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Replant diseases (RDs), intraspecific negative plant–soil feedback, often stem from nutrient deficiency, allelopathy, or pathogen accumulation. However, the RDs of certain crops are long-lasting and their causes remain unknown. We examined Panax quinquefolius RD in a space-for-time soil sequence representing crop rotation restoration over 1, 10, and 20 years using multiomics and bioassays. Compared with the soils with no ginseng cultivation history, we found 110 significant potential factors related to RD, surprisingly, 53 of which remained unrestored after 20 years. Soil pH and the levels of organic nutrients (amino acids, carbohydrates, and alditols), allelopathic-promoting metabolites (phenolic acids, amines, pyridines, etc.), and beneficial bacteria (Sphingomonas, Burkholderia-Caballeronia-Paraburkholderia, and Terrabacter) and fungi (Acremonium, Penicillium, and Naganishia) decreased, while the levels of allelochemicals (pyruvic and fatty acids) increased. The expression of all metabolic pathways was significantly down-regulated, with the exception of the up-regulated fatty acid-related metabolic pathways. We confirmed that decreased organic nutrient levels and increased levels of allelochemicals impaired P. quinquefolius growth. Soil metabolic factors rather than microbial factors were dominant by network analysis. In conclusion, we found that the overall changes in nutrient levels and metabolic and microbial factors contributed to short-term RD (1–10 year) persistence, whereas long-term RD (after 20 years) primarily resulted from disordered soil metabolite levels and pathways. This research will help deepen our understanding of the relationship between RD and potential changes in the factors influencing RD that are caused by soil legacy effects of valuable plants and provide theoretical guidance for effective soil quality improvement.

Polyepoxysuccinic acid (PESA) was modified by glycidyl (Gly) to obtain a phosphate-free and nitrogen-free polymer (Gly-PESA), and its scale and corrosion inhibition properties were studied.The effects of Gly-PESA concentration, calcium ion concentration and temperature to scale inhibition performance were studied by static scale inhibition method. The corrosion inhibition performance of Gly-PESA was studied by static weight-loss method. The morphology and structure of calcium scale and steel surface were characterized by spectroscopic and microscopic methods. The scale inhibition efficiency of Gly-PESA for CaCO3 and CaSO4 was 98.06% and 92.6%, respectively. Under the same experimental conditions, the scale inhibition effect of Gly-PESA was obviously better than that of PESA. Gly-PESA could effectively inhibit the growth of CaCO3 and CaSO4 crystals and cause their crystal lattice distortion or crystal dispersion. The corrosion inhibition efficiency of Gly-PESA for carbon steel was 78.17%. The adsorption of Gly-PESA on the surface of the steel test piece followed Langmuir adsorption isotherm, and formed a protective film, which increased the corrosion resistance of the steel test piece, thus effectively protecting the steel test piece. Therefore, Gly-PESA was a green scale and corrosion inhibitor, which solved the problem of environmental pollution.

Subsurface drip irrigation in arid areas has the potential to replace traditional mulched drip irrigation to achieve green and sustainable cotton production. However, the suitable irrigation amount and frequency are still unclear, which seriously limits the ability of this model to improve water productivity and water-saving potential. Therefore, a field experiment was carried out from 2021 to 2023; a split plot experimental design was adopted with two irrigation amounts (W1, 3177 m3 ha−1; W2, 3840 m3 ha−1) and three irrigation frequencies (F1, 9; F2, 8; F3, 7). The effects of different irrigation strategies on the soil microenvironment, moisture content, biomass, and water use efficiency (WUE) of cotton organs were evaluated. The W2 treatment improved the soil moisture content, increased the soil temperature gradient, and reduced the soil conductivity, thereby increasing the moisture content and biomass of various organs. Moreover, compared with the F1 treatment, the F2 and F3 treatments were more likely to increase the soil moisture content, soil temperature gradient, WUEStem, WUELeaf and WUEBoll. In addition, the water consumption of the F2 and F3 treatments decreased by 3.9 % and 0.9 %, respectively, compared with that of the F1 treatment. These findings indicate that W2F2 can reduce water consumption while increasing boll biomass and WUEBoll. Further analysis revealed that under W2F2, WUEBoll was positively correlated with soil temperature gradient and soil conductivity and negatively correlated with leaf moisture content (LMC) and water consumption. In summary, with an irrigation amount of 3840 m3 ha−1, delaying the initial irrigation event and increasing the irrigation quota (8 irrigation events) improve the water environment in cotton fields, reducing soil temperature fluctuations and surface salt accumulation and synergistically increasing the boll biomass of cotton organs and WUEBoll. This irrigation strategy represents an effective cotton cultivation method to maximize cotton yield and improve resource utilization efficiency.

Colorectal cancer (CRC) is one of the most common malignant cancers. Emodin is a lipophilic anthraquinone commonly found in medicinal herbs and known for its antitumor properties. However, its clinical utility has been hampered by low druggability. We designed and synthesized a new compound named Emodin succinimidyl ethyl ester (ESEE), which improves the bioavailability and preserves the original pharmacological effects of Emodin. In vitro, we have confirmed that ESEE induces apoptosis in colon cancer cells, suppresses cell proliferation, migration, and invasion, and inhibits the growth of subcutaneous transplantation tumors associated with colon cancer. And, in vivo, ESEE robustly inhibited tumor growth. Human Ether-a-go-go Related Gene (hERG) is aberrantly expressed in various cancer cells, where they play an important role in cancer progression. Focal adhesion kinase (FAK) is a tyrosine kinase overexpressed in cancer cells and plays an important role in the progression of tumors to a malignant phenotype. Mechanistically, the anti-CRC properties of ESEE are exerted through direct binding with hERG, which impedes the FAK/PI3K/AKT signaling axis-dependent apoptotic cascade.

Soil bacteria are important participants in biogeochemical cycles, and the stability of their community structure is not only affected by fluctuations in time and environment, but also by the participation and regulation of anthropogenic interference. With the increasing reclamation of farmland in the agropastoral transitional zone of northern China, it is imperative to understand the characteristics of soil bacterial communities in response to seasonal variations and anthropogenic reclamation. In this study, desert grassland, artificial shrubland, and desert grassland reclaimed farmland on the western side of the Mu Us Sandy Land were used as research objects. The following main results were obtained through soil sampling in April and September, and physicochemical analyses combined with 16S high-throughput sequencing: seasonal variations increased soil pH and soil water content, whereas land reclamation significantly increased soil total carbon, total phosphorus, soil available phosphorus, and soil available potassium contents. Changes in soil physicochemical properties altered the structure of soil bacterial communities to varying degrees, with Actinobacteriota and Acidobacteriota being the differential phyla among the three sampling sites under seasonal variations (p

A 91-year-old Chinese male was hospitalized on June 28, 2021, due to a sudden fever. The patient had a long history of smoking, a 10-year history of type 2 diabetes, a family history of hypertension, and a history of coronary heart disease and lower extremity arterial occlusive disease. He presented with cough, sputum, and dry and wet rales in both lungs. A computed tomography scan revealed multiple infectious lesions in both lungs and a small pleural effusion. His procalcitonin level was 1.75 ng/mL. Microscopic examination of the sputum revealed abundant fungal spores and hyphae. Sputum culture results revealed Aspergillus quadrilineatus, which was confirmed by matrix-assisted laser desorption/ionization time-of-flight and internal transcribed spacer gene sequencing. Fungal drug sensitivity testing revealed that azoles (excluding fluconazole) and echinocandins exhibited high activity against Aspergillus quadrilineatus. The patient's condition improved following intravenous voriconazole treatment for 2 weeks, after which he was discharged. Subsequently, the patient was hospitalized six times for pulmonary infections, with the most recent hospitalization being on March 8, 2024. The symptoms improved, and the patient was discharged on March 15, 2024.

Summary: The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for β-glucan-induced trained immunity in macrophages and ensuing antitumor activity. Unexpectedly, the shunt pathway, but not the classical cholesterol synthesis pathway, catalyzed by SQLE, is required for trained immunity induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), the shunt pathway metabolite, activates liver X receptor and increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein for metabolic switching into glycolysis. Hence, our findings identify 24(S),25-EC as a key metabolite for trained immunity and provide important insights into how SQLE regulates trained-immunity-mediated antitumor activity.

Summary: Individuals within the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD) often experience disruptive mental behaviors and sleep-wake disturbances. The hallmark of ALS/FTD is the pathological involvement of TAR DNA-binding protein 43 (TDP-43). Understanding the role of TDP-43 in the circadian clock holds promise for addressing these behavioral abnormalities. In this study, we unveil TDP-43 as a pivotal regulator of the circadian clock. TDP-43 knockdown induces intracellular arrhythmicity, disrupts transcriptional activation regulation, and diminishes clock genes expression. Moreover, our experiments in adult mouse reveal that TDP-43 knockdown, specifically within the suprachiasmatic nucleus (SCN), induces locomotor arrhythmia, arrhythmic c-Fos expression, and depression-like behavior. This observation offers valuable insights into the substantial impact of TDP-43 on the behavioral aberrations associated with ALS/FTD. In summary, our study illuminates the significance of TDP-43 in circadian regulation, shedding light on the circadian regulatory mechanisms that may elucidate the pathological underpinnings of ALS/FTD.

Background: Kidney renal clear cell carcinoma (KIRC), with low survival rate, is the most frequent subtype of renal cell carcinoma. Recently, more and more studies indicate that cuproptosis-related genes (CRGs) and long non-coding RNAs (lncRNAs) play a vital role in the occurrence and development of many types of cancers. However, the roles of cuproptosis-related lncRNAs (CRlncRNAs) in the KIRC was uncertain. Results: In our study, CRlncRNAs were obtained by coexpression between differentially expressed and prognostic CRGs and differentially expressed and prognostic lncRNAs, and an 8-CRlncRNAs (AC007743.1, AC022915.1, AP005136.4, APCDD1L-DT, HAGLR, LINC02027, MANCR and SMARCA5-AS1) risk model was established according to least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. This risk model could differentiate immune cell infiltration, immune function and gene mutation. Conclusions: This 8-CRlncRNAs risk model may be promising for the clinical prediction of prognoses, tumor immune, immunotherapy response and chemotherapeutic response in KIRC patients.

In order to address the complexity of fracture damage behavior in metallic materials during service, the thermography technique was used to analyze the temperature evolution behavior of Q460 steel during cyclic deformation. The microscopic organization and microstructural mechanical properties of the crack tip (CT) region of the specimen were also examined to study the fatigue damage mechanism and crack propagation mechanism of Q460 steel from the perspectives of microstructure and energy evolution. The results showed that under the action of fatigue load, dislocation formation and motion occurred in the specimen, accompanied by energy release, which led to a change in surface temperature. The temperature of the fatigue failure area rapidly increased, leading to the formation of a large number of low-angle grain boundaries (LAGB). The nano-indentation results effectively studied the mechanical properties of the stress field area at the CT and revealed that the fatigue crack propagation process of Q460 steel is a result of the synergistic effect between the variation of grain orientation the crack region and the aggregation of a large number of micro-defects in the work-hardened zone. Based on the fatigue heat generation mechanism and entropy evolution mechanism, the study comprehensively analyzed consistency and differences in the damage mechanisms of Q460 steel under tensile load and fatigue load, employing temperature as a bridge. The research results ensure the safety and reliability of Q460 steel during its operation and provide new insights into the study of fatigue fracture behavior in metallic materials.

Bevacizumab is widely used in the treatment of colorectal cancer, liver cancer, and other advanced solid tumors because of its multiple targets, no genetic testing and better safety. Globally, the use of bevacizumab in the clinic has been climbing year by year based on several large-scale, multicenter prospective studies. While bevacizumab undeniably has a good clinical safety profile, it has also been associated with adverse effects such as drug-related hypertension and anaphylaxis. In our recent clinical work, we met a female patient with acute aortic coarctation previously treated with multiple cycles of bevacizumab, who was admitted with sudden onset of back pain. Because the patient had just had an enhanced CT of the chest and abdomen a month earlier, no abnormal lesions apparently associated with low back pain were found. So when the patient was seen on this occasion, our clinical diagnosis was first considered to be neuropathic pain, but a further multiphase enhancement CT was done again for further exclusion and the final diagnosis was acute aortic dissection. The patient later died within 1 hour after the chest pain had worsened again while waiting for a surgical blood supply within 72 hours of presentation. The risk of fatal acute aortic dissection is not sufficiently emphasized in the revised instructions for bevacizumab, although the adverse effects associated with aortic dissection and aneurysm are mentioned. Our report is of high practical value in raising clinicians’ vigilance and safe management of patients using bevacizumab worldwide.

Elaborating on the fate tendency of thifluzamide (thiazole-amide fungicide) in buckwheat based on nationwide application is vital for grain security and human health based on nationwide application. A rapid and sensitive analytical method was developed to trace thifluzamide in buckwheat matrices using an ultrahigh-performance liquid chromatography-tandem triple quadrupole mass spectrometer (UHPLC-MS/MS), with a retention time of 2.90 min and limit of quantitation (LOQ) of 0.001 mg/kg. Thifluzamide could be stably stored for 84 d in buckwheat matrices under –20 °C under dark condition. The occurrence, dissipation and terminal magnitudes of thifluzamide were reflected by the primary deposition of 0.02–0.55 mg/kg, half-lives of 12–14 d, and highest residues of 0.41 mg/kg. The long-term risks (ADI%) of thifluzamide were 37.268 %–131.658 % in registered crops, and the risks for the rural population were significantly higher than those of the urban population. The unacceptable dietary risks of thifluzamide should be continuously emphasized for children aged 2–7 with an ADI% values of 100.750 %–131.658 %. A probabilistic model was further introduced to evaluate the risk discrepancy of thifluzamide in buckwheat, showing the risks in Tartary buckwheat (Fagopyrum tararicum Gaerth) were 1.5–75.4 times than that in sweet buckwheat (Fagopyrum esculentum Moench). Despite the low risks for dietary buckwheat, the high-potential health hazards of thifluzamide should be pay more attention given the increasing applications and cumulative effects.

Focal segmental glomerulosclerosis 7 (FSGS7, # 616002) is a condition marked by significant proteinuria with or without features of nephrotic syndrome. Heterozygous mutations in the PAX2 gene on chromosome 10q24 can cause FSGS7. Here, we generated an induced pluripotent stem cell line SDQLCHi062-A from a thirteen -years-old boy with FSGS7 caused by heterozygous mutation (c.226 G>A, p.G76S) in the PAX2 gene (OMIM * 167409). The established iPSC line was validated by pluripotency markers expression, original gene mutation and demonstrated trilineage differentiation potential in vitro.

Triple negative breast cancer (TNBC) presents a formidable challenge due to the lack of effective treatment modalities. Immunotherapy stands as a promising therapeutic approach; however, the emergence of drug resistance mechanisms within tumor cells, particularly those targeting apoptosis and pyroptosis, has hampered its clinical efficacy. SHP2 is intricately involved in diverse physiological processes, including immune cell proliferation, infiltration, and tumor progression. Nevertheless, the precise contribution of SHP2 to tumor cell pyroptosis resistance remains inadequately understood. Herein, we demonstrate that SHP2 inhibition hampers the proliferative, migratory, and invasive capabilities of TNBC, accompanied by noticeable alterations in cellular membrane architecture. Mechanistically, we provide evidence that SHP2 depletion triggers the activation of Caspase-1 and GSDMD, resulting in GSDMD-dependent release of LDH, IL-1β, and IL-18. Furthermore, computational analyses and co-localization investigations substantiate the hypothesis that SHP2 may hinder pyroptosis through direct binding to JNK, thereby impeding JNK phosphorylation. Our cellular experiments further corroborate these findings by demonstrating that JNK inhibition rescues pyroptosis induced by SHP2 knockdown. Strikingly, in vivo experiments validate the suppressive impact of SHP2 knockdown on tumor progression via enhanced JNK phosphorylation. Additionally, SHP2 knockdown augments tumor sensitivity to anti-PD-1 therapy, thus reinforcing the pro-pyroptotic effects and inhibiting tumor growth. In summary, our findings elucidate the mechanism by which SHP2 governs TNBC pyroptosis, underscoring the potential of SHP2 inhibition to suppress cell pyroptosis resistance and its utility as an adjunctive agent for tumor immunotherapy.

A human induced pluripotent stem cell (iPSC) line (SDASi001-A) was generated from patient with Schimke immune-osseous dysplasia (SIOD), carrying heterozygous mutations in SMARCAL1 gene. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating delivery of OCT4, SOX2, KFL4, BCL-XL and c-MYC. The iPSC line expresses pluripotency markers, displays a normal karyotype, and has the ability to differentiate into cells of three germ layers in vitro. This iPSC line represents a valuable cell model for SIOD in humans.

Bactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.

Chemical topping with 1,1-dimethylpiperidinium chloride (DPC) has been considered a promising measure to inhibit apical dominance in cotton (Gossypium hirsutum L.). However, knowledge of the plant growth and canopy development of cotton under chemical topping with DPC remains limited, and the effect of this practice on lint yield and defoliation is unclear. A two-year (2019–2020) field experiment was conducted with two varieties, Xinluzao 60 (L60, DPC-insensitive) and Jinken1402 (JK1402, DPC-sensitive), and four topping methods, manual topping (MT), no topping (NT), DPC+ (fortified DPC) and DPC. We found that the lint yields of L60 and JK1402 treated with DPC were equivalent to those of L60 and JK1402 treated with DPC+ but were enhanced by 0.9–4.7% in L60 and 6.7–11.8% in JK1402 relative to those under MT and NT, with no significant difference in fiber quality. This was mainly due to the change in plant growth and canopy structure. In particular, compared with MT, application of DPC shortened the upper branches and extended the duration of the leaf area index peak. Moreover, in the late reproductive period, DPC application increased the number of upper leaves and reduced diffuse noninterceptance. Notably, the light transmittance rate (LLR) of JK1402 treated with DPC was higher than that of MT in the middle and lower parts of the canopy. Furthermore, there was positive correlation between LLR and defoliation rate. Therefore, chemical topping with DPC provided an effective alternative for manual topping.

Synthetic mRNAs are rising rapidly as alternative therapeutic agents for delivery of proteins. However, the practical use of synthetic mRNAs has been restricted by their low cellular stability as well as poor protein production efficiency. The key roles of poly(A) tail on mRNA biology inspire us to explore the optimization of tail sequence to overcome the aforementioned limitations. Here, the systematic substitution of non-A nucleotides in the tails revealed that cytidine-containing tails can substantially enhance the protein production rate and duration of synthetic mRNAs both in vitro and in vivo. Such C-containing tails shield synthetic mRNAs from deadenylase CCR4-NOT transcription complex, as the catalytic CNOT proteins, especially CNOT6L and CNOT7, have lower efficiency in trimming of cytidine. Consistently, these enhancement effects of C-containing tails were observed on all synthetic mRNAs tested and were independent of transfection reagents and cell types. As the C-containing tails can be used along with other mRNA enhancement technologies to synergically boost protein production, we believe that these tails can be broadly used on synthetic mRNAs to directly promote their clinical applications.

Perfluorooctanoic acid (PFOA), a typical perfluoroalkyl group compound, has received worldwide attention due to its significant environmental toxicity. Following regulatory bans on the production and emission of PFOA, concerns have been raised about the potential health risks and the safety of novel perfluoroalkyl analogues. HFPO-DA (trade name Gen-X) and HFPO-TA are two perfluoroalkyl analogues known to be bioaccumulative, whose level of toxicity and whether they are safe alternatives to PFOA remain unclear. In the following study, the physiological and metabolic effects of exposure to PFOA and its novel analogues were explored in zebrafish using 1/3 LC50 (PFOA 100 μM, Gen-X 200 μM, HFPO-TA 30 μM). At the same LC50 toxicological effect, exposure to PFOA and HFPO-TA resulted in abnormal phenotypes such as spinal curvature, pericardial edema and aberrant body length, while Gen-X was little changed. Metabolically, PFOA, HFPO-TA and Gen-X all significantly increased total cholesterol in exposed zebrafish with PFOA and HFPO-TA also increasing total triglyceride levels. Transcriptome analysis showed that the number of differentially expressed genes in PFOA, Gen-X, and HFPO-TA treated conditions compared to control groups were 527, 572, and 3, 933, respectively. KEGG and GO analysis of differentially expressed genes revealed pathways and functions related to lipid metabolism as well as significant activation of the peroxisome proliferators-activated receptor (PPARs) pathway. Furthermore, RT-qPCR analysis identified significant dysregulation in the downstream target genes of PPARα, which is responsible for lipid oxidative catabolism, and the SREBP pathway, which is responsible for lipid synthesis. In conclusion, both perfluoroalkyl analogues HFPO-TA and Gen-X exhibit significant physiological and metabolic toxicity to aquatic organisms and their environmental accumulation should be closely regulated.

CH4 is one of the most important greenhouse gases responsible for climate change. The effect of algal decomposition on CH4 emission fluxes in aquaculture environments is unknown. This study determined the relative abundance of methanogens in aquaculture in northern China. We determined various parameters in the water and sediment after the decomposition of Chaetomorpha valida. The results showed that the relative abundance of methanogens increased significantly during the decomposition of C. valida. The average CH4 emission flux was 50.64 mg m-2 h-1 when the density of C. valida was 25 mg cm-3, which was 11 times higher than that at a density of 0 mg cm-3. The concentrations of dissolved oxygen (DO), nitrite, nitrate and sulfate in the aquaculture pond significantly decreased during the decomposition of C. valida. The formation of a strong anaerobic reduction environment promoted the formation and release of CH4. Our results confirmed that the decomposition of C. valida enhanced the CH4 emission flux. The average CH4 emission fluxes ranged from 4.62 to 50.64 mg m-2 h-1. It is particularly important to remove decomposed algae in a timely manner and control greenhouse gas emissions from aquaculture ponds to mitigate climate change.

The frequent invasion of organisms poses a serious threat to biodiversity, ecosystem service functions, and economic development. Invasions from terrestrial systems have been well studied, but invasions from marine systems still lack a literature review, especially for invasive algae. With the frequent invasion of non-native algae, marine biodiversity and its sustainable use are threatened, and thus, the in-depth investigation of the biological mechanisms and ecological impacts of invasive alien marine algae has become particularly important. Here, we conducted a literature review of a series of studies that were undertaken by identified experts on algae invasions, including information on the classification of invasive algae in the ecosystem, mechanisms of invasion success (including the invader’s biological traits, interactions with native species, and adaptive evolution), and the impact on the native community and environment of the invaded area. In addition, we put forward suggestions for relevant research on invasive algae to overcome the current obstacles and provide references for future research on invasive marine algae. This review could be used to inform biological regulations and provides a scientific basis for the protection of marine biodiversity, sustainable environmental development, and the restoration of blue carbon ecosystems.

Nafion by-product 2 (Nafion BP2), an emerging fluorinated sulfonic acid commonly used in polymer electrolyte membrane technologies, has been detected in various environmental and human matrices. To date, however, few studies have explored its toxicity. In this study, zebrafish embryos were exposed to Nafion BP2 at concentrations of 20, 40, 60, 80, 100, 120, 140, and 160 mg/L from fertilization to 120 post-fertilization (hpf), and multiple developmental parameters (survival rate, hatching rate, and malformation rate) were then determined. Results showed that Nafion BP2 exposure led to a significant decrease in survival and hatching rates and an increase in malformations. The half maximal effective concentration (EC50) of Nafion BP2 for malformation at 120 hpf was 55 mg/L, which is higher than the globally important contaminant perfluorooctane sulfonate (PFOS, 6 mg/L). Furthermore, exposure to Nafion BP2 resulted in additional types of malformations compared to PFOS exposure. Pathologically, Nafion BP2 caused abnormal early foregut development, with exfoliation of intestinal mucosa, damage to lamina propria, and aberrant proliferation of lamina propria cells. Nitric oxide content also decreased markedly. In addition, embryos showed an inflammatory response following Nafion BP2 exposure, with significantly increased levels of pro-inflammatory factors C4 and IL-6. Acidic mucin in the hindgut increased more than two-fold. 16 S rRNA sequencing revealed a marked increase in the pathogen Pseudomonas otitidis. Furthermore, pathways involved in intestinal protein digestion and absorption, inflammatory response, and immune response were significantly altered. Our findings suggest that the intestine is a crucial toxicity target of Nafion BP2 in zebrafish, thus highlighting the need to evaluate its health risks.

Pregnancy is a period of major endocrine and metabolic changes which modulate both maternal and child’s health. Pregnancy exposures such as gestational diabetes mellitus (GDM), elevated maternal pre-pregnancy body-mass-index (BMI) and gestational weight gain (GWG) are risk factors for type 2 diabetes, overweight, and metabolic syndrome not only in the mother. Maternal diabetes and obesity to induce marked abnormalities in glucose homeostasis and insulin secretion in the fetus, and are linked to obesity, diabetes, and metabolic disease in the offspring. In recent years, the study of metabolomics has begun to receive increasing international attention, especially as it pertains to medical research. This is due in part to the potential for discovery of new biomarkers in the metabolome and to a new understanding of the “exposome”, which refers to the endogenous and exogenous compounds that reflect external exposures. Consequently, metabolomics research into pregnancy-related issues has increased. Biomarkers discovered through metabolomics may shed some light on the etiology of certain pregnancy-related complications and their adverse effects on future maternal health and infant development and improve current clinical management. The discoveries and methods used in these studies will be compiled and summarized within the following paper. A further focus of this paper is the use of hair as a biological sample, which is gaining increasing attention across diverse fields due to its noninvasive sampling method and the metabolome stability. At the end we have concluded that maternal BMI and glycemia are associated with different components of the new born metabolism, consistent with their independent effects on new born size at birth. Maternal BMI is associated with a new born metabolic signature characteristic of insulin resistance and risk of type 2 diabetes in adults. Thus we can say that metabolomics is a useful tool and it helps to develop targeted therapeutic tool to investigate these complications at early stages.

Exposure to environmental pollutants, including dioxin-like pollutants, can cause numerous health issues. A common exposure route to pollutants is through contaminated foods, and thus the gastrointestinal system and gut microbiota are often exposed to high amounts of pollutants. Multiple studies have focused on the imbalance in intestinal microbiota composition caused by dioxin-like pollutants. Here, we examined the effects of polychlorinated biphenyl 126 (PCB126) on the composition and functions of gut microbes through metagenomic sequencing, and explored the correlations between microflora dysbiosis and aryl hydrocarbon receptor (AHR) signaling. Adult male wild-type and Ahr-/- mice with a C57BL/6 background were weekly exposed to 50 μg/kg body weight of PCB126 for 8 weeks. Results showed that PCB126 had the opposite effect on gut microbiota composition and diversity in the wild-type and Ahr-/- mice. Functional prediction found that PCB126 exposure mainly altered carbon metabolism and signal regulatory pathways in wild-type mice but impacted DNA replication and lipopolysaccharide biosynthesis in Ahr-/- mice. In wild-type mice, PCB126 exposure induced liver injury, decreased serum lipid content, and delayed gastrointestinal motility, which were significantly correlated to several specific bacterial taxa, such as Helicobacter. Following AHR knockout, however, the holistic effects of PCB126 on the host were lessened or abolished. These results suggest that PCB126 may disrupt host metabolism and gut microbiota dynamics via AHR activation. Overall, our findings provide new insight into the complex interactions between host metabolism and gut microbiota, which may contribute to grouped assessment of environmental pollutants in the future.

As the world's most populous country, China has witnessed rapid urbanization in recent decades, with population migration from rural to urban (RU) regions as the major driving force. Due to the large gap between rural and urban consumption and investment level, large-scale RU migration impacts air pollutant emissions and creates extra uncertainties for air quality improvement. Here, we integrated population migration assessment, an environmentally extended input–output model and structural decomposition analysis to evaluate the NOx, SO2 and primary PM2.5 emissions induced by RU migration during China's urbanization from 2005 to 2015. The results show that RU migration increased air pollutant emissions, while the increases in NOx and SO2 emissions peaked in approximately 2010 at 2.4 Mt and 2.2 Mt, accounting for 9.2% and 8.7% of the national emissions, respectively. The primary PM2.5 emissions induced by RU migration also peaked in approximately 2012 at 0.3 Mt, accounting for 2.8% of the national emissions. The indirect emissions embodied in consumption and investment increased, while household direct emissions decreased. The widening gap between urban and rural investment and consumption exerted a major increasing effect on migration-induced emissions; in contrast, the falling emission intensity contributed the most to the decreasing effect benefitting from end-of-pipe control technology applications as well as improving energy efficiency. The peak of air pollutant emissions induced by RU migration indicates that although urbanization currently creates extra environmental pressure in China, it is possible to reconcile urbanization and air quality improvement in the future with updating urbanization and air pollution control policies.

In this work, Ti6Al4V alloy was treated by a duplex treatment of double glow plasma surface molybdenizing-laser surface texturing (LST) aiming to realize surface strengthening and manipulate its tribological behavior. The double glow plasma surface alloying (DGPSA) with molybdenum (Mo) was firstly conducted on the Ti6Al4V alloy and followed by LST to prepare round dimple-shape texture with a density of 5%, 7%, 11%. The results showed that Mo and Mo/Ti solid solution phases were detected in the Mo-layer by X-ray diffraction (XRD), the received Mo-layer with a thickness of about 13 μm was uniform and compact. Double glow plasma surface molybdenizing significantly improved the surface hardness and elastic modulus of Ti6Al4V alloy by nanoindentation test. The gradient distributed Mo-layer was tightly adhered to the Ti6Al4V alloy matrix through scratching and indentation tests. Duplex treated Ti6Al4V alloy with a 5% texture density suggested better wear resistance in comparison to the untreated Ti6Al4V alloy, which was confirmed by a 48.7% lower specific wear rate than that of Ti6Al4V alloy. Taking advantages of DGPSA and LST, duplex treatment of double glow plasma surface molybdenizing-laser surface texturing was established to create on the working surface of Ti6Al4V alloy with promisingly improved tribological behavior.

Higher performance is steadily required in the field of material surface engineering, especially in terms of surface degradation of mechanical parts and repair and renewal of surfaces. By preparing a more reasonable surface design and improving the surface composition and structure of the material, the surface modification layer can provide an important potential solution to the surface degradation problem. The coatings obtained by double glow plasma surface alloying (DGPSA) technology are a compelling method in current and future applications because of a unique combination of characteristics including pollution-free, the gradient distribution of the alloying elements and the strong metallurgical bonding between the alloying layer and the matrix. In recent years, with the increasing requirements for the surface properties of materials in various environments, the layer prepared by DGPSA technology is developing toward alloying, functionalization and nanometer. This review begins with a brief introduction of double glow plasma surface alloying. The recent developments of the double glow plasma surface alloying technology for improving various surface performance are systematically reviewed in the sight of applied material, background, duplex treatment and duplex coating preparation.

Sorafenib is a multi-kinase blocker and one of the few suggested drug treatments for aggressive hepatocellular carcinoma (HCC) patients. However, drug resistance to sorafenib may often occur over time and cause further tumor aggression. Recently, cancer stem cells were found in HCC and were speculated to be involved in tumor progression. SOX9 is highly expressed in HCC cancer stem cells and promotes cell proliferation and self-renewal. Meanwhile, HCC patients with higher SOX9 expression show poorer prognosis. Whether SOX9 is involved in sorafenib resistance in HCC is still unclear. Here, we found that sorafenib treatment increased the proportion of SOX9 positive cells in HCC cell lines. Overexpression of exogenous SOX9 in HCC increased sorafenib resistance both in vitro and in vivo, whereas down-regulation led to inhibition of sorafenib resistance. Knock-down of SOX9 by RNA interference caused down-regulation of downstream genes, including ATP binding cassette subfamily G member 2 (ABCG2). The drug resistance to sorafenib caused by SOX9 overexpression could be ameliorated by ABCG2 inhibition in HCC cell lines. In the cohort of patients taken sorafenib, we found that patients with lower SOX9 expression had more prolonged overall survival (OS) and progression-free survival (PFS). Univariate and multivariate Cox analysis shows that SOX9 expression exerts as an independent risk factor for the OS and PFS of HCC patients with sorafenib treatment. These findings demonstrate that SOX9 enhances sorafenib resistance and may regulate this process by modulating ABCG2 expression.

Increasing evidence revealed that circular RNAs (circRNAs) play important roles in tumor progression. In the present study, we explored the roles and underlying mechanisms of hsa_circ_0075341 in cervical cancer development. Our data showed that the expression of hsa_circ_0075341 was significantly upregulated and associated with larger tumor size, advanced FIGO stage, and lymph-node metastasis in cervical cancer patients. Hsa_circ_0075341 inhibition reduced cervical cancer cell proliferation and invasion in vitro. In mechanism, hsa_circ_0075341 negatively regulated miR-149-5p in cervical cancer progression. In addition, AURKA was confirmed as a direct target of miR-149-5p in cervical cancer and positively regulated by hsa_circ_0075341. Collectively, our data suggested that hsa_circ_0075341 promoted cervical cancer cell proliferation and invasion through regulating the miR-149-5p/AURKA axis, which provided a novel therapeutic target for cervical cancer treatment.

Bacterial outer membrane vesicles (OMVs) play a vital role in the mechanism of host―pathogen communication, while emerging evidence suggests that OMVs regulate host immune responses through differentially packaged small noncoding RNAs (sncRNAs) to target host mRNA function. Therefore, we identified differentially packaged sncRNAs in Helicobacter pylori OMVs and showed transfer of OMV sncRNAs to human gastric adenocarcinoma cells in this study. Our data revealed that sncRNAs (sR-2509025 and sR-989262) were enriched in OMVs, and reduced lipopolysaccharide or OMV-induced interleukin 8 (IL-8) secretion by cultured AGS cells. Collectively, these findings are consistent with the hypothesis that sncRNAs in H. pylori OMVs play a novel role in the mechanism of host―pathogen interaction, whereby H. pylori evades the host immune response.

Induced pluripotent stem cells (iPSCs) have great potential for treating age-related diseases, but the genome integrity of iPSCs is critically important. Here, we demonstrate that non-homologous end joining (NHEJ), rather than homologous recombination (HR), is less efficient in iPSCs from old mice than young mice. We further find that Sirt6 is downregulated in iPSCs from old mice. Sirt6 directly binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus promoting DNA-PKcs phosphorylation at residue S2056, leading to efficient NHEJ. Rescue experiments show that introducing a combination of Sirt6 and the Yamanaka factors during reprogramming significantly promotes DNA double-strand break (DSB) repair by activating NHEJ in iPSCs derived from old mice. Thus, our study suggests a strategy to improve the quality of iPSCs derived from old donors by activating NHEJ and stabilizing the genome.

Widely distributed fluorocarboxylic acids have aroused worldwide environmental concerns due to its toxicity, persistence, and bioaccumulation. Enzyme-based eco-friendly biodegradation techniques have become increasingly important in treating fluorocarboxylic acids. Here we utilized in silico and in vitro approaches to investigate the defluorination mechanism of fluoroacetate dehalogenase (FAcD) toward monofluoropropionic acids at atomic-level. The experimentally determined kcat and kM for defluorination of 2-fluoropropionic acid are 330 ± 60 min−1 and 6.12 ± 0.13 mM. The in silico results demonstrated positive/negative correlations between activation barriers and structural parameters (e.g. distance and angle) under different enzymatic conformations. We also screened computationally and tested in vitro (enzyme assay and kinetic study) the catalytic proficiency of FAcD toward polyfluoropropionic acids and perfluoropropionic acids which are known to be challenging for enzymatic degradation. The results revealed potential degradation activity of FAcD enzyme toward 2,3,3,3-tetrafluoropropionic acids. Our work will initiate the development of a new “integrated approach” for enzyme engineering to degrade environmentally persistent fluorocarboxylic acids. Keywords: Quantum mechanics/molecular mechanics, Enzymatic Defluorination, Enzymatic conformations, Substitution effect

Long non-coding RNAs (lncRNAs) play important roles in tumor initiation and progression, including cervical cancer (CC). However, the effects and underlying mechanisms of STXBP5-AS1 in CC are still unknown. The expression of STXBP5-AS1, miR-96-5p, and PTEN in CC was explored by qRT-PCR. CCK-8 and transwell assays were used to determine the roles of STXBP5-AS1 on CC progression. Luciferase report assay and RIP assay were used to explore the correction between STXBP5-AS1, miR-96-5p and PTEN in CC. In our study, we showed that the expression of STXBP5-AS1 and PTEN was reduced while miR-96-5p expression was upregulated in CC. STXBP5-AS1 overexpression significantly reduced CC cells proliferation and invasion ability by suppressing miR-96-5p expression. MiR-96-5p promoted CC cells progression via regulating PTEN expression. Furthermore, STXBP5-AS1 was identified as a ceRNA to upregulate PTEN via sponging miR-96-5p in CC. Taken together, our findings revealed that STXBP5-AS1 might function as a ceRNA to drive CC cells proliferation and invasion via regulating miR-96-5p/PTEN axis.