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Abstract Peroxisomal l-bifunctional enzyme (EHHADH) plays a role in the classic peroxisomal fatty acid β-oxidation pathway; however, the relationship between EHHADH expression and diabetic kidney disease has not been well understood. Here, we found that endogenous EHHADH levels were strongly correlated with the progression and severity of diabetic nephropathy in T2D patients. EHHADH knockout mice exhibited worsened renal tubular injury in diabetic mice. Furthermore, EHHADH is a modulator of pexophagy. In renal tubular epithelial cells (RTECs) in vitro, the knockdown of EHHADH induced a dramatic loss of peroxisomes. The loss of peroxisomes in EHHADH-deficient RTECs was restored by either an autophagic inhibitor 3-methyladenine or bafilomycin A1 both in vitro and in vivo. NBR1 was required for pexophagy in EHHADH-knockdown cells, where the level of reactive oxygen species (ROS) was increased, while inhibition of ROS blocked pexophagy. In summary, our findings revealed EHHADH deficiency accelerated renal injury in DKD as a modulator of pexophagy.

Abstract Background Gastric cancer (GC) lacks serum biomarkers with clinical diagnostic value. Multi-omics analysis is an important approach to discovering cancer biomarkers. This study aimed to identify and validate serum biomarkers for GC diagnosis by cross-analysis of proteomics and transcriptomics datasets. Methods A cross-omics analysis was performed to identify overlapping differentially expressed genes (DEGs) between our previous aptamer-based GC serum proteomics dataset and the GC tissue RNA-Seq dataset in The Cancer Genome Atlas (TCGA) database, followed by lasso regression and random forest analysis to select key overlapping DEGs as candidate biomarkers for GC. The mRNA levels and diagnostic performance of these candidate biomarkers were analyzed in the original and independent GC datasets to select valuable candidate biomarkers. The valuable candidate biomarkers were subjected to bioinformatics analysis to select those closely associated with the biological behaviors of GC as potential biomarkers. The clinical diagnostic value of the potential biomarkers was validated using serum samples, and their expression levels and functions in GC cells were validated using in vitro cell experiments. Results Four candidate biomarkers (ILF2, PGM2L1, CHD7, and JCHAIN) were selected. Their mRNA levels differed significantly between tumor and normal tissues and showed different diagnostic performances for GC, with areas under the receiver operating characteristic curve (AUROCs) of 0.629–0.950 in the TCGA dataset and 0.736–0.840 in the Gene Expression Omnibus (GEO) dataset. In the bioinformatics analysis, only ILF2 (interleukin enhancer-binding factor 2) gene levels were associated with immune cell infiltration, some checkpoint gene expression, chemotherapy sensitivity, and immunotherapy response. Serum levels of ILF2 were higher in GC patients than in controls, with an AUROC of 0.944 for the diagnosis of GC, and it was also detected in the supernatants of GC cells. Knockdown of ILF2 by siRNA significantly reduced the proliferation and colony formation of GC cells. Overexpression of ILF2 significantly promotes the proliferation and colony formation of gastric cancer cells. Conclusions Trans-omics analysis of proteomics and transcriptomics is an efficient approach for discovering serum biomarkers, and ILF2 is a potential diagnostic biomarker and therapeutic target of gastric cancer.

Based on the fractional order sliding mode load observer, this paper presents an anti-disturbance speed control method of permanent magnet semi-direct drive transmission system for overhead manned equipment. The dynamic model of semi-direct drive transmission system is established using the Lagrange equation. Furthermore, the mathematical model of the permanent magnet synchronous motor (PMSM) is established based on the coordinate transformation theory. Subsequently, the fractional order sliding mode observer (FOSMO), which combines nonsingular terminal sliding mode control and fractional order theory is designed to observe the load disturbance changes in the permanent magnet semi-direct drive transmission system. Then, the concept of “active damping” is used to design the speed loop PI controller, and combined with the designed FOSMO to construct the composite speed controller. The designed composite speed controller is further improved by the anti-saturation design and parameter optimization. The results demonstrate that the designed FOSMO can accurately estimate the load disturbance on the PMSM output shaft. Additionally, the designed composite speed controller can realize stable speed control in the case of complex load disturbance, which meets the anti-disturbance speed control requirements of the permanent magnet semi-direct drive transmission system, and the control system’s robustness is further enhanced by adding the anti-saturation link.

Abstract Objective This study aims to compare the feasibility and effectiveness of automatic deep learning network and radiomics models in differentiating low tumor stroma ratio (TSR) from high TSR in pancreatic ductal adenocarcinoma (PDAC). Methods A retrospective analysis was conducted on a total of 207 PDAC patients from three centers (training cohort: n = 160; test cohort: n = 47). TSR was assessed on hematoxylin and eosin-stained specimens by experienced pathologists and divided as low TSR and high TSR. Deep learning and radiomics models were developed including ShuffulNetV2, Xception, MobileNetV3, ResNet18, support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and logistic regression (LR). Additionally, the clinical models were constructed through univariate and multivariate logistic regression. Kaplan–Meier survival analysis and log-rank tests were conducted to compare the overall survival time between different TSR groups. Results To differentiate low TSR from high TSR, the deep learning models based on ShuffulNetV2, Xception, MobileNetV3, and ResNet18 achieved AUCs of 0.846, 0.924, 0.930, and 0.941, respectively, outperforming the radiomics models based on SVM, KNN, RF, and LR with AUCs of 0.739, 0.717, 0.763, and 0.756, respectively. Resnet 18 achieved the best predictive performance. The clinical model based on T stage alone performed worse than deep learning models and radiomics models. The survival analysis based on 142 of the 207 patients demonstrated that patients with low TSR had longer overall survival. Conclusions Deep learning models demonstrate feasibility and superiority over radiomics in differentiating TSR in PDAC. The tumor stroma ratio in the PDAC microenvironment plays a significant role in determining prognosis. Critical relevance statement The objective was to compare the feasibility and effectiveness of automatic deep learning networks and radiomics models in identifying the tumor-stroma ratio in pancreatic ductal adenocarcinoma. Our findings demonstrate deep learning models exhibited superior performance compared to traditional radiomics models. Key points • Deep learning demonstrates better performance than radiomics in differentiating tumor-stroma ratio in pancreatic ductal adenocarcinoma. • The tumor-stroma ratio in the pancreatic ductal adenocarcinoma microenvironment plays a protective role in prognosis. • Preoperative prediction of tumor-stroma ratio contributes to clinical decision-making and guiding precise medicine. Graphical Abstract

Salinity is a common abiotic stress in the culture of penaeid shrimp. Through post-transcriptional regulation of gene transcripts, microRNAs (miRNAs) play an important role in the adaptation to a stressful environment. However, the involvement of miRNAs in the salinity stress response of shrimp remains unclear. In the present study, the sequence and expression profile of miRNAs in the hepatopancreas of low-salinity-treated Penaeus monodon were obtained by the high-throughput sequencing technique. A total of 679 miRNAs were identified, including 167 miRNAs that were significantly differentially expressed after low-salinity exposure (p < 0.05). Remarkably, most of these miRNAs were downregulated, suggesting that a series of genes were activated to participate in stress response. In addition, 43 miRNAs differentially expressed at all treatment were selected as putative key modulators. Enrichment analysis of genes targeted by these miRNAs indicated that a network that consists of the nervous system, the immune system, and the endocrine system played a crucial role in maintaining the homeostasis of P. monodon under low-salinity stress. These findings may help contribute to a better understanding of the mechanism that regulates salinity tolerance in shrimp and provide valuable genetic information for subsequent studies.

Abstract Purpose This study aimed to construct a mortality model for the risk stratification of intensive care unit (ICU) patients with sepsis by applying a machine learning algorithm. Methods Adult patients who were diagnosed with sepsis during admission to ICU were extracted from MIMIC-III, MIMIC-IV, eICU, and Zigong databases. MIMIC-III was used for model development and internal validation. The other three databases were used for external validation. Our proposed model was developed based on the Extreme Gradient Boosting (XGBoost) algorithm. The generalizability, discrimination, and validation of our model were evaluated. The Shapley Additive Explanation values were used to interpret our model and analyze the contribution of individual features. Results A total of 16,741, 15,532, 22,617, and 1,198 sepsis patients were extracted from the MIMIC-III, MIMIC-IV, eICU, and Zigong databases, respectively. The proposed model had an area under the receiver operating characteristic curve (AUROC) of 0.84 in the internal validation, which outperformed all the traditional scoring systems. In the external validations, the AUROC was 0.87 in the MIMIC-IV database, better than all the traditional scoring systems; the AUROC was 0.83 in the eICU database, higher than the Simplified Acute Physiology Score III and Sequential Organ Failure Assessment (SOFA),equal to 0.83 of the Acute Physiology and Chronic Health Evaluation IV (APACHE-IV), and the AUROC was 0.68 in the Zigong database, higher than those from the systemic inflammatory response syndrome and SOFA. Furthermore, the proposed model showed the best discriminatory and calibrated capabilities and had the best net benefit in each validation. Conclusions The proposed algorithm based on XGBoost and SHAP-value feature selection had high performance in predicting the mortality of sepsis patients within 24 h of ICU admission.

Abstract Modern omics technologies can generate massive amounts of biomedical data, providing unprecedented opportunities for individualized precision medicine. However, traditional statistical methods cannot effectively process and utilize such big data. To meet this new challenge, machine learning algorithms have been developed and applied rapidly in recent years, which are capable of reducing dimensionality, extracting features, organizing data and forming automatable data-driven clinical decision systems. Data-driven clinical decision-making have promising applications in precision medicine and has been studied in digestive diseases, including early diagnosis and screening, molecular typing, staging and stratification of digestive malignancies, as well as precise diagnosis of Crohn's disease, auxiliary diagnosis of imaging and endoscopy, differential diagnosis of cystic lesions, etiology discrimination of acute abdominal pain, stratification of upper gastrointestinal bleeding (UGIB), and real-time diagnosis of esophageal motility function, showing good application prospects. Herein, we reviewed the recent progress of data-driven clinical decision making in precision diagnosis of digestive diseases and discussed the limitations of data-driven decision making after a brief introduction of methods for data-driven decision making.

Salinization of freshwater ecosystems is a pressing global issue. Changes in salinity can exert severe pressure on aquatic animals and jeopardize their survival. Procambarus clarkii is a valuable freshwater aquaculture species that exhibits some degree of salinity tolerance, making it an excellent research model for freshwater aquaculture species facing salinity stress. In the present study, crayfish were exposed to acute low salt (6 ppt) and high salt (18 ppt) conditions. The organisms were continuously monitored at 6, 24, and 72 h using RNA-Seq to investigate the mechanisms of salt stress resistance. Transcriptome analysis revealed that the crayfish responded to salinity stress with numerous differentially expressed genes, and most of different expression genes was observed in high salinity group for 24h. GO and KEGG enrichment analyses indicated that metabolic pathways were the primary response pathways in crayfish under salinity stress. This suggests that crayfish may use metabolic pathways to compensate for energy loss caused by osmotic stress. Furthermore, gene expression analysis revealed the differential expression of immune and antioxidant-related pathway genes under salinity stress, implying that salinity stress induces immune disorders in crayfish. More genes related to cell proliferation, differentiation, and apoptosis, such as the Foxo, Wnt, Hippo, and Notch signaling pathways, responded to high-salinity stress. This suggests that regulating the cellular replication cycle and accelerating apoptosis may be necessary for crayfish to cope with high-salinity stress. Additionally, we identified 36 solute carrier family (SLC) genes related to ion transport, depicting possible ion exchange mechanisms in crayfish under salinity stress. These findings aimed to establish a foundation for understanding crustacean responses to salinity stress and their osmoregulatory mechanisms.

The effects of three feed additives in a low fish meal diet on growth, antioxidant capacity and intestinal microbiota of Penaeus monodon were studied to enhance the understanding of these effects and to provide basic data and a reference for the formulation and optimization of feed for P. monodon. A total of 630 healthy, homogenous shrimp (4.58 ± 0.05 g) were randomly divided into seven groups with three replicates per group and 30 shrimp per replicate in a breeding barrel (500 L). The additive names and amounts were 0 (CT); vitamin B6, 100 mg/kg (V1); vitamin B6, 200 mg/kg (V2); phytase, 1000 U/kg (P1); phytase, 2000 U/kg (P2); 0.2% yucca extract (Y1); and 0.4% yucca extract (Y2). The experiment lasted 8 weeks. The results showed that compared to CT, V1 and Y1 had a significant increasing tendency toward weight gain (WG) (p < 0.05) and had a significant decreasing tendency in the food conversion ratio (FCR) (p < 0.05). P2 had a significant increasing tendency in α-amylase activity (p < 0.05), and P1 had a significant increasing tendency in total superoxide dismutase (T-SOD) (p < 0.05). The next-generation sequencing of intestinal microbiota showed that Proteobacteria was the most abundant phylum in the seven groups, accounting for 29.33%, 56.67%, 55%, 45.33%, 73%, 39.33% and 64.33% of the total. Compared to CT, the Proteobacteria was significantly high (p < 0.05) in P2 and Y2, and the Bacteroidota in all other groups decreased significantly (p < 0.05). The functional prediction of FAPROTAX indicated that there was no significant difference (p > 0.05) in functional components among all groups. According to growth performance, antioxidant capacity and effects on intestinal microbiota, vitamin B6 (100 mg/kg), phytase (2000 U/kg) and yucca extract (0.2%) can be recommended as additives for the diet of P. monodon.

PuGa alloy shows hydrogenation corrosive reaction exposed in a hydrogen atmosphere, which affects material microstructures and decreases the related performance. Considering the high toxicity and radioactivity of PuGa alloy, experimental conditions and technical constraints, it is difficult to study this project through experimental method. Therefore, first-principle simulations were applied to study the adsorption behavior of H atom in PuGa alloy and on (111) surface, which included the electronic structure of PuGa alloy and the adsorption process of H. Hydrogen atom prefers to adopt in tetrahedral-Pu3Ga site in PuGa bulk with an adsorption energy of -0.75 eV. In contrast, on the PuGa alloy (111) surface, hydrogen atom prefers to adopt in fcc/hcp-Pu3 site with the maximum absolute value of the adsorption energy of 0.62 eV. H atom has a lower diffusion barrier at the adjacent adsorption sites of Ga atom, especially a barrier energy less than 0.3 eV on the surface. In this study, the mechanism of H atom adsorption behaviors on the material surface is revealed in atomic scale, and can provide the theoretical support to reduce the influence of H on the material structures and properties.

In recent years, as the marine environment has been deteriorated, the aquaculture water environment has also been negatively affected to varying degrees. Negative environmental factors make extremely damaging to organisms, resulting in stress-induced diseases and high mortality rates of cultured shrimp. Therefore, stress resistance breeding of Litopenaeus vannamei and evaluating the stress tolerance of the breeding population are urgently needed now. Litopenaeus vannamei collected from Thailand (T) and the United States (M) were used as parents, while four progeny populations of TT, MM, TM, and MT were constructed by diallel cross, with a total of 20 families. The tolerance of young shrimp to high ammonia-N, high pH, and low salt was compared through a 96-h acute toxicity test; the heterosis of each mating combination was analyzed; and the tolerance of parents and offspring was evaluated. Here we show that under 96 h of high ammonia-N, high pH, and low salt stress, the mortality rates of each family were 19.52%–92.22%, 23.33%–92.22%, and 19.33%–80.00%, respectively. There were significant differences in the tolerance of different families to ammonia-N, pH, and salinity stress (P < 0.05). The population with a female parent from the United States had stronger tolerance to ammonia-N, pH, and low salt stress than the population with a female parent from Thailand. The population with a male parent from Thailand had weaker tolerance to pH and low salt stress than the population with a male parent from the United States, but it was superior to the population with a male parent from the United States under ammonia-N stress. The heterosis rates of the hybrid population TM in acute high ammonia-N, high pH and low salinity were 81.67%, 44.58% and −10.13%, respectively; However, the heterosis rates of the MT population were 14.89%, 38.89%, and −8.96%, respectively. The overall resistance of the four populations showed MM > MT > TT > TM. The population TM had obvious heterosis in high ammonia-N and high pH tolerance traits, and the family MM7 had a strong low salt tolerance, so it can be considered a candidate family for subsequent breeding work. Moreover, variability in stress resistance and heterosis of stress resistance of different populations obtained by family selection was discussed in this paper. The experimental results provide a basis for screening new strains of vannamei shrimp with strong stress resistance through family breeding.

Abstract Background Diabetic nephropathy (DN) is a complex disease involving the upregulation of many inflammation-related proteins. Alternative polyadenylation (APA), a crucial post-transcriptional regulatory mechanism, has been proven to play vital roles in many inflammatory diseases. However, it is largely unknown whether and how APA exerts function in DN. Methods We performed transcriptomics and proteomics analysis of glomeruli samples isolated from 50 biopsy-proven DN patients and 25 control subjects. DaPars and QAPA algorithms were adopted to identify APA events from RNA-seq data. The qRT-PCR analysis was conducted to verify 3′UTR length alteration. Short and long 3ʹUTRs isoforms were also overexpressed in podocytes under hyperglycemia condition for examining protein expression. Results We detected transcriptome-wide 3′UTR APA events in DN, and found that APA-mediated 3ʹUTR lengthening of genes (APA genes) increased their expression at protein but not mRNA level. Increased protein level of 3′UTR lengthening gene was validated in podocytes under hyperglycemia condition. Pathway enrichment analysis showed that APA genes were enriched in inflammation-related biological processes including endoplasmic reticulum stress pathways, NF-κB signaling and autophagy. Further bioinformatics analysis demonstrated that 3′UTR APA of genes probably altered the binding sites for RNA-binding proteins, thus enhancing protein translation. Conclusion This study revealed for the first time that 3′UTR lengthening of APA genes contributed to the progression of DN by elevating the translation of corresponding proteins, providing new insight and a rich resource for investigating DN mechanisms.

Litopenaeus vannamei stands out globally in aquaculture for its fast growth, broad salt tolerance, disease resistance, and high protein levels. Selective breeding requires the precise estimation of the variance components and genetic parameters for important traits. This study formed lineages from 20 full sibling families of L. vannamei, with progenitors from Thailand and the USA. We then assessed the genetic resilience traits of juvenile shrimp from these families to high ammonia-N, high pH, and low salinity by performing a 96 h acute toxicity test. Mortality rates for the families under 96 h exposure to high ammonia-N, high pH, and low salinity were 19.52–92.22%, 23.33–92.22%, and 19.33–80.00%, respectively, showing significant variance in stress tolerance among families (p < 0.05). Survival heritability estimates, using threshold male and female models, were 0.44 ± 0.12 in high ammonia-N, 0.41 ± 0.12 in high pH, and 0.27 ± 0.08 in low salinity, respectively. Genetic correlations between growth and stress resistance traits varied from 0.0137 ± 0.2406 to 0.8327 ± 0.0781, and phenotypic correlations ranged from 0.0019 ± 0.0590 to 0.6959 ± 0.0107, indicating a low-to-high positive correlation significant at (p < 0.05). It was found that the survival rate of families No. 2 and No. 9 was higher under high ammonia-N and high pH stresses, while the survival rate of family No. 10 was higher under low salinity stress after comparing two selection criteria, the breeding values and phenotypic values. Thus, these three families are identified as potential breeding program candidates. Through the creation of a genetic parameter estimation model, the genetic variances across mating combinations for stress resistance traits were obtained and families with heightened stress resistance were identified, laying the groundwork for enhanced genetic selection of L. vannamei.

The escalating demand for processed foods has led to the widespread industrial use of glucose isomerase (GI) for high-fructose corn syrup (HFCS) production. This reliance on GIs necessitates continual Co2+ supplementation to sustain high catalytic activity across multiple reaction cycles. In this study, Serratia marcescens GI (SmGI) was immobilized onto surfaces of the metal-organic framework (MOF) material MOF (Co)-525 to generate MOF (Co)-525-GI for use in catalyzing glucose isomerization to generate fructose. Examination of MOF (Co)-525-GI structural features using scanning electron microscopy-energy dispersive spectroscopy, Fourier-transform infrared spectroscopy, and ultraviolet spectroscopy revealed no structural changes after SmGI immobilization and the addition of Co2+. Notably, MOF (Co)-525-GI exhibited optimal catalytic activity at pH 7.5 and 70 °C, with a maximum reaction rate (Vmax) of 37.24 ± 1.91 μM/min and Km value of 46.25 ± 3.03 mM observed. Remarkably, immobilized SmGI exhibited sustained high catalytic activity over multiple cycles without continuous Co2+ infusion, retaining its molecular structure and 96.38% of its initial activity after six reaction cycles. These results underscore the potential of MOF (Co)-525-GI to serve as a safer and more efficient immobilized enzyme technology compared to traditional GI-based food-processing technologies.

The aim of this experiment was to investigate the effects of the partial substitution of fish meal with soybean products and chicken meal on the growth performance, antioxidant capacity and intestinal microbiota of Penaeus monodon. A total of 450 healthy, consistent shrimp were randomly divided into five groups, with three replicates per group and 30 shrimp per replicate. The proportion of fish meal substituted with soybean products and chicken meal in the five feed groups was 0% (FM), 40% (40SC), 60% (60SC), 80% (80SC) and 100% (100SC). The experiment lasted for 8 weeks. The results showed that, compared to the FM group, the 40SC and 60SC groups had a decrease in WG and SR, but there was no significant difference (p > 0.05). In contrast, compared to the FM group, the FCR in the 100SC group was significantly increased (p < 0.05), while there was no significant difference among the FM and 40SC, 60SC and 80SC groups (p > 0.05). Compared to the FM group, the ACP in the 80SC and 100SC groups significantly increased (p < 0.05), while the 40SC and 60SC groups had no significant difference (p > 0.05). The AKP in the 100SC group was significantly higher than that in the FM group (p < 0.05), while there were no significant differences among the other four groups (p > 0.05). There were no significant differences in T-AOC and T-SOD among all the treatment groups (p > 0.05). The next-generation sequencing of the intestinal microbiota showed that Proteobacteria was the most abundant phylum in the five groups, accounting for 37.67%, 66%, 40%, 40% and 43.33%, respectively. Compared to the FM group, the Fusobacteriota in the other four groups decreased significantly (p < 0.05). The functional prediction of FAPROTAX indicated that no functional components were observed which are harmful to the body. Considering the effects on growth performance, antioxidant capacity and intestinal microbiota, it is feasible to use soybean products and chicken meal to replace 60% of fish meal in the feed of P. monodon.

Abstract Monoclonal gammopathy has emerged as an important cause of renal injury. Since the clinicopathologic features related to monotypic monoclonal gammopathy of renal significance with IgM monoclonal gammopathy (IgM-MGRS) are poorly described and it is uncertain if intervention improves renal survival and mortality, we report a series of such patients, characterizing their clinicopathologic spectrum and outcomes. We retrospectively analyzed 38 patients referred to one medical center between 2009 and 2019 with detectable serum monoclonal IgM by immunofixation, performance of a bone marrow biopsy and kidney biopsy-proven MGRS. Of the 38 patients identified, about half patients were amyloidosis, followed by cryoglobulinemic glomerulonephritis. Patients were divided into two groups on the basis of their kidney pathology: amyloid and non-amyloid. Patients with non-amyloidosis were more likely to have renal dysfunction, hematuria, anemia and hypocomplementemia and κ light chain was predominant in this sub-group. Amyloid patients were more often treated with chemotherapy than the non-amyloid patients (P = 0.002). There were no significant differences between amyloid and non-amyloid patients in mortality (48% vs 29%, P = 0.467) and incidence of ESRD (19% vs 59%, P = 0.103). The incidence of ESRD was lower in patients treated with chemotherapy and/or ASCT, compared to those without chemotherapy (25% vs 57%, P = 0.049), and it was also lower in the hematologic responders than non-responders (10% vs 40%, P = 0.047). Our study confirmed a diverse variety of clinicopathological features and outcomes in patients with IgM-MGRS. Chemotherapy and/or ASCT and deep hematologic responses might improve renal prognosis.

Introduction: Aptamers are valuable for bioassays, but aptamer-target binding is susceptible to reaction conditions. In this study, we combined thermofluorimetric analysis (TFA) and molecular dynamics (MD) simulations to optimize aptamer-target binding, explore underlying mechanisms and select preferred aptamer.Methods: Alpha-fetoprotein (AFP) aptamer AP273 (as the model) was incubated with AFP under various experimental conditions, and melting curves were measured in a real-time PCR system to select the optimal binding conditions. The intermolecular interactions of AP273-AFP were analysed by MD simulations with these conditions to reveal the underlying mechanisms. A comparative study between AP273 and control aptamer AP-L3-4 was performed to validate the value of combined TFA and MD simulation in selecting preferred aptamers.Results: The optimal aptamer concentration and buffer system were easily determined from the dF/dT peak characteristics and the melting temperature (Tm) values on the melting curves of related TFA experiments, respectively. A high Tm value was found in TFA experiments performed in buffer systems with low metal ion strength. The molecular docking and MD simulation analyses revealed the underlying mechanisms of the TFA results, i.e., the binding force and stability of AP273 to AFP were affected by the number of binding sites, frequency and distance of hydrogen bonds, and binding free energies; these factors varied in different buffer and metal ion conditions. The comparative study showed that AP273 was superior to the homologous aptamer AP-L3-4.Conclusion: Combining TFA and MD simulation is efficient for optimizing the reaction conditions, exploring underlying mechanisms, and selecting aptamers in aptamer-target bioassays.

Background: Salinity is one of the main influencing factors in the culture environment and is extremely important for the survival, growth, development and reproduction of aquatic animals.Methods: In this study, a comparative transcriptome analysis (maintained for 45 days in three different salinities, 30 psu (HC group), 18 psu (MC group) and 3 psu (LC group)) was performed by high-throughput sequencing of economically cultured Penaeus monodon. P. monodon gill tissues from each treatment were collected for RNA-seq analysis to identify potential genes and pathways in response to low salinity stress.Results: A total of 64,475 unigenes were annotated in this study. There were 1,140 upregulated genes and 1,531 downregulated genes observed in the LC vs. HC group and 1,000 upregulated genes and 1,062 downregulated genes observed in the MC vs. HC group. In the LC vs. HC group, 583 DEGs significantly mapped to 37 signaling pathways, such as the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, and PI3K-Akt signaling pathway; in the MC vs. HC group, 444 DEGs significantly mapped to 28 signaling pathways, such as the MAPK signaling pathway, Hippo signaling pathway and calcium signaling pathway. These pathways were significantly associated mainly with signal transduction, immunity and metabolism.Conclusions: These results suggest that low salinity stress may affect regulatory mechanisms such as metabolism, immunity, and signal transduction in addition to osmolarity in P. monodon. The greater the difference in salinity, the more significant the difference in genes. This study provides some guidance for understanding the low-salt domestication culture of P. monodon.

As the intensive development of aquaculture persists, the demand for fishmeal continues to grow; however, since fishery resources are limited, the price of fishmeal remains high. Therefore, there is an urgent need to develop new sources of protein. They are rich in proteins, fatty acids, amino acids, chitin, vitamins, minerals, and antibacterial substances. Maggot meal-based diet is an ideal source of high-quality animal protein and a new type of protein-based immune enhancer with good application prospects in animal husbandry and aquaculture. In the present study, we investigated the effects of three different diets containing maggot protein on the growth and intestinal microflora of Litopenaeus vannamei. The shrimp were fed either a control feed (no fly maggot protein added), FM feed (compound feed with 30% fresh fly maggot protein added), FF feed (fermented fly maggot protein), or HT feed (high-temperature pelleted fly maggot protein) for eight weeks. The results showed that fresh fly maggot protein in the feed was detrimental to shrimp growth, whereas fermented and high-temperature-pelleted fly maggot protein improved shrimp growth and survival. The effects of different fly maggot protein treatments on the intestinal microbiota of L. vannamei also varied. Fermented fly maggot protein feed and high-temperature-pelleted fly maggot protein feed increased the relative abundance of Ruegeria and Pseudomonas, which increased the abundance of beneficial bacteria and thus inhibited the growth of harmful bacteria. In contrast, fresh fly maggot proteins alter the intestinal microbiome, disrupting symbiotic relationships between bacteria, and causing invasion by Vibrio and antibiotic-resistant bacteria. These results suggest that fresh fly maggot proteins affect the composition of intestinal microorganisms, which is detrimental to the intestinal tract of L. vannamei, whereas fermented fly maggot protein feed affected the growth of L. vannamei positively by improving the composition of intestinal microorganisms.

In this work, we prepared a green, cheap material by chelating humic acid with ferric ions (HA-Fe) and used it as an anode material in LIBs for the first time. From the SEM, TEM, XPS, XRD, and nitrogen adsorption–desorption experimental results, it was found that the ferric ion can chelate with humic acid successfully under mild conditions and can increase the surface area of materials. Taking advantage of the chelation between the ferric ions and HA, the capacity of HA-Fe is 586 mAh·g−1 at 0.1 A·g−1 after 1000 cycles. Moreover, benefitting from the chelation effect, the activation degree of HA-Fe (about 8 times) is seriously improved compared with pure HA material (about 2 times) during the change–discharge process. The capacity retention ratio of HA-Fe is 55.63% when the current density increased from 0.05 A·g−1 to 1 A·g−1, which is higher than that of HA (32.55%) and Fe (24.85%). In the end, the storage mechanism of HA-Fe was investigated with ex-situ XPS measurements, and it was found that the C=O and C=C bonds are the activation sites for storage Li ions but have different redox voltages.

Introduction: Membranous nephropathy (MN) is a common chronic kidney disease in adults and a major challenge of clinical practice for its treatment. Despite major advances, since the discovery of the phospholipase A2 receptor as the major autoantigen of podocytes in MN, the mechanisms leading to glomerular damage remain elusive. Pyroptosis, a newly discovered type of programed necrotic cell death mainly mediated by gasdermin, was found to be responsible for podocyte injury in MN in our recent work. Objectives: The aim of this study was to explore the therapeutic effect of an FDA-approved drug, disulfiram (DSF), in the treatment of MN by inhibiting pyroptosis. Methods and Results: DSF significantly alleviated C3a/C5a-induced podocyte injury in vitro and renal lesions in passive Heymann nephritis (PHN) rats, as reflected by the decreased percentage of propidium iodide staining podocytes, decreased lactate dehydrogenase release from cultured podocytes and improvement in 24-h urine protein, serum albumin, serum creatinine, abnormal alterations of podocyte injury markers Desmin and WT-1 and podocyte foot process fusion in PHN rats. The protective effect of DSF on podocyte injury in vitro and in vivo can be ascribed to its inhibition of the activation and membrane translocation of the pyroptosis executor gasdermin D (GSDMD) in podocytes. DSF also inhibited the increase and activation of the pyroptosis signaling pathway NLRP3-ASC-Caspase-1/IL-18/GSDMD in C3a/C5a-treated podocytes and renal tissue of PHN rats. Conclusion: DSF is a potential drug for MN treatment, and its clinical application needs to be further investigated.

Abstract Podocyte damage mediated by in situ complement activation in the glomeruli is a key factor in the pathogenesis of membranous nephropathy (MN), but the molecular mechanism has not been fully elucidated. Pyroptosis is a special type of programmed cell death, mediate inflammatory response and induce tissue injury. However, it is not clear whether pyroptosis is involved in the development and progression of MN. Here, we report that pyroptosis plays an important role in promoting podocyte injury in MN. We first observed the occurrence of pyroptosis in the kidneys of MN patients and validated that complement stimulation triggered pyroptosis in podocytes and that inhibiting pyroptosis reversed complement-induced podocyte damage in vitro. In addition, stimulation of complement caused mitochondrial depolarization and reactive oxygen species (ROS) production in podocytes, and inhibition of ROS reversed complement-induced pyroptosis in podocytes. Interestingly, inhibition of pyroptosis in turn partially alleviated these effects. Furthermore, we also found the involvement of pyroptosis in the kidneys of passive Heymann nephritis (PHN) rats, and inhibitors of pyroptosis-related molecules relieved PHN-induced kidney damage in vivo. Our findings demonstrate that pyroptosis plays a critical role in complement-induced podocyte damage in MN and mitochondrial dysfunction is an important mechanism underlying this process. It provides new insight that pyroptosis may serve as a novel therapeutic target for MN treatment in future studies.

The heterogeneity of cell-of-origin for papillary renal cell carcinoma (pRCC) remains unknown. Here, with single-cell ATAC-seq from normal human kidney cells and ATACseq profiles from pRCC samples, the authors show that pRCC can originate from kidney collecting duct principal cells and this subtype is associated with advanced pRCC.

In order to investigate the expression of lncRNAs in the ovaries of Qira black sheep at different stages of the estrous cycle, Qira black sheep were used as experimental materials in this experiment, and after estrus synchronization, ovarian tissues at four different stages of the estrous cycle were collected to extract total RNA.The samples at different stages were first subjected to genome-wide analysis using RNA-seq technology; target genes of lncRNAs were predicted using co-expression methods; and then GO and KEGG analysis of target genes was performed. Genes related to the estrous cycle of Qira black sheep were also selected to study their transcriptional differences. Finally, lncRNA-miRNA and mRNA-lncRNA-miRNA interaction networks were established to further analyze the effect of lncRNA alignment on Qira black sheep reproduction. The results showed that in the differentially expressed part, 14 lncRNAs were differentially expressed in Estrous VS Diestrus; the differential expression levels of lncRNAs in the two comparison groups of Estrous VS Metestrus and Estrus VS Proestrus were 18 and 24, respectively. The results of GO and KEGG functional enrichment analysis showed that differentially expressed lncRNAs and their target genes were mainly involved in reproduction-related pathways such as retinol metabolism, ovarian sterol production and endosterol biosynthesis. In the combined analysis of lncRNA-miRNA and mRNA-lncRNA-miRNA, genes related to reproduction, such as LNC011583, LNC003443 and bta-miR-202, were found, thus it can be seen that lncRNAs have some effect in the reproduction of Qira black sheep.

Thermal stimulation methods of hydrate exploitation with chemical self-heating solution began to be investigated in the recent years. However, the exothermic characteristics of chemical self-heating solution during the gas hydrate exploitation process was not investigated systematically now. In this work, the effects of reagent concentration, acid variety, acid concentration on the exothermic characteristics were investigated by a self-designed high pressure autoclave with a 11.75 L volume, whose diameter and length is 100 and 1,500 mm, respectively. The experimental results showed that the temperature of hydrate reservoir will change in a wide range (from 100°C to −3°C) during the injection process of self-heating solution which was a large challenge to control the rate of heat release. During the self-heating solution injection, the temperature decreased quickly because of the strong endothermic reaction of hydrate dissociation promoted by the salt effect of self-heating solution, and then the temperature increased quickly because of exothermic reaction of self-heating solution. The exothermic rate of self-heating solution increased with the increase of reagent concentration, the acid concentration and the acidity. In all of the experiments, the temperatures near the inlet entrance were much higher than that in the deeper area, which illustrated that the effective heating area is the areas near the entrance. In the end, the different injection mode of mixed injection and sectional injection was also investigated, and it was found that the temperature peak in the near area with mixed injection mode is higher than that with sectional injection mode, however, the exothermic performance with sectional injection mode is better than that with mixed injection in the area far away from the inlet entrance. The exothermic characteristics studies of self-heating solution in this work can lay the necessary foundation of the further studies of self-heating solution in the exploitation of natural gas hydrate.

A novel flame retardant hexa (4- (9,10-dihydro-9-oxa-10-phosphaphenanthrene-10 -sulfide)-hydroxymethylphenoxy) cyclotriphosphazene (HAP-DOPS) with double functional groups was synthesized, and poly (lactic acid) (PLA) composites were prepared by melt extrusion. The flame retardancy and thermal degradation behavior of flame retardant PLA composites were studied by limiting oxygen index (LOI), vertical burning test (UL-94), cone calorimeter test (CCT), and thermogravimetric-infrared spectroscopy analysis (TG-IR). The experimental results showed that HAP-DOPS had a good flame-retardant effect on PLA. At flame retardant content of 5 wt%, the PLA/HAP-DOPS composite achieved a V-0 rating (UL-94, 3.2 mm) and a LOI value of 26.6%. The heat release rate (HRR) and total heat release (THR) of PLA composites were decreased by adding HAP-DOPS. The flame retardancy index (FRI) of PLA/HAP-DOPS-7.5 wt% was 1.0257, which showed good flame retardancy. The results of TG-IR showed that HAP-DOPS mainly had a gas-phase flame-retardant effect in PLA.

In order to solve the inefficient use of multi-source heterogeneous data information cross fusion and the low accuracy of prediction of landslide displacement, the current research proposed a new prediction model combining variable selection, sparrow search algorithm, and deep extreme learning machine. A cement mine in Fengxiang, Shaanxi Province, was studied as a case. The study first identified the variables related to landslide displacement of rock slope, and removed redundant variables by using Pearson correlation and gray correlation analysis. To avoid the impacts of random input weights and random thresholds in the DELM model, the SSA algorithm is used to optimize the model’s parameters, which can generate the optimal parameter combinations. The results showed an enhanced generalization ability of the model by removal of redundant variables by Pearson correlation and gray correlation analysis, and higher accuracy in the prediction of landside displacement of rock slope by SSA-DELM compared to other traditional machine learning algorithms. The current study is significant in the literature on rock slope disaster analysis.

Background: Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease (CKD) worldwide, tubular injury is the driving force during the pathogenesis and progression of DN. Thus, we aim to utilize the connectivity map (CMap) with renal tubulointerstitial transcriptomic profiles of biopsy-proven DN to identify novel drugs for treating DN.Methods: We interrogated the CMap profile with tubulointerstitial transcriptomic data from renal biopsy-proven early- and late-stage DN patients to screen potential drugs for DN. Therapeutic effects of candidate drug were assessed in Murine model of diabetic kidney disease (STZ-induced CD-1 mice), and HK-2 cells and immortalized bone marrow-derived macrophages (iBMDMs).Results: We identified CAY10603, a specific inhibitor of histone deacetylase 6 (HDAC6), as a potential drug that could significantly reverse the altered genes in the tubulointerstitial component. In DN patients and mice, upregulation of HDAC6 was mainly observed in renal tubular cells and infiltrated macrophages surrounding the diluted tubules. In both early- and late-onset diabetic mice, daily CAY10603 administration effectively alleviated renal dysfunction and reduced macrophage infiltration, tubular injury and tubulointerstitial fibrosis. Mechanistically, CAY10603 suppressed NLRP3 activation in both HK-2 cells and iBMDMs.Conclusion: CAY10603 exhibited therapeutic potential for DN by suppressing NLRP3 inflammasome activation in both tubular cells and macrophages.

Glutaredoxins (Grxs) are glutathione-dependent oxidoreductases that belong to the thioredoxin (Trx) superfamily and are an essential part of the redox system in living organisms. However, there is a serious lack of sequence information and functional validation associated with Grxs in crustaceans. In this study, a new Grx gene (PmGrx5) was identified and characterized in black tiger shrimp (Penaeus monodon). The full-length cDNA of PmGrx5 is 787 bp and consists of 114 bp 5′-UTR, 232 bp 3′-UTR, and 441 bp ORF, encoding a hypothetical protein of 146 amino acids. The putative PmGrx5 protein is 16.27 kDa with a theoretical isoelectric point of 5.90. Sequence alignment showed that PmGrx5 had the highest amino acid sequence homology with Grx5 from Penaeus vannamei at 98.63% and clustered with Grx5 from other crustaceans. Quantitative real-time PCR (qRT-PCR) analysis showed that PmGrx5 was expressed in all tissues examined, with a higher expression in the testis, stomach, lymphoid organ, and gill. PmGrx5 was continuously expressed during development, with the highest expression in zoea I. Ammonia-N stress and bacterial infection both differentially upregulated PmGrx5 expression in the hepatopancreas and gill. In addition, when PmGrx5 was inhibited, the expression of some other antioxidant enzymes was upregulated at the beginning of ammonia-N stress, but as the stress time increased, the expression of antioxidant enzymes was inhibited, the expression of apoptotic genes was increased, and the GSH content was significantly reduced. Inhibition of PmGrx5 led to a greater risk of oxidative damage in shrimp. In addition, the relationship between SNPs in exons of the PmGrx5 gene and tolerance to ammonia-N stress was identified and analysed. A total of nine SNPs were successfully identified, eight of which were significantly associated with ammonia and nitrogen stress tolerance trait in shrimp (P < 0.05). The present study shows that PmGrx5 is involved in redox regulation and plays an important role in shrimp resistance to marine environmental stresses. Meanwhile, this study will provide a basis for molecular marker breeding in shrimp.

This paper discusses the robust trajectory tracking control of an autonomous tractor-trailer in agricultural applications. Firstly, considering the model parameter uncertainties and various disturbances, the kinematic and dynamic models of the autonomous tractor-trailer system are established. Moreover, the coordinate transformation is adopted to convert the trajectory tracking error into a new unconstrained error state space model. On this basis, the prescribed performance control (PPC) technique is designed to ensure the convergence speed and final tracking control accuracy of the tractor-trailer control system. Then, this paper designs a double closed-loop control structure. The posture control level adopts the model predictive control (MPC) method, and the dynamic level adopts the sliding mode control (SMC) method. At the same time, it is worth mentioning that the nonlinear disturbance observer (NDO) is designed to estimate all kinds of system disturbances and compensate for the tracking control system to improve the system’s robustness. Finally, the proposed control strategy is validated through comparative simulations, demonstrating its effectiveness in achieving robust trajectory tracking of the autonomous tractor-trailer system.

The cell types and developmental trajectories of shrimp cells based on the transcriptional level have not been established, and gene expression profile and function at the single-cell level is unclear. We aimed to use scRNA-seq to construct a single-cell resolution transcriptional map of hepatopancreas and haemocytes in shrimp to analyse the molecular mechanisms of the immune response to ammonia nitrogen stress. In the present study, seven cell clusters were successfully identified in each of the two tissues (haemocytes, Hem1-7; hepatopancreas, Hep1-7) based on specifically-expressed marker genes. The developmental starting points of haemocytes and hepatopancreatic cells were Hem2 and Hep1, respectively. We propose that Hem2 has oligopotent potential as the initiation site for haemocyte development and that Hem4 and Hem5, located at the end of development, are the most mature immune cell types in haemocytes. Hep5 and Hep6 were the developing terminal cells of hepatopancreas. The antioxidant system and proPO system of shrimp were activated under ammonia nitrogen stress. A large number of DEGs were involved in oxidative stress, detoxification metabolism, and immune defence. In particular, important response genes such as AMPs, proPO, and GST were not only marker genes for identifying cell groups but also played an important role in shrimp cell differentiation and functional plasticity. By successfully applying 10× Genomics based scRNA-seq to the study of shrimp, the single-cell transcriptional profiles of hepatopancreatic cells and haemocytes of shrimp innate immune responses under ammonia stress were constructed for the first time. This atlas of invertebrate hepatopancreatic cells and haemocytes at single-cell resolution identifies molecular events that underpin shrimp innate immune system responses to stress.

The triple-dip La Niña in 2020–23 is characterized by persisting southeasterly wind anomalies over the tropical central and eastern Pacific. Our results show that the wind anomalies are associated with the anomalously negative phase of the first two leading modes of the annual cycle (antisymmetric and symmetric modes about the equator) of sea surface temperature (SST) in the tropical Pacific. The two modes account for 82.2% and 13.5% of the total variance, linking to the seasonal swing of SST between the northern and southern hemispheres and the temporal evolution of El Niño-Southern Oscillation, respectively. During 2020–23, the persistently and anomalously negative phase of the symmetric mode enhances easterly wind over the tropical central Pacific, while the antisymmetric mode strengthens the southeasterly wind over the tropical eastern Pacific. The anomalously negative phase of the antisymmetric mode is associated with the contrast of SST anomalies between the northern and southern hemispheres, which provided a favorable background for the triple-dip La Niña in 2020–23.

CircRNAs are essential in regulating follicle growth and development and the female reproductive system at multiple levels. However, the molecular mechanism by which circRNAs regulate reproduction in sheep is unclear and requires further exploration. In this study, RNA sequencing was performed to reveal the circRNA expression profiles in the ovaries of Cele black sheep and Hetian sheep during estrus. Analysis of the number of circRNAs in their host genes revealed that 5031 genes could produce 20,835 circRNAs. Among the differentially expressed circRNAs (DEcircRNA), 75 were upregulated, and 105 were downregulated. Functional enrichment analysis showed that the host genes of DEcircRNA were involved in several pathways, including the MAPK and Hippo signaling pathway. In addition, we constructed a subnetwork of competitive endogenous RNA (ceRNA) containing 4 mRNAs, 4 microRNAs (miRNAs), and 10 circRNAs, potentially related to follicle development. Functional circRNAs (e.g., novel_circ_0003851, novel_circ_0015526, novel_circ_0008117) were found to act as ceRNAs for follicle growth and development-related mRNAs (CUEDC1, KPNB1, ZFPM2) by sponging functional miRNAs (miR-29a, miR-29b, miR-17-5p). Finally, through an RNA pull-down assay, oar-miR-125b was selected and confirmed as the target miRNA of novel-circ-0041512. We analyzed the overall expression of circRNAs in sheep ovaries. Further, we explored the potential mechanisms underlying the circRNA functions, providing a theoretical basis for the genetic progress of reproductive traits in sheep.

Na+/H+-exchanger (NHE) assumes a significant part in different particle transport in creatures. A clone of Penaeus monodon NHE cDNA was examined in this study (PmNHE), and its impact on high-concentration ammonia nitrogen stress was researched. The 877-amino acid (aa) protein was encoded by a full-length PmNHE cDNA that was 2788 base pairs (bp) long and had a 2643-bp open reading frame (ORF). The findings show that PmNHE was expressed in all of the P. monodon organs that were tested, including the intestine, muscle, hemolymph, heart, hepatopancreas, stomach, epidermis, gill, testis, and ovary, and the intestine and muscle were found to have the highest levels of PmNHE expression. The expression of PmNHE in the gill tissue of P. monodon was significantly up-regulated under high levels of ammonia nitrogen stress. The expression of PmNHE in the intestine of P. monodon under high-concentration ammonia nitrogen stress was significant. When exposed to high concentrations of ammonia nitrogen stress, P. monodon exhibited shorter survival times than the two control groups. Hence, it is suggested in the present study that PmNHE may have a significant impact on the environment with high levels of ammonia nitrogen.

Conventional AlSi materials always have a coarse and discontinuous Si structure, which limits their application as thermal management materials. Fortunately, nature has evolved efficient strategies to form complex microstructures that exhibit excellent wear resistance and thermal properties; one such example is found in the red deer antler. Here, inspired by the antler structure, AlSi composites with a novel fenestrated network-particle structure (FN) and with a common isolated island structure (II) are designed and prepared. Subsequently, the dynamic formation of FN is tracked and studied using computational fluid dynamics (CFD) simulation. To investigate the reinforcement mechanisms of FN, the wear resistances and thermal properties of FN and II are compared and analyzed. Simulation and experimental results show that the reconstruction of a semi-continuous structure promotes the formation of a striated structure, whereas flowing Si particles provide some sites for the formation of the fenestrated structure. The dynamic formation of FN is strongly influenced by the convection–diffusion process and the flow path. Moreover, this biomimetic FN structure exhibits better wear resistance and thermal properties than II, owing to its strong structural support and high expansion resistance. This work is expected to provide new perspectives on the microstructural design of thermal management materials with good wear resistance.

As a highly conserved transcription factor family, DMRTs (Doublesex and Mab-3-related transcription factors) are involved in sex determination and sexual differentiation in numerous animals. In the present study, we identified a DM (Doublesex/Mab-3)-domain gene in Penaeus monodon, which we named PmDMRT11E because it shared many similarities with DMRT11E homologs and has a close relationship in the phylogeny of different species. The three-dimensional structure and amino acid alignments indicated the stability and conservation of the DM domain. Real-time PCR analysis revealed that PmDMRT11E was highly and preferentially expressed in the testis of sub-adult shrimp. During embryogenesis, the expression level of PmDMRT11E was higher at the nauplius than at other periods. PmDMRT11E dsRNA injection significantly decreased the transcription factor Sox9 and increased ovarian marker Foxl2 expression, implying its important regulatory role in the mechanism of male determination. Moreover, dsDMRT11E caused abnormal sperm development, indicating that PmDMRT11E may be closely related to gonadal development and spermatogenesis.

The present study used PFC numerical software to examine the mechanical properties and fracture propagation characteristics of the fractured rock mass under coupling of heavy rainfall infiltration and mining unloading. Based on the engineering background of the Dexing mine, the pore water pressure is set to 0, 0.5, 1.0, 1.5, and 2.0 mpa, the true triaxial lateral unloading rate is 0.3 mpa/level and 0.6 mpa/level, and the water content state of rock is dry, natural, and saturated. Then, the true triaxial compression numerical simulation test is carried out, and the results showed that with the increase of the water content, the rock compaction stage increases, the elastic stage shortens, and the yield stage becomes more obvious. The faster the unloading rate is, the greater the influence on the rock strain is. After unloading, the stress jump point appears and the strain increase rate becomes larger, the volume of the rock increases and occurs as large s in the unloading direction, and finally it leads to severe brittle failure of the rock. With the increase of rock pore water pressure, the compressive strength and the peak strain of the rock decrease, and the pore water pressure accelerates the process of rock failure.

The Candidate Phyla Radiation (CPR), as a newly discovered and difficult-to-culture bacterium, accounts for the majority of the bacterial domain, which may be related to various oral diseases, including dental caries. Restricted by laboratory culture conditions, there is limited knowledge about oral CPR. Advances in metagenomics provide a new way to study CPR through molecular biology. Here, we used metagenomic assembly and binning to reconstruct more and higher quality metagenome-assembled genomes (MAGs) of CPR from oral dental plaque. These MAGs represent novel CPR species, which differed from all known CPR organisms. Relative abundance of different CPR MAGs in the caries and caries-free group was estimated by mapping metagenomic reads to newly constructed MAGs. The relative abundance of two CPR MAGs was significantly increased in the caries group, indicating that there might be a relationship with caries activity. The detection of a large number of unclassified CPR MAGs in the dataset implies that the phylogenetic diversity of CPR is enormous. The results provide a reference value for exploring the ecological distribution and function of uncultured or difficult-to-culture microorganisms.

The East Asian monsoon (EAM) exhibits a robust annual cycle with significant interannual variability. Here, the authors find that the EAM annual cycle can be decomposed into the equinoctial and solstitial modes in the combined sea level pressure, 850-hPa low-level wind, and rainfall fields. The solstitial mode shows a zonal pressure contrast between the continental thermal low and the western Pacific subtropical high, reaching its peak in July and dominating the East Asian summer monsoon. The equinoctial mode shows an approximate zonal contrast between the low-level cyclone over the east of the Tibetan Plateau and the western Pacific anticyclone over the east of the Philippines. It prevails during the spring rainy season in South China and reaches its peak in April. The interannual variations of the lead–lag phase of the two modes may result in the negative correlation of rainfall anomalies in North China between spring and fall and in South China between winter and summer, which provides a potential basis for the across-seasonal prediction of rainfall. The warm phase of ENSO in winter could give rise to the reverse interseasonal rainfall anomalies in South China, while the SST anomaly in the Northwest Pacific Ocean may regulate the rainfall anomaly in North China.

As a distributed energy source, open-pit mine solar photothermal-photoelectric membrane distillation can convert solar energy into heat and electrical energy to provide power for a membrane distillation water purification system. In mine sewage treatment, the solar membrane distillation system has the advantages of high desalination rate, good water quality and low cost. However, this system has not been widely promoted and applied because of its high energy consumption and low membrane flux. Different operating parameters have a greater impact on the operating efficiency of the solar membrane distillation system. In this study, a natural cooling film distillation system was built, the response surface method was used to analyze it, and a multi-objective optimization algorithm was used to optimize the operating conditions and improve the energy efficiency of the system. In our experiment, the hot end feed temperature, hot end feed flow rate, cold end cooling water flow rate, and membrane area were used as variables, and the membrane flux, thermal efficiency, and energy consumption values were investigated as target values. We used a support vector machine (SVM) with improved fitting, and substituted the fitting prediction model into the response surface method for the relationship between the variable and the target value. Collaborative analysis was followed by substituting the model into a non-dominated sorting genetic algorithm-II (NSGA-II). After the optimization operation, the optimal working conditions were obtained to improve the operating efficiency of the solar membrane distillation system, which will enable open-pit mine prosumers to realize intelligent management of solar energy generation, storage and consumption simultaneously.

With the maturity of the Internet of Things, 5G communication, big data and artificial intelligence technologies, open-pit mine intelligent transportation systems based on unmanned vehicles has become a trend in smart mine construction. Traditional open-pit mine transportation systems rely on human power for command, which often causes vehicle delay and congestion. The operation of unmanned vehicles in an open pit mine relies on many sensors. Using big data from the sensors, we optimize vehicle paths and build an efficient intelligent transportation system. Based on large amounts of data, such as unmanned vehicle GPS data, vehicle equipment information, production plan data, etc., with the goal of reducing vehicle transportation costs, total unmanned vehicle delay time, and ore content fluctuation rate, a multi-objective intelligent scheduling model for open-pit mine unmanned vehicles was established, and it is aligned with actual open pit mine production. Next, we use artificial intelligence algorithms to solve the scheduling problem. To improve the convergence, distribution and diversity of the classical fast non-dominated sorting genetic algorithm (NSGA-II) to solve constrained high-dimensional multi-objective problems, we propose a decomposition-based constrained dominance principle genetic algorithm (DBCDP-NSGA-II), retaining feasible and non-feasible solutions in sparse areas, and compare it with four other commonly-used multi-objective optimization algorithms. Simulation analysis shows our algorithm provides the best overall performance results of the multi-objective models. Furthermore, we apply intelligent scheduling models and optimization algorithms to mining practice and obtain new truck operation routes and schedules, reducing truck operation costs by 18.2%, truck waiting time by 55.5%, and ore content fluctuation by 40.3%. For open-pit mine unmanned transportation, the approach provides a variety of optimized solutions for minimum transportation costs, minimum waiting time, minimum ore content fluctuation rate, and a balance of the three indicators. Through an artificial intelligence algorithm, this study realizes intelligent unmanned vehicle path planning and improves the operation efficiency of open-pit mine intelligent transportation systems.

Tubular cell senescence is a common biologic process and contributes to the progression of chronic kidney disease (CKD); however, the molecular mechanisms regulating tubular cell senescence are poorly understood. Here, we report that integrin β3 (ITGB3) expression was increased in tubular cells and positively correlated with fibrosis degree in CKD patients. ITGB3 overexpression could induce p53 pathway activation and the secretion of TGF-β, which, in turn, resulted in senescent and profibrotic phenotype change in cultured tubular cells. Moreover, according to the CMAP database, we identified isoliquiritigenin (ISL) as an agent to inhibit ITGB3. ISL treatment could suppress Itgb3 expression, attenuate cellular senescence, and prevent renal fibrosis in mice. These results reveal a crucial role for integrin signaling in cellular senescence, potentially identifying a new therapeutic direction for kidney fibrosis.

In China, mining blasting vibration has seriously threatened the safety and stability of high and steep rock slopes. In this paper, taking the east mining area of Jianshan Phosphorus Mine as the research background, combined with field survey, field blasting test, numerical simulation and theoretical analysis, we systematically studied the adjacent high-steep rock slope and the layered blasting technology of complex ore. Based on wide hole spacing blasting numerical simulation and field tests, the use of 8 × 4 m hole network parameters, oblique line hole-by-hole initiation method, detonator delay using 35 ms between holes, 65 ms between rows and 500 ms within the holes, the rock mass rate was reduced and the drilling workload was decreased. In addition, regression analysis was carried out on a large amount of vibration test data, and the attenuation law and propagation law of blasting vibration of adjacent high and steep slopes were predicted, which provided a reference for mine production blasting. By establishing a mathematical model of cumulative damage of rock mass blasting, it shows that the depth of impact of mining blasting on the slope of Jianshan open-pit was 0–3.6m, but the blasting did not cause overall damage to the adjacent high and steep slopes. In the future, this model can be used to predict rock damage caused by subsequent blasting.

ObjectivesCombination therapy with mycophenolate mofetil, tacrolimus and steroids are effective in achieving complete remission in lupus nephritis (LN). Combination therapy uniquely downregulated caspase-1 compared with monotherapies, which can cleave gasdermin D (GSDMD) and was recently identified as the pyroptosis executioner. We therefore investigated whether combination therapy enabled the suppression of caspase-1/GSDMD-mediated pyroptosis in LN.MethodsExpression and activation of GSDMD were detected in kidney specimens of the human and mouse with LN using immunohistochemical staining and immunoblotting. Primary podocytes isolated from MRL/lpr mice were incubated with LPS+ATP, and pretreated with monotherapy or combination therapy. Inhibition of caspase-1/GSDMD-induced pyroptosis by combination therapy were assessed in MRL/lpr mice and human specimens. Pyroptosis was examined using a FAM caspase-1 kit and flow cytometry. The correlation between pyroptosis in peripheral blood and the systemic lupus erythematosus disease activity index (SLEDAI) was analyzed.ResultsKidney tissue specimens from LN patients and mice exhibited greatly increased expression levels and cleavage of GSDMD. In cultured podocytes, combination treatment significantly suppressed the activation of NLRP3 and caspase-1 and reduced GSDMD N-terminal levels. Combination therapy repressed disease progression through inhibition of caspase-1/GSDMD-mediated pyroptosis in both humans and MRL/lpr mice. Caspase-1/PI positive cell numbers in peripheral blood were positively correlated with SLE-DAI. LN patients with complete remission and partial remission had remarkably reduced caspase-1/PI positive cell numbers compared to baseline. Ac-FLTD-CMK, a GSDMD-derived inhibitor, prevented the development of LN.ConclusionCombination therapy suppressed caspase-1/GSDMD-mediated pyroptosis in vitro and in vivo and reduced disease progression.

Mitogen-activated protein kinase kinase 4 (MKK4) is a component of the JNK signaling pathway and plays an important role in immunity and stress resistance. In this study, MKK4 cDNA was cloned, and its bacterial infection and low-salinity challenge responses were researched. The full-length PmMKK4 cDNA was 1582 bp long, with an 858-bp open reading frame (ORF) encoding a 285-amino acid (aa) protein. Results showed that PmMKK-4 was expressed in all examined tissues of P. monodon. The PmMKK4 expression level was found to be lowest in eyestalk ganglion and highest in muscle (approximately 41.25 times than in eyestalk ganglion). Following the infection of Staphylococcus aureus, PmMKK4 was up-regulated in both hepatopancreatic and gill tissues. However, after infection with Vibrio harveyi, PmMKK4 was down-regulated for a period of time in gill tissue, with fluctuating up- and down-regulation in hepatopancreas tissue. Furthermore, after infection with Vibrio anguillarum, gill tissue and hepatopancreas tissue showed a continuous downward trend. The PmMKK4 gene in the gill tissue and hepatopancreas tissue of P. monodon was activated after low-salinity stress. The expression change of PmMKK4 in gill tissue was more significant. The research showed that the PmMKK4 gene plays an important role in both innate immunities after pathogen infection and adaptation in a low-salt environment.

Tetrahydrobiopterin (BH4) is a vital coenzyme for several enzymes involved in diverse enzymatic reactions in animals, and BH4 deficiency can lead to metabolic and neurological disorders due to dysfunction in its metabolism. In the silkworm natural homozygous mutant leml, the key enzyme sepiapterin reductase (BmSPR) in the de novo synthesis pathway of BH4 is inactivated, resulting in severe deficiency of BH4 synthesis. However, it is not known why the leml larvae can survive to the second-instar stage and which pathways lead to their death when BH4 is deficient. Here, we quantified BH4 and found that the fertilized eggs contained large amounts of BH4 transferred from the mother to the offspring, maintaining its normal development in the embryo and the first instar. Subsequently, we investigated the multiple pathways in which BH4 is involved as a cofactor. The results showed that BH4 deficiency in silkworms blocked the melanin synthesis pathway, caused an insufficient degree of epidermal sclerosis, disordered tyrosine metabolism, and damaged mitochondria. On the other hand, BH4 deficiency led to the uncoupling of nitric oxide synthase (BmNOS), a reduced NO production, and a significantly reduced fat in fat body catalyzation by phospholipase A2, resulting in an impaired immune system. Meanwhile, the uncoupling of BmNOS increased the O2− content, damaged the DNA, and caused the apoptosis of the body cells. Taken together, BH4 is critical for the life and death of leml mutants. This study lays a foundation for the further exploration of lepidopteran insects and provides an important basis for the treatment of human BH4 deficiency-related diseases.

Doublesex (Dsx) is a polymorphic transcription factor of the DMRTs family, which is involved in male sex trait development and controls sexual dimorphism at different developmental stages in arthropods. However, the transcriptional regulation of the Dsx gene is largely unknown in decapods. In this study, we reported the cDNA sequence of PmDsx in Penaeus monodon, which encodes a 257 amino acid polypeptide. It shared many similarities with Dsx homologs and has a close relationship in the phylogeny of different species. We demonstrated that the expression of the male sex differentiation gene Dsx was predominantly expressed in the P. monodon testis, and that PmDsx dsRNA injection significantly decreased the expression of the insulin-like androgenic gland hormone (IAG) and male sex-determining gene while increasing the expression of the female sex-determining gene. We also identified a 5′-flanking region of PmIAG that had two potential cis-regulatory elements (CREs) for the PmDsx transcription. Further, the dual-luciferase reporter analysis and truncated mutagenesis revealed that PmDsx overexpression significantly promoted the transcriptional activity of the PmIAG promoter via a specific CRE. These results suggest that PmDsx is engaged in male reproductive development and positively regulates the transcription of the PmIAG by specifically binding upstream of the promoter of the PmIAG. It provides a theoretical basis for exploring the sexual regulation pathway and evolutionary dynamics of Dmrt family genes in P. monodon.

Glutaredoxin (Grx) is a glutathione-dependent oxidoreductase that is an important component of the redox system in organisms. However, there is a serious lack of sequence information and functional validation related to Grx in crustaceans. In this study, a novel Grx was identified in Penaeus monodon (PmGrx2). The full-length cDNA of PmGrx2 is 998 bp, with an open reading frame (ORF) of 441 bp, encoding 119 amino acids. Sequence alignment showed that PmGrx2 had the highest identity with Grx2 of Penaeus vannamei at 96.64% and clustered with Grx2 of other crustaceans. Quantitative real-time PCR (qRT-PCR) analysis showed that PmGrx2 was expressed in all examined tissues, with higher expression levels in the stomach and testis. PmGrx2 was continuously expressed during development and had the highest expression level in the zygote stage. Both ammonia-N stress and bacterial infection could differentially induce the expression of PmGrx2 in hepatopancreas and gills. When PmGrx2 was inhibited, the expression of antioxidant enzymes was suppressed, the degree of apoptosis increased, and the GSH content decreased with the prolongation of ammonia-N stress. Inhibition of PmGrx2 resulted in shrimp being exposed to a greater risk of oxidative damage. In addition, an SNP locus was screened on the exons of PmGrx2 that was significantly associated with an ammonia-N-stress-tolerance trait. This study suggests that PmGrx2 is involved in redox regulation and plays an important role in shrimps’ resistance to marine environmental stresses.

The traditional Marx generators based on avalanche BJTs usually use a DC voltage source to charge the storage capacitors, and many theoretical studies have proved that the existence of DC voltage source leads to low energy efficiency. This paper proposes a novel nanosecond Marx generator based on avalanche BJTs, which is charged by a series-resonant power supply. This power supply charges all capacitors with a constant average current and all BJTs avalanche breakdown stage by stage without any triggering signals. When the resistors are replaced by inductors, the efficiency can be further improved. The pulse repetition frequency can be adjusted by controlling the resonant average current. The output voltage can be increased by connecting more avalanche BJTs in series or increasing the number of stages of the Marx generators. The control method and the structure of the circuit are simple. Experimental results show that negative pulses with an adjustable frequency of 10–60 kHz, a pulse width of 8.45 ns, and an amplitude of 4 kV were obtained on a resistive load. The energy efficiency of the Marx generator was increased to 94%.

Mitogen-activated protein kinase kinase (MAPKK), a component of the MAPK signal transduction pathway, plays a crucial role in stress resistance and immunity. Herein, a MAPKK cDNA from Penaeus monodon (black tiger shrimp) was cloned (PmMAPKK), and its effect on bacterial infection and low-salinity stress was investigated. The full-length PmMAPKK cDNA was 3665 bp long, with a 1224-bp open reading frame (ORF), encoding a 408-amino acid (aa) protein. Results revealed that PmMAPKK was expressed in all examined tissues of P. monodon, including hepatopancreas, gills, and lymphoid organ. The PmMAPKK expression level was found to be highest in ovary (approximately 8.7-fold higher than in hepatopancreas), and lowest in testis (approximately 0.54 times that in hepatopancreas). In early developmental stages of P. monodon, PmMAPKK expression was highest during the zygote stage. From the zoea1 stage onward, a steady decrease in expression was registered. Meanwhile, in the bacterial infection experiment, the hepatopancreas was found to be more sensitive than gills after bacterial infection. Following infection with Staphylococcus aureus and Vibrio anguillarum, PmMAPKK expression was appeared significantly higher than that in the control group (P < 0.05). However, infection with Vibrio harveyi caused a significant decrease in the expression level compared to the control group (P