the SAR92 representative strain HTCC2207 were all shown to catabolize DMSP as a carbon source. All the SAR92 clade strains exhibited DMSP lyase activity producing dimethylsulfide (DMS) and their genomes encoded a ratified DddD DMSP lyase. In contrast, only HTCC2207 and two isolated strains contained the DMSP demethylase dmdA gene and potentially simultaneously demethylated and cleaved DMSP to produce methanethiol (MeSH) and DMS. In SAR92 clade strains with dddD and dmdA, transcription of these genes was inducible by DMSP substrate. Bioinformatic analysis indicated that SAR92 clade bacteria containing and transcribing DddD and DmdA were widely distributed in global oceans, especially in polar regions. This study highlights the SAR92 clade of oligotrophic bacteria as potentially important catabolizers of DMSP and sources of the climate-active gases MeSH and DMS in marine environments, particularly in polar regions.IMPORTANCECatabolism of dimethylsulfoniopropionate (DMSP) by marine bacteria has important impacts on the global sulfur cycle and climate. However, whether and how members of most oligotrophic bacterial groups participate in DMSP metabolism in marine environments remains largely unknown. In this study, by characterizing culturable strains, we have revealed that bacteria of the SAR92 clade, an abundant oligotrophic group of Gammaproteobacteria in coastal seawater, can catabolize DMSP through the DMSP lyase DddD-mediated cleavage pathway and/or the DMSP demethylase DmdA-mediated demethylation pathway to produce climate-active gases dimethylsulfide and methanethiol. Additionally, we found that SAR92 clade bacteria capable of catabolizing DMSP are widely distributed in global oceans. These results indicate that SAR92 clade bacteria are potentially important DMSP degraders and sources of climate-active gases in marine environments that have been overlooked, contributing to a better understanding of the roles and mechanisms of the oligotrophic bacteria in oceanic DMSP degradation.

Salinity change induces distinct climate feedbacks of nitrogen removal in saline lakes.

Current estimations of nitrogen biogeochemical cycling and N2O emissions in global lakes as well as predictions of their future changes are overrepresented by freshwater datasets, while less consideration is given to widespread saline lakes with different salinity (representing salinization or desalinization). Here, we show that N2O production by denitrification is the main process of reactive nitrogen (Nr, the general abbreviations of NH4+-N, NO2--N and NO3--N) removal in hypersaline lake sediments (e.g. Lake Chaka). The integration of our field measurements and literature data shows that in response to natural salinity decrease, potential Nr removal increases while N2O production decreases. Furthermore, denitrification-induced N2 production exhibits higher salinity sensitivity than denitrification-induced N2O production, suggesting that the contribution of N2O to Nr removal decreases with decreasing salinity. This field-investigation-based salinity response model of Nr removal indicates that under global climate change, saline lakes in the process of salinization or desalination may have distinct Nr removal and climate feedback effects: salinized lakes tend to generate a positive climate feedback, while desalinated lakes show a negative feedback. Therefore, salinity change should be considered as an important factor in assessing future trend of N2O emissions from lakes under climate change.

Cost-effective production of alginate oligosaccharides from Laminaria japonica roots by Pseudoalteromonas agarivorans A3.

BACKGROUND: Alginate oligosaccharides (AOs) are the degradation products of alginate, a natural polysaccharide abundant in brown algae. AOs generated by enzymatic hydrolysis have diverse bioactivities and show broad application potentials. AOs production via enzymolysis is now generally with sodium alginate as the raw material, which is chemically extracted from brown algae. In contrast, AOs production by direct degradation of brown algae is more advantageous on account of its cost reduction and is more eco-friendly. However, there have been only a few attempts reported in AOs production from direct degradation of brown algae. RESULTS: In this study, an efficient Laminaria japonica-decomposing strain Pseudoalteromonas agarivorans A3 was screened. Based on the secretome and mass spectrum analyses, strain A3 showed the potential as a cell factory for AOs production by secreting alginate lyases to directly degrade L. japonica. By using the L. japonica roots, which are normally discarded in the food industry, as the raw material for both fermentation and enzymatic hydrolysis, AOs were produced by the fermentation broth supernatant of strain A3 after optimization of the alginate lyase production and hydrolysis parameters. The generated AOs mainly ranged from dimers to tetramers, among which trimers and tetramers were predominant. The degradation efficiency of the roots reached 54.58%, the AOs production was 33.11%, and the AOs purity was 85.03%. CONCLUSION: An efficient, cost-effective and green process for AOs production directly from the underutilized L. japonica roots by using strain A3 was set up, which differed from the reported processes in terms of the substrate and strain used for fermentation and the AOs composition. This study provides a promising platform for scalable production of AOs, which may have application potentials in industry and agriculture.

Spartinivicinus marinus sp. nov., isolated from intertidal sediment.

A Gram-stain-negative, aerobic, flagellated, and long rod-shaped bacterium, designated strain SM1973T, was isolated from an intertidal sediment sample collected from the coast of Qingdao, PR China. Strain SM1973T grew at 15-37 °C and with 0-5.5 % NaCl. It reduced nitrate to nitrite and hydrolysed aesculin but did not hydrolyse casein and gelatin. The strain showed the highest 16S rRNA gene sequence similarity (98.2 %) to the type strain of Spartinivicinus ruber. The phylogenetic trees based on the 16S rRNA genes and single-copy orthologous clusters showed that strain SM1973T clustered with S. ruber, forming a separate lineage within the family Zooshikellaceae. The major cellular fatty acids were summed feature 3 (C16 : 1 ω7с and/or C16 : 1 ω6с) and C16 : 0. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The main respiratory quinone was ubiquinone-9. The genomic DNA G+C content of strain SM1973T was 40.4 mol%. Based on the polyphasic evidence presented in this paper, strain SM1973T is considered to represent a novel species within the genus Spartinivicinus, for which the name Spartinivicinus marinus sp. nov. is proposed. The type strain is SM1973T (=MCCC 1K04833T=KCTC 72846T).

DC101, an anti-VEGFR2 agent, promotes high-endothelial venule formation and immune infiltration versus SAR131675 and fruquintinib.

There is an increasing interest in combining immune checkpoint inhibitors (ICIs) with anti-angiogenic drugs to enhance their anti-tumor effects. In this study, three anti-angiogenic agents, DC101 (acting on VEGFR2), SAR131675 (acting on VEGFR3), and fruquintinib (a small-molecule inhibitor acting on multiple targets) were administered to B16F1-OVA-loaded C57BL/6 mice. Immune cells infiltration in the tumor tissues, vascular normalization, and high-endothelial venule (HEV) formation were assessed to provide evidence for drug combination. Both DC101 and fruquintinib significantly slowed the melanoma growth and increased the proportion of CD3+ and CD8+ T cells infiltration compared with SAR131675, of note, the effect of DC101 was more pronounced. Moreover, DC101 and fruquintinib increased the interferon-γ and perforin levels, meanwhile, DC101 increased the granzyme B levels, whereas fruquintinib and SAR131675 did not. Only the fruquintinib-treated group showed decreased regulatory T cells infiltration. We found upregulation of PD-L1 expression in tumor cells and CD45+ immune cells in DC101-treated group as well as upregulation of PD-1 expression on CD3+ T cells. However, fruquintinib only increased PD-L1 expression in tumors. Both DC101 and fruquintinib reduced the proportion of CD31+ vessels, while DC101 increased the ratio of α-SMA +/CD31+ cells and reduced the expression of HIF-1α more than fruquintinib. Moreover, DC101 enhanced the infiltration of dendritic cells and B cells, and local HEV formation. In conclusion, our data indicate that DC101 may be a better choice for the combined clinical application of ICIs and anti-angiogenic agents.

Salinimicrobium profundisediminis sp. nov., isolated from deep-sea sediment of the Mariana Trench.

A Gram-stain-negative, aerobic, rod-shaped, non-gliding bacterial strain, designated as MT39T, was isolated from a deep-sea sediment sample collected from the Mariana Trench. Strain MT39T grew optimally at 35°C and pH 7.0, and could tolerate up to 10% (w/v) NaCl. The strain was positive for catalase and negative for oxidase. The genome of strain MT39T was 4 033 307 bp, with a 41.1 mol % genomic G+C content and 3514 coding sequences. Phylogenetic analysis based on 16S rRNA gene sequences placed strain MT39T within the genus Salinimicrobium, showing the highest 16S rRNA gene sequence similarity to Salinimicrobium terrea CGMCC 1.6308T (98.1%). The average nucleotide identity and in silico DNA-DNA hybridization values between strain MT39T and the type strains of seven Salinimicrobium species were all less than the threshold values to discriminate bacterial species, indicating that strain MT39T is affiliated with a novel species within the genus. The major cellular fatty acids of strain MT39T were iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH. Polar lipids of strain MT39T included phosphatidylethanolamine, one unidentified aminolipid and four unidentified lipids. Menaquinone-6 was the only respiratory quinone in strain MT39T. On the basis of the polyphasic data present in this study, strain MT39T represents a novel species of the genus Salinimicrobium, for which the name Salinimicrobium profundisediminis sp. nov. is proposed, with type strain being MT39T (=MCCC 1K07832T=KCTC 92381T).

Sewage sludge application stimulated soil N2O emissions with a low heavy metal pollution risk in Eucalyptus plantations.

Sewage sludge (SS) has been extensively used as an alternative fertilizer in forest plantations, which are beneficial in supplying timbers and mitigating climate change. However, whether the extra nitrogen (N) applied by SS would enhance the soil nitrous oxide (N2O) emission, an important greenhouse gas, in forest plantations have not been well understood. The objective of this study is to evaluate the ecological effects of SS application on soils, by investigating the soil N2O emission and the toxicity of the potentially toxic elements (PTEs) in soil. A field fertilization experiment was conducted in Eucalyptus plantations with four fertilization rates (0 kg m-2, 1.5 kg m-2, 3.0 kg m-2, and 4.5 kg m-2). The soil N2O emissions were monitored at a soil depth of 0-10 cm using static chamber method, soil chemical properties, and PTEs were determined at soil depths of 0-10 cm, 10-20 cm, and 20-40 cm. The average soil N2O emission rate was 8.1 µg N2O-N h-1 m-2 in plots without SS application (control). The application of SS significantly increased the soil N2O emissions by 7-10 times as to control. The increased N2O emissions were positively related to the soil total phosphorus and nitrogen and negatively correlated with copper and zinc, which increased with the SS application. However, the potential ecological risk index (Ei) and the comprehensive potential ecological risk index (RI) of PTEs were lower than 40 and 150 respectively, which indicating a low toxicity of PTEs to soil health. After seven months of SS application, the priming effects of SS on soil N2O emissions gradually diminished. These findings suggest that the application of SS may increase N2O emissions at the initial stages of application (<7 months) and may have a low PTEs pollution risk, even at a high SS addition rate (4.5 kg m-2).

MCANet: shared-weight-based MultiheadCrossAttention network for drug-target interaction prediction.

Accurate and effective drug-target interaction (DTI) prediction can greatly shorten the drug development lifecycle and reduce the cost of drug development. In the deep-learning-based paradigm for predicting DTI, robust drug and protein feature representations and their interaction features play a key role in improving the accuracy of DTI prediction. Additionally, the class imbalance problem and the overfitting problem in the drug-target dataset can also affect the prediction accuracy, and reducing the consumption of computational resources and speeding up the training process are also critical considerations. In this paper, we propose shared-weight-based MultiheadCrossAttention, a precise and concise attention mechanism that can establish the association between target and drug, making our models more accurate and faster. Then, we use the cross-attention mechanism to construct two models: MCANet and MCANet-B. In MCANet, the cross-attention mechanism is used to extract the interaction features between drugs and proteins for improving the feature representation ability of drugs and proteins, and the PolyLoss loss function is applied to alleviate the overfitting problem and the class imbalance problem in the drug-target dataset. In MCANet-B, the robustness of the model is improved by combining multiple MCANet models and prediction accuracy further increases. We train and evaluate our proposed methods on six public drug-target datasets and achieve state-of-the-art results. In comparison with other baselines, MCANet saves considerable computational resources while maintaining accuracy in the leading position; however, MCANet-B greatly improves prediction accuracy by combining multiple models while maintaining a balance between computational resource consumption and prediction accuracy.

Spatiotemporal Winter Wheat Water Status Assessment Improvement Using a Water Deficit Index Derived from an Unmanned Aerial System in the North China Plain.

Agricultural droughts cause a great reduction in winter wheat productivity; therefore, timely and precise irrigation recommendations are needed to alleviate the impact. This study aims to assess drought stress in winter wheat with the use of an unmanned aerial system (UAS) with multispectral and thermal sensors. High-resolution Water Deficit Index (WDI) maps were derived to assess crop drought stress and evaluate winter wheat actual evapotranspiration rate (ETa). However, the estimation of WDI needs to be improved by using more appropriate vegetation indices as a proximate of the fraction of vegetation cover. The experiments involved six irrigation levels of winter wheat in the harvest years 2019 and 2020 at Luancheng, North China Plain on seasonal and diurnal timescales. Additionally, WDI derived from several vegetation indices (VIs) were compared: near-infrared-, red edge-, and RGB-based. The WDIs derived from different VIs were highly correlated with each other and had similar performances. The WDI had a consistently high correlation to stomatal conductance during the whole season (R2 between 0.63-0.99) and the correlation was the highest in the middle of the growing season. On the contrary, the correlation between WDI and leaf water potential increased as the season progressed with R2 up to 0.99. Additionally, WDI and ETa had a strong connection to soil water status with R2 up to 0.93 to the fraction of transpirable soil water and 0.94 to the soil water change at 2 m depth at the hourly rate. The results indicated that WDI derived from multispectral and thermal sensors was a reliable factor in assessing the water status of the crop for irrigation scheduling.

Rational pemetrexed combined with CIK therapy plus anti-PD-1 mAbs administration sequence will effectively promote the efficacy of CIK therapy in non-small cell lung cancer.

Cytokine-induced killer (CIK) cells are heterogeneous cells composed mainly of CD3+CD56+ T cells. As an important treatment method of adoptive therapy, it has shown promising efficacy in many clinical trials, especially in combination with multidrug therapy. However, the maximal antitumor efficacy of CIK therapy in the combined administration of multidrug and CIK therapies and which administration scheme can maximize the antitumor efficacy of CIK therapy are still remain unclear. In this study, we observed that pemetrexed administration prior to the injection of CIK cells maximizes the efficacy of CIK therapy. Anti-PD-1 mAbs should be administered prior to CIK cell injection to maximize the efficacy of the therapy. However, administering anti-PD-1 mAbs after CIK cell injection significantly affects the binding rate of anti-PD-1 mAbs to the PD-1 receptor on CIK cells, affecting the efficacy of the antitumor therapy. In conclusion, our study observed that a rational administration sequence of pemetrexed combined with CIK therapy and anti-PD-1 mAbs significantly promotes the efficacy of CIK therapy, providing an experimental basis for the combination therapy mode and regimen of CIK therapy in clinical practice. We hope that this study can provide patients with lung adenocarcinoma with a prolonged survival time.

Controlling factors and health risks of groundwater chemistry in a typical alpine watershed based on machine learning methods.

Groundwater is a key water resource in alpine watersheds, but its quality is deteriorating due to human activities. The Golmud River watershed is a representative alpine watershed in Northwest China, and it was chosen to explore groundwater chemistry, associated controlling factors, source contributions, and potential health risks. The analysis includes the use of a self-organizing map (SOM), positive matrix factorization (PMF), ionic ratios, and a Monte Carlo simulation. The content of total dissolved solids in phreatic water was higher in the dry season and increased from the mountainous zone to the fine-soil plain-overflowing zone. Additionally, the water type varied from HCO3- to Cl- types whereas confined groundwater was chemically stable and of a HCO3- type. The SOM results showed a visual correlation between the ions in groundwater. The combination of SOM, PMF, and ionic ratios identified water-rock action as a dominant factor of groundwater chemistry. It was also found that Clusters I and III were mainly influenced by silicate weathering (a total contribution of 38.4 %), whereas evaporation was dominant in Cluster VI (a contribution of 32.5 %). Anthropogenic pollution was mainly associated with clusters V and IV and was related to industrial and agricultural activities during the snowmelt and wet seasons, and fluorine deposition formed by residential coal heating during the dry season (contributions of 1.4 % and 23.8 % in Clusters V and IV, respectively). The sudden increases in B3+ and Li+ in Cluster II were due to inputs from small tributaries (a contribution of 3.9 %). The probabilistic health risk assessment showed that fluoride posed a greater non-carcinogenic risk to human health than Sr2+, B3+, and NO3-, and its potential threat to children was more significant during the dry season than in other seasons. It is necessary for local governments to establish urgent fluoride emission control policies within the Golmud River watershed.