Thermal tunable silicon valley photonic crystal ring resonators at the telecommunication wavelength.

Tunable ring resonators are essential devices in integrated circuits. Compared to conventional ring resonators, valley photonic crystal (VPC) ring resonators have a compact design and high quality factor (Q-factor), attracting broad attention. However, tunable VPC ring resonators haven't been demonstrated. Here we theoretically demonstrate the first tunable VPC ring resonator in the telecommunication wavelength region, the resonance peaks of which are tuned by controlling the temperature based on the thermal-optic effect of silicon. The design is ultracompact (12.05 µm by 10.44 µm), with a high Q-factor of 1281.00. By tuning the temperature from 100 K to 750 K, the phase modulation can reach 7.70 π, and the adjustment efficiency is 0.062 nm/K. Since thermal tuning has been broadly applied in silicon photonics, our design can be readily applied in integrated photonic circuits and will find broad applications. Furthermore, our work opens new possibilities and deepens the understanding of designing novel tunable VPC photonic devices.

Complete genome sequence of a novel fusarivirus from Rhizoctonia solani AG-3 PT strain 3P-2-2.

Here, we describe a novel mycovirus, tentatively designated as "Rhizoctonia solani fusarivirus 6" (RsFV6), which was discovered in Rhizoctonia solani AG-3 PT strain 3P-2-2. The virus has a single-stranded positive-sense RNA (+ssRNA) genome of 6141 nucleotides containing two open reading frames (ORFs) and a poly(A) tail. ORF1 encodes a large polypeptide of 1,862 amino acids (aa) with conserved RNA-dependent RNA polymerase (RdRp) and helicase (Hel) domains. ORF2 encodes a putative 167-aa protein of unknown function. BLASTp searches revealed that the ORF1-encoded polypeptide showed the highest sequence similarity (70.67% identity) to that of Rhizoctonia solani fusarivirus 3 (RsFV3), which was isolated from Rhizoctonia solani AG-2-2LP. Multiple sequence alignments and phylogenetic analysis based on RdRp and Hel sequences indicated that RsFV6 could be a novel member of the genus Alphafusarivirus family Fusariviridae.

Bloom-induced internal release controlling phosphorus dynamics in large shallow eutrophic Lake Taihu, China.

High phosphorus (P) concentrations are commonly observed in lakes during algal blooms despite massive efforts on external nutrient reduction. However, the knowledge about the relative contribution of internal P loading linked with algal blooms on lake phosphorus (P) dynamics remains limited. To quantify the effect of internal loading on P dynamics, we conducted extensive spatial and multi-frequency nutrient monitoring from 2016 to 2021 in Lake Taihu, a large shallow eutrophic lake in China, and its tributaries (2017-2021). The in-lake P stores (ILSP) and external loading were estimated and then internal P loading was quantified from the mass balance equation. The results showed that the in-lake total P stores (ILSTP) ranged from 398.5 to 1530.2 tons (t), and exhibited a dramatic intra- and inter-annual variability. The annual internal TP loading released from sediment ranged from 1054.3 to 1508.4 t, which was equivalent to 115.6% (TP loading) of the external inputs on average, and responsible for the fluctuations of ILSTP on a weekly scale. High-frequency observations exemplified that ILSTP increased by 136.4% during algal blooms in 2017, while by only 47.2% as a result of external loading after heavy precipitation in 2020. Our study demonstrated that both bloom-induced internal loading and storm-induced external loading are likely to run counter significantly to watershed nutrient reduction efforts in large shallow lakes. More importantly, bloom-induced internal loading is higher than storm-induced external loading over the short term. Given the positive feedback loop between internal P loadings and algal bloom in eutrophic lakes, which explains the significant fluctuation of P concentration while nitrogen concentration decreased. It is emphasized that internal loading and ecosystem restoration are unignorable in shallow lakes, particularly in the algal-dominated region.

Susceptibility factor RTP1 negatively regulates Phytophthora parasitica resistance via modulating UPR regulators bZIP60 and bZIP28.

The unfolded protein response (UPR) is a conserved stress adaptive signaling pathway in eukaryotic organisms activated by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). UPR can be elicited in the course of plant defense, playing important roles in plant-microbe interactions. The major signaling pathways of plant UPR rely on the transcriptional activity of activated forms of ER membrane-associated stress sensors bZIP60 and bZIP28, which are transcription factors that modulate expression of UPR genes. In this study, we report the plant susceptibility factor Resistance to Phytophthora parasitica 1 (RTP1) is involved in ER stress sensing and rtp1-mediated resistance against P. parasitica is synergistically regulated with UPR, as demonstrated by the simultaneous strong induction of UPR and ER stress-associated immune genes in Arabidopsis thaliana rtp1 mutant plants during the infection by P. parasitica. We further demonstrate RTP1 contributes to stabilization of the ER membrane-associated bZIP60 and bZIP28 through manipulating the bifunctional protein kinase/ribonuclease IRE1-mediated bZIP60 splicing activity and interacting with bZIP28. Consequently, we find rtp1bzip60 and rtp1bzip28 mutant plants exhibit compromised resistance accompanied with attenuated induction of ER stress-responsive immune genes and reduction of callose deposition in response to P. parasitica infection. Taken together, we demonstrate RTP1 may exert negative modulating roles in the activation of key UPR regulators bZIP60 and bZIP28, which are required for rtp1-mediated plant resistance to P. parasitica. This facilitates our understanding of the important roles of stress adaptive UPR and ER stress in plant immunity.

New insights into eutrophication management: Importance of temperature and water residence time.

Eutrophication and harmful cyanobacterial blooms threaten water resources all over the world. There is a great controversy about controlling only phosphorus or controlling both nitrogen and phosphorus in the management of lake eutrophication. The primary argument against the dual nutrients control of eutrophication is that nitrogen fixation can compensate the nitrogen deficits. Thus, it is of great necessary to study the factors that can significantly affect the nitrogen fixation. Due to the difference of climate and human influence, the water quality of different lakes (such as water temperature, N:P ratio and water residence time) is also quite different. Numerous studies have reported that the low N:P ratio can intensify the nitrogen fixation capacities. However, the effects of temperature and water residence time on the nitrogen fixation remain unclear. Thus, 30 shallows freshwater lakes in the eastern plain of China were selected to measure dissolved N2 and Ar concentrations through N2: Ar method using a membrane inlet mass spectrometer to quantify the nitrogen fixation capacities and investigate whether the temperature and water residence time have a great impact on nitrogen fixation. The results have shown that the short lake water residence time can severely inhibit the nitrogen fixation capacities through inhibiting the growth of nitrogen-fixing cyanobacteria, changing the N:P ratio and resuspending the solids from sediments. Similarly, lakes with low water temperature also have a low nitrogen fixation capacity, suggesting that controlling nitrogen in such lakes is feasible if the growth of cyanobacteria is limited by nitrogen.

Reciprocal transrepression between FOXF2 and FOXQ1 controls basal-like breast cancer aggressiveness.

FOXF2 and FOXQ1, forkhead box transcription factor superfamily members, are encoded by neighboring genes located on human chromosome 6p25.3 and play opposite roles in epithelial-mesenchymal transition (EMT) and metastasis in basal-like breast cancer (BLBC). However, the relationship between FOXF2 and FOXQ1 in cancer remains unknown. Here, we found mutual transcriptional repression between FOXF2 and FOXQ1, and the reciprocal negative feedback loop controlled EMT, aggressiveness, and chemoresistance in BLBC cells. We further demonstrated that FOXF2 recruited nuclear receptor corepressor 1 and histone deacetylase 3 to the FOXQ1 promoter to inhibit its transcription in BLBC cells, but FOXQ1 did not exert such an effect on FOXF2. Our findings reveal novel mechanisms underlying the determination of BLBC aggressiveness and the transrepressive function of FOXF2 in a basal-like cell subtype-specific manner. Therefore, blocking the vicious cycle of the abnormal reciprocal feedback loop between FOXF2 and FOXQ1 to induce cell differentiation and restore tissue homeostasis is a promising strategy for the treatment of aggressive BLBC.-Kang, L.-J., Yu, Z.-H., Cai, J., He, R., Lu, J.-T., Hou, C., Wang, Q.-S., Li, X.-Q., Zhang, R., Feng, Y.-M. Reciprocal transrepression between FOXF2 and FOXQ1 controls basal-like breast cancer aggressiveness.

LC-MS bioanalysis of intact proteins and peptides.

Bioanalysis assays that reliably quantify biotherapeutics and biomarkers in biological samples play pivotal roles in drug discovery and development. Liquid chromatography coupled with mass spectrometry (LC-MS), owing to its superior specificity, faster method development and multiplex capability, has evolved as one of the most important platforms for bioanalysis of biotherapeutics, particularly new scaffolds such as half-life extension platforms for proteins and peptides, as well as antibody drug conjugates. Intact LC-MS analysis is orthogonal to bottom-up surrogate peptide approach by providing whole molecule quantitation and high-level sequence and structure information. Here we review the latest development in LC-MS bioanalysis of intact proteins and peptides by summarizing recent publications and discussing the important topics such as the comparison between top-down intact analysis and bottom-up surrogate peptide approach, as well as simultaneous quantitation and catabolite identification. Key bioanalytical issues around intact protein bioanalysis such as sensitivity, data processing strategies, specificity, sample preparation and LC condition are elaborated. For peptides, topics including quantitation of intact peptide vs. digested surrogate peptide, metabolites, sensitivity, LC condition, assay performance, internal standard and sample preparation are discussed.

Simultaneous Catabolite Identification and Quantitation of Large Therapeutic Protein at the Intact Level by Immunoaffinity Capture Liquid Chromatography-High-Resolution Mass Spectrometry.

As therapeutic recombinant fusion proteins become more widely applicable for the treatment of various types of diseases, there is an increased demand for universal methods such as liquid chromatography (LC)-mass spectrometry (MS) for the determination of their pharmacokinetic properties, particularly their catabolism. The most common approach of analyzing proteins by LC-MS is to digest them into peptides, which can serve as surrogates of the protein. Alternatively, we have developed a novel high-resolution mass spectrometry (HRMS) based approach for analyzing large-molecule proteins at the intact level in biological samples without digestion. We established an immunoaffinity capture LC-HRMS method to quantify the intact parent molecule while simultaneously identifying catabolites for recombinant fusion proteins. We describe this method using dulaglutide, a glucagon-like peptide 1 (GLP1)-Fc fusion protein. Two proteolytic sites within the GLP1 peptide sequence of dulaglutide were identified using this novel LC-HRMS analysis in vivo in mice. These proteolytic sites were identified with the intact molecule being quantified simultaneously. Together with the trypsin digestion based LC-MS/MS analysis using surrogate peptides from different domains of the analyte, an insightful understanding of the pharmacokinetics and in vivo biotransformation of dulaglutide was obtained. Thus, this method enables simultaneous acquisition of both intact drug concentration and important catabolite information for this recombinant fusion protein, providing valuable insight into the integrity of the molecule and its catabolism in vivo. This is critical for designing and screening novel protein therapeutics and for understanding their pharmacokinetics and pharmacodynamics. With continuing advancement of LC-HRMS and software, this method can be very beneficial in drug discovery and development.

Budesonide Nebulization in the Treatment of Neonatal Ventilator Associated Pneumonia.

OBJECTIVE: To investigate the clinical effect of budesonide nebulization in the treatment of ventilator associated pneumonia of newborns and its safety. METHODS: Forty-five newborns who had ventilator associated pneumonia and were admitted into the Binzhou People's Hospital between May 2014 and May 2015 were selected and included as an observation group. Moreover, another forty-five newborns who had ventilator associated pneumonia but did not undergo budesonide treatment in 2014 were randomly selected and included as a control group. Patients in the observation group were given budesonide suspension nebulization in addition to the conventional treatment. The evaluation indicators for therapeutic effect were compared between the two groups. The changes of head circumference, height and weight and death rate were observed by follow up after treatment. RESULTS: The mechanical ventilation time, time for recovering from chest X-ray scan and hospitalization time of patients in the observation group were shorter than that of the control group, and the difference had statistical significance (P<0.05). The oxygen index of the patients in the observation group was significantly improved compared to that of the control group, and the difference had statistical significance (P<0.05). Patients in the two groups were followed up for six months after discharge. The head circumference, height and weight of the patients in the observation group in the 3rd and 6th month were compared to those of the control group, suggesting no significant differences (P>0.05). The cumulative death rate of the observation group in the 6th month after treatment was significantly lower than that of the control group, and the difference had statistical significance (P<0.05). CONCLUSION: Treating ventilator associated pneumonia of newborns with budesonide nebulization can effectively shorten mechanical ventilation time, time for recovering from chest X-ray scan and hospitalization time, improve pulmonary diffusion function and reduce the death rate, without affecting the growth and development of patients in the future.

Identification and validation of a novel signature based on macrophage marker genes for predicting prognosis and drug response in kidney renal clear cell carcinoma by integrated analysis of single cell and bulk RNA sequencing.

Macrophages are found in a variety of tumors and play a critical role in shaping the tumor microenvironment, affecting tumor progression, metastasis, and drug resistance. However, the clinical relevance of marker genes associated with macrophage in kidney renal clear cell carcinoma (KIRC) has yet to be documented. In this study, we initiated a thorough examination of single-cell RNA sequencing (scRNA-seq) data for KIRC retrieved from the Gene Expression Omnibus (GEO) database and determined 244 macrophage marker genes (MMGs). Univariate analysis, LASSO regression, and multivariate regression analysis were performed to develop a five-gene prognostic signature in The Cancer Genome Atlas (TCGA) database, which could divide KIRC patients into low-risk (L-R) and high-risk (H-R) groups. Then, a nomogram was constructed to predict the survival rate of KIRC patients at 1, 3, and 5 years, which was well assessed by receiver operating characteristic curve (ROC), calibration curve, and decision curve analyses (DCA). Functional enrichment analysis showed that immune-related pathways (such as immunoglobulin complex, immunoglobulin receptor binding, and cytokine-cytokine receptor interaction) were mainly enriched in the H-R group. Additionally, in comparison to the L-R cohort, patients belonging to the H-R cohort exhibited increased immune cell infiltration, elevated expression of immune checkpoint genes (ICGs), and a higher tumor immune dysfunction and exclusion (TIDE) score. This means that patients in the H-R group may be less sensitive to immunotherapy than those in the L-R group. Finally, IFI30 was validated to increase the ability of KIRC cells to proliferate, invade and migrate in vitro. In summary, our team has for the first time developed and validated a predictive model based on macrophage marker genes to accurately predict overall survival (OS), immune characteristics, and treatment benefit in KIRC patients.

Decreasing denitrification rates poses a challenge to further decline of nitrogen concentration in Lake Taihu, China.

Nitrogen (N) concentrations in many lakes have decreased substantially in recent years due to external load reduction to mitigate harmful algal blooms. However, little attention has been paid to the linkage between the lakes' nitrogen removal efficiency and improved water quality in lakes, especially the variation of denitrification rate (DNR) under decreasing N concentrations. To understand the efficiency of N removal under improving water quality and its influence on the N control targets in Lake Taihu, a denitrification model based on in situ experimental results was developed and long-term (from 2007 to 2022) water quality and meteorological observations were used to estimate DNR and relate it to the amount of N removal (ANR) from the lake. The concentration of total nitrogen (TN) in Lake Taihu decreased from 3.28 mg L-1 to 1.41 mg L-1 from 2007 to 2022 but the reduction showed spatial heterogeneity. The annual mean DNR decreased from 45.6 µmol m-2 h-1 to 4.2 µmol m-2 h-1, and ANR decreased from 11.85×103 t yr-1 to 1.17×103 t yr-1 during the study years. N budget analysis suggested that the amount of N removed by denitrification accounted for 23.3 % of the external load in 2007, but decreased to only 4.0 % in 2022. Thus, the contribution of N removal by internal N cycling decreased significantly as water quality improved. Notably, the proportion of ANR in winter to total ANR increased from 14 % in 2007 to 23 % in 2022 due to warming. This could potentially lead to N deficiencies in spring and summer, thus limiting the availability of N to phytoplankton. A TN concentration of less than 1.0 mg L-1 in the lake and 1.5 mg L-1 in the inflowing lake zones in spring contribute to local N-limitation in Lake Taihu for cyanobacteria control. Our study revealed a general pattern that N removal efficiency decreases with improved water quality, which is instructive for eutrophic lakes in nitrogen management.

Teclistamab: Mechanism of action, clinical, and translational science.

Multiple myeloma (MM) remains incurable despite improvements in treatment options. B-cell maturation antigen (BCMA) is predominantly expressed in B-lineage cells and represents a promising new target for MM. Teclistamab (TECVAYLITM ) is the first T-cell redirecting bispecific antibody approved for patients with MM. Targeting both CD3 receptor complex on T cells and BCMA on myeloma cells, teclistamab leads to T-cell activation and subsequent lysis of BCMA+ cells. The recommended dose of teclistamab is 1.5 mg/kg subcutaneous weekly after two step-up doses of 0.06 and 0.3 mg/kg, which was selected after review of safety, efficacy, pharmacokinetic, and pharmacodynamic data. Exposure-response analyses of efficacy and safety data were also used to confirm the teclistamab dose. Teclistamab resulted in a high rate of deep and durable responses (63% overall response, 45.5% complete response or better, with 22 months median duration of response) in patients with triple-exposed relapsed/refractory MM. Common adverse reactions included cytokine release syndrome, hematologic abnormalities, and infections. Teclistamab is currently being investigated as monotherapy as well as combination therapy across different MM indications.

Evaluating the use of locked nucleic acid capture probes in hybrid LC-MS/MS analysis of siRNA analytes.

Background: Hybrid LC-MS assays for oligonucleotides rely on capture probes to develop assays with high sensitivity and specificity. Locked nucleic acid (LNA) probes are thermodynamically superior to existing capture probes, but are not currently used for hybrid LC-MS assays. Materials & methods: Using two lipid-conjugated double-stranded siRNA compounds as model analytes, hybrid LC-MS/MS assays using LNA probes were developed. Results: The workflows demonstrated the superiority of the LNA probes, optimized sample preparation conditions to maximize analyte recovery, evaluated the need for analyte-specific internal standards, and demonstrated that advanced mass spectrometric technology can increase assay sensitivity by up to 20-fold. Conclusion: The workflow can be used in future bioanalytical studies to develop effective hybrid LC-MS/MS methods for siRNA analytes.

Use of fermented Chinese medicine residues as a feed additive and effects on growth performance, meat quality, and intestinal health of broilers.

Introduction: The purpose of this research was to investigate how dietary supplementation with fermented herbal residues (FCMR) affected birds' development capacity, quality of meat, gut barrier, and cecum microbiota. Methods: 540 cyan-shank partridge birds aged 47 days were chosen and divided into two groups of six replicates each and 45 birds for each replicate. The control group (CON) received a basal diet, while the trial group decreased a basic diet containing 5% FCMR. Results and discussion: The findings revealed that the addition of FCMR decreased FCR and increased ADG in broilers (P < 0.05). Adding FCMR increased steaming loss in broiler chicken breasts (p < 0.05). Supplementation with FCMR significantly enhanced VH/CD and VH in the bird's intestine (jejunum, duodenum, and ileum) (p < 0.05). In addition, the addition of FCMR significantly down-regulated mRNA expression of INF-γ, IL-6, IL-1ß, and TNF-α and up-regulated mRNA expression of ZO-1, Occludin, and Claudin (P < 0.05). Microbial 16S rDNA high-throughput sequencing study revealed that supplements with FCMR modified the cecum microbiota, and α-diversity analysis showed that supplementation with FCMR reduced the cecum bacterial abundance in broilers (P < 0.05). At the phylum level, the relative abundance of Spirochaetota increased considerably following FCMR supplementation (P < 0.05). The broiler cecum's close lot of Prevotellaceae_UCG-001 (P < 0.05), Desulfovibrio, Muribaculaceae, and Fusobacterium (p < 0.05) reduced when FCMR was supplemented. Supplementation with FCMR can promote growth capacity and maintain intestinal health in birds by enhancing gut barrier function and modulating the inflammatory response and microbial composition.

The effects of fermented feedstuff derived from Citri Sarcodactylis Fructus by-products on growth performance, intestinal digestive enzyme activity, nutrient utilization, meat quality, gut microbiota, and metabolites of broiler chicken.

This research aimed to assess the impact of fermented Citri Sarcodactylis Fructus by-products (FCSF) on the growth performance, gut digestive enzyme activity, nutrient utilization efficiency, gut microbiota, and their metabolites in broiler chickens. A total of 1,080 male broiler chickens were allocated into four groups (T1-T4) consisting of 6 replicates per group, each containing 45 chickens. The basal diet was provided to group T1, while groups T2, T3, and T4 were supplemented with 1%, 3%, and 5% FCSF in the basal diet, respectively. The experimental period was 42 days. The findings revealed that supplementing FCSF improved the FW and ADG of broiler chickens, and led to a reduction in the F/G, ADFI, and mortality rate of broiler chickens (p < 0.05). Furthermore, supplementation with 3% and 5% FCSF improved the thigh yield, semi-eviscerated carcass yield, slaughter yield, and lipase activity in the duodenum and ileum of birds (p < 0.05). Additionally, supplementing 3% FCSF enhanced the activity of protease in the duodenum of broilers (p < 0.05). Moreover, supplementing 3% FCSF enhanced the utilization of total phosphorus, dry matter, crude protein, and crude ash in the feed by broilers (p < 0.05). Compared with the control group, supplementation of 3% and 5% FCSF reduced the serine content in broiler chicken breast meat (p < 0.05). Supplementing 1% FCSF significantly increased the C14:0, C14:1, and C20:1 content in the breast meat compared to the other experimental groups (p < 0.05). The levels of C20:4n6 and C23:0 in the breast meat of birds of FCSF supplemented groups were lower than in T1 (p < 0.05). Furthermore, the content of ∑ω-3PUFA decreased after supplementing with 3% and 5% FCSF (p < 0.05). 16SrDNA showed that supplementing 3% FCSF reduced the ACE, Chao1, and Shannon indices in the cecum of birds (p < 0.05). Supplementing 3% FCSF also decreased the abundance of the phylum Desulfobacterota and improved genera Coprobacter and Prevotella in the cecum of broiler chickens (p < 0.05). Metabolomic analysis of the gut microbiota revealed that supplementing 3% FCSF upregulated 6 metabolites and downregulated 16 metabolites (p < 0.05). Moreover, supplementing 3% FCSF downregulated 12 metabolic pathways and upregulated 3 metabolic pathways (p < 0.05). In summary our findings indicate that supplementing FCSF can improve the growth performance of broiler chickens by enhancing intestinal digestive enzyme activity, nutrient utilization, improving gut microbial diversity, and influencing the metabolism of gut microbiota.

Correlation analysis of polyamine metabolism and reproductive hormone levels in goose ovarian follicles.

To investigate the relationship between polyamine metabolism and reproductive hormones in ovarian follicles of Sichuan white geese, follicle polyamine content and reproductive hormone levels and gene expressions related to polyamine metabolism, steroidogenesis and steroid hormone receptors were detected by HPLC, ELISA and RT-qPCR. The results showed that the overall trend of spermidine and spermine levels increased first and then decreased as increasing follicle size, with the highest level in F3 and F5 follicles (P < 0.05). Putrescine and 17ß-estradiol (E2) levels in hierarchical follicles were significantly lower than those in prehierarchical follicles (P < 0.05). Progesterone (P4) first increased and then decreased, with the highest level in the F5 follicle (P < 0.05). The expression levels of estrogen receptor 1 (ER1) showed an overall increase as increasing follicle size (except in F3 follicles), while estrogen receptor 2 (ER2) in hierarchical follicles was significantly lower than that in the prehierarchical follicles (P < 0.05). In addition, the overall expression level of progesterone receptor (PR) decreased, with no significant differences among F1, F2 and F3 follicles (P > 0.05). Yolk putrescine contents were positively correlated with yolk E2 concentrations and PR expression levels (P < 0.05), A significant positive correlation of spermidine levels with yolk P4 concentrations and PR expressions was also observed, as well as the spermine levels with yolk P4 concentrations (P < 0.05). In summary, polyamines were involved in the regulation of follicular development in geese, and this regulation played a role in affecting steroidogenesis and the expression of genes related to hormone receptors.

Effects of exogenous spermidine on autophagy and antioxidant capacity in ovaries and granulosa cells of Sichuan white geese.

Autophagy can inhibit ovarian senescence induced by oxidative stress and regulate follicle development and atresia, but its mechanism is still unclear. Exogenous spermidine can induce autophagy and scavenge reactive oxygen species (ROS). In this experiment, oxidative stress in Sichuan white geese ovaries and follicular granulosa cells (GCs) was caused by 3-nitropropionic acid (3-NPA) and spermidine was added to explore the effect of exogenous spermidine inducing autophagy and inhibiting oxidative stress in vivo and in vitro. Research results showed that putrescine, spermidine and spermine contents in goose ovaries in the group treated with spermidine combined with 3-NPA were 2.70, 1.94, and 1.70 times higher than those in the group treated with 3-NPA, respectively (P < 0.05). The contents of spermidine and spermine in GCs were 1.37 and 0.89 times higher in the spermidine in combination with the 3-NPA group than in the 3-NPA group, respectively (P < 0.05). LC3 and p62 were mainly expressed in the follicular granulosa layer. The LC3-II/I ratio and p62 level in GCs in the spermidine combined with 3-NPA treatment group were 1.37 and 0.77 times higher than that of the 3-NPA treatment group, respectively (P < 0.05). 3-NPA treatment significantly increased ROS level and the apoptosis rate in GCs, while the combined treatment of spermidine and 3-NPA reversed this change (P < 0.05). In conclusion, spermidine alleviated the oxidative damage induced by 3-NPA by improving the antioxidant capacity of ovaries and follicular GCs of Sichuan white geese and may be alleviated by inducing autophagy in GCs.

This study investigated the effects of exogenous spermidine on oxidative stress induced by 3-nitropropionic acid (3-NPA) in ovaries and granulosa cells of Sichuan white geese. In ovarian tissue, spermidine can reduce malondialdehyde accumulation induced by 3-NPA by increasing antioxidant enzyme activity, thus alleviating the oxidative damage induced by 3-NPA. In addition, spermidine can also improve the morphological structure of follicles and alleviate the structural damage caused by 3-NPA. Our results showed that autophagy-associated proteins are mainly concentrated in the granulosa layer of follicles and spermidine can alter their expression. Subsequently, we found that spermidine could induce autophagy and reduce the accumulation of reactive oxygen species and apoptosis rate induced by 3-NPA in granulosa cells. Therefore, we speculate that spermidine can alleviate oxidative stress induced by 3-NPA by inducing autophagy in granulosa cells. In conclusion, spermidine can relieve oxidative stress induced by 3-NPA by increasing the activity of antioxidant enzymes, and may also relieve oxidative stress by inducing autophagy.

Spatial and seasonal change in algal community structure and its interaction with nutrient dynamics in a gravel-bed urban river.

Harmful algal blooms frequently occur in urban rivers due to intense human activities. However, little is known about the change in algal community structure and its interactions with nutrient dynamics in gravel-bed urban rivers. In present study, water samples were collected from a gravel-bed River Xin'an, China for five months over four seasons and a rainy month to measure algal community structure, dissolved nitrogen gas (N2) and Argon (Ar) concentrations, and other water quality parameters. The results showed that the harmful Cyanophyta accounted for 31.6 ± 24.1% of the total community in the hot season while Bacillariophyta contributed more than 60% to the community in the other three seasons. The N2 was supersaturated in the moderate and cold seasons but it was unsaturated in the hot season, along with high concentrations of nitrogen-fixing cyanobacteria (Anabaena), indicating that the nitrogen fixation capacity was strong and even stronger than denitrification and anammox in the hot season. However, nitrogen fixation was not the main source of nitrogen in the water column. The concentrations of nutrients and Chla in the downstream river were significantly higher than those in the upstream river (p < 0.001 for nutrients and p = 0.029 for Chla), suggesting that human activities along the river greatly affected nutrient concentrations, as well as algal growth. Our study provides new insights into the algal community succession in a gravel-bed urban river and puts forward effective measures such as controlling exogenous nutrient input and dredging organic sediment for mitigating the harmful algal blooms in urban rivers.

Oxic urban rivers as a potential source of atmospheric methane.

Urban rivers play a vital role in global methane (CH4) emissions. Previous studies have mainly focused on CH4 concentrations in urban rivers with a large amount of organic sediment. However, to date, the CH4 concentration in gravel-bed urban rivers with very little organic sediment has not been well documented. Here, we collected water samples from an oxic urban river (Xin'an River, China; annual mean dissolved oxygen concentration was 9.91 ± 1.99 mg L-1) with a stony riverbed containing very little organic sediment. Dissolved CH4 concentrations were measured using a membrane inlet mass spectrometer to investigate whether such rivers potentially act as an important source of atmospheric CH4 and the corresponding potential drivers. The results showed that CH4 was supersaturated at all sampling sites in the five sampling months. The mean CH4 saturation ratio (ratio of river dissolved CH4 concentration to the corresponding CH4 concentration that is in equilibrium with the atmosphere) across all sampling sites in the five sampling months was 204 ± 257, suggesting that the Xin'an River had a large CH4 emission potential. The CH4 concentration was significantly higher in the downstream river than in the upstream river (p < 0.05), which suggested that human activities along the river greatly impacted the CH4 level. Statistical analyses and incubation experiments indicated that algae can produce CH4 under oxic conditions, which may contribute to the significantly higher CH4 concentration in August 2020 (p < 0.001) when a severe algal bloom occurred. Furthermore, other factors, such as heavy rainfall events, dissolved organic carbon concentration, and water temperature, may also be vital factors affecting CH4 concentration. Our study enhances the understanding of dissolved CH4 dynamics in oxic urban rivers with very little organic sediment and further proposes feasible measures to control the CH4 concentration in urban rivers.

The A53T mutation is key in defining the differences in the aggregation kinetics of human and mouse α-synuclein.

Despite a 95% sequence similarity, the aggregation of human and mouse α-synuclein is remarkably different, as the human form is slower than the mouse form in forming fibrils but is associated with Parkinson's disease in both humans and transgenic mice. Here, the amino acid code underlying these differences is investigated by comparing the lag times, growth rates, and secondary structure propensities of a systematic series of eight human-mouse chimeras. Fluorescence analysis of these variants shows that the A53T substitution dominates the growth kinetics, while the lag phase is affected by a combination of the A53T and S87N substitutions. The secondary structure propensities derived from an NMR chemical shift analysis of the monomeric forms of the human-mouse variants enable us to establish a link between the changes in the conformational properties in the region of position 53 upon mutation and the corresponding changes in growth rates. These results suggest that the presence of an alanine residue at position 53 may be an evolutionary adaptation to minimize Parkinson's disease in humans and indicates that effective drug development efforts may be directed to target this N-terminal region of the sequence.