Selective extinction and habitat nestedness are the main drivers of lizard nestedness in the Zhoushan Archipelago.

Nested subset pattern (nestedness) is an important part of the theoretical framework of island biogeography and community ecology. However, most previous studies often used nestedness metrics or randomization algorithms that are vulnerable to type I error. In this study, we investigated the nestedness of lizard assemblages on 37 islands in the Zhoushan Archipelago, China. We used the line-transect method to survey species occurrence, abundance, and habitat types of lizards on 37 islands during 2 breeding seasons in 2021 and 2022. We applied the nested metric WNODF and the conservative rc null model to control for type I error and quantify the significance of nestedness. Spearman rank correlations were used to evaluate the role of 4 habitat variables (island area, 2 isolation indices, and habitat diversity) and 4 ecological traits (body size, geographic range size, clutch size, and minimum area requirement) in generating nestedness. The results of WNODF analyses showed that lizard assemblages were significantly nested. The habitat-by-site matrix estimated by the program NODF was also significantly nested, supporting the habitat nestedness hypothesis. The nestedness of lizard assemblages were significantly correlated with island area, habitat diversity, clutch size, and minimum area requirement. Overall, our results suggest that selective extinction and habitat nestedness were the main drivers of lizard nestedness in our system. In contrast, the nestedness of lizard assemblages was not due to passive sampling or selective colonization. To maximize the number of species preserved, our results indicate that we should protect both large islands with diverse habitats and species with large area requirement and clutch size.

Assessing the causal relationship between blood metabolites and low back pain: a Mendelian randomization study.

AIM: Low back pain (LBP) is one of the most common health problems worldwide. This study aimed to determine whether blood metabolites were causally linked to the risk of LBP. METHODS: Based on summary-level genome-wide association studies, we designed a Mendelian randomization (MR) study. Instrumental variables were selected for each blood metabolite with the following criteria: genome-wide significance levels of < 5e-8 and independent clumping (r2 < 0.001, distance < 10,000 kb). Inverse-variance weighting (IVW) was used as the primary statistical method. The weighted median (WM) method and MR-Egger regression were implemented to complement IVW. Subsequently, sensitivity analyses were conducted, including Cochran's Q test, MR-Egger intercept analysis, scatter plots, leave-one-out analysis, and funnel plots. RESULTS: IVW revealed that higher levels of lactate (odds ratio [OR] = 0.974, 95% confidence interval [CI] 0.953-0.995, P = 0.017), medium low-density lipoprotein triglycerides (OR = 0.990, 95% CI 0.983-0.997, P = 0.005) and albumin (OR = 0.985, 95% CI 0.973-0.998, P = 0.019) had a causal effect on decreased risk of LBP, whereas positive causality was detected between genetic predisposition to tyrosine and LBP (OR = 1.016, 95% CI 1.001-1.032, P = 0.043). Estimates from WM and MR-Egger were consistent with the direction of the IVW method. Additionally, there was no evidence of heterogeneity or pleiotropy in this study. CONCLUSION: This MR study demonstrated that four blood metabolites were causally related to LBP. It is possible to enhance the diagnosis of LBP, prognostic outcome predictions, and the personalization of therapy by analyzing novel signatures of metabolites.

SDH, a novel diarylheptane compound, alleviates dextran sulfate sodium (DSS)-induced colitis by reducing Th1/Th2/Th17 induction and regulating the gut microbiota in mice.

Ulcerative colitis, a chronic inflammatory condition affecting the rectum and colon to varying degrees, is linked to a dysregulated immune response and the microbiota. Sodium (aS,9R)-3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) emerges as a novel diarylheptane compound aimed at treating inflammatory bowel diseases. However, the mechanisms by which SDH modulates these conditions remain largely unknown. In this study, we assessed SDH's impact on the clinical progression of dextran sodium sulfate (DSS)-induced ulcerative colitis. Our results demonstrated that SDH significantly mitigated the symptoms of DSS-induced colitis, reflected in reduced disease activity index scores, alleviation of weight loss, shortening of the colorectum, and reduction in spleen swelling. Notably, SDH decreased the proportion of Th1/Th2/Th17 cells and normalized inflammatory cytokine levels in the colon. Furthermore, SDH treatment modified the gut microbial composition in mice with colitis, notably decreasing Bacteroidetes and Proteobacteria populations while substantially increasing Firmicutes, Actinobacteria, and Patescibacteria. In conclusion, our findings suggest that SDH may protect the colon from DSS-induced colitis through the regulation of Th1/Th2/Th17 cells and gut microbiota, offering novel insights into SDH's therapeutic potential.

Brain white matter changes and their associations with non-motor dysfunction in orthostatic hypotension in α-synucleinopathy: A NODDI study.

BACKGROUND: The specific non-motor symptoms associated with α-synucleinopathies, including orthostatic hypotension (OH), cognitive impairment, and emotional abnormalities, have been a subject of ongoing controversy over the mechanisms underlying the development of a vicious cycle among them. The distinct structural alterations in white matter (WM) in patients with α-synucleinopathies experiencing OH, alongside their association with other non-motor symptoms, remain unexplored. This study employs axial diffusivity and density imaging (NODDI) to investigate WM damage specific to α-synucleinopathies with concurrent OH, delivering fresh evidence to supplement our understanding of the pathogenic mechanisms and pathological rationales behind the occurrence of a spectrum of non-motor functional impairments in α-synucleinopathies. METHODS: This study recruited 49 individuals diagnosed with α-synucleinopathies, stratified into an α-OH group (n = 24) and an α-NOH group (without OH, n = 25). Additionally, 17 healthy controls were included for supine and standing blood pressure data collection, as well as neuropsychological assessments. Magnetic resonance imaging (MRI) was utilized for the calculation of NODDI parameters, and tract-based spatial statistics (TBSS) were employed to explore differential clusters. The fibers covered by these clusters were defined as regions of interest (ROI) for the extraction of NODDI parameter values and the analysis of their correlation with neuropsychological scores. RESULTS: The TBSS analysis unveiled specific cerebral regions exhibiting disparities within the α-OH group as compared to both the α-NOH group and the healthy controls. These differences were evident in clusters that indicated a decrease in the acquisition of the neurite density index (NDI), a reduction in the orientation dispersion index (ODI), and an increase in the isotropic volume fraction (FISO) (p < 0.05). The extracted values from these ROIs demonstrated significant correlations with clinically assessed differences in supine and standing blood pressure, overall cognitive scores, and anxiety-depression ratings (p < 0.05). CONCLUSION: Patients with α-synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model, and there is a correlation with the onset and progression of non-motor functional impairments.

Case report: Ureteric bud intestinal-type adenocarcinoma involving the cervix was misdiagnosed as a large cervical fibroid.

Background: Malignant tumors of the ureteric bud are not common, and cervical involvement is even rarer. So far, there have been no such cases in the literature. Case summary: A 50-year-old woman developed intermittent light bleeding in the past 7 months and lower abdominal pain in the past 2 months. The human papillomavirus 16 (HPV) DNA, P16 chemical staining, thinPrep cytology test (TCT), and cervical and cervical canal tissue biopsy were all negative. Pelvic color Doppler ultrasound exhibited incomplete mediastinal uterus and heterogeneous echo from the cervical canal to the posterior wall of the cervix. Pelvic contrast-enhanced CT showed left cervical mass, left retroperitoneal mass, absence of the left kidney, and mediastinal uterus. An increase in human epididymal protein 4 (HE4) (133.6 pmol/L) was detected, while other tumor markers were at normal levels. Based on these examination results, a diagnosis of "cervical fibroids, left retroperitoneal mass, incomplete mediastinal uterus, left kidney deficiency"[SIC] was conducted, and expanded hysterectomy, right adnexectomy, and left retroperitoneal mass resection were performed. Through intraoperative rapid pathological diagnosis, postoperative pathological diagnosis combined with the re-evaluation of laboratory, and imaging and intraoperative examination results, the patient was diagnosed with ureteric bud intestinal-type adenocarcinoma involving the cervix. The patient has been tracked and followed up for approximately 11 months. She underwent six courses of chemotherapy. At present, the medication has been discontinued for 4 months, and there is no recurrence, metastasis, or deterioration of the tumor. Conclusion: For large masses of the cervix, it is feasible for the operation to be performed, improving the prognosis. There were a few limitations. A preoperative aspiration biopsy of masses was not performed to differentiate benign from malignant. Preoperative urography was not performed to clarify the function of the malformed urinary system structure. Partial cystectomy should be performed simultaneously with the resection of the ureteric bud for intestinal-type adenocarcinoma. In this case, a partial cystectomy was not performed, which can only be compensated with postoperative chemotherapy. Moreover, this patient did not undergo genetic screening, and it is currently unclear whether there are any genetic mutations associated with ureteric bud intestinal adenocarcinoma.

Efficient Selective Adsorption of Rubidium and Cesium from Practical Brine Using a Metal-Organic Framework-Based Magnetic Adsorbent.

Rubidium (Rb) and cesium (Cs) have important applications in highly technical fields. Salt lakes contain huge reserves of Rb and Cs with industrial significance, which can be utilized after extraction. In this study, a composite magnetic adsorbent (Fe3O4@ZIF-8@AMP, AMP = ammonium phosphomolybdate) was prepared and its adsorption properties for Rb+ and Cs+ were studied in simulated and practical brine. The structure of the adsorbent was characterized by SEM, XRD, N2 adsorption-desorption, FT-IR, and vibrating sample magnetometer (VSM). The adsorbent had good adsorption affinity for Rb+ and Cs+. The Langmuir model and pseudo-second-order dynamics described the adsorbing isotherm and kinetic dates, respectively. The adsorption capacity and adsorption rate of Fe3O4@ZIF-8@AMP were increased by 1.86- and 2.5-fold compared with those of powdered crystal AMP, owing to the large specific surface area and high dispersibility of the adsorbent in the solution. The adsorbent was rapidly separated from the solution within 17 s using an applied magnetic field owing to the good magnetic properties. The composite adsorbent selectively adsorbed Rb+ and Cs+ from the practical brine even in the presence of a large number of coexisting ions. The promising adsorbent can be used to extract Rb+ and Cs+ from aqueous solutions.

Research on the brewing technology of Dangshen Huangjiu with low biogenic amines and high functional factors.

BACKGROUND: Biogenic amines (BA) are hazardous components in Huangjiu (HJ). To ensure the quality of Dangshen Huangjiu (DSHJ), an orthogonal experiment L9 (33) was proposed to optimize the process by the main brewing factors (pre-fermentation temperature, pre- and post-fermentation time) that may affect BA and functional factors in DSHJ. DSHJ was produced with low BA content and high functional factors. Gas chromatography-ion mobility spectrometry combined with a multivariate statistical method (GC-IMS-MSM) was used to analyze the volatile components in the brewing process of DSHJ. RESULTS: The optimum brewing process parameters of DSHJ were as follows: pre-fermentation temperature, 28 °C; pre-fermentation time, 9 days; post-fermentation time, 18 days. The average content of BA in DSHJ was 33.12 mg L-1, and the sensory score, total phenol content and DPPH free radical scavenging rate of DSHJ were significantly higher than those of HJ. A total of 14 esters, 7 acids, 7 alcohols, 1 ketone, 5 aldehydes and 1 pyrazine in DSHJ and HJ were identified by GC-IMS. There were no significant differences (P > 0.05) in DSHJ and HJ in the soaking rice and saccharification stage. 11 components, such as ethyl acetate, and 12 components, such as acetic acid, were the different components of HJ and DSHJ in pre-fermentation and post-fermentation stages, respectively. In the post-fermentation stage, the contents of 8 components in DSHJ such as ethyl acetate were higher than in HJ. CONCLUSION: The preparation process parameters of DSHJ optimized by orthogonal experiments can ensure that DSHJ has the advantages of low BA content, high total phenol content and good antioxidant activity. Sensory score and GC-IMS-MSM analysis found that DSHJ prepared using the optimal process had the characteristics of good taste and rich aroma. © 2024 Society of Chemical Industry.

Case Report: TRPV4 gene mutation causing neuronopathy, distal hereditary motor, type VIII.

Neuronopathy, distal hereditary motor, type VIII is an exceedingly rare autosomal dominant genetic disorder, also known as congenital non-progressive distal spinal muscular atrophy. It is characterized by progressive weakness in distal motor function and atrophy of muscles, without accompanying sensory impairment. Presently, there is limited literature on this condition, and accurate epidemiological data regarding its incidence remains unavailable. We report a paediatric case of distal hereditary motor, type VIII that is caused by a heterozygous missense mutation in the TRPV4 gene (NM_021625): c.805C>T. The proband is a 7-year-old male child. During pregnancy, his mother had prenatal ultrasound revealing "inward turning of the feet", a condition persisting after birth. The proband is currently unable to stand independently, exhibiting bilateral clubfoot deformity. Although possessing normal cognitive function, he cannot walk unaided. Computed radiography findings reveal pelvic tilt, bilateral knee joint valgus, and bilateral clubfoot. The patient underwent familial exome sequencing, revealing a mutation in the TRPV4 gene (NM_021625): c.805C>T (p.Arg269Cys). Considering the patient's medical history, clinical manifestations, imaging studies, and genetic test results, the diagnosis for this individual is Neuronopathy, distal hereditary motor, type VIII. This report documents a case involving the TRPV4 gene mutation associated with Neuronopathy, distal hereditary motor, type VIII, contributing valuable case reference for the early diagnosis of this condition.

The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.

Differential Sampling of AC Waveforms Based on a Commercial Digital-to-Analog Converter for Reference.

This paper introduces an innovative differential sampling technique for calibrating AC waveforms, leveraging a commercially available 16-bit digital-to-analog converter (DAC) as the reference standard. The novelty of this approach lies in its enhanced stability over traditional direct sampling methods, especially as the frequency of the AC waveform increases. Notably, this technique provides a cost-effective sampler alternative to the differential sampling methods that rely on a programmable Josephson voltage standard (PJVS). A critical aspect of this methodology is the precise measurement of the DAC's output voltage, for which a static measurement strategy is adopted to utilize the exceptional linearity and transfer accuracy of the Keysight 3458A (Santa Rosa, CA, USA) in its standard DCV mode. The differential sampling method has demonstrated good accuracy, achieving a near 1 µV/V agreement with a pulse-driven AC Josephson voltage standard (ACJVS) across a 40 Hz to 200 Hz frequency range. The method attained an expanded uncertainty (k = 2) of 1 part in 106 while measuring a 0.707107 VRMS sine wave at 50 Hz, showcasing its efficacy in precise AC waveform calibration.

Evaluating the adoption of irrigation technology in a well-irrigated winter wheat－summer maize cropping system.

Determining suitable irrigation technology is of paramount for promoting water-saving agriculture, particularly for winter wheat-summer maize rotation system in well-irrigated regions. To optimize and assess the efficacy of various irrigation technologies (specifically, semi-fixed sprinkler irrigation, walking sprinkler, semi-automatic buried telescopic sprinkler irrigation, thin-soft spray tape irrigation, drip irrigation, self-driven winch sprinkler and manually moving spray gun irrigation, marked as A, B, C, D, E, F and G) applied in south central North China Plain, we first conducted an economic analysis for the winter wheat-summer maize rotation. Subsequently, employing a comprehensive set of 20 indicators spanning economic, societal, technological, ecological, and resource aspects, we employed a TOPSIS model with integrative weighting approach using "AHP + Entropy". We also employed principal component analysis and the Sankey diagram method to explore characteristics of different irrigation techniques and indexes. Irrigation mode E, conserving energy by 63.19% compared to mode B and offering labor savings five times greater than the mode D. The highest economic benefit for the rotation system was observed with the mode C, resulting in a 25.26% increase compared to the mode G. The top three irrigation modes based on scores were D, G, and E, with scores of 0.532, 0.490, and 0.474, respectively. The Sankey diagram revealed distinct preferences among different agricultural entities for specific irrigation modes. For specific stakeholders, we recommend irrigation modes D, G, F, and B for small farmers, large and specialized family businesses, family farms, and farmer cooperatives, respectively. In conclusion, our findings provide valuable scientific support and recommendations for the practical application of irrigation technology in agricultural production.

The impact of microbial inoculants on large-scale composting of straw and manure under natural low-temperature conditions.

Understanding large-scale composting under natural conditions is essential for improving waste management and promoting sustainable agriculture. In this study, corn straw (400 tons) and pig manure (200 tons) were composted with microbial inoculants. The thermophilic phase of composting lasted for fourteen weeks, resulting in an alkaline final product. Microbial systems with low-temperature initiation and high-temperature fermentation played a crucial role in enhancing lignocellulose degradation and humic substances (HS) formation. Adding microbes, including Rhodanobacter, Pseudomonas, and Planococcus, showed a positive correlation with degradation rates of cellulose, hemicellulose, and lignin. Bacillus, Planococcus, and Acinetobacter were positively correlated with HS formation. Microorganisms facilitated efficient hydrolysis of lignocelluloses, providing humic precursors to accelerate composting humification through phenolic protein and Maillard pathways. This study provides significant insights into large-scale composting under natural conditions, contributing to the advancement of waste management strategies and the promotion of sustainable agriculture.

HSFA3 functions as a positive regulator of HSFA2a to enhance thermotolerance in perennial ryegrass.

Perennial ryegrass (Lolium perenne) is a widely used cool season turfgrass with outstanding turf quality and grazing tolerance. High temperature is the key factor restricting the distribution of perennial ryegrass in temperate and sub-tropic regions. In this study, we found that one HEAT SHCOK TRANSCRIPTION FACOTR (HSF) class A gene from perennial ryegrass, LpHSFA3, was highly induced by heat stress. LpHSFA3 is localized in nucleus and functions as a transcription factor. Ectopic overexpression of LpHSFA3 in Arabidopsis improved thermotolerance and rescued heat sensitive deficiency of athsfa3 mutant. Overexpression of LpHSFA3 in perennial ryegrass enhanced heat tolerance and increased survival rate in summer season as evidenced by decreased EL and MDA, increased number of green leaves and total chlorophyll content. LpHSFA3 binds to the HSE region in LpHSFA2a promoter to constitutively activate the expression of LpHSFA2a and downstream heat stress responsive genes. Ectopic overexpression of LpHSFA2a consequently rescued thermal sensitivity of athsfa3 mutant and enhanced thermotolerance of athsfa2 mutant. Perennial ryegrass protoplasts with overexpression of LpHSFA3 and LpHSFA2a exhibited induction of similar subsets of heat responsive genes. These results indicated that transcription factor LpHSFA3 functions as positive regulator of LpHSFA2a to improve thermotolerance of perennial ryegrass, providing further evidence to understand the regulatory networks of plant heat stress response.

A SCYL2 gene from Oryza sativa is involved in phytosterol accumulation and regulates plant growth and salt stress.

Rice is a crucial food for humans due to its high nutritional value. Phytosterols, essential components of the plant membrane lipid bilayer, play a vital role in plant growth and contribute significantly to lipid-lowering, antitumor, and immunomodulation processes. In this study, SCY1-like protein kinases 2 (SCYL2) was found to be closely related to the accumulation of phytosterols. The levels of campesterol, stigmasterol, and ß-sitosterol significantly increased in transgenic rice seeds, husks, and leaves, whereas there was a considerable reduction in scyl2 plants. Subsequent investigations revealed the crucial role of SCYL2 in plant development. Mutations in this gene led to stunted plant growth while overexpressing OsSCYL2 in Arabidopsis and rice resulted in larger leaves, taller plants, and accelerated development. When subjected to salt stress, Arabidopsis plants overexpressed OsSCYL2 showed significantly higher germination rates than wild-type plants. Similarly, transgenic rice seedlings displayed better growth than both ZH11 and mutant plants, exhibiting lower malondialdehyde (MDA) content and higher peroxidase (POD), and catalase (CAT) activities. Conversely, scyl2 plants exhibited more yellow leaves or even death. These findings suggested that OsSCYL2 proteins might be involved in phytosterols synthesis and play an important role during plant growth and development. This study provides a theoretical basis for developing functional rice.

Quercetin attenuates cisplatin-induced mitochondrial apoptosis via PI3K/Akt mediated inhibition of oxidative stress in pericytes and improves the blood labyrinth barrier permeability.

Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc. Oxidative stress levels, mitochondrial function and endothelial barrier changes were observed in vitro by using DCFH-DA probe detection, flow cytometry, JC-1 probe, immunofluorescence and the establishment in vitro BLB models, etc. QU pretreatment activates the PI3K/AKT signaling pathway, inhibits CDDP-induced oxidative stress, protects mitochondrial function, and reduces mitochondrial apoptosis in PCs. However, PI3K/AKT specific inhibitor (LY294002) partially reverses the protective effects of QU. In addition, in vitro BLB models were established by coculturing PCs and endothelial cells (ECs), which suggests that QU both reduces the CDDP-induced apoptosis in PCs and improves the endothelial barrier permeability. On the whole, the research findings suggest that QU can be used as a novel treatment to reduce CDDP-induced ototoxicity.

Efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists for renal and cardiovascular outcomes in patients with chronic kidney disease: a meta-analysis of randomized clinical trials.

Objective: To systematically review the efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD). Methods: We systematically searched six databases to identify randomized controlled trials (RCTs) about nonsteroidal MRAs for CKD, from inception to 22 August 2023. Two reviewers independently screened the retrieved articles, extracted data, and assessed the risk of bias of included RCTs using the Cochrane risk of bias tool. We then conducted meta-analysis of the data using Stata 17.0 software. Results: 11 RCTs (n = 15,817) were included in this meta-analysis. Compared with placebo, nonsteroidal MRAs significantly reduced the proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baseline [RR = 0.85, 95% CI (0.78, 0.92), p < 0.001], although the magnitude of eGFR reduction was greater [WMD = -2.83, 95% CI (-3.95, -1.72), p < 0.001]. The experimental group also had lower incidence of composite renal outcome [RR = 0.86, 95% CI (0.79, 0.93), p < 0.001] and greater reduction in urine albumin-to-creatinine ratio (UACR) from baseline [WMD = -0.41, 95% CI (-0.49, -0.32), p < 0.001], as well as reduced cardiovascular events [RR = 0.88, 95% CI (0.80, 0.95), p = 0.003]. MRAs did not increase any adverse events compared to placebo [RR = 1.00, 95% CI (0.99, 1.01), p = 0.909], but had higher incidence of hyperkalemia [RR = 2.05, 95% CI (1.85, 2.280), p < 0.001]. Compared with eplerenone, there was no significant difference in the proportion of patients with ≥40% decline in eGFR [RR = 0.57, 95% CI (0.18, 1.79), p = 0.335] or hyperkalemia [RR = 0.95, 95%CI (0.48, 1.88), p = 0.875]. Conclusion: Nonsteroidal MRAs can reduce the incidence of end-stage renal disease and cardiovascular adverse events in patients. Although there was still a risk of hyperkalemia compared to placebo, there was no significant difference in any adverse events compared to either placebo or eplerenone. It has become a new option for drug treatment of CKD patients, but more clinical trials are still needed to verify its efficacy and safety. Especially further direct comparison of the nonsteroidal MRAs to eplerenone in view of the relatively small number of patients reviewed are needed.

Fitness difference between two synonymous mutations of Phytophthora infestans ATP6 gene.

BACKGROUND: Sequence variation produced by mutation provides the ultimate source of natural selection for species adaptation. Unlike nonsynonymous mutation, synonymous mutations are generally considered to be selectively neutral but accumulating evidence suggests they also contribute to species adaptation by regulating the flow of genetic information and the development of functional traits. In this study, we analysed sequence characteristics of ATP6, a housekeeping gene from 139 Phytophthora infestans isolates, and compared the fitness components including metabolic rate, temperature sensitivity, aggressiveness, and fungicide tolerance among synonymous mutations. RESULTS: We found that the housekeeping gene exhibited low genetic variation and was represented by two major synonymous mutants at similar frequency (0.496 and 0.468, respectively). The two synonymous mutants were generated by a single nucleotide substitution but differed significantly in fitness as well as temperature-mediated spatial distribution and expression. The synonymous mutant ending in AT was more common in cold regions and was more expressed at lower experimental temperature than the synonymous mutant ending in GC and vice versa. CONCLUSION: Our results are consistent with the argument that synonymous mutations can modulate the adaptive evolution of species including pathogens and have important implications for sustainable disease management, especially under climate change.

Triplet-branch network with contrastive prior-knowledge embedding for disease grading.

Since different disease grades require different treatments from physicians, i.e., the low-grade patients may recover with follow-up observations whereas the high-grade may need immediate surgery, the accuracy of disease grading is pivotal in clinical practice. In this paper, we propose a Triplet-Branch Network with ContRastive priOr-knoWledge embeddiNg (TBN-CROWN) for the accurate disease grading, which enables physicians to accordingly take appropriate treatments. Specifically, our TBN-CROWN has three branches, which are implemented for representation learning, classifier learning and grade-related prior-knowledge learning, respectively. The former two branches deal with the issue of class-imbalanced training samples, while the latter one embeds the grade-related prior-knowledge via a novel auxiliary module, termed contrastive embedding module. The proposed auxiliary module takes the features embedded by different branches as input, and accordingly constructs positive and negative embeddings for the model to deploy grade-related prior-knowledge via contrastive learning. Extensive experiments on our private and two publicly available disease grading datasets show that our TBN-CROWN can effectively tackle the class-imbalance problem and yield a satisfactory grading accuracy for various diseases, such as fatigue fracture, ulcerative colitis, and diabetic retinopathy.

Comparative Analysis of Intestinal Inflammation and Microbiota Dysbiosis of LPS-Challenged Piglets between Different Breeds.

Post-weaning diarrhea is common in piglets, causing huge economic losses worldwide. Associations between LPS challenge, intestinal inflammation, and microbiota have been reported in Duroc × Landrace × Yorkshire (DLY) crossbred pigs. However, the effects of LPS challenge in other breeds remain unclear. In the current study, we performed a comprehensive comparative analysis of the effects of LPS challenge on jejunal mucosal morphology, jejunal microbial composition, and serum indexes in two pig breeds: DLY and Heigai, an indigenous Chinese breed. The results showed that LPS caused considerable damage to the mucosal morphology, enhanced serum levels of inflammatory cytokines and the intestinal permeability index, and lowered the antioxidant capacity index. LPS challenge also changed the microbial composition and structure of the jejunum, significantly increased the abundances of Escherichia-Shigella in DLY pigs, and decreased those of Gemella and Saccharimonadales in Heigai pigs. Furthermore, LPS challenge triggered functional changes in energy metabolism and activities related to the stress response in the jejunal bacterial community, alleviating the inflammatory response in Heigai pigs. This study also revealed that Heigai pigs had a weaker immune response to LPS challenge than DLY pigs, and identified several genera related to the breed-specific phenotypes of Heigai pigs, including Gemella, Saccharimonadales, Clostridia_UCG_014, Terrisporobacter, and Dielma. Our collective findings uncovered differences between Heigai and DLY pigs in intestinal inflammation and microbiota dysbiosis induced by LPS challenge, providing a theoretical basis for unraveling the mechanism of intestinal inflammation in swine and proposing microbial candidates involved in the resistance to diarrhea in piglets.

Identification of Gene-Allele System Conferring Alkali-Tolerance at Seedling Stage in Northeast China Soybean Germplasm.

Salinization of cultivated soils may result in either high salt levels or alkaline conditions, both of which stress crops and reduce performance. We sampled genotypes included in the Northeast China soybean germplasm population (NECSGP) to identify possible genes that affect tolerance to alkaline soil conditions. In this study, 361 soybean accessions collected in Northeast China were tested under 220 mM NaHCO3:Na2CO3 = 9:1 (pH = 9.8) to evaluate the alkali-tolerance (ATI) at the seedling stage in Mudanjiang, Heilongjiang, China. The restricted two-stage multi-locus model genome-wide association study (RTM-GWAS) with gene-allele sequences as markers (6503 GASMs) based on simplified genome resequencing (RAD-sequencing) was accomplished. From this analysis, 132 main effect candidate genes with 359 alleles and 35 Gene × Environment genes with 103 alleles were identified, explaining 90.93% and 2.80% of the seedling alkali-tolerance phenotypic variation, respectively. Genetic variability of ATI in NECSGP was observed primarily within subpopulations, especially in ecoregion B, from which 80% of ATI-tolerant accessions were screened out. The biological functions of 132 candidate genes were classified into eight functional categories (defense response, substance transport, regulation, metabolism-related, substance synthesis, biological process, plant development, and unknown function). From the ATI gene-allele system, six key genes-alleles were identified as starting points for further study on understanding the ATI gene network.