Environmentally relevant exposure to cotinine induces neurobehavioral toxicity in zebrafish (Danio rerio): A study using neurobehavioral and metabolomic approaches.

As an important psychoactive substance, cotinine is ubiquitous in aquatic environment and poses a threat to aquatic organisms. However, the mechanism of its adverse health impacts remains unclear. We evaluated the effects of cotinine exposure at environmentally relevant concentrations on the development and locomotor behavior of zebrafish (Danio rerio) larvae using neurotransmitters and whole endogenous metabolism. Mild developmental toxicity and significant neurobehavior disorder, such as spontaneous movement (1-1000 µg/L), 48 hpf tactile response (50, 100, and 1000 µg/L), and 144 hpf swimming speed (1, 10, 100, 500, and 1000 µg/L), were observed in zebrafish. Exposure to cotinine led to significant alterations in 11 neurotransmitters, including homogentisic acid, serotonin, glutamic acid and aspartic acid, etc. 298 metabolites were identified and two pathways - linoleic acid metabolism and taurine and hypotaurine metabolism - were delineated. In addition, amino acid neurotransmitters were significantly correlated with metabolites such as arachidonic acid as well as its derivatives, steroidal compounds, and amino acids. Serotonin demonstrates a noteworthy correlation with 31 out of 40 differentially expressed neurotransmitters, encompassing lipids, amino acids, and other compounds. These novel findings contribute to a comprehensive understanding of the ecological risks associated with cotinine contamination in surface waters.

Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the ß-common receptor in mice with cerebral ischemic stroke.

AIM: To explore the neuroprotective effects of ARA290 and the role of ß-common receptor (ßCR) in a mouse model of middle cerebral artery occlusion (MCAO). METHODS: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and ßCR were measured by western blot. RESULTS: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against ßCR. CONCLUSION: ARA290 provided a neuroprotective effect via ßCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.

A simple one-electron expression for electron rotational factors.

Within the context of fewest-switch surface hopping (FSSH) dynamics, one often wishes to remove the angular component of the derivative coupling between states J and K. In a previous set of papers, Shu et al. [J. Phys. Chem. Lett. 11, 1135-1140 (2020)] posited one approach for such a removal based on direct projection, while we isolated a second approach by constructing and differentiating a rotationally invariant basis. Unfortunately, neither approach was able to demonstrate a one-electron operatorÔ whose matrix element JÔK was the angular component of the derivative coupling. Here, we show that a one-electron operator can, in fact, be constructed efficiently in a semi-local fashion. The present results yield physical insight into designing new surface hopping algorithms and are of immediate use for FSSH calculations.

Practical phase-space electronic Hamiltonians for ab initio dynamics.

Modern electronic structure theory is built around the Born-Oppenheimer approximation and the construction of an electronic Hamiltonian Hel(X) that depends on the nuclear position X (and not the nuclear momentum P). In this article, using the well-known theory of electron translation (Γ') and rotational (Γ″) factors to couple electronic transitions to nuclear motion, we construct a practical phase-space electronic Hamiltonian that depends on both nuclear position and momentum, HPS(X,P). While classical Born-Oppenheimer dynamics that run along the eigensurfaces of the operator Hel(X) can recover many nuclear properties correctly, we present some evidence that motion along the eigensurfaces of HPS(X,P) can better capture both nuclear and electronic properties (including the elusive electronic momentum studied by Nafie). Moreover, only the latter (as opposed to the former) conserves the total linear and angular momentum in general.

Dihydroergotamine protects against ischemic stroke by modulating microglial/macrophage polarization and inhibiting inflammation in mice.

OBJECTIVES: The search for drugs that can protect the brain tissue and reduce nerve damage in acute ischemic stroke has emerged as a research hotspot. We investigated the potential protective effects and mechanisms of action of dihydroergotamine against ischemic stroke. METHODS: C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO), and dihydroergotamine at a dose of 10 mg/kg/day was intraperitoneally injected for 14 days. Adhesive removal and beam walking tests were conducted 1, 3, 5, 7, 10, and 14 days after MCAO surgery. Thereafter, the mechanism by which dihydroergotamine regulates microglia/macrophage polarization and inflammation and imparts ischemic stroke protection was studied using enzyme-linked immunosorbent assay, immunofluorescence staining, and western blotting. RESULTS: From the perspective of a drug repurposing strategy, dihydroergotamine was found to inhibit oxygen-glucose deprivation damage to neurons, significantly improve cell survival rate, and likely exert a protective effect on ischemic brain injury. Dihydroergotamine significantly improved neural function scores and survival rates and reduced brain injury severity in mice. Furthermore, dihydroergotamine manifests its protective effect on ischemic brain injury by reducing the expression of TNF-α and IL-1ß in mouse ischemic brain tissue, inhibiting the polarization of microglia/macrophage toward the M1 phenotype and promoting polarization toward the M2 phenotype. CONCLUSION: This study is the first to demonstrate the protective effect of dihydroergotamine, a first-line treatment for migraine, against ischemic nerve injury in vitro and in vivo.

SISTER OF FCA physically associates with SKB1 to regulate flowering time in Arabidopsis thaliana.

BACKGROUND: Proper flowering time is important for the growth and development of plants, and both too early and too late flowering impose strong negative influences on plant adaptation and seed yield. Thus, it is vitally important to study the mechanism underlying flowering time control in plants. In a previous study by the authors, genome-wide association analysis was used to screen the candidate gene SISTER OF FCA (SSF) that regulates FLOWERING LOCUS C (FLC), a central gene encoding a flowering suppressor in Arabidopsis thaliana. RESULTS: SSF physically interacts with Protein arginine methyltransferase 5 (PRMT5, SKB1). Subcellular co-localization analysis showed that SSF and SKB1 interact in the nucleus. Genetically, SSF and SKB1 exist in the same regulatory pathway that controls FLC expression. Furthermore, RNA-sequencing analysis showed that both SSF and SKB1 regulate certain common pathways. CONCLUSIONS: This study shows that PRMT5 interacts with SSF, thus controlling FLC expression and facilitating flowering time control.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

Constructing a Nomogram Model to Estimate the Risk of Ventilator-Associated Pneumonia for Elderly Patients in the Intensive Care Unit.

BACKGROUND: Ventilator-associated pneumonia (VAP) causes heavy losses in terms of finances, hospitalization, and death for elderly patients in the intensive care unit (ICU); however, the risk is difficult to evaluate due to a lack of reliable assessment tools. We aimed to create and validate a nomogram to estimate VAP risk to provide early intervention for high-risk patients. METHODS: Between January 2016 and March 2021, 293 patients from a tertiary hospital in China were retrospectively reviewed as a training set. Another 84 patients were enrolled for model validation from April 2021 to February 2022. Least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analysis were employed to select predictors, and a nomogram model was constructed. The calibration, discrimination, and clinical utility of the nomogram were verified. Finally, a web-based online scoring system was created to make the model more practical. RESULTS: The predictors were hypoproteinemia, long-term combined antibiotic use, intubation time, length of mechanical ventilation, and tracheotomy/intubation. The area under the curve (AUC) was 0.937 and 0.925 in the training and validation dataset, respectively, suggesting the model exhibited effective discrimination. The calibration curve demonstrated high consistency with the observed result and the estimated values. Decision curve analysis (DCA) demonstrated that the nomogram was clinically applicable. CONCLUSIONS: We have created a novel nomogram model that can be utilized to anticipate VAP risk in elderly ICU patients, which is helpful for healthcare professionals to detect patients at high risk early and adopt protective interventions.

Global warming potential assessment under reclaimed water and livestock wastewater irrigation coupled with co-application of inhibitors and biochar.

The application of nitrification inhibitors (nitrapyrin) and urease inhibitors (N-(N-butyl) thiophosphoric triamide) under conventional water resources has been considered as an effective means to improve nitrogen utilization efficiency and mitigate soil greenhouse gas emissions. However, it is not known whether the inhibitors still have an inhibitory effect under unconventional water resources (reclaimed water and livestock wastewater) irrigation and whether their use in combination with biochar improves the mitigation effect. Therefore, unconventional water resources were used for irrigation, with groundwater (GW) control. Nitrapyrin and N-(N-butyl) thiophosphoric triamide were used alone or in combination with biochar in a pot experiment, and CO2, N2O, and CH4 emissions were measured. The results showed that irrigation of unconventional water resources exacerbated global warming potential (GWP). All exogenous substance treatments increased CO2 and CH4 emissions and suppressed N2O emissions, independent of the type of water, compared to no substances (NS). The inhibitors were ineffective in reducing the GWP whether or not in combination with biochar, and the combined application of inhibitors with biochar further increased the GWP. This study suggests that using inhibitors and biochar in combination to regulate the greenhouse effect under unconventional water resources irrigation should be done with caution.

Identification of key factors affecting neonicotinoid residues in crops and risk of dietary exposure.

Neonicotinoids, widely used on farmland, are ubiquitous in food; however, their distribution among various crops and associated exposure risks at the provincial level in China remain unclear. We collected 19 types of crop samples (fruits, vegetables, and tea) from farmland in nine prefectural cities in Zhejiang Province, China. We analyzed nine commonly used neonicotinoids in the edible portions of these crops. A notable detection rate (42.1 %-82.9 %) and high residual neonicotinoid concentrations (278 ± 357 ng/g) were observed. Tea exhibited the highest residue, followed by fruits, and vegetables showed the lowest (P < 0.05). Neonicotinoid ratios in crops to soil (R_C/S) and soil to water (R_S/W) were defined to discern insecticide distribution across different environments. Increased water solubility leads to increased migration of neonicotinoids (R_S/W) from agricultural soils to water through runoff, thereby increasing the relative contribution of nitenpyram and dinotefuran in water. In comparison with other studied compounds, all crops demonstrated the strongest soil uptake of thiamethoxam, denoted by the highest R_C/S value. Elevated R_C/S values in tea, pickled cabbage, and celery suggest increased susceptibility of these crops to neonicotinoid absorption from the soil (P < 0.05). Estimated dietary intake for teenagers, adults and elders was 8.9 ± 0.5, 8.9 ± 0.6, and 8.8 ± 0.3 µg/kg/d, respectively, below the reference dose (57 µg/kg/d). Teenagers, compared to adults and elders, exhibited significantly higher neonicotinoid exposure through fruit consumption, emphasizing the need for increased attention to neonicotinoid exposure among vulnerable populations.

Enhanced Chemoradiotherapy for MRSA-Infected Osteomyelitis Using Immunomodulatory Polymer-Reinforced Nanotherapeutics.

The eradication of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its development of biofilm-induced antibiotic resistance and impaired innate immunity, which often leads to frequent surgical failure. Here, the design, synthesis, and performance of X-ray-activated polymer-reinforced nanotherapeutics that modulate the immunological properties of infectious microenvironments to enhance chemoradiotherapy against multidrug-resistant bacterial deep-tissue infections are reported. Upon X-ray radiation, the proposed polymer-reinforced nanotherapeutic generates reactive oxygen species and reactive nitrogen species. To robustly eradicate MRSA biofilms at deep infection sites, these species can specifically bind to MRSA and penetrate biofilms for enhanced chemoradiotherapy treatment. X-ray-activated nanotherapeutics modulate the innate immunity of macrophages to prevent the recurrence of osteomyelitis. The remarkable anti-infection effects of these nanotherapeutics are validated using a rat osteomyelitis model. This study demonstrates the significant potential of a synergistic chemoradiotherapy and immunotherapy method for treating MRSA biofilm-infected osteomyelitis.

Total angular momentum conservation in Ehrenfest dynamics with a truncated basis of adiabatic states.

We show that standard Ehrenfest dynamics does not conserve linear and angular momentum when using a basis of truncated adiabatic states. However, we also show that previously proposed effective Ehrenfest equations of motion [M. Amano and K. Takatsuka, "Quantum fluctuation of electronic wave-packet dynamics coupled with classical nuclear motions," J. Chem. Phys. 122, 084113 (2005) and V. Krishna, "Path integral formulation for quantum nonadiabatic dynamics and the mixed quantum classical limit," J. Chem. Phys. 126, 134107 (2007)] involving the non-Abelian Berry force do maintain momentum conservation. As a numerical example, we investigate the Kramers doublet of the methoxy radical using generalized Hartree-Fock with spin-orbit coupling and confirm that angular momentum is conserved with the proper equations of motion. Our work makes clear some of the limitations of the Born-Oppenheimer approximation when using ab initio electronic structure theory to treat systems with unpaired electronic spin degrees of freedom, and we demonstrate that Ehrenfest dynamics can offer much improved, qualitatively correct results.

Nematic Spin Correlations Pervading the Phase Diagram of FeSe_{1-x}S_{x}.

We use resonant inelastic x-ray scattering (RIXS) at the Fe-L_{3} edge to study the spin excitations of uniaxial-strained and unstrained FeSe_{1-x}S_{x} (0≤x≤0.21) samples. The measurements on unstrained samples reveal dispersive spin excitations in all doping levels, which show only minor doping dependence in energy dispersion, lifetime, and intensity, indicating that high-energy spin excitations are only marginally affected by sulfur doping. RIXS measurements on uniaxial-strained samples reveal that the high-energy spin-excitation anisotropy observed previously in FeSe is also present in the doping range 0200 K in x=0.18 and reaches a maximum around the nematic quantum critical doping (x_{c}≈0.17). Since the spin-excitation anisotropy directly reflects the existence of nematic spin correlations, our results indicate that high-energy nematic spin correlations pervade the regime of nematicity in the phase diagram and are enhanced by the nematic quantum criticality. These results emphasize the essential role of spin fluctuations in driving electronic nematicity and highlight the capability of uniaxial strain in tuning spin excitations in quantum materials hosting strong magnetoelastic coupling and electronic nematicity.

Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer.

BACKGROUND: As an unconventional subpopulation of T lymphocytes, γδ T cells can recognize antigens independently of major histocompatibility complex restrictions. Recent studies have indicated that γδ T cells play contrasting roles in tumor microenvironments-promoting tumor progression in some cancers (eg, gallbladder and leukemia) while suppressing it in others (eg, lung and gastric). γδ T cells are mainly enriched in peripheral mucosal tissues. As the cervix is a mucosa-rich tissue, the role of γδ T cells in cervical cancer warrants further investigation. METHODS: We employed a multiomics strategy that integrated abundant data from single-cell and bulk transcriptome sequencing, whole exome sequencing, genotyping array, immunohistochemistry, and MRI. RESULTS: Heterogeneity was observed in the level of γδ T-cell infiltration in cervical cancer tissues, mainly associated with the tumor somatic mutational landscape. Definitely, γδ T cells play a beneficial role in the prognosis of patients with cervical cancer. First, γδ T cells exert direct cytotoxic effects in the tumor microenvironment of cervical cancer through the dynamic evolution of cellular states at both poles. Second, higher levels of γδ T-cell infiltration also shape the microenvironment of immune activation with cancer-suppressive properties. We found that these intricate features can be observed by MRI-based radiomics models to non-invasively assess γδ T-cell proportions in tumor tissues in patients. Importantly, patients with high infiltration levels of γδ T cells may be more amenable to immunotherapies including immune checkpoint inhibitors and autologous tumor-infiltrating lymphocyte therapies, than to chemoradiotherapy. CONCLUSIONS: γδ T cells play a beneficial role in antitumor immunity in cervical cancer. The abundance of γδ T cells in cervical cancerous tissue is associated with higher response rates to immunotherapy.

Dosimetric analysis of brachial plexopathy after stereotactic body radiotherapy: Significance of organ delineation.

OBJECTIVES: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy. MATERIALS AND METHODS: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression. RESULTS: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-Dmax) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-Dmax) was 11.2 Gy (median) lower than BP-Dmax. Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BEDmax LQL and BP-BED0.3cc LQL, α/ß = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively. CONCLUSION: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED0.3cc LQL and BP-BEDmax LQL as potential predictors of RIBP2.

Surface hopping, electron translation factors, electron rotation factors, momentum conservation, and size consistency.

For a system without spin-orbit coupling, the (i) nuclear plus electronic linear momentum and (ii) nuclear plus orbital electronic angular momentum are good quantum numbers. Thus, when a molecular system undergoes a nonadiabatic transition, there should be no change in the total linear or angular momentum. Now, the standard surface hopping algorithm ignores the electronic momentum and indirectly equates the momentum of the nuclear degrees of freedom to the total momentum. However, even with this simplification, the algorithm still does not conserve either the nuclear linear or the nuclear angular momenta. Here, we show that one way to address these failures is to dress the derivative couplings (i.e., the hopping directions) in two ways: (i) we disallow changes in the nuclear linear momentum by working in a translating basis (which is well known and leads to electron translation factors) and (ii) we disallow changes in the nuclear angular momentum by working in a basis that rotates around the center of mass [which is not well-known and leads to a novel, rotationally removable component of the derivative coupling that we will call electron rotation factors below, cf. Eq. (96)]. The present findings should be helpful in the short term as far as interpreting surface hopping calculations for singlet systems (without spin) and then developing the new surface hopping algorithm in the long term for systems where one cannot ignore the electronic orbital and/or spin angular momentum.

CD39 inhibition and VISTA blockade may overcome radiotherapy resistance by targeting exhausted CD8+ T cells and immunosuppressive myeloid cells.

Although radiotherapy (RT) has achieved great success in the treatment of non-small cell lung cancer (NSCLC), local relapses still occur and abscopal effects are rarely seen even when it is combined with immune checkpoint blockers (ICBs). Here, we characterize the dynamic changes of tumor-infiltrating immune cells after RT in a therapy-resistant murine tumor model using single-cell transcriptomes and T cell receptor sequencing. At the early stage, the innate and adaptive immune systems are activated. At the late stage, however, the tumor immune microenvironment (TIME) shifts into immunosuppressive properties. Our study reveals that inhibition of CD39 combined with RT preferentially decreases the percentage of exhausted CD8+ T cells. Moreover, we find that the combination of V-domain immunoglobulin suppressor of T cell activation (VISTA) blockade and RT synergistically reduces immunosuppressive myeloid cells. Clinically, high VISTA expression is associated with poor prognosis in patients with NSCLC. Altogether, our data provide deep insight into acquired resistance to RT from an immune perspective and present rational combination strategies.

Impact of radiation dose to the immune system on disease progression and survival for early-stage non-small cell lung cancer treated with stereotactic body radiation therapy.

OBJECTIVES: Although the effects of estimated dose of radiation to immune cells (EDRIC) in stage III NSCLC, LA-NSCLC, LS-SCLC and esophageal cancer on clinical outcomes have been studied, its impact in early-stage non-small cell lung cancer (ES-NSCLC) is unknown. In this study, we evaluated the role of EDRIC and identified the factors influencing EDRIC in this population. METHODS AND MATERIALS: We retrospectively analyzed 211 pathologically confirmed ES-NSCLC patients who were treated with SBRT between 2007 and 2020. EDRIC was calculated based on the model developed by Jin et al. and improved by Ladbury et al. Kaplan-Meier method and Cox proportional hazards regression were adopted to estimate CSS, PFS, LPFS, and DMFS. Pearson correlation was used to assess the correlation between variables. We further validated our findings in an independent cohort of 119 patients with ES-NSCLC. RESULTS: A total of 211 patients were included with median follow-up of 48 months in the training cohort. The median EDRIC was 2.178 Gy (range: 0.426-6.015). GTV showed a positive correlation with EDRIC (r = 0.707, P = 0.000). In multivariate analysis, higher EDRIC was significantly associated with worse CSS (HR = 1.468, P = 0.009) and DMFS (HR = 1.491, P = 0.016). Considering each EDRIC quartile, there was a significant difference in CSS between 1st and 4th and 1st and 3rd quartile (P = 0.000, P = 0.004, respectively); and DMFS between 1st and 4th,1st and 3rd, and 1st and 2nd quartile (P = 0.000, P = 0.000, P = 0.008, respectively). In the subgroup and validation cohort, EDRIC was also the important prognostic predictor of CSS and DMFS using multivariate analysis. CONCLUSION: EDRIC was an independent predictor of CSS and DMFS in ES-NSCLC, and it was affected by GTV and tumor location. Though EDRIC is a critical determinant of treatment outcomes, it is quantifiable and potentially modifiable. Additional researches exploring the feasibility of achieving lower EDRIC while maintaining adequate tumor coverage during radiotherapy are warranted.

SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer.

High-dose hypofractionated radiotherapy (HRT) is an important anticancer treatment modality that activates antitumor host immune responses. However, HRT for oligometastases of colorectal cancer (CRC) has shown frustrating results in the clinic. As part of immune evasion, myeloid cells express signal regulatory protein α (SIRPα) to inhibit phagocytosis by phagocytes in the tumor microenvironment (TME). We postulated that SIRPα blockade enhances HRT by alleviating the inhibitory action of SIRPα on phagocytes. We demonstrated that SIRPα on myeloid cells was upregulated in the TME after HRT. When SIRPα blockade was administered with HRT, we observed superior antitumor responses compared with anti-SIRPα or HRT alone. When anti-SIRPα was administered to local HRT, the TME could become a tumoricidal niche that was heavily infiltrated by activated CD8+ T cells, but with limited myeloid-derived suppressor cells and tumor-associated macrophages. While CD8+ T cells were required for the effectiveness of the anti-SIRPα + HRT combination. The triple therapy with anti-SIRPα + HRT + anti-PD-1 had superior antitumor responses compared with the combination of any two therapies and established a strong and long-lasting adaptive immunological memory. Collectively, SIRPα blockade provides a novel way to overcome HRT resistance in oligometastatic CRC patients. Our results herein provide a valuable cancer treatment strategy that has the potential to be translated into clinical practice.

Sorption and mobility of cadmium in soil impacted by irrigation waters.

Soil contamination by Cd has drawn global attention, while how irrigation waters modulate Cd sorption and mobility in soil remains obscure. We address this by investigating how cropped sandy soil irrigated with different waters altered Cd sorption and mobility using a rhizobox experiment followed by a batch experiment. Maize were planted in the rhizoboxes and irrigated by reclaimed water (RW), livestock wastewater (LW) and deionized water (CK), respectively. The bulk soil sampled from each treatment after 60 days of growth was employed to measure the Cd sorption and mobility using the isothermal adsorption and desorption experiments. The results showed that, in a small rhizobox experiment, the adsorption rate of Cd by the bulk soil in the adsorption phase was much faster than the desorption rate in desorption phase. Irrigation with RW and LW both reduced the Cd adsorption capacity of soil, and the reducing degree brought by LW was more obvious. Cd desorption rate was very low but keep increasing in the desorption stage, and pre-RW irrigation had the potential to increase Cd desorption from soil. Although the results were obtained based on the bulk soil sampled from a rhizobox experiment, our study strongly suggests that the altered Cd adsorption and desorption behavior in the soil caused by the RW and LW irrigation may risk the farmland ecosystem and deserve more concern.