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The wastewater discharge from the process of chrome plating, which contains 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) and chromium (Cr), may be toxic to biofilm. In this study we found that the biofilm formed by Pseudomonas aeruginosa PAO1 was inhibited by exposure to a combination of F-53B and Cr(VI). The combined pollution damaged the cell membranes and the structure of the biofilm, and inhibited the production of the Pseudomonas quinolone-based signal, which affected biofilm formation. Moreover, the secretion of extracellular polymeric substances decreased as a result of this combined exposure. Exposure to F-53B and Cr(VI) individually or in combination could induce the excessive accumulation of intracellular reactive oxygen species (ROS), and the ROS positive rate of the bacteria increased under the treatment with 0.2 mmol/L of Cr(VI) and 250 nmol/L of F-53B, respectively. In addition, the activities of superoxide dismutase (SOD) and catalase (CAT) were enhanced for scavenging ROS in the bacteria that were exposed to Cr(VI) and F-53B. As an antioxidant, rutin was used to repair the toxicity of Cr(VI) and F-53B towards the biofilm formed by the bacteria. When rutin was added to the bacteria medium, with either Cr(VI) or F-53B as pollutant, or with the combined pollutants, the extracellular protein content of the bacteria recovered to 0.84, 0.94, and 0.85 times that of the control, respectively. Meanwhile, the accumulation of ROS and the activities of SOD and CAT decreased, which indicated that the addition of rutin can alleviate the oxidative stress and promote the antioxidant stress system.

The construction of tightly integrated heterostructures with metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) has been confirmed to be an effective way for improved hydrogen evolution. However, the reported tightly integrated MOF/COF hybrids were usually limited to the covalent connection of COFs with aldehyde groups and NH

Rotavirus (RV) mainly infects intestinal epithelial cells, which leads to diarrhea in newborn piglets with dysfunction in the intestinal mucosal mechanical barrier. Sodium butyrate (SB) is one of the metabolites excreted by gut microbes. However, the protective effect of SB on RV infection induced intestinal mucosal mechanical barrier injury and its potential mechanism has not been well elucidated. In the present study, IPEC-J2 cells with RV infection was a model of intestinal mucosal mechanical barrier injury. Our results demonstrated that the appropriate concentration of SB can effectively alleviate TJ structural damage and up-regulating the expression of TJ-related genes. Furthermore, the appropriate concentration of SB can effectively reverse the increase of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) level induced by RV infection. Meanwhile, the levels of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px) and antioxidant proteins NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase-1 (HO-1) were increased through SB treatment. In addition, we found that SB increased cellular antioxidant capacity by activating the adenosine monophosphate-activated protein kinase (AMPK)-nuclear factor erythroid 2-related factor (Nrf2) signaling pathway and the cytoprotective effect of SB is limited by GPR109A siRNA. Thus, our findings revealed that SB reduces oxidative stress caused by RV infection and restores the intestinal mucosal mechanical barrier function by activating the AMPK-Nrf2 signal pathway mediated by the receptor GPR109A.

Although multi-parent populations (MPPs) integrate the advantages of linkage and association mapping populations in the genetic dissection of complex traits and especially combine genetic analysis with crop breeding, it is difficult to detect small-effect quantitative trait loci (QTL) for complex traits in multiparent advanced generation intercross (MAGIC), nested association mapping (NAM), and random-open-parent association mapping (ROAM) populations. To address this issue, here we proposed a multi-locus linear mixed model method, namely mppQTL, to detect QTLs, especially small-effect QTLs, in these MPPs. The new method includes two steps. The first is genome-wide scanning based on a single-locus linear mixed model; the P-values are obtained from likelihood-ratio test, the peaks of negative logarithm P-value curve are selected by group-lasso, and all the selected peaks are regarded as potential QTLs. In the second step, all the potential QTLs are placed on a multi-locus linear mixed model, all the effects are estimated using expectation-maximization empirical Bayes algorithm, and all the non-zero effect vectors are further evaluated via likelihood-ratio test for significant QTLs. In Monte Carlo simulation studies, the new method has higher power in QTL detection, lower false positive rate, lower mean absolute deviation for QTL position estimate, and lower mean squared error for the estimate of QTL size (r(2)) than existing methods because the new method increases the power of detecting small-effect QTLs. In real dataset analysis, the new method (19) identified five more known genes than the existing three methods (14). This study provides an effective method for detecting small-effect QTLs in any MPPs.

Surgery remains the mainstay treatment for parapharyngeal space (PPS) tumors. Given the rapid advance and increasing usage of endoscopic and robotic techniques, we aimed to investigate the surgical trends of PPS tumors in our institution and analyze their impact on patients' treatment outcomes.All patients who underwent surgical resection of PPS tumors from 2014 to 2021 at the Eye, Ear, Nose, and Throat Hospital of Fudan University were retrospectively reviewed. Student's t-test, Chi-square test, and multinomial logistic regression analyses were used to compare the surgical outcomes between groups.Of the included 389 patients, the recipients of endoscopic surgery have largely increased in our center, with 17 of 134 cases (12.7%) in the group 2014-2017 and 187 of 255 cases (73.3%) in the group 2018-2021. The use of transoral and trans-nasal approaches increased in recent years (5.2% in 2014-2017 vs. 26.0% in 2018-2021), while that of trans-mandibular and lateral skull base approaches decreased (5.9% in 2014-2017 vs. 0.8% in 2018-2021). Decreased blood loss of operation and decreased risks of postoperative neurovascular complications were observed in the group 2018-2021. Similar findings were observed among patients receiving endoscopic surgery when compared with those receiving conventional surgery.In our institution, the overall trends in the surgical management of PPS tumors moved towards minimally invasive approaches with the assistance of endoscopy or surgical robots. The two surgical techniques were feasible and safe, and to a great extent, contributed to the improved surgical outcomes we observed in recent years.

Unsupervised graph-level representation learning has recently shown great potential in a variety of domains, ranging from bioinformatics to social networks. Plenty of graph contrastive learning methods have been proposed to generate discriminative graph-level representations recently. They typically design multiple types of graph augmentations and enforce a graph to have consistent representations under different views. However, these techniques mostly neglect the intrinsic hierarchical structure of the graph, resulting in a limited exploration of semantic information for graph representation. Moreover, they often rely on a large number of negative samples to prevent collapsing into trivial solutions, while a great need for negative samples may lead to memory issues during optimization in graph domains. To address the two issues, this paper develops an unsupervised graph-level representation learning framework named Hierarchical Graph Contrastive Learning (HGCL), which investigates the hierarchical structural semantics of a graph at both node and graph levels. Specifically, our HGCL consists of three parts, i.e., node-level contrastive learning, graph-level contrastive learning, and mutual contrastive learning to capture graph semantics hierarchically. Furthermore, the Siamese network and momentum update are further involved to release the demand for excessive negative samples. Finally, the experimental results on both benchmark datasets for graph classification and large-scale OGB datasets for transfer learning demonstrate that our proposed HGCL significantly outperforms a broad range of state-of-the-art baselines.

The fast and high response detection of neurotoxic H2S is of great importance for the environment. In this paper, directly electrospinning technology on the ceramic tube is developed to improve the response of H2S detector based on superlong SnO2 fibers. The submillimeter continuous fibers are deposited directly on ceramic tubes by in-situ electrospinning method and can keep morphology of fibers during calcination. By employing this technology, CuO-doped SnO2 fiber H2S detectors are fabricated, and 10% atom CuO-doped SnO2 H2S detector shows the highest response of 40 toward 1 ​ppm ​H2S at 150 ​°C while the response is only 3.6 for the H2S detector prepared in traditional route. In addition, the in-situ electrospinning H2S detectors show faster response and recovery compared to the H2S detectors fabricated by the conventional way. The high and fast response of H2S detectors based on in-situ electrospinning can be ascribed to the continuous fiber structure and CuO modification. The present in-situ electrospinning technology may provide a new strategy for the development of other gas-detectors and bio-detectors with fast and high response.

Bivalves have evolved effective strategies to combat different pathogens in the environment. They rely on innate immunity to deal with the invasion of various bacteria, viruses, and other microorganisms. However, the molecular mechanisms underlying the responses remain largely unknown. Herein, we constructed 21 transcriptomes of the hemocytes after lipopolysaccharide (LPS), peptidoglycan (PGN) and polyinosinic-polycytidylic acid (poly(I:C)) stimulation to investigate the molecular mechanisms underlying adaptations and plastic responses to different pathogen-related molecular patterns (PAMPs) in pearl oyster Pinctada fucata martensii. Transcriptome analysis revealed 1986-3427 responsive genes enriched in the major immune and cell cycle-related pathways at different times after PAMP stimulation, and the expression patterns of genes under these pathways are complex and diverse. Moreover, "lysosomes" were enriched 6 h after LPS and PGN stimulation, while "peroxisomes" were only enriched in poly(I:C) group. These results suggest different response strategies of pearl oyster to different PAMPs. Furthermore, we identified 261 pattern-recognition receptors (PRRs) including 4 retinoic acid-inducible gene I-like receptors, 38 NOD-like receptors, 83 Toll-like receptors, and 136 C-type lectins in the genome of P. f. martensii. The diverse expression patterns of these PRRs after different PAMP stimulation indicated that pearl oyster evolved complex and specific recognition systems due to tandem repeat and diverse domain combination, which may help pearl oyster cope with the different pathogens in the environment. The present study improved our understanding of the molecular response of pearl oyster to different PAMP stimulation.

To evaluate the efficacy and safety of low-dose trimethoprim (TMP)-sulfamethoxazole (SMX) (TMP-SMX) as the primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in adult recipients of kidney transplantation.Three kinds of prescriptions in kidney recipients were documented, including 20 mg TMP/100 mg SMX oral daily, 20 mg TMP/100 mg SMX oral every other day, and nonprophylaxis. The primary outcome was the incidence of PJP in the first 180 days of follow-up after kidney transplantation. The secondary outcomes were changes in renal and liver function.Among the 1469 recipients, 1066 (72.56%) received 20 mg TMP/100 mg SMX daily, 127 (8.65%) received 20 mg TMP/100 mg SMX every other day, and 276 (18.79%) did not have prophylaxis prescription. The 276 recipients in the nonprophylaxis group had 124.92 person-years of follow-up, during which PJP occurred in 29 patients, for an incidence rate of 23.21 (95% confidence interval 15.76-32.72) per 100 person-years. The TMP-SMX daily group and the TMP-SMX every other day group had 524.89 and 62.07 person-years of follow-up, respectively, with no occurrence of PJP. There was no significant difference among the three groups in changes in renal and liver function (P0.05, respectively). A total of 111 recipients in each group were enrolled in the propensity score matching analysis. It was revealed that the 111 nonprophylaxis recipients had 51.27 person-years of follow-up and 10 PJP cases. Prophylaxis was considered effective because there was a significant difference between the three groups (P0.001).Low-dose TMP-SMX prophylaxis significantly reduces the incidence of PJP within 6 months after kidney transplantation and has a favorable safety profile.

The exploration of multifunctional nanomedicine has prompted interest in improving glioblastoma (GBM) prognosis. In this study, we constructed tumor microenvironment (TME)-responsive magnetic therapeutic nanoparticles (BK@MTNPs) as a multifunctional drug delivery platform. It contains the following components. [Des-arg(Sheets et al., 2020 [9])]bradykinin (BK), which contributes to the transient opening of the blood-brain barrier (BBB) and targeting of GBM cells; nanoparticles (NPs) encapsulated in MTNPs, which act as an in vivo magnetic resonance (MR) imaging agent; crizotinib, which is an inhibitor of protein kinase c-Met; and the immune drug anti-PDL1 antibody. These components were loaded into BK@MTNPs for complete tumoricidal effects. Abundant glutathione in the TME can promote BK@MTNP degradation by interrupting the disulfide bonds between cysteine residues. Such BK@MTNPs support a synergistic tumoricidal effect by inducing DNA damage, activating the transcription of the tumor suppressor gene PTEN, inhibiting glioblastoma stem cell function, activating cytotoxic T lymphocytes, and reprogramming tumor-associated macrophages. BK@MTNPs showed a significant increase in antitumor activity compared with free drugs in vitro. Furthermore, in mice bearing orthotopic GBM, treatment with BK@MTNPs resulted in marked tumor inhibition and greatly extended survival time with minimal side effects. This study demonstrates the advantages of chemo-immunotherapeutic NPs accumulated in the GBM area and their effective inhibition of GBM growth, thus establishing a delivery platform to promote antitumor immunity against GBM.

Dairy products have been suggested to be related to the prevention of overweight or obesity, hypertension, and type 2 diabetes mellitus (T2DM). These associations are currently controversial, however, and a systematic quantitative meta-analysis is lacking. In this study, we examined the associations between dairy products and the risk of overweight or obesity, hypertension, and T2DM and tested for dose–response relations. We comprehensively searched PubMed, Embase, and Web of Science up to April 2021. Cohort studies were included if dairy food consumption was reported at a minimum of 3 levels or as continuous variables, and the associations were assessed with overweight or obesity, hypertension, and T2DM. Summary RRs and 95% CIs were estimated for the dose–response association. Restricted cubic splines were used to evaluate the linear or nonlinear relations. Among the 9887 articles retrieved, 42 articles were included. For overweight or obesity, a linear association was observed for total dairy, milk, and yogurt. The risk decreased by 25%, 7%, and 12% per 200-g/d increase for total dairy, high-fat dairy, and milk, respectively, and by 13% per 50-g/d increment of yogurt. For hypertension, a nonlinear association was observed with total dairy, whereas significant inverse associations were found for low-fat dairy (RR: 0.94; 95% CI: 0.90, 0.98) and milk (RR: 0.94; 95% CI: 0.92, 0.97) per 200-g/d intake increase. For T2DM, all types of dairy food consumption except for milk and low-fat dairy products showed nonlinear associations, with total dairy and yogurt intake associated with 3% and 7% lower risk per 200-g/d and 50-g/d intake increase, respectively. In conclusion, our study suggests that total dairy is associated with a low risk of overweight or obesity, hypertension, and T2DM, especially milk and yogurt for overweight or obesity, low-fat dairy and milk for hypertension, and yogurt for T2DM.