A novel doxorubicin/CTLA-4 blocker co-loaded drug delivery system improves efficacy and safety in antitumor therapy.

Doxorubicin's antitumor effectiveness may be constrained with ineffective tumor penetration, systemic adverse effects, as well as drug resistance. The co-loading of immune checkpoint inhibitors and doxorubicin into liposomes can produce synergistic benefits and address problems, including quick drug clearance, toxicity, and low drug penetration efficiency. In our previous study, we modified a nanobody targeting CTLA-4 onto liposomes (LPS-Nb36) to be an extremely potent CTLA-4 signal blocker which improve the CD8+ T-cell activity against tumors under physiological conditions. In this study, we designed a drug delivery system (LPS-RGD-Nb36-DOX) based on LPS-Nb36 that realized the doxorubicin and anti-CTLA-4 Nb co-loaded and RGD modification, and was applied to antitumor therapy. We tested whether LPS-RGD-Nb36-DOX could targets the tumor by in vivo animal photography, and more importantly, promote cytotoxic T cells proliferation, pro-inflammatory cytokine production, and cytotoxicity. Our findings demonstrated that the combination of activated CD8+ T cells with doxorubicin/anti-CTLA-4 Nb co-loaded liposomes can effectively eradicate tumor cells both in vivo and in vitro. This combination therapy is anticipated to have synergistic antitumor effects. More importantly, it has the potential to reduce the dose of chemotherapeutic drugs and improve safety.

Fluorescence Turn-on Detection of Perfluorooctanoic Acid (PFOA) by Perylene Diimide-Based Metal-Organic Framework.

A novel, water-stable, perylene diimide (PDI) based metal-organic framework (MOF), namely, U-1, has been synthesized for selective and sensitive detection of perfluorooctanoic acid (PFOA) in mixed aqueous solutions. The MOF shows highly selective fluorescence turn-on detection via the formation of a PFOA-MOF complex. This PFOA-MOF complex formation was confirmed by various spectroscopic techniques. The detection limit of the MOF for PFOA was found to be 1.68 µM in an aqueous suspension. Upon coating onto cellulose paper, the MOF demonstrated a significantly lower detection limit, down to 3.1 nM, which is mainly due to the concentrative effect of solid phase extraction (SPE). This detection limit is lower than the fluorescence sensors based on MOFs previously reported for PFAS detection. The MOF sensor is regenerable and capable of detecting PFOA in drinking and tap water samples. The PDI-MOF-based sensor reported herein represents a novel approach, relying on fluorescence turn-on response, that has not yet been thoroughly investigated for detecting per- and polyfluoroalkyl substances (PFAS) until now.

PDZK1 confers sensitivity to sunitinib in clear cell renal cell carcinoma by suppressing the PDGFR-ß pathway.

BACKGROUND: Sunitinib has emerged as the primary treatment for advanced or metastatic clear cell renal cell carcinoma (ccRCC) due to its significant improvement in patients' average survival time. However, drug resistance and adverse effects of sunitinib pose challenges to its clinical benefits. METHODS: The differentially expressed genes (DEGs) associated with sunitinib sensitivity and resistance in ccRCC were investigated. Cell counting kit-8, plate colony formation, flow cytometry and subcutaneous xenograft tumor model assays were employed to explore the effects of PDZK1 on ccRCC. Further research on the molecular mechanism was conducted through western blot, co-immunoprecipitation, immunofluorescence co-localization and immunohistochemical staining. RESULTS: We elucidated that PDZK1 is significantly downregulated in sunitinib-resistant ccRCC specimens, and PDZK1 negatively regulates the phosphorylation of PDGFR-ß and the activation of its downstream pathways through interaction with PDGFR-ß. The dysregulated low levels of PDZK1 contribute to inadequate inhibition of cell proliferation, tumor growth, and insensitivity to sunitinib treatment. Notably, our preclinical investigations showed that miR-15b antagomirs enhance sunitinib cytotoxic effects against ccRCC cells by upregulating PDZK1 levels, suggesting their potential in overcoming sunitinib resistance. CONCLUSIONS: Our findings establish the miR-15b/PDZK1/PDGFR-ß axis as a promising therapeutic target and a novel predictor for ccRCC patients' response to sunitinib treatment.

Soil microeukaryotic communities and phosphorus-cycling microorganisms respond to chloropicrin fumigation and azoxystrobin application.

Fumigants and fungicides are effective at controlling soil-borne pathogens but might also adversely affect soil beneficial microbes, such as soil phosphorus (P) solubilizing microbes, further altering nutrient cycling processes. Therefore, this study investigated the effects of the fumigant chloropicrin (CP) and the fungicide azoxystrobin (AZO) on soil microeukaryotes and P-cycling related soil bacteria through a greenhouse experiment. Soil microeukaryotic communities and bacterial communities containing two phosphomonoesterase encoding genes (phoC and phoD) were analysed using high-throughput sequencing methods. Results showed that, when applied at the field recommended application dosage, the fungicide AZO had no significant influence on the community structure of soil microeukaryotes and phoD-containing bacteria. However, in CP-fumigated soils, the soil microeukaryotic community composition changed from fungi-dominated to protist-dominated. CP fumigation significantly decreased the total phoC/phoD gene copy number but increased the relative abundance of some phoC/phoD-containing bacteria (such as Sinorhizobium and Streptomyces), which are significantly positively correlated to available P compositions in soil. The structural equation model (SEM) confirmed that CP fumigation could affect soil available P content directly by altering phoC-/phoD-containing bacteria, or indirectly by affecting phoC/phoD gene abundance and acid/alkaline phosphatases activity in soil. The inconsistent changes in phoC/phoD-containing bacteria, phoC/phoD gene number, and the phosphomonoesterase activities indicated that enzyme secretion may not be the only way for P solubilizing soil microorganisms to regulate P availability after soil fumigation. The outcome of this study can provide theoretical support for the design of soil beneficial microorganism recovery strategies and the regulation of phosphate fertilizer after soil fumigation.

Vegetation communities and soil properties along the restoration process of the Jinqianghe mine site in the Qilian Mountains, China.

The study explores the impact of mine grassland restoration on plant communities and soil properties in alpine grasslands, a subject of significant interest due to the observed relationship between grassland changes, plant communities, and soil properties. While prior research has mainly focused on the consequences of grassland degradation on plant diversity and soil characteristics, the specific effects of varying restoration degrees in alpine mining grasslands at the regional scale remain poorly understood. To address this knowledge gap, we established 15 sampling plots (0.5m×0.5m) across five different restoration degrees within alpine mining grasslands in the Qilian Mountains, China. Our objective was to assess the variations in plant diversity and soil properties along these restoration gradients. We conducted comprehensive analyses, encompassing soil properties [soil water content (SWC), available nitrogen (AN), total phosphorus (TP), nitrate nitrogen (NO3-N), ammonium nitrogen (NH4-N), total nitrogen (TN), available phosphorus (AP), soil organic carbon (SOC), nitrate nitrogen, soil pH, and electrical conductivity (EC)], plant characteristics (height, density, frequency, coverage, and aboveground biomass), and plant diversity indices (Simpson, Shannon-Wiener, Margalef, Dominance, and Evenness indexes). Our findings included the identification and collection of 18 plant species from 11 families and 16 genera across the five restoration degrees: Very Low Restoration Degree (VLRD), Low Restoration Degree (LRD), Moderate Restoration Degree (MRD), High Restoration Degree (HRD), and Natural Grassland (NGL). Notably, species like Carex duriuscula, Cyperus rotundus, and Polygonum viviparum showed signs of recovery. Principal component analysis and Pearson correlation analysis revealed that soil pH, SWC, SOC, NO3-N, and AN were the primary environmental factors influencing plant communities. Specifically, soil pH and EC decreased as restoration levels increased, while SWC, AN, TP, NH4-N, TN, AP, SOC, and NO3-N exhibited a gradual increase with greater restoration efforts. Furthermore, the HRD plant community demonstrated similarities to the NGL, indicating the most effective natural recovery. In conclusion, our study provides valuable insights into the responses of plant community characteristics, plant diversity, and soil properties across varying restoration degrees to environmental factors. It also elucidates the characteristics of plant communities along recovery gradients in alpine grasslands.

The Impact of Artificial Restoration of Alpine Grasslands in the Qilian Mountains on Vegetation, Soil Bacteria, and Soil Fungal Community Diversity.

To understand how the soil microbial community structure responds to vegetation restoration in alpine mining areas, this study specifically examines the grassland ecosystem in the Qianmalong mining area of the Qilian Mountains after five years of artificial restoration. High-throughput sequencing methods were employed to analyze soil bacteria and fungi microbial characteristics in diverse grassland communities. Combined with modifications in vegetation diversity as well as soil physicochemical properties, the impact of vegetation restoration on soil microbiome diversity in this alpine mining area was investigated. The findings indicated that the dominant plants were Cyperus rotundus, Carex spp., and Elymus nutans. As the extent of the grassland's restoration increased, the number of plant species, importance values, and plant community diversity showed an increasing trend. The plant functional groups were mainly dominated by Cyperaceae, followed by Poaceae. Plant height, density, plant cover, frequency, and aboveground biomass showed an increasing trend, and soil water content (SWC) increased. While soil pH and soil electrical conductivity (EC) exhibited a declining trend, available phosphorus (AP), total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (NO3-N), soil organic carbon (SOC), and soil water content (SWC) showed an increasing trend. The dominant bacterial communities were Actinobacteriota, Proteobacteria, Acidobacteriota, Chloroflexi, Firmicutes, and Gemmatimonadota, while the dominant fungal communities were Ascomycota, Mortierellomycota, Basidiomycota, unclassified_k_Fungi, and Glomeromycota. Significant differences were detected within soil microbial community composition among different degrees of restoration grasslands, with bacteria generally dominating over fungi. SWC, TP, and TN were found to be the main soil physicochemical factors affecting the distribution of soil bacterial communities' structure; however, SOC, TN, and NO3-N were the primary factors influencing the soil distribution of fungal communities. The results of this study indicate that different degrees of vegetation restoration in alpine mining areas can significantly affect soil bacterial and fungal communities, and the degree of restoration has varying effects on the soil bacteria and fungi community structure in alpine mining areas.

Chlorpyrifos degradation and its impacts on phosphorus bioavailability in microplastic-contaminated soil.

Pesticide residues and microplastics (MPs) in agricultural soils are two major concerns for soil health and food safety. The degradation of chlorpyrifos (CPF), an organophosphorus pesticide, releases phosphates. This process may be affected by the presence of MPs in the soil. The combination of CPF and MPs presence in the soil may thus produce interaction effects that alter the soil phosphorus (P) balance. This study explores the degradation pathways of CPF (6 mg kg-1, 12 mg kg-1 of CPF addition) in soils with different levels of polylactic acid MPs (PLA-MPs) (0.0 %, 0.1 %, 0.5 %, 1.0 % w/w), and analyzes soil P fractions and phosphatase enzyme activities to investigate soil P bioavailability under different treatments. Results show that the degradation of CPF fits to a first-order decay model, with half-lives (DT50) ranging from 11.0 to 14.8 d depending on PLA-MPs treatment. The concentration of its metabolite 3, 5, 6-trichloropyridine 2-phenol (TCP) reached a peak of 0.93-1.67 mg kg-1 within 7-14 days. Similarly, the degradation of CPF led to a significant transient increase in P bioavailability within 3-7 days (p < 0.05), with a peak range of 22.55-26.01 mg kg-1 for Olsen-P content and a peak range of 4.63-6.76 % for the proportions of available P fractions (H2O-P+NaHCO3-P+NaOH-P), before returning to prior levels (Olsen-P: 11.28-19.52 mg kg-1; available soil P fractions: 4.15-5.61 %). CPF degradation (6 mg kg-1) was significantly inhibited in soil with 1.0 % PLA-MPs addition. The effects of MPs and CPF on soil P fractions occur at different time frames, implying that their modes of action and interactions with soil microbes differ.

Catalytic dehydrogenative coupling and reversal of methanol-amines: advances and prospects.

The development of efficient hydrogen release and storage processes to provide environmentally friendly hydrogen solutions for mobile energy storage systems (MESS) stands as one of the most challenging tasks in addressing the energy crisis and environmental degradation. The catalytic dehydrogenative coupling of methanol and amines (DCMA) and its reverse are featured by high capacity for hydrogen release and storage, enhanced capability to purify the produced hydrogen, avoidance of carbon emissions and singular product composition, offering the environmentally and operationally benign strategy of overcoming the challenges associated with MESS. Particularly, the cycle between these two processes within the same catalytic system eliminates the need for collecting and transporting spent fuel back to a central facility, significantly facilitating easy recharging. Despite the promising attributes of the above strategy for environmentally friendly hydrogen solutions, challenges persist, primarily due to the high thermodynamic barriers encountered in methanol dehydrogenation and amide hydrogenation. By systematically summarizing various reaction mechanisms and pathways involving Ru-, Mn-, Fe-, and Mo-based catalytic systems in the development of catalytic DCMA and its reverse and the cycling between the two, this review highlights the current research landscape, identifies gaps, and suggests directions for future investigations to overcome these challenges. Additionally, the critical importance of developing efficient catalytic systems that operate under milder conditions, thereby facilitating the practical application of DCMA in MESS, is also underscored.

(-)-Epicatechin ameliorates type 2 diabetes mellitus by reshaping the gut microbiota and Gut-Liver axis in GK rats.

As one of the most abundant plant polyphenols in the human diet, (-)-epicatechin (EC) can improve insulin sensitivity and regulate glucose homeostasis. However, the primary mechanisms involved in EC anti-T2DM benefits remain unclear. The present study explored the effects of EC on the gut microbiota and liver transcriptome in type 2 diabetes mellitus (T2DM) Goto-Kakizaki rats for the first time. The findings showed that EC protected glucose homeostasis, alleviated systemic oxidative stress, relieved liver damage, and increased serum insulin. Further investigation showed that EC reshaped gut microbiota structure, including inhibiting the proliferation of lipopolysaccharide (LPS)-producing bacteria and reducing serum LPS. In addition, transcriptome analysis revealed that the insulin signaling pathway may be the core pathway of the EC anti-T2DM effect. Therefore, EC may modulate the gut microbiota and liver insulin signaling pathways by the gut-liver axis to alleviate T2DM. As a diet supplement, EC has promising potential in T2DM prevention and treatment.

Effects of positive end-expiratory pressure on regional cerebral oxygen saturation in elderly patients undergoing thoracic surgery during one-lung ventilation: a randomized crossover-controlled trial.

BACKGROUND: A significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV. METHODS: Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP-0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. RESULTS: After exclusion, thirty-six patients (36.11% female; age range: 60-76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10). CONCLUSIONS: PEEP with 10 cmH2O makes rSO2 decrease compared with 0 cmH2O. Applying PEEP with 5 cmH2O during OLV in elderly patients can improve oxygenation and maintain high rSO2 levels, without significantly increasing peak airway pressure compared to not using PEEP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.

Effect of Perineural or Intravenous Betamethasone on Femoral Nerve Block Outcomes in Knee Arthroplasty: A Randomized, Controlled Study.

OBJECTIVES: Despite the use of multimodal analgesia, patients undergoing knee arthroplasty still encounter residual moderate pain. The addition of betamethasone to local anesthetic has been shown to improve postoperative pain. However, it remains uncertain whether the positive effects of perineural or intravenous administration of betamethasone on analgesia outcomes lead to better early mobility and postoperative recovery. METHODS: Between June 2022 and February 2023, a total of 159 patients who were undergoing knee arthroplasty were included in this study. These patients were allocated randomly into three groups: (i) the NS group, received ropivacaine 0.375% and intravenous 3mL 0.9% normal saline; (ii) the PNB group, received ropivacaine 0.375% plus perineural betamethasone (12mg) 3mL and intravenous 3mL 0.9% normal saline; and (iii) the IVB group, received ropivacaine 0.375% and intravenous betamethasone (12mg) 3mL. RESULTS: Both perineural and intravenous administration of betamethasone led to improved median (IQR) numeric rating scale (NRS) scores on the 6-meter walk test, with a score of 1.0 (1.0-2.0) for both groups, compared with 2.0 (1.0-2.0) for the NS group (p = 0.003). Compared to the NS group, both the PNB and IVB groups showed significant reductions in NRS scores at 24 and 36 h after surgery, along with a significant increase in ROM at 24, 36, and 48 h post-operation. Additionally, it exhibited lower levels of cytokine IL-1ß and TNF-α in fluid samples, as well as lower level of HS-CRP in blood samples in the PNB and IVB groups compared to the NS group. CONCLUSION: The administration of perineural and intravenous betamethasone demonstrated an enhanced analgesic effect following knee arthroplasty. Furthermore, it was associated with reduced levels of IL-1ß, TNF-α, and HS-CRP, as well as enhanced knee ROM, which is conducive to early ambulation and postoperative rehabilitation after knee arthroplasty.

Activation of CRF/CRFR1 Signaling in the Central Nucleus of the Amygdala Contributes to Chronic Stress-Induced Exacerbation of Neuropathic Pain by Enhancing GluN2B-NMDA Receptor-Mediated Synaptic Plasticity in Adult Male Rats.

Exacerbation of pain by chronic stress and comorbidity of pain with stress-related disorders such as depression and post-traumatic stress disorder, represent significant clinical challenges. Previously we have documented that chronic forced swim (FS) stress exacerbates neuropathic pain in spared nerve injury (SNI) rats, associated with an up-regulation of GluN2B-containing N-methyl-D-aspartate receptors (GluN2B-NMDARs) in the central nucleus of the amygdala (CeA). However, the molecular mechanisms underlying chronic FS stress (CFSS)-mediated exacerbation of pain sensitivity in SNI rats still remain unclear. In this study, we demonstrated that exposure of CFSS to rats activated the corticotropin-releasing factor (CRF)/CRF receptor type 1 (CRFR1) signaling in the CeA, which was shown to be necessary for CFSS-induced depressive-like symptoms in stressed rats, and as well, for CFSS-induced exacerbation of pain hypersensitivity in SNI rats exposed to chronic FS stress. Furthermore, we discovered that activation of CRF/CRFR1 signaling in the CeA upregulated the phosphorylation of GluN2B-NMDARs at tyrosine 1472 (pGluN2BY1472) in the synaptosomal fraction of CeA, which is highly correlated to the enhancement of synaptic GluN2B-NMDARs expression that has been observed in the CeA in CFSS-treated SNI rats. In addition, we revealed that activation of CRF/CRFR1 signaling in the CeA facilitated the CFSS-induced reinforcement of long-term potentiation as well as the enhancement of NMDAR-mediated excitatory postsynaptic currents in the basolateral amygdala (BLA)-CeA pathway in SNI rats. These findings suggest that activation of CRF/CRFR1 signaling in the CeA contributes to chronic stress-induced exacerbation of neuropathic pain by enhancing GluN2B-NMDAR-mediated synaptic plasticity in rats subjected to nerve injury. PERSPECTIVE: Our present study provides a novel mechanism for elucidating stress-induced hyperalgesia and highlights that the CRF/CRFR1 signaling and the GluN2B-NMDAR-mediated synaptic plasticity in the CeA may be important as potential therapeutic targets for chronic stress-induced pain exacerbation in human neuropathic pain. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Mulch film to plastic debris: A survey of agricultural soils of Hebei Province, North China.

A significant amount of residual plastic film fragments (RPFF) accumulate in soil because of the widespread use and insufficient recycling of mulch films, substantially contaminating the ecosystem with plastic waste. However, information on RPFF abundance in agricultural soils that use long-term plastic film mulch is limited. In this study, 304 soil samples from 11 cities in Hebei Province, China, were used to examine the presence of RPFF in agricultural soils. We discovered that the main recycling techniques used in Hebei Province were manual picking (48.00%) and manual-mechanical recycling (31.90%), with the majority of recovered mulch (63.15%) disposed as waste. Residual plastic film fragment concentrations ranged from 0.48 to 155.33 kg/ha, with an average of 25.23 kg/ha. The north-central portion of Hebei Province has a more severe residual film pollution problem than the other regions. Notable variations in RPFF amounts were observed among plots planted with different crops and with years of mulching, peaking at 29.50 kg/ha after 5-10 years of mulching. Consequently, to reduce the amount of plastic waste that continues to accumulate in soils owing to agricultural needs, the management of plastic mulch, including its use, recycling, and disposal must be improved.

Exposure risk to rural Residents: Insights into particulate and gas phase pesticides in the Indoor-Outdoor nexus.

Rural residents are exposed to both particulate and gaseous pesticides in the indoor-outdoor nexus in their daily routine. However, previous personal exposure assessment mostly focuses on single aspects of the exposure, such as indoor or gaseous exposure, leading to severe cognition bias to evaluate the exposure risks. In this study, residential dust and silicone wristbands (including stationary and personal wearing ones) were used to screen pesticides in different phases and unfold the hidden characteristics of personal exposure via indoor-outdoor nexus in intensive agricultural area. Mento-Carlo Simulation was performed to assess the probabilistic exposure risk by transforming adsorbed pesticides from wristbands into air concentration, which explores a new approach to integrate particulate (dust) and gaseous (silicone wristbands) pesticide exposures in indoor and outdoor environment. The results showed that particulate pesticides were more concentrated in indoor, whereas significantly higher concentrations were detected in stationary outdoor wristbands (p < 0.05). Carbendazim and chlorpyrifos were the most frequently detected pesticides in dust and stationary wristbands. Higher pesticide concentration was found in personal wristbands worn by farmers, with the maximum value of 2048 ng g-1 for difenoconazole. Based on the probabilistic risk assessment, around 7.1 % of farmers and 2.6 % of bystanders in local populations were potentially suffering from chronic health issues. One third of pesticide exposures originated mainly from occupational sources while the rest derived from remoting dissipation. Unexpectedly, 43 % of bystanders suffered the same levels of exposure as farmers under the co-existence of occupational and non-occupational exposures. Differed compositions of pesticides were found between environmental samples and personal pesticide exposure patterns, highlighting the need for holistic personal exposure measurements.

Hidden risk of terrestrial food chain contamination from organochlorine insecticides in a vegetable cultivation area of Northwest Bangladesh.

Organochlorine insecticide (OCI) exposures in terrestrial food chains from historical or current applications were studied in a vegetable production area in northwest Bangladesh. A total of 57 subsoil, 57 topsoil, and 57 vegetable samples, as well as 30 cow's milk samples, were collected from 57 farms. Multiple OCI residues were detected using GC-MS/MS with modified QuEChERS in 20 % of subsoils, 21 % of topsoils, 23 % of vegetables, and 7 % of cow's milk samples. Diversified OCI residues were detected in subsoils (17 residues with a concentration of 179.15 ± 148.61 µg kg-1) rather than in topsoils (3 DDT residues with a concentration of 25.76 ± 20.19 µg kg-1). Isomeric ratios indicate intensive historical applications of OCIs. According to Dutch and Chinese standards, the lower concentrations of individual OCI residues in the soil indicate negligible to slight soil pollution, assuming local farmers follow local pesticide use regulations. However, a maximum of 78.24 µg kg-1 ΣAldrines and 35.57 µg kg-1 ΣHCHs were detected (1-4 residues) in 60 % of brinjal, 28 % of cucumber, 29 % of sponge gourd, and 20 % of lady's finger samples, which could be a result of either historical or current OCI applications, or both. A strong positive correlation between aldrines in subsoils and cucurbit vegetables indicates greater bioaccumulation. Cow milk samples contained up to 6.96 µg kg-1 ΣDDTs, which resulted either from rationing contaminated vegetables or grazing on contaminated land. Individual OCI in both vegetables and cow's milk was below the respective maximum residue limits of US and FAO/WHO CODEX and poses little or no risk to human health. However, combined exposure to multiple pesticides could increase human health risks. A cumulative health risk assessment of multiple pesticide residues is suggested to assess the suitability of those soils for cultivation and grazing, as well as the safety of vegetables and cow's milk for human consumption.

Preparation of healing-promoting and fibrosis-inhibiting asymmetric poly(ethylene glycol-b-L-phenylalanine)/cRGD-modified hyaluronate sponges and their applications in hemorrhage and nasal mucosa repair.

Acute or chromic bleeding, such as epistaxis, requires hemostatic materials to assist hemostasis. Even in complex cases, hemostatic materials must have other functions, including the promotion of healing and prevention of adhesion. Herein, a series of fibrosis-suppressive functional cRGD-modified crosslinking hyaluronic acid sponges were prepared. The in vitro hemostatic efficiency and mechanism were determined using blood clotting time, blood coagulation index, lactate dehydrogenase (LDH) and thromboxane B2 (TX-B2) ELISA, and proteomics. Among the prepared sponges, both poly(ethylene-b-L-Phe) (PEBP)-and cRGD contained SPN4 and exhibited the highest platelet concentration and activation efficiency as well as the most effective coagulative effect. In addition, no significant cytotoxicity was observed for the sponges in rat airway epithelial cells. The in vivo hemostatic and adhesion-preventive effects of the sponges were evaluated using rat models of liver injury and sidewall defect-cecum abrasion. PEBP-containing sponges effectively prevented postoperative adhesion and cRGD-modified sponges exhibited excellent hemostatic effects. Finally, the comprehensive repair effects of the sponges were evaluated using a rabbit maxillary sinus mucosal injury model, based on CT, MRI examination, and pathological staining. SPN4 exhibited the best comprehensive reparative effects, including the promotion of mucosal repair and infection inhibition. Thus, SPN4 is a promising multifunctional hemostatic material.

Wireless Deep Brain Stimulation by Ultrasound-Responsive Molecular Piezoelectric Nanogenerators.

Implantable neural stimulation devices are becoming prevalent in bioelectronic medicine for the precise treatment of various clinical diseases. Nevertheless, the limited lifespan and buckling size of the implanted devices remain significant obstacles for chronic clinical application. In this study, we developed an ultrasound-driven battery-free neurostimulator based on a high-performance mini-sized nanogenerator and demonstrated its successful application for the deep-brain-stimulation (DBS) therapy of Parkinson's disease in a rat model. This soft piezoelectric-triboelectric hybrid nanogenerators (PTNG) are made of porous thin-films of molecular piezoelectric materials, which have great advantages of facile, scalable, low-temperature, and flexible processing. Without any bucky accessory control circuits, the subcutaneously implanted soft PTNG can function as a wirelessly powered neurostimulator, allowing for the adjustment of stimulation parameters through external programmable ultrasound pulses. This DBS electroceutical application of energy-harvesting thin-film devices based on molecular piezoelectric materials provides valuable insight into the development of a soft high-performance bioelectronic device.

Optimal postoperative delirium prediction after coronary artery bypass grafting surgery: a prospective cohort study.

Background: Postoperative delirium (POD) presents as a serious neuropsychiatric syndrome in patients undergoing off-pump coronary artery bypass grafting (OPCABG) surgery. This is correlated with higher mortality, cognitive decline, and increased costs. The Age-adjusted Charlson Comorbidity Index (ACCI) is recognized as an independent predictor for mortality and survival rate. The purpose of our study is to estimate the predictive value of the ACCI on the POD in patients undergoing OPCABG surgery. Methods: This prospective cohort study enrolled patients undergoing OPCABG surgery between December 2020 and May 2021 in Qilu Hospital. Patients were divided into the low-ACCI group (score, 0-3) and the high-ACCI group (score ≥4) according to their ACCI scores. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and CAM were used to diagnose POD within 7 days after surgery. The general, laboratory, and clinical data of the patients were recorded and collected. The characteristic ROC curve was applied to further assess the predictive value of the ACCI for POD in patients following OPCABG surgery. Results: A total of 89 patients were enrolled, including 45 patients in the low-ACCI group and 44 patients in the high-ACCI group. The incidence of POD was higher in the high-ACCI group than in the low-ACCI group (45.5% vs. 15.6%, P = 0.003). Multivariate logistic regression analyses showed that the ACCI (OR, 2.433; 95% CI, 1.468-4.032; P = 0.001) was an independent risk factor for POD. The ACCI accurately predicted POD in patients following OPCABG surgery with an AUC of 0.738, and the Hosmer-Lemeshow goodness of fit test yielded X2 = 5.391 (P = 0.145). Conclusion: The high-ACCI group showed a high incidence of POD. The ACCI was an independent factor associated with POD in patients following OPCABG surgery. In addition, the ACCI could accurately predict POD in patients following OPCABG surgery. Clinical Trial Registration: ClinicalTrials.gov, identifier CHiCTR2100052811.

XPOT Disruption Suppresses TNBC Growth through Inhibition of Specific tRNA Nuclear Exportation and TTC19 Expression to Induce Cytokinesis Failure.

Transfer RNAs (tRNAs) impact the development and progression of various cancers, but how individual tRNAs are modulated during triple-negative breast cancer (TNBC) progression remains poorly understood. Here, we found that XPOT (Exportin-T), a nuclear export protein receptor of tRNAs, is associated with poor prognosis in breast cancer and directly orchestrates the nuclear export of a subset of tRNAs, subsequently promoting protein synthesis and proliferation of human TNBC cells. XPOT knockdown inhibited TNBC cell proliferation in vitro, and RNA-seq indicated that XPOT is involved in the completion of cytokinesis in TNBC cells. High-throughput sequencing of tRNA revealed that XPOT specifically influenced a subset of tRNA isodecoders involved in nucleocytoplasmic trafficking, including tRNA-Ala-AGC-10-1. Through codon preferential analysis and protein mass spectrometry, we found that XPOT preferentially transported nuclear tRNA-Ala-AGC-10-1 to the cytoplasm, driving the translation of TPR Repeat Protein 19 (TTC19). TTC19 is also indispensable for cytokinesis and proliferation of TNBC cells. Altogether, these findings provide a novel regulatory translation mechanism for preferential tRNA isodecoder nucleocytoplasmic transport through XPOT, which coordinates the spatial location of specific tRNA and the translation of mRNA to facilitate TNBC proliferation and progression. Targeting XPOT may be a novel therapeutic strategy for treating TNBC.