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Abstract Metformin has shown outstanding anti-inflammatory and osteogenic abilities. Mesenchymal stem cell-derived extracellular vesicles (EVs) reveal promising therapeutic potency by carrying various biomolecules. This study explored the effects of metformin on the therapeutic potential of EVs derived from human periodontal ligament stem cells (PDLSCs) for periodontitis. PDLSCs were cultured in osteogenic medium with or without metformin, and the supernatant was then collected separately to extract EVs and metformin-treated EVs (M-EVs). After identifying the characteristics, we evaluated the anti-inflammatory and osteogenic effects of EVs and M-EVs in vivo and in vitro. Osteogenic differentiation of PDLSCs was markedly enhanced after metformin treatment, and the effect was dramatically inhibited by GW4896, an inhibitor of EVs’ secretion. Metformin significantly increased EVs’ yields and improved their effects on cell proliferation, migration, and osteogenic differentiation. Moreover, metformin significantly enhanced the osteogenic ability of EVs on inflammatory PDLSCs. Animal experiments revealed that alveolar bone resorption was dramatically reduced in the EVs and M-EVs groups when compared to the periodontitis group, while the M-EVs group showed the lowest levels of alveolar bone loss. Metformin promoted the osteogenic differentiation of PDLSCs partly through EVs pathway and significantly enhanced the secretion of PDLSCs-EVs with superior pro-osteogenic and anti-inflammatory potential, thus improving EVs’ therapeutic potential on periodontitis.

Abstract Hormonal changes in pregnant and lactating women significantly affect bone metabolism and overall stress levels, positioning them as a unique group within the orthodontic population. Fluctuations in estrogen, progesterone, prolactin, and other hormones are closely linked to bone remodeling and the periodontal tissue’s response to inflammation caused by dental plaque. Hormones such as thyrotropin, leptin, and melatonin also play crucial roles in pregnancy and bone remodeling, with potential implications for orthodontic tooth movement. Additionally, adverse personal behaviors and changes in dietary habits worsen periodontal conditions and complicate periodontal maintenance during orthodontic treatment. Notably, applying orthodontic force during pregnancy and lactation may trigger stress responses in the endocrine system, altering hormone levels. However, these changes do not appear to adversely affect the mother or fetus. This review comprehensively examines the interaction between hormone levels and orthodontic tooth movement in pregnant and lactating women, offering insights to guide clinical practice.

Abstract To develop and validate a diagnostic prediction model based on blood parameters for predicting the pertussis in children. A retrospective study of 477 children with suspected pertussis at Zigong First People’s Hospital was performed between January 2020 and December 2021. The patients were randomly divided into training cohort and validation cohort. Stepwise regression and R software was performed to develop and validate the model. Stepwise regression analysis showed that white blood cell (WBC), hematocrit (HCT), lymphocyte (LYMPH), C-reactive protein (CRP) and platelet distribution width to mean platelet volume ratio (PDW-MPV-R) were found to be independent factors associated with pertussis. The model containing WBC, CRP and PDW-MPV-R had the best performance. The area under curve (ROC, 0.77 for the training cohort and 0.80 for the validation cohort) of the model indicated satisfactory discriminative ability. The sensitivity and specificity of the model were 72.1% and 72.6% in training cohort and 74% and 72.1%, respectively, in validation cohort. Based on the ROC analysis, calibration plots, and decision curve analysis, we concluded that the model exhibited excellent performance. A model based on blood parameters is sufficiently accurate to predict the probability of pertussis in children, and may provide some reference for clinical decisions.

Abstract Introduction ABP 938 is being developed as a biosimilar candidate to aflibercept reference product (RP), a biologic used for certain angiogenic eye disorders. This study was designed to provide a comparative analytical assessment of the structural and functional attributes of ABP 938 and aflibercept RP sourced from the United States (US) and the European Union (EU). Methods Structural and functional characterization studies were performed using state-of-the-art analytical techniques that were appropriate to assess relevant quality attributes and capable of detecting qualitative and quantitative differences in primary structure, higher-order structure and biophysical properties, product-related substances and impurities, general properties, and biological activities. Results ABP 938 had the same amino acid sequence and exhibited similar secondary and tertiary structures, and biological activity as aflibercept RP. There were minor differences in a small number of biochemical attributes which are not expected to impact clinical performance. In addition, aflibercept RP sourced from the US and EU were analytically similar. Conclusions ABP 938 was structurally and functionally similar to aflibercept RP. Since aflibercept RP sourced from the US and EU were analytically similar, this allows for the development of a scientific bridge such that a single-source RP can be used in nonclinical and clinical studies.

Abstract Objectives Calcifying nanoparticles (CNPs), referred to as nanobacteria (NB), are recognized to be associated with ectopic calcification. This study aims to isolate and culture CNPs from the dental plaque of patients with periodontal disease and investigate their possible role in unravelling the aetiology of periodontal disease. Material and Methods Supragingival and subgingival plaques were sampled from 30 periodontitis patients for CNPs isolation and culture. Alkaline phosphatase (ALP) content changes were tracked over time. Positive samples underwent thorough morphological identification via hematoxylin and eosin (HE) staining, Alizarin red S (ARS), and transmission electron microscopy (TEM). The chemical composition of CNPs analysis involved calcium (Ca) and phosphorus (P) content determination, Fourier transform infrared spectroscopy (FTIR), and X‐ray diffraction (XRD). Results The subgingival plaque dental group exhibited a higher CNPs isolation rate at 36.67% (11/30) compared to the supragingival dental plaque group at 66.67% (20/30). ALP activity varied among the positive, negative and control groups. Morphological observation characterized the CNPs as round, oval, and ellipsoid particles with Ca deposits. Chemical analysis revealed the Ca/P ratio was 0.6753. Hydroxyl, methyl, carbonate, phosphate, hydrogen phosphate, and dihydrogen phosphate were detected by FTIR; the main chemical components detected by XRD were hydroxyapatite and tricalcium phosphate. Conclusion CNPs were found in periodontitis‐related dental plaque and exhibited the potential to develop calcified structures resembling dental calculus. However, the potential involvement of ALP in CNPs formation requires deeper exploration, as does the precise nature of its role and the interrelation with periodontitis demand a further comprehensive investigation.

Abstract Objectives The objective of this systematic review and meta-analysis was to evaluate the effect of chewing gum on orthodontic pain and to determine the rate of bracket breakage associated with fixed orthodontic appliances. Methods This review and its reporting were performed according to the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Six electronic databases were searched up to March 16, 2023, to identify relevant studies that met the inclusion and exclusion criteria. Furthermore, grey literature resources were searched. The Cochrane Collaboration Risk of Bias tool 2 was used to assess the quality of the included studies. Meta-analysis was conducted using RevMan, and sensitivity analysis and publication bias analysis were performed using STATA software. GRADE tool was used to evaluate the certainty of evidence. Results Fifteen studies with 2116 participants were ultimately included in this review, and 14 studies were included in the meta-analysis. Compared with the blank group, chewing gum had a significant pain relieving effect at all times after fixation of the initial archwire (P ≤ 0.05). No significant difference was found between the chewing gum group and the analgesics group at any timepoints (P > 0.05). Only four studies evaluated the rate of bracket breakage and revealed that chewing gum did not increase the rate of bracket breakage. The sensitivity analysis showed that there was no significant difference in the pooled outcomes after the included studies were removed one at times, and Egger analysis revealed no significant publication bias in included studies (P > 0.05). Conclusions Chewing gum is a non-invasive, low-cost and convenient method that has a significant effect on relieving orthodontic pain and has no effect on the rate of bracket breakage. Therefore, chewing gum can be recommended as a suitable substitute for analgesics to reduce orthodontic pain.

Excessive reactive oxygen species (ROS) may lead to oxidative damage and metabolic disorder. The pathogenesis of human bowel inflammation is closely related to oxidative damage of intestinal epithelial cells caused by ROS. This study aimed to explore the high-value utilization of the byproducts of sea cucumber in antioxidant food for colitis prevention. The technology of protease hydrolysis combined with Cordyceps militaris fermentation was used to obtain fermented sea cucumber viscera protease hydrolysates (FSVHs). The results revealed that FSVH could enhance antioxidant capacity and alleviate oxidative damage and apoptosis by activating the Nrf2/HO-1 pathway and triggering the self-protection immune mechanisms. Moreover, the FSVH supplementation could upregulate antioxidant-related metabolic pathways of Caco-2 cells such as glutathione metabolism, confirming the enhanced antioxidant capacity of damaged cells. In summary, FSVH could exert protective effects on Caco-2 cells in response to oxidative damage, providing a promising prospect for sea cucumber resource utilization and colitis prevention.

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients.Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0–24 h).Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0–24 h nor normalized AUCss, 0–24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = −0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0–24 h (r = −0.414, p = 0.049). Patients with AUCss, 0–24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0–24 h < 50 mg·h/L or patients with AUCss, 0–24 h 50–100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose.Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023.

The ceramic CBN grinding wheels are widely used in the fields of forming and precision machining, and the research on them is of great significance in improving the machining quality and efficiency of workpieces. The research progress of ceramic CBN grinding wheels in recent years is summarized from various aspects, including CBN abrasive grains, modifier addition, preparation and grinding performances. Additionally, the future development prospects are also discussed. Regarding CBN abrasive grains, the synthesis of CBN single crystal is explored, and the surface treatment of CBN abrasive grains, as well as the treatment methods when adding a strong magnetic field, are introduced. Concerning modifier, the influences of adding pore forming agents, oxides, metal materials and nano-materials on the performances of ceramic CBN grinding wheels are discussed. In the preparation of ceramic CBN grinding wheels, the methods of forming and sintering are described. Moreover, the grinding applications of ceramic CBN grinding wheels on difficult-to-machine materials such as steel, nickel base alloy and titanium alloy are introduced, and the factors affecting the grinding performances of CBN grinding wheels are proposed.

Abstract Background Mutations in colony-stimulating factor 1 receptor (CSF1R) are known to cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), which has been recently demonstrated as a primary microgliopathy characterized by cognitive impairment. Although the molecular mechanism underlying CSF1R-mediated microgliopathy remains unclear, therapeutic strategies have generally targeted modulation of microglial function. In particular, the microglial inhibitor, minocycline, has been shown to attenuate learning and memory deficits in several neurodegenerative diseases. The objectives of this study were to investigate the pathogenic mechanisms underlying ALSP and to explore the therapeutic effects of minocycline in an in vivo model of ALSP. We hypothesized that inhibiting microglial activation via minocycline could reverse the behavior and pathological defects in ALSP model mice. Methods We generated a Csf1r haploinsufficiency mouse model of ALSP using CRISPR/Cas9 genome editing and conducted electrophysiological recordings of long-term potentiation (LTP) and behavioral tests to validate the recapitulation of clinical ALSP characteristics in 8- to 11-month-old mice. RNA-sequencing was used to explore enriched gene expression in the molecular pathogenesis of ALSP. Microglial activation was assessed by immunofluorescent detection of Iba1 and CD68 in brain sections of male ALSP mice and pro-inflammatory activation and phagocytosis were assessed in Csf1r +/− microglia. Therapeutic effects were assessed by behavioral tests, histological analysis, and morphological examination after four weeks of intraperitoneal injection with minocycline or vehicle control in Csf1r +/− mice and wild-type control littermates. Results We found that synaptic function was reduced in LTP recordings of neurons in the hippocampal CA1 region, while behavioral tests showed impaired spatial and cognitive memory specifically in male Csf1r +/− mice. Increased activation, pro-inflammatory cytokine production, and enhanced phagocytic capacity were also observed in Csf1r +/− microglia. Treatment with minocycline could suppress the activation of Csf1r +/− microglia both in vitro and in vivo. Notably, the behavioral and pathological deficits in Csf1r +/− mice were partially rescued by minocycline administration, potentially due to inhibition of microglial inflammation and phagocytosis in Csf1r +/− mice. Conclusions Our study shows that CSF1R deficiency results in aberrant microglial activation, characterized by a pro-inflammatory phenotype and enhanced phagocytosis of myelin. Our results also indicate that microglial inhibition by minocycline can ameliorate behavioral impairment and ALSP pathogenesis in CSF1R-deficient male mice, suggesting a potential therapeutic target for CSF1R-related leukoencephalopathy. Collectively, these data support that minocycline confers protective effects against CSF1R-related microgliopathy in male ALSP model mice.

Systemic lupus erythematosus (SLE) is a chronic recurrent autoimmune disease affecting almost all organs. This study was conducted to investigate cognitive impairment of SLE mice (MRL/lpr mice), and explore associated pathological mechanism. Behavior tests (open-field test, elevated plus-maze test, forced swimming test, sucrose preference test, and Morris water maze test) were conducted in MRL/MPJ and MRL/lpr mice. ELISA test was performed to determine levels of antibodies (anti-dsDNA, anti-RPA, anti-ACA, and anti-NR2a/b) and inflammatory factors [tumour necrosis factor a (TNF-a), interleukin (IL)-6, IL-8, and IL-10]. Micro-vascular endothelial cells (MVECs) were isolated, identified, and divided into MVECs (NC), anti-NR2a/2b, memantine, glycine, dexamethasone, and IL-1b groups. Cell proliferation was measured using cell counting kit-8 (CCK-8) assay, and Western blotting was applied to evaluate ELAM-1, VCAM-1, ICAM-1, IKBa, p-IKBa expression. MRL/lpr mice demonstrated lower locomotion/exploration ability, higher anxiety, obvious depression symptoms, lower learning/memory capability compared with MRL/MPJ mice. MRL/lpr mice demonstrated high levels of anti-NR2a/b antibody and auto-antibodies. NMDA receptor antagonist (memantine) significantly increased, and NMDA receptor agonist (glycine) significantly decreased MVECs proliferation compared with NC group ( p < 0.05). Memantine significantly reduced and glycine predominantly enhanced TNF-a, IL-6, IL-8, and IL-10 levels compared with NC group ( p < 0.05). NMDA receptor antagonist and agonist modulated adhesion molecules expression in MVECs. ELAM-1, VCAM-1, and ICAM-1 expressions were significantly down-modulated in memantine group, and remarkably up-modulated in glycine group compared with NC group ( p < 0.05). NMDA receptor antagonist and agonist regulated phosphorylation of p-IKBa. The above effects of memantine evenly equaled to dexamethasone, and glycine evenly equaled to IL-1b. In conclusion, cognitive impairment of MRL mice might be associated with NMDA receptor-mediated inflammatory response and production of adhesion molecules in MRL/lpr mice-derived MVECs.

Aquaculture provides essential food for humans, and the health of farmed species is particularly important for the aquaculture industry. Aquaculture environment could be a sink of plastic debris (PDs) due to the enclosed character and heavy use of plastics. Gut microbiota of aquaculture species could respond to the exogenous pollutants and regulate the health of hosts. Here, variations in gut microbiota of Apostichopus japonicus induced by the ingested nanoplastics (NPs) were investigated by a lab experiment. We selected a NPs concentration gradient of 100 mg/kg and 500 mg/kg to simulate microplastic pollution to A. japonicus, and the significant differences in gut microbiota composition after 21 days of NP exposure were evaluated. According to the high-throughput sequencing from time series samples, a decrease of diversity in gut microbiota of A. japonicus with dietary NPs was observed. In addition, the gut microbiota compositions of sea cucumbers with and without NPs exposure were also distinct, expressing as enrichment of Bacteroidota while reducement of Proteobacteria under NPs stresses. Combined the results of network analysis, the less complexity and stability of gut microbiota in sea cucumbers with dietary NPs were proved. Based on the neutral community model, the ingested NPs elevated the contribution of stochastic processes for the gut microbiota assembly in sea cucumbers. Our study showed that substantial variations in gut microbiota of A. japonicus under NPs stresses, and also explored the underlying mechanisms regulating these changes. This research would offer new meaningful insights into the toxicity of NPs on sea cucumbers, contributing a solid fundament to improve the health of sea cucumbers under NPs stresses.

Mechanical components often experience fatigue loading from various waveform conditions during their operational lifespan. However, the underlying mechanisms through which variations in loading waveform affect the fatigue life of components remain unclear. Thus, this study conducted tension–compression fatigue experiments on 34CrNi3MoVA steel specimens under the same stress amplitude with different waveforms (cosine, triangular, sawtooth, and reverse sawtooth) to investigate the effects of loading waveform variations on the cyclic strain hardening behaviors, the fatigue fracture failure, and the fatigue life. The results indicated that specimens under different waveforms all exhibited cyclic strain hardening. The fatigue cyclic hardening level progressively increased in the order of cosine, triangular, and sawtooth waveforms, resulting in a continuous increase in cyclic saturation strain amplitude. The analysis of fatigue fractures demonstrated a consistent increase in both the initiation and propagation zone areas in the order of cosine, triangular, and sawtooth waveforms, and the boundary between the propagation and final fracture zones gradually shifted from a straight to a curved shape. The influence mechanisms of cyclic loading waveforms on the fatigue life of specimens were analyzed based on the energy dissipation, leading to the development of a universal fatigue life prediction model applicable to different waveform conditions, the model was then verified with the reverse sawtooth wave specimens and resulted in a prediction error less than 15%. The study is expected to serve as a significant guide for predicting and evaluating the fatigue life of mechanical components under various fatigue loading conditions.

As the main components of mechanical products and important transmission components of mechanical motion, shaft workpieces (SW) need to undergo high-speed motion while also withstanding high torque motion, which has high processing requirements. At the same time, the processing quality of the workpieces determines the success of the entire processing process, and the quality-inspection methods and the accuracy of the technology directly affect the evaluation of the product. This paper designs an intelligent detection system for the surface shape error (SSE) of SW that combines multiple sensors. Based on the principle of sensor use and specific experimental status, the overall scheme of the detection system is designed, followed by research on the spatial positioning algorithm and surface measurement algorithm of the workpiece to be tested. We then compensate and correct the errors with the algorithm. The effectiveness of the system is verified by measuring the surface size of the workpiece. Finally, the radial circular runout error is taken as an example to verify the detection system. The results show that the measurement error is less than 5%, and the accuracy of the system is high.

Cancer immunotherapy, including the inhibition of immune checkpoints, improves the tumor immune microenvironment and is an effective tool for cancer therapy. More effective and alternative inhibitory targets are critical for successful immune checkpoint blockade therapy. The interaction of the immunomodulatory ligand B7 family with corresponding receptors induces or inhibits T cell responses by sending co-stimulatory and co-inhibitory signals respectively. Blocking the glycosylation of the B7 family members PD-L1, PD-L2, B7-H3, and B7-H4 inhibited the self-stability and receptor binding of these immune checkpoint proteins, leading to immunosuppression and rapid tumor progression. Therefore, regulation of glycosylation may be the “golden key” to relieve tumor immunosuppression. The exploration of a more precise glycosylation regulation mechanism and glycan structure of B7 family proteins is conducive to the discovery and clinical application of antibodies and small molecule inhibitors.

Ceramics with high MoAlB content were rapidly synthesized via thermal explosion by using Mo/Al/B mixed powders as the raw materials. The effects of raw material ratio and heating mode on the phase composition of the products were studied through DSC, X-ray polycrystalline diffractometer, and SEM. Results showed that ceramics with high MoAlB contents could be prepared from 1.1Mo/1.2Al/1.05B powders by using a tubular furnace at 800 °C for 1 min. They could also be obtained from 1.1Mo/1.1Al/1B powders through spark plasma sintering at 1000 °C without holding. Finally, the reaction mechanism of MoAlB material synthesis via thermal explosion was proposed on the basis of thermodynamics analysis.

Abstract Background We previously demonstrated that nasal administration of periodontitis gene vaccine (pVAX1-HA2-fimA) or pVAX1-HA2-fimA plus IL-15 as adjuvant provoked protective immunity in the periodontal tissue of SD rats. This study evaluated the immune effect of pVAX1-HA2-fimA plus CpG-ODN 1826 as an adjuvant in the SD rat periodontitis models to improve the efficacy of the previously used vaccine. Methods Periodontitis was induced in maxillary second molars in SD rats receiving a ligature and infected with Porphyromonas gingivalis. Forty-two SD rats were randomly assigned to six groups: A, control without P. gingivalis; B, P. gingivalis with saline; C, P. gingivalis with pVAX1; D, P. gingivalis with pVAX1-HA2-fimA; E, P. gingivalis with pVAX1-HA2-fimA/IL-15; F, P. gingivalis with pVAX1-HA2-fimA+CpG ODN 1826 (30 µg). The levels of FimA-specific and HA2-specific secretory IgA antibodies in the saliva of rats were measured by ELISA. The levels of COX-2 and RANKL were detected by immunohistochemical assay. Morphometric analysis was used to evaluate alveolar bone loss. Major organs were observed by HE staining. Results 30 μg could be the optimal immunization dose for CpG-ODN 1826 and the levels of SIgA antibody were consistently higher in the pVAX1-HA2-fimA+CpG-ODN 1826 (30 µg) group than in the other groups during weeks 1–8 (P

In this study, we investigated the formation of TiC nanosheets from carbon black and Ti3AlC2 mixtures in NaCl-KCl eutectic salt. The effects of raw material ratio, molten salt ratio, and heating temperature on TiC formation were studied in detail. Results show that carbon black may enhance the decomposition of amounts of Ti3AlC2 at 1,100°C by heat treatment without salt addition, while molten salt plays key roles in the total decomposition of Ti3AlC2 and the formation of TiC nanosheets at 1,000°C. Higher heating temperature and excess carbon black benefits the synthesis of high content TiC. The as-synthesized TiC nanosheets are approximately 15 nm thick and 80–220 nm long. We propose a possible reaction mechanism that governs TiC formation in molten salts and explain the observations based on kinetic considerations.

The interaction of non-kinase transmembrane glycoprotein CD44 with ligands including hyaluronic acid (HA) is closely related to the occurrence and development of tumors. Changes in CD44 glycosylation can regulate its binding to HA, Siglec-15, fibronectin, TM4SF5, PRG4, FGF2, collagen and podoplanin and activate or inhibit c-Src/STAT3/Twist1/Bmi1, PI3K/AKT/mTOR, ERK/NF-κB/NANOG and other signaling pathways, thereby having a profound impact on the tumor microenvironment and tumor cell fate. However, the glycosylation of CD44 is complex and largely unknown, and the current understanding of how CD44 glycosylation affects tumors is limited. These issues must be addressed before targeted CD44 glycosylation can be applied to treat human cancers.

ABSTRACT Apostichopus japonicus (sea cucumber) is one of the most valuable aquaculture species in China; however, different diseases can limit its economic development. Recently, a novel disease, body vesicular syndrome (BVS), was observed in A. japonicus aquaculture. Diseased animals displayed no obvious phenotypic characteristics; however, after boiling at the postharvest stage, blisters, lysis, and body ruptures appeared. In this study, a multiomics strategy incorporating analysis of the gut microbiota, the pond microbiome, and A. japonicus genotype was established to investigate BVS. Detailed analyses of differentially expressed proteins (DEPs) and metabolites suggested that changes in cell adhesion structures, caused by disordered fatty acid β-oxidation mediated by vitamin B5 deficiency, could be a putative BVS mechanism. Furthermore, intestinal dysbacteriosis due to microbiome variations in pond water was considered a potential reason for vitamin B5 deficiency. Our BVS index, based on biomarkers identified from the A. japonicus gut microbiota, was a useful tool for BVS diagnosis. Finally, vitamin B5 supplementation was successfully used to treat BVS, suggesting an association with BVS etiology. IMPORTANCE Body vesicular syndrome (BVS) is a novel disease in sea cucumber aquaculture. As no phenotypic features are visible, BVS is difficult to confirm during aquaculture and postharvest activities, until animals are boiled. Therefore, BVS could lead to severe economic losses compared with other diseases in sea cucumber aquaculture. In this study, for the first time, we systematically investigated BVS pathogenesis and proposed an effective treatment for the condition. Moreover, based on the gut microbiota, we established a noninvasive diagnostic method for BVS in sea cucumber.

BackgroundPancreatic cancer (PC) is a highly malignant tumor of the digestive system. The number of elderly patients with PC is increasing, and older age is related to a worse prognosis. Accurate prognostication is crucial in treatment decisions made for people diagnosed with PC. However, an accurate predictive model for the prognosis of these patients is still lacking. We aimed to construct nomograms for predicting the overall survival (OS) of elderly patients with PC.MethodsPatients with PC, older than 65 years old from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database, were selected and randomly divided into training cohort (n = 4,586) and validation cohort (n = 1,966). Data of patients in 2016–2018 (n = 1,761) were used for external validation. Univariable and forward stepwise multivariable Cox analysis was used to determine the independent prognostic factors. We used significant variables in the training set to construct nomograms predicting prognosis. The performance of the models was evaluated for their discrimination and calibration power based on the concordance index (C-index), calibration curve, and the decision curve analysis (DCA).ResultsAge, insurance, grade, surgery, radiation, chemotherapy, T, N, and American Joint Commission on Cancer were independent predictors for OS and thus were included in our nomogram. In the training cohort and validation cohort, the C-indices of our nomogram were 0.725 (95%CI: 0.715–0.735) and 0.711 (95%CI: 0.695–0.727), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves showed similar results. The calibration curves showed a high consensus between observations and predictions. In the external validation cohort, C-index (0.797, 95%CI: 0.778–0.816) and calibration curves also revealed high consistency between observations and predictions. The nomogram-related DCA curves showed better clinical utility compared to tumor-node-metastasis staging. In addition, we have developed an online prediction tool for OS.ConclusionsA web-based prediction model for OS in elderly patients with PC was constructed and validated, which may be useful for prognostic assessment, treatment strategy selection, and follow-up management of these patients.

The thermal stability of MoAlB powder was studied. The effects of vacuum, Ar protection, molten salt treatment, and additives (B and C) on its thermal stability were studied. Results showed that MoAlB powder would react with a small amount of O2 in the furnace under vacuum and low temperature to form MoB, Al3Mo, B2O3, and Al2O3. At higher temperature, MoAlB first decomposed into MoB and Al. Al was oxidized to Al2O3. The thermal stability of MoAlB powder was better under the protection of Ar. However, molten salt heat treatment and additives such as B and C could promote the decomposition of MoAlB

The serine protease inhibitor Kazal type (SPINK) family includes SPINK1-14 and is the largest branch in the serine protease inhibitor family. SPINKs play an important role in pancreatic physiology and disease, sperm maturation and capacitation, Nager syndrome, inflammation and the skin barrier. Evidence shows that the unregulated expression of SPINK1, 2, 4, 5, 6, 7, and 13 is closely related to human tumors. Different SPINKs exhibit various regulatory modes in different tumors and can be used as tumor prognostic markers. This article reviews the role of SPINK1, 2, 4, 5, 6, 7, and 13 in different human cancer processes and helps to identify new cancer treatment targets.

Leaching characteristics of filter materials of the improved subsurface drainage are very important for nitrogen and phosphorus loss. In this paper, the leaching characteristic of soil, sand, straw, and zeolite under different layouts were studied by HYDRUS-2D simulation based on calibration and validation according to laboratory data. Two scenarios were considered, including different soil and filter layouts, and mixed filter materials of straw and sand or zeolite. The results indicate that zeolite showed good adsorption characteristics of both ammonia nitrogen and phosphorus, while the straw’s adsorption characteristics were very different between ammonia nitrogen and phosphorus. Nitrogen and phosphorus concentrations of the outflow were mostly determined by the materials around the outlet. Compared with the cases of no lower soil, when the lower soil depth was 5 cm, the ammonia nitrogen concentrations under sand and straw decreased 54.5% and 96.3%, and the corresponding decreased phosphorus concentrations were 84.1% and 96.2%. In views of mixed filter with straw and the different layouts, that the ratio of straw and sand was 1:1, or the ratio of straw and zeolite was 2:1; at the same time, sand and zeolite should be set around the outlet, and may be better for ammonia nitrogen and total phosphorus concentrations reduction.

The risk assessment of water environments provides important references for water environment risk management. In this paper, the water environment risk of the upper rivers of the Baiyangdian Lake is assessed, considering both cumulative and sudden environmental risk. For the cumulative environmental risk assessment of the rivers, the characteristics of pollution transmissibility and accumulation in rivers was considered firstly. Furthermore, suggestions for the control of water environment pollution in the Baiyangdian Basin are given. The results indicate that the cumulative water environment risks of the Xiaoyi River—Dingzhou County, Xiaoyi River—Anguo County, Xiaoyi River—Boye County, and Xiaoyi River—Li County are high. The amount of fertilizer applied per unit of cultivated area, water quality, rate of water quality above the standard in water function zoning, and the ratio of environmental investment to gross domestic product (GDP) are important factors influencing the cumulative water environment risk. For sudden water environment assessments, the Xiaoyi River—Boye County is high. In the future, reducing the intensity of fertilizer application, strengthening the water quality control of the rivers, as well as upgrading the industry, should be carried out to protect the water environment in the Baiyangdian Basin.

Abstract Marine mammals are an important part of ocean ecosystems, of which, whales play a vital role in the marine food chain. In this study, the mucosa and contents from different intestinal tract segments (ITSs) of a stranded dwarf minke whale (Balaenoptera acutorostrata) were analyzed. The gut microbiota were sequenced using high‐throughput sequencing technology, based on a 16S rRNA approach. The microbial composition of the intestinal mucosa and its contents were similar in every single ITS. Large intestine microbiota richness and diversity were significantly higher when compared to the duodenum and jejunum. The dominant bacteria in the gut were Firmicutes and Actinobacteria; the former was enriched in the large intestine, whereas the latter was more abundant in the duodenum and jejunum. Our findings provide novel insights for microbiota in B. acutorostrata.

To prevent and control non-point source pollution, many policies have been carried out by government in China. However, the effectiveness of these policies has rarely been evaluated. In this study, the potential and spatial distribution of agricultural non-point source pollution in the Baiyangdian Basin are reported. This investigation considers multiple parameters under various policies with county as a basic unit. The results for the potential pollution from chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total nitrogen (TN) and total phosphorus (TP) are 60.89×104, 3.93×104, 87.05×104 and 15.10×104 Mg, with corresponding intensities of 190, 12, 272 and 47 kg ha-1 for the Baiyangdian Basin in 2016. The highest pollution from COD is attributed to livestock and poultry breeding, whereas TN and TP are dominantly produced by rural domestic sources, and NH3-N is mostly derived from planting. Spatially, distribution of the counties producing larger non-point source pollution presented a northeast to southwest direction, consistent with the Taihang mountain alignment in the basin. The counties with high pollution intensities are mostly in the south and east of the basin. Agricultural non-point source pollution control and prevention policies contributed in pollution reduction. Compared with 2016, the total potential pollution of COD, NH3-N, TN and TP in 2020 decrease by 45.1%, 14.7%, 37.9% and 37.4%, respectively, whereas for an assumed future time (F2), the decreases are 59%, 51.4%, 56.2% and 55.7%, respectively. Prevention measures should focus on reducing pollution from livestock and poultry breeding as well as planting.

Water shortage and soil salinization are the main issues threatening the sustainable development of agriculture and ecology in the Hetao Irrigation District (HID). The application of water-saving practices is required for sustainable agricultural development. However, further study is required to assess the effects of these practices on water and salt dynamics in the long term. In this study, the impacts of different water-saving practices on water and salt dynamics were investigated in the HID, Northwest China. The SAHYSMOD (integrated spatial agro-hydro-salinity model) was used to analyze the water and salt dynamics for different water-saving irrigation scenarios. The results indicate that the SAHYSMOD model shows a good performance after successful calibration (2007–2012) and validation (2013–2016). The soil salinity of cultivated land in the middle and upper reaches of the irrigation district decreased slightly, while that in the lower reaches increased significantly over the next 10 years under current irrigation and drainage conditions. It is predicted that if the amount of water diverted is reduced by up to 15%, the maximum water-saving volume could reach 650 million m3 yr–1. For the fixed reduction rate of total water diversion, the prioritized measure should be given to reduce the amount of field irrigation quota, and then to improve the water efficiency of the canal system. Although a certain amount of water can be saved through various measures, the effect of water saving in the irrigation district should be analyzed comprehensively, and the optimal water management scheme should be determined by considering the ecological water requirement in the HID.

The sea cucumber (Apostichopus japonicus) occupies a basal position during the evolution of deuterostomes and is also an important aquaculture species. In order to identify more immune effectors, transcriptome sequencing of A. japonicus coelomocytes in response to lipopolysaccharide (LPS) challenge was performed using the Illumina HiSeq™ 2000 platform. One hundred and seven differentially expressed genes were selected and divided into four functional categories including pathogen recognition (25 genes), reorganization of cytoskeleton (27 genes), inflammation (41 genes) and apoptosis (14 genes). They were analyzed to elucidate the mechanisms of host-pathogen interactions and downstream signaling transduction. Quantitative real-time polymerase chain reactions (qRT-PCRs) of 10 representative genes validated the accuracy and reliability of RNA sequencing results with the correlation coefficients from 0.88 to 0.98 and p-value

The Linnan Sag is one of the main oil-producing units in the Huimin Depression, Eastern China, and the pore pressure gradients obtained from drill stem tests (DSTs) range from 9.0 to 16.0 MPa/km. Uncertainty about the origin and distribution of abnormally high pressures in the Linnan Sag has led to different interpretations of hydrocarbon accumulation and resource assessments, and it interferes with safe drilling. In the Linnan Sag, mudstone compaction curves are substantially affected by several non-compaction factors, and the normal trend of the compaction curve is difficult to determine. The determination of the origin and distribution of overpressure in the Linnan Sag is a challenge. In this study, the factors that may affect mudstone compaction—such as the shale volume, higher calcareous, and organic matter content—were carefully examined and processed. The pressures in the mudstones were estimated by the corrected mudstone compaction curves, which were compiled from acoustic, density, and neutron logs, and calibrated using DST and mud weight data. The log response−vertical effective stress and acoustic velocity-density crossplots were used to identify the mechanisms that generate overpressure. The comprehensive compaction curve shows that the mudstones in the overpressured layer exhibit clear disequilibrium compaction characteristics. The logging response crossplots demonstrate that those overpressured points were consistent with the loading curve. The findings suggest that, the fundamental mechanism resulting in overpressures is the disequilibrium compaction of thick Paleocene mudstones. Hydrocarbon generation and vertical transfer of overpressure may be the main unloading mechanisms, which corresponds to the overpressure points that deviate from the loading curves. Since organic matter cracking may occur in formations at depths greater than 4000 m (Ro > 1.0%), the contribution of hydrocarbon generation to overpressuring is expected to be limited. The transfer of overpressure through opening faults is therefore considered to be the main cause of higher overpressure in local sandstones. The overpressures in the mudstones are characterized by a gradual decrease from the center to the margin in the Linnan Sag. The pressure in the isolated sand bodies are generally similar to that in the surrounding mudstones, whereas it can be lower or higher when the overpressure in the sand bodies are vertically transferred by faults to other pressure systems. The results of this analysis provide an indication of the magnitude, mechanism, and distribution of overpressure in the Linnan Sag. This insight can be used to guide further exploration of the Linnan Sag and similar geological basins.

Agricultural drainage plays an effective role in preventing waterlogging and salinity disasters and also is the main transport pathway for agricultural non-point source pollutants into rivers and lakes. Hence, the water quality of agricultural drainage should be a point of focus. In this paper, nitrogen and phosphorus loss under improved subsurface drainage with different filter materials (gravel, layered sand-gravel, mixed sand-gravel, straw) were studied by a three-year field experiment (2016−2018) compared with the conventional subsurface drainage. The pH values, total nitrogen, ammonia nitrogen, nitrate nitrogen, total phosphorus and soluble reactive phosphate were considered. The results showed that the nitrogen and phosphorus concentrations of drain outflow under improved subsurface drainage with gravel filter were larger than that with layered sand-gravel filter and mixed sand-gravel filter. The improved subsurface drainages with layered sand-gravel filter and mixed sand-gravel filter had an effect on reducing the ammonia nitrogen, total phosphorus and soluble reactive phosphate concentrations of the outflow. Meanwhile, the characteristics of nitrogen and phosphorus loss under the improved subsurface drainage with straw filter were different from that with layered sand-gravel filter and mixed sand-gravel filter. For the improved subsurface drainage with layered sand-gravel filter outflow, the ammonia nitrogen, total phosphorus, and soluble reactive phosphate concentrations were about 13%−78%, 38%−63%, 40%−68% less, and total nitrogen, nitrate nitrogen concentrations were 24%−80%,18%−96% more than that under conventional subsurface drainage. Meanwhile, for the improved subsurface drainage with straw filter outflow, compared with conventional subsurface drainage outflow, the percentage changes of the total nitrogen, nitrate nitrogen, ammonia nitrogen, total phosphorus and the soluble reactive phosphate concentrations were about −76%−62%, −77%−78%, −152%−−274%, −103%−−400% and −221%−−291%, respectively. Additionally, in the outflow of all subsurface drainage patterns, there were much higher total nitrogen and nitrate nitrogen concentrations which should be focused on and the agricultural water management should be adopted.

Objective. This study aimed to investigate the chemosensitive augmentation effect and mechanism of HDAC inhibitor Vorinostat (SAHA) in combination with arsenic trioxide (ATO) on proliferation and apoptosis of K562 cells.Methods. The CCK-8 assay was used to compare proliferation of the cells. Annexin-V and PI staining by flow cytometry and acridine orange/ethidium bromide stains were used to detect and quantify apoptosis. Western blot was used to detect expression of p21, Akt, pAkt, p210, Acetyl-Histone H3, and Acetyl-Histone H4 proteins.Results. SAHA and ATO inhibited proliferation of K562 cells in an additive and time- and dose-dependent manner. SAHA in combination with ATO showed significant apoptosis of K562 cells in comparison to the single drugs alone (p < 0.01). Both SAHA and ATO alone and in combination showed lower levels of p210 expression. SAHA and SAHA and ATO combined treatment showed increased levels of Acetyl-Histone H3 and Acetyl-Histone H4 protein expression. SAHA alone showed increased expression of p21, while ATO alone and in combination with SAHA showed no significant change. SAHA and ATO combined therapy showed lower levels of Akt and pAkt protein expression than SAHA or ATO alone.Conclusion. SAHA and ATO combined treatment inhibited proliferation, induced apoptosis, and showed a chemosensitive augmentation effect on K562 cells. The mechanism might be associated with increasing histone acetylation levels as well as regulating the Akt signaling pathway.

Sea urchins have long been used as research model organisms for developmental biology and evolutionary studies. Some of them are also important aquaculture species in East Asia. In this work, we report the construction of RAD-tag based high-density genetic maps by genotyping F1 interspecific hybrids derived from a crossing between a female sea urchin Strongylocentrotus nudus and a male Strongylocentrotus intermedius. With polymorphisms present in these two wild individuals, we constructed a female meiotic map containing 3,080 markers for S. nudus, and a male meiotic map for S. intermedius which contains 1,577 markers. Using the linkage maps, we were able to anchor a total of 1,591 scaffolds (495.9 Mb) accounting for 60.8% of the genome assembly of Strongylocentrotus purpuratus. A genome-wide scan resulted in the identification of one putative QTL for body size which spanned from 25.3 cM to 30.3 cM. This study showed the efficiency of RAD-Seq based high-density genetic map construction using F1 progenies for species with no prior genomic information. The genetic maps are essential for QTL mapping and are useful as framework to order and orientate contiguous scaffolds from sea urchin genome assembly. The integration of the genetic map with genome assembly would provide an unprecedented opportunity to conduct QTL analysis, comparative genomics, and population genetics studies.

Mitogen-activated protein kinase (MAPK) cascades have important functions in plant growth, development, and response to various stresses. The MAPKK and MAPKKK gene families in tomato have never been systematically analyzed. In this study, we performed a genome-wide analysis of the MAPKK and MAPKKK gene families in tomato and identified 5 MAPKK genes and 89 MAPKKK genes. Phylogenetic analyses of the MAPKK and MAPKKK gene families showed that all the MAPKK genes formed four groups (groups A, B, C, and D), whereas all the MAPKKK genes were classified into three subfamilies, namely, MEKK, RAF, and ZIK. Evolutionary analysis showed that whole genome or chromosomal segment duplications were the main factors responsible for the expansion of the MAPKK and MAPKKK gene families in tomato. Quantitative real-time RT-PCR analysis showed that the majority of MAPKK and MAPKKK genes were expressed in all tested organs with considerable differences in transcript levels indicating that they might be constitutively expressed. However, the expression level of most of these genes changed significantly under heat, cold, drought, salt, and Pseudomonas syringae treatment. Furthermore, their expression levels exhibited significant changes in response to salicylic acid and indole-3-acetic acid treatment, implying that these genes might have important roles in the plant hormone network. Our comparative analysis of the MAPKK and MAPKKK families would improve our understanding of the evolution and functional characterization of MAPK cascades in tomato.

We consider the 3D fluid system with the linear Soret effect. We obtain a logarithmically improved regularity criterion in the BMO space.