Methylmercury in commercial fish species from the Erhai Lake Basin, Southwest China: concentrations, health risk assessment, and implications for future monitoring.

Erhai Lake, a highland lake situated in Southwest China, provides critical aquatic protein sources for the local community, and its preservation is vital due to the sensitivity of alpine freshwater ecosystems to disturbance. However, there is a lack of research on the contamination status of methylmercury (MeHg) in aquatic organisms of the Erhai Lake Basin. MeHg concentrations in important commercial fish species from the Erhai Lake were examined, and the potential health risks associated with human consumption were assessed. Our results showed significant inter-species differences in fish muscle MeHg: the carnivorous S. asotus exhibited the highest level (303 ng/g; ww), while that of the detritivorous R. ocellatus was the lowest (3.86 ng/g). Moreover, MeHg concentrations in P. fulvidraco and C. auratus collected from the Luoshi River (a major tributary of Erhai Lake) were significantly higher compared to those from the Erhai Lake, indicating possible river-based input of MeHg into the Erhai Lake. Additionally, our study revealed a significant positive correlation between the MeHg levels and the length as well as weight of the examined fish species. All the fish species analyzed in our study had MeHg concentrations within the limits of China's food safety standard. Nevertheless, a relatively low consumption quantity of 16 g per day of certain species (i.e., S. asotus) may still pose potential health risks especially for children. The present study provides baseline data for MeHg monitoring and risk assessment in the Erhai Lake Basin, and warrants continued monitoring and source investigation.

ß-resorcylic acid released by Limosilactobacillus reuteri protects against cisplatin-induced ovarian toxicity and infertility.

Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, ß-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L. reuteri or ß-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, ß-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that ß-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.

Distribution, trophic magnification and risk of trace metals and perfluoroalkyl acids in marine organisms from Haizhou Bay.

Haizhou Bay, a semi-enclosed key aquaculture area in East China, has had relatively limited research focused on trace metals and perfluoroalkyl acids (PFAAs) in its biota. This study characterized the distribution, biomagnification and health risks of selected trace metals and PFAAs in various marine organisms from Haizhou Bay. Among the species examined, zinc (Zn) was the most prevalent metal, followed by copper (Cu) and chromium (Cr), whereas cadmium (Cd), total mercury (THg), and methylmercury (MeHg) contents were relatively low. Perfluorooctane sulfonate (PFOS) was the most abundant PFAA, followed by perfluorooctanoic acid (PFOA). The calculated trophic magnification factors (TMFs) were above one for Cr, THg, MeHg, and all PFAAs except perfluorobutanoic acid (PFBA) and perfluorotetradecanoic acid (PFTeDA). Across animal groups, gastropods exhibited relatively low levels of THg, MeHg, and perfluorosulfonic acids (∑PFSAs). By comparison, fish generally had lower levels of Cd and Cu compared to other animal groups, and demersal fish had significantly higher MeHg compared to gastropods. Certain organisms, such as cephalopods and shrimps, were found to pose potential health risks due to elevated levels of Cd, while levels of other studied metals, PFOS and PFOA generally appeared to be within safe limits for human consumption. Further research is needed to assess the sources and impacts of these and other contaminants.

Landform and lithospheric development contribute to the assembly of mountain floras in China.

Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the 'floristic geo-lithology hypothesis', which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.

The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury.

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.

Inhibition of cyclin-dependent kinase 7 mitigates doxorubicin cardiotoxicity and enhances anticancer efficacy.

AIMS: The anthracycline family of anticancer agents such as doxorubicin (DOX) can induce apoptotic death of cardiomyocytes and cause cardiotoxicity. We previously reported that DOX-induced apoptosis is accompanied by cardiomyocyte cell cycle re-entry. Cell cycle progression requires cyclin-dependent kinase 7 (CDK7)-mediated activation of downstream cell cycle CDKs. This study aims to determine whether CDK7 can be targeted for cardioprotection during anthracycline chemotherapy. METHODS AND RESULTS: DOX exposure induced CDK7 activation in mouse heart and isolated cardiomyocytes. Cardiac-specific ablation of Cdk7 attenuated DOX-induced cardiac dysfunction and fibrosis. Treatment with the covalent CDK7 inhibitor THZ1 also protected against DOX-induced cardiomyopathy and apoptosis. DOX treatment induced activation of the proapoptotic CDK2-FOXO1-Bim axis in a CDK7-dependent manner. In response to DOX, endogenous CDK7 directly bound and phosphorylated CDK2 at Thr160 in cardiomyocytes, leading to full CDK2 kinase activation. Importantly, inhibition of CDK7 further suppressed tumour growth when used in combination with DOX in an immunocompetent mouse model of breast cancer. CONCLUSION: Activation of CDK7 is necessary for DOX-induced cardiomyocyte apoptosis and cardiomyopathy. Our findings uncover a novel proapoptotic role for CDK7 in cardiomyocytes. Moreover, this study suggests that inhibition of CDK7 attenuates DOX-induced cardiotoxicity but augments the anticancer efficacy of DOX. Therefore, combined administration of CDK7 inhibitor and DOX may exhibit diminished cardiotoxicity but superior anticancer activity.

Weissella cibaria Relieves Gut Inflammation Caused by Escherichia coli through Inflammation Modulation and Gut Microbiota Regulation.

The emergence of multi-drug-resistant (MDR) pathogens has considerably challenged the development of new drugs. Probiotics that inhibit MDR pathogens offer advantages over chemical antibiotics and drugs due to their increased safety and fewer side effects. This study reported that Weissella cibaria P-8 isolated from pickles showed excellent antibacterial activity against intestinal pathogens, particularly the antibacterial activity against MDR Escherichia coli B2 was the highest. This study showed that the survival rates of W. cibaria P-8 at pH 2.0 and 0.3% bile salt concentration were 72% and 71.56%, respectively, and it still had antibacterial activity under pepsin, trypsin, protease K, and catalase hydrolysis. Moreover, W. cibaria P-8 inhibits the expression of inflammatory factors interleukin-1ß, tumor necrosis factor-α, and interleukin-6, upregulates the interleukin-10 level, and increases total antioxidant capacity and superoxide dismutase enzyme activity in serum. W. cibaria P-8 also efficiently repairs intestinal damage caused by E. coli infection. The gut microbiota analysis demonstrated that W. cibaria P-8 colonizes the intestine and increases the abundance of some beneficial intestinal microorganisms, particularly Prevotella. In conclusion, W. cibaria P-8 alleviated MDR E. coli-induced intestinal inflammation by regulating inflammatory cytokine and enzyme activity and rebalancing the gut microbiota, which could provide the foundation for subsequent clinical analyses and probiotic product development.

The Mh-miR393a-TIR1 module regulates Alternaria alternata resistance of Malus hupehensis mainly by modulating the auxin signaling.

miRNAs govern gene expression and regulate plant defense. Alternaria alternata is a destructive fungal pathogen that damages apple. The wild apple germplasm Malus hupehensis is highly resistant to leaf spot disease caused by this fungus. Herein, we elucidated the regulatory and functional role of miR393a in apple resistance against A. alternata by targeting Transport Inhibitor Response 1. Mature miR393 accumulation in infected M. hupehensis increased owing to the transcriptional activation of MIR393a, determined to be a positive regulator of A. alternata resistance to either 'Orin' calli or 'Gala' leaves. 5' RLM-RACE and co-transformation assays showed that the target of miR393a was MhTIR1, a gene encoding a putative F-box auxin receptor that compromised apple immunity. RNA-seq analysis of transgenic calli revealed that MhTIR1 upregulated auxin signaling gene transcript levels and influenced phytohormone pathways and plant-pathogen interactions. miR393a compromised the sensitivity of several auxin-signaling genes to A. alternata infection, whereas MhTIR1 had the opposite effect. Using exogenous indole-3-acetic acid or the auxin synthesis inhibitor L-AOPP, we clarified that auxin enhances apple susceptibility to this pathogen. miR393a promotes SA biosynthesis and impedes pathogen-triggered ROS bursts by repressing TIR1-mediated auxin signaling. We uncovered the mechanism underlying the miR393a-TIR1 module, which interferes with apple defense against A. alternata by modulating the auxin signaling pathway.

Stromal-derived MAOB promotes prostate cancer growth and progression.

Prostate cancer (PC) develops in a microenvironment where the stromal cells modulate adjacent tumor growth and progression. Here, we demonstrated elevated levels of monoamine oxidase B (MAOB), a mitochondrial enzyme that degrades biogenic and dietary monoamines, in human PC stroma, which was associated with poor clinical outcomes of PC patients. Knockdown or overexpression of MAOB in human prostate stromal fibroblasts indicated that MAOB promotes cocultured PC cell proliferation, migration, and invasion and co-inoculated prostate tumor growth in mice. Mechanistically, MAOB induces a reactive stroma with activated marker expression, increased extracellular matrix remodeling, and acquisition of a protumorigenic phenotype through enhanced production of reactive oxygen species. Moreover, MAOB transcriptionally activates CXCL12 through Twist1 synergizing with TGFß1-dependent Smads in prostate stroma, which stimulates tumor-expressed CXCR4-Src/JNK signaling in a paracrine manner. Pharmacological inhibition of stromal MAOB restricted PC xenograft growth in mice. Collectively, these findings characterize the contribution of MAOB to PC and suggest MAOB as a potential stroma-based therapeutic target.

Cholinergic signaling via muscarinic M1 receptor confers resistance to docetaxel in prostate cancer.

Docetaxel is the most commonly used chemotherapy for advanced prostate cancer (PC), including castration-resistant disease (CRPC), but the eventual development of docetaxel resistance constitutes a major clinical challenge. Here, we demonstrate activation of the cholinergic muscarinic M1 receptor (CHRM1) in CRPC cells upon acquiring resistance to docetaxel, which is manifested in tumor tissues from PC patients post- vs. pre-docetaxel. Genetic and pharmacological inactivation of CHRM1 restores the efficacy of docetaxel in resistant cells. Mechanistically, CHRM1, via its first and third extracellular loops, interacts with the SEMA domain of cMET and forms a heteroreceptor complex with cMET, stimulating a downstream mitogen-activated protein polykinase program to confer docetaxel resistance. Dicyclomine, a clinically available CHRM1-selective antagonist, reverts resistance and restricts the growth of multiple docetaxel-resistant CRPC cell lines and patient-derived xenografts. Our study reveals a CHRM1-dictated mechanism for docetaxel resistance and identifies a CHRM1-targeted combinatorial strategy for overcoming docetaxel resistance in PC.

Occurrence, dietary influence and risks of selected trace metals in different coastal predatory species.

The global issue of ongoing trace metal emissions and legacy accumulation from diverse sources is posing threats to coastal wildlife. This study characterized the distribution of five metals in relation to dietary ecology (carbon and nitrogen stable isotopes: δ15N and δ13C) in representative predatory species (starfish, fish, and seabird) collected from the coast of Qingdao, northeastern China. Zinc (Zn) was the most abundant metal across species, followed by copper (Cu), chromium (Cr), cadmium (Cd), total and methylated mercury (THg and MeHg). Among the studied species, black-tailed gulls (Larus crassirostris) occupied the highest trophic position, followed by three predatory fish species, whereas the northern Pacific seastar (Asterias amurensis) had the lowest trophic position. The starfish exhibited high capacity to accumulate Cd, Cr and Cu. Conversely, black-tailed gulls exhibited high levels of Zn, while Hg was highest in predatory fishes. Across species, Cr, MeHg, THg and MeHg:THg showed significant positive correlations with δ13C, suggesting the influence of inshore food sources on their accumulation. Both MeHg and THg were significantly and positively correlated with δ15N, with MeHg demonstrating a greater slope, indicating their potential trophic magnification. We assessed health risks from the studied metals using established toxicity reference thresholds. Elevated risks of Hg were identified in three predatory fish species, while other metals and species remain within safe limits. These findings emphasize the significance of foraging patterns in influencing trace metal accumulation in coastal predators and highlight the importance of further monitoring.

RBL2 Regulates Cardiac Sensitivity to Anthracycline Chemotherapy.

Background: Anthracycline chemotherapies cause heart failure in a subset of cancer patients. We previously reported that the anthracycline doxorubicin (DOX) induces cardiotoxicity through the activation of cyclin-dependent kinase 2 (CDK2). Objectives: The aim of this study was to determine whether retinoblastoma-like 2 (RBL2/p130), an emerging CDK2 inhibitor, regulates anthracycline sensitivity in the heart. Methods: Rbl2-/- mice and Rbl2+/+ littermates received DOX (5 mg/kg/wk for 4 weeks intraperitoneally, 20 mg/kg cumulative). Heart function was monitored with echocardiography. The association of RBL2 genetic variants with anthracycline cardiomyopathy was evaluated in the SJLIFE (St. Jude Lifetime Cohort Study) and CPNDS (Canadian Pharmacogenomics Network for Drug Safety) studies. Results: The loss of endogenous Rbl2 increased basal CDK2 activity in the mouse heart. Mice lacking Rbl2 were more sensitive to DOX-induced cardiotoxicity, as evidenced by rapid deterioration of heart function and loss of heart mass. The disruption of Rbl2 exacerbated DOX-induced mitochondrial damage and cardiomyocyte apoptosis. Mechanistically, Rbl2 deficiency enhanced CDK2-dependent activation of forkhead box O1 (FOXO1), leading to up-regulation of the proapoptotic protein Bim. The inhibition of CDK2 desensitized Rbl2-depleted cardiomyocytes to DOX. In wild-type cardiomyocytes, DOX exposure induced Rbl2 expression in a FOXO1-dependent manner. Importantly, the rs17800727 G allele of the human RBL2 gene was associated with reduced anthracycline cardiotoxicity in childhood cancer survivors. Conclusions: Rbl2 is an endogenous CDK2 inhibitor in the heart and represses FOXO1-mediated proapoptotic gene expression. The loss of Rbl2 increases sensitivity to DOX-induced cardiotoxicity. Our findings suggest that RBL2 could be used as a biomarker to predict the risk of cardiotoxicity before the initiation of anthracycline-based chemotherapy.

Enhancing rice production sustainability and resilience via reactivating small water bodies for irrigation and drainage.

Rice farming threatens freshwater resources, while also being increasingly vulnerable to drought due to climate change. Rice farming needs to become more sustainable and resilient to climate change by improving irrigation drainage systems. Small water bodies, used to store drainage water and supply irrigation in traditional rice farming systems have gradually been abandoned in recent decades. This has resulted in a higher water footprint (WF) associated with rice farming due to increased freshwater usage and wastewater release, also leaving rice production more vulnerable to extreme weather events. Here, we propose how protecting and reactivating small water bodies for rice irrigation and drainage can decrease rice production WF in China by 30%, save 9% of China's freshwater consumption, increase irrigation self-sufficiency from 3% to 31%, and alleviate yield loss in dry years by 2-3%. These findings show that redesigning rice irrigation drainage systems can help meet water scarcity challenges posed by climate change.

Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation.

The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans. Integrative multiomics and genetically engineered bacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophage death. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclear accumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septic inflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveal a microbe-immune axis that is disrupted in pregnant septic hosts, highlighting the potential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategies for sepsis.

MVF-SleepNet: Multi-View Fusion Network for Sleep Stage Classification.

Sleep stage classification is of great importance in human health monitoring and disease diagnosing. Clinically, visual-inspected classifying sleep into different stages is quite time consuming and highly relies on the expertise of sleep specialists. Many automated models for sleep stage classification have been proposed in previous studies but their performances still exist a gap to the real clinical application. In this work, we propose a novel multi-view fusion network named MVF-SleepNet based on multi-modal physiological signals of electroencephalography (EEG), electrocardiography (ECG), electrooculography (EOG), and electromyography (EMG). To capture the relationship representation among multi-modal physiological signals, we construct two views of Time-frequency images (TF images) and Graph-learned graphs (GL graphs). To learn the spectral-temporal representation from sequentially timed TF images, the combination of VGG-16 and GRU networks is utilized. To learn the spatial-temporal representation from sequentially timed GL graphs, the combination of Chebyshev graph convolution and temporal convolution networks is employed. Fusing the spectral-temporal representation and spatial-temporal representation can further boost the performance of sleep stage classification. A large number of experiment results on the publicly available datasets of ISRUC-S1 and ISRUC-S3 show that the MVF-SleepNet achieves overall accuracy of 0.821, F1 score of 0.802 and Kappa of 0.768 on ISRUC-S1 dataset, and accuracy of 0.841, F1 score of 0.828 and Kappa of 0.795 on ISRUC-S3 dataset. The MVF-SleepNet achieves competitive results on both datasets of ISRUC-S1 and ISRUC-S3 for sleep stage classification compared to the state-of-the-art baselines. The source code of MVF-SleepNet is available on Github (https://github.com/YJPai65/MVF-SleepNet).

Loss of Rbl2 (Retinoblastoma-Like 2) Exacerbates Myocardial Ischemia/Reperfusion Injury.

Background The postmitotic state of adult cardiomyocytes, maintained by the cell cycle repressor Rbl2 (retinoblastoma-like 2), is associated with considerable resistance to apoptosis. However, whether Rbl2 regulates cardiomyocyte apoptosis remains unknown. Methods and Results Here, we show that ablation of Rbl2 increased cardiomyocyte apoptosis following acute myocardial ischemia/reperfusion injury, leading to diminished cardiac function and exaggerated ventricular remodeling in the long term. Mechanistically, ischemia/reperfusion induced expression of the proapoptotic protein BCL2 interacting protein 3 (Bnip3), which was augmented by deletion of Rbl2. Because the Bnip3 promoter contains an adenoviral early region 2 binding factor (E2F)-binding site, we further showed that loss of Rbl2 upregulated the transcriptional activator E2F1 but downregulated the transcriptional repressor E2F4. In cultured cardiomyocytes, treatment with H2O2 markedly increased the levels of E2F1 and Bnip3, resulting in mitochondrial depolarization and apoptosis. Depletion of Rbl2 significantly augmented H2O2-induced mitochondrial damage and apoptosis in vitro. Conclusions Rbl2 deficiency enhanced E2F1-mediated Bnip3 expression, resulting in aggravated cardiomyocyte apoptosis and ischemia/reperfusion injury. Our results uncover a novel antiapoptotic role for Rbl2 in cardiomyocytes, suggesting that the cell cycle machinery may directly regulate apoptosis in postmitotic cardiomyocytes. These findings may be exploited to develop new strategies to limit ischemia/reperfusion injury in the treatment of acute myocardial infarction.

MicroRNA candidate miRcand137 in apple is induced by Botryosphaeria dothidea for impairing host defense.

MicroRNA (miRNA)-mediated gene silencing is a master gene regulatory pathway in plant-pathogen interactions. The differential accumulation of miRNAs among plant varieties alters the expression of target genes, affecting plant defense responses and causing resistance differences among varieties. Botryosphaeria dothidea is an important phytopathogenic fungus of apple (Malus domestica). Malus hupehensis (Pamp.) Rehder, a wild apple species, is highly resistant, whereas the apple cultivar "Fuji" is highly susceptible. Here, we identified a 22-nt miRNA candidate named miRcand137 that compromises host resistance to B. dothidea infection and whose processing was affected by precursor sequence variation between M. hupehensis and "Fuji." miRcand137 guides the direct cleavage of and produced target-derived secondary siRNA against Ethylene response factor 14 (ERF14), a transcriptional activator of pathogenesis-related homologs that confers disease resistance to apple. We showed that miRcand137 acts as an inhibitor of apple immunity by compromising ERF14-mediated anti-fungal defense and revealed a negative association between miRcand137 expression and B. dothidea sensitivity in both resistant and susceptible apples. Furthermore, MIRCAND137 was transcriptionally activated by the invading fungi but not by the fungal elicitor, implying B. dothidea induced host miRcand137 as an infection strategy. We propose that the inefficient miRcand137 processing in M. hupehensis decreased pathogen-initiated miRcand137 accumulation, leading to higher resistance against B. dothidea.

Improved estimation of nitrogen dynamics in paddy surface water in China.

Paddy surface water is the direct source of artificial drainage and surface runoff leading to N loss from rice paddy fields. Quantifying the N dynamics in paddy surface water on a large scale is challenging because of model deficiencies and the limitations of field measurements. This study analyzed the N dynamics and the influencing factors in paddy surface water in the three main Chinese rice-growing regions: Northeast Plain, Yangtze River Basin, and Southeast Coast. An improved first-order kinetic model was proposed to evaluate the total nitrogen (TN) dynamics at a countrywide scale by improving the calculation method of the initial TN concentration (C0) and providing the optimum value of attenuation coefficient (k). The results show that: (1) the average reduction rate of TN concentration on the 7th day after fertilization increased with the growth period (85%, 90%, and 95% during the basal, tillering, and panicle fertilization periods, respectively); (2) the attenuation coefficient k for the growth periods was ranked as follows: panicle fertilization period > tillering fertilization period > basal fertilization period. The Yangtze River Basin had the highest average k value (0.31-0.34), followed by the Southeast Coast (0.24-0.41) and Northeast Plain (0.22-0.30); and (3) the improved first-order kinetic model performed well in the N dynamics estimation (R2 > 0.6). High TN concentration with high fertilizer application amounts and precipitation caused the Yangtze River Basin to have a high N runoff loss risk. The proposed universal model realizes the simulation of N dynamics from a single site to multi-sites while greatly saving multi-site monitoring costs. This study provides a basis for effectively optimizing N management and preventing N loss in rice paddies.

Discovery of a novel antibacterial protein CB6-C to target methicillin-resistant Staphylococcus aureus.

Given a serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with methicillin-resistant Staphylococcus aureus as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, Sephadex G-75 column, QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31.405 kDa by SDS-PAGE. LC-MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% identity with chitosanase (Csn) produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 µg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in in vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.