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Abstract With the increase in the number of cases of autoimmune encephalitis (AE), the cerebrospinal fluid (CSF) of people living with HIV (PLWH) showing abnormal behavior, cognitive impairment or abnormal movements should be actively screened for the antibody panel of AE. Early recognition and treatment can prevent severe seizures or coma and markedly improve the prognosis of patients. The first-line immunotherapy for AE includes intravenous methylprednisolone and immunoglobulin. However, whether long-time immunosuppressive maintenance therapy is needed is debated. For PLWH, immunosuppressive therapy and even steroids could be more challenging. Here, we review and summarize the clinical characteristics often reported cases and report one case from our center to improve the diagnosis and treatment of anti-N-methyl-d-aspartate receptor encephalitis in PLWH.

Abstract Introduction Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug–drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. Methods HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. Results No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17–6.02, P

Abstract Background Patients infected with HIV are at high risk of developing Epstein-Barr Virus (EBV)-related diseases. The genotype and viral biological behavior of EBV infection in patients with human immunodeficiency virus-1 (HIV) in China remain unclear. This study analyzed the characteristics of EBV in patients infected with HIV in southeastern China. Methods A total of 162 HIV-infected patients and 52 patients without HIV were enrolled in this study. EBV viral load in blood was determined by fluorescence quantitative PCR. EBV typing was performed using saliva according to polymorphisms in the EBNA3C region. EBV LMP-1 carboxy terminus (C-ter) was sequenced, and compared with the epidemic strains in the world. Results Among HIV infected patients, the EBV strain variant was mainly EBV-1, while EBV-2 had a higher viral load than EBV-1 (P = 0.001) and EBV-1/2 (P = 0.002). HIV infected patients had higher active virus replication. The EBV LMP-1 variants were mainly the China1 variant. HIV-infected patients had different nucleic acid positions of 30-bp deletion (del30) and had a higher incidence of high 33-bp tandem repeats (rep33) copies than non-HIV-infected patients. There was a difference in the mutations of EBV LMP-1 C-ter del30 and ins15 between HIV infected patients and the control group (P

Abstract Background Patients with human immunodeficiency virus-associated cryptococcal meningitis (HIV-CM) have persistent intracranial inflammation despite negative cerebrospinal fluid (CSF) fungal cultures after optimal treatment for CM, which could be devastating for the central nervous system. However, a definitive treatment strategy for persistent intracranial inflammation despite optimal antifungal therapies is undefined. Methods We identified 14 HIV-CM patients with persistent intracranial inflammation and conducted a 24-week, prospective, interventional study. All participants received lenalidomide (25 mg, p.o.) on days 1 to 21 of a 28-day cycle. Follow-up lasted for 24 weeks with visits at baseline and weeks 4, 8, 12, and 24. The primary endpoint was the change in clinical manifestations, routine CSF parameters, and MRI findings after lenalidomide treatment. An exploratory analysis was made on changes in cytokine levels in CSF. Safety and efficacy analyses were undertaken in patients who received at least one dose of lenalidomide. Results Of 14 participants, 11 patients completed the 24 weeks of follow-up. Rapid clinical remission following lenalidomide therapy was observed. Clinical manifestations (fever, headache, altered mentation) were reversed fully by week-4 and remained stable during follow-up. A significant reduction in white blood cell (WBC) count in CSF was noted occurred at week-4 (P = 0.009). The median protein concentration in CSF decreased from 1.4 (0.7–3.2) g/L at baseline to 0.9 (0.6–1.4) at week-4 (P = 0.004). The median albumin concentration in CSF decreased from 79.2 (48.4–149.8) mg/L at baseline to 55.3 (38.3–89.0) mg/L at week-4 (P = 0.011). The WBC count, protein level, and albumin level in CSF remained stable and approached a normal range through week-24. There was no significant change in immunoglobulin-G, intracranial pressure (ICP), or chloride-ion concentration at each visit. Brain MRI demonstrated multiple lesions to be absorbed post-therapy. Levels of tumor necrosis factor-α granulocyte colony stimulating factor, interleukin (IL)-6, and IL-17A decreased significantly during 24-week follow-up. Two (14.3%) patients had mild skin rash, which resolved spontaneously. Lenalidomide-related serious adverse events were not observed. Conclusion Lenalidomide could improve persistent intracranial inflammation in HIV-CM patients significantly and was well tolerated without serious adverse events observed. And the additional randomized controlled study is required to further validate the finding.

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a fatal immunological syndrome resulting from excessive production of inflammatory cytokines. The conventional therapies for HLH, which are based on cytotoxic agents, are not always efficacious and safe, especially in patients with severe immunodeficiency. Ruxolitinib, a strong inhibitor of Janus kinase (JAK) 1/2, has already been evaluated as salvage and first-line therapy for HLH. Despite its promising efficacy and tolerability in the treatment of secondary HLH, the efficacy and safety of ruxolitinib in HLH patients with HIV infection remain to be investigated.Case presentationTwo men (ages: 45 and 58 years) both presented at our hospital with a high fever. They were found to be HIV-positive with severe immunodeficiency and opportunistic infections. Their laboratory tests showed severe pancytopenia, hypofibrinogenemia, hypertriglyceridemia, and increased levels of inflammatory factors and ferritin. Hemophagocytosis was found in the bone marrow, and abdominal computed tomography or ultrasonography showed splenomegaly. Both patients were diagnosed with infection-induced HLH due to severe immunodeficiency. Given they were both highly immunocompromised, we chose ruxolitinib as a first-line treatment alternative to cytotoxic chemotherapy. Rapid remission of clinical symptoms and normalization of laboratory parameters were achieved after ruxolitinib therapy. Neither patient had any associated adverse drug reactions or other laboratory abnormalities. Both patients were eventually discharged and ruxolitinib was discontinued as their disease alleviated, and they did not show signs of relapse during the 3- and 5-month of follow-up examinations.ConclusionWe described two cases of AIDS-related secondary HLH treated with ruxolitinib. Our cases highlight the feasibility of using ruxolitinib as a first-line therapy in patients with HIV infection and secondary HLH. Nevertheless, the safety and efficacy of this novel treatment need to be evaluated in large clinical trials in the future.

BackgroundThe HIV-1 reservoir is a major barrier to curative strategies. Inflammation is an important factor for HIV-1 reservoir persistence. Lenalidomide regulates inflammatory cytokines efficiently. We examined whether lenalidomide could inhibit HIV-1 transcription and reduce systemic inflammation in people living with HIV.MethodsLenalidomide was administered orally for 48 weeks to patients with HIV-associated cryptococcal meningitis (HIV-CM). A HIV-1 latency model was treated with or without lenalidomide ex vivo for 5 days. The primary endpoints were change in HIV reservoir markers and inflammatory cytokines in both the cohort and cell model.ResultsThirteen participants were enrolled from May 2019 to September 2020. The median change in cell-associated (CA) HIV RNA between baseline and 48 weeks was 0.81 log10 copies/million peripheral blood mononuclear cells (PBMCs). The CA HIV RNA decreased significantly in the cohort (P = 0.021). Serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) gradually diminished with lenalidomide treatment until 48 weeks (P = 0.007, P = 0.014, respectively). C-reactive protein/IL-6/TNF-α and CA HIV RNA were significantly correlated (P = 0.0027, 0.0496, and 0.0346, respectively). Lenalidomide also significantly decreased HIV core P24 (P = 0.0038) and CA HIV RNA in CD8-depleted PBMCs (P = 0.0178) ex vivo. TNF-α and IL-6 were significantly reduced in the CD8-depleted PBMC supernatant (P = 0.004, P

Abstract The similarity test of ship stiffened plate structures under underwater explosions is a cost-effective and efficient method to evaluate the vitality of ships and guide the design of their shock resistance. This study focuses on the nonlinear impact response model tests of ship stiffened plate structures and their similarity laws with actual ships. The vertical motion of the ship stiffened plate structure is characterized by the Hurst index, and an equivalent relationship between the Hurst index of the model and the prototype is derived from classical similarity law. Based on the Hurst index, a similarity transformation relationship between the strain signals of the model and prototype is established. To verify the conclusions, similarity experiments of underwater explosions were conducted on both the model and the prototype. The original signals were grouped by the natural vibration period to determine the variation of the Hurst index over time. The model experiment strain signals for each natural vibration period were converted and compared with the prototype experiment results to verify the method's effectiveness. Simultaneously, the Hurst index of the stiffened plate structure under explosive shock load and its similarity transformation relationship with the prototype were simulated and analyzed. This provides theoretical and technical support for conducting analogous nonlinear response experiments for ship underwater explosions.

Large ships and submarines are the main equipment and mobile platforms supporting three-dimensional naval space operations. However, with the increasing damage power and strike accuracy of warheads, plus the diversity of destroying elements, their living environment is facing increasingly severe threats. It is thus necessary to work on the damage and protection of naval vessels subjected to blast loading. The blast-induced damage and protection of naval vessels is an interdisciplinary issue that involves the integration of explosion mechanics, fluid mechanics, structural mechanics, materials science and other disciplines in which many challenges are yet to be addressed. In view of some of the key issues involved, this paper systematically summarizes the research progress on blast load characteristics, damage mechanisms and protection technologies and equipment at home and abroad in recent years. The shortcomings of the current research are pointed out and the development trends of ship explosion damage and protection are predicted. This study can provide valuable references for future research on the efficient damage and protection of naval vessels.

Abstract A long-standing hypothesis proposes that certain RNA(s) must exhibit structural roles in microtubule assembly. Here, we identify a long noncoding RNA (TubAR) that is highly expressed in cerebellum and forms RNA–protein complex with TUBB4A and TUBA1A, two tubulins clinically linked to cerebellar and myelination defects. TubAR knockdown in mouse cerebellum causes loss of oligodendrocytes and Purkinje cells, demyelination, and decreased locomotor activity. Biochemically, we establish the roles of TubAR in promoting TUBB4A–TUBA1A heterodimer formation and microtubule assembly. Intriguingly, different from the hypomyelination-causing mutations, the non-hypomyelination-causing mutation TUBB4A-R2G confers gain-of-function for an RNA-independent interaction with TUBA1A. Experimental use of R2G/A mutations restores TUBB4A–TUBA1A heterodimer formation, and rescues the neuronal cell death phenotype caused by TubAR knockdown. Together, we uncover TubAR as the long-elusive structural RNA for microtubule assembly and demonstrate how TubAR mediates microtubule assembly specifically from αβ-tubulin heterodimers, which is crucial for maintenance of cerebellar myelination and activity.

Our study examined the relationships between riparian plant communities and their soil properties along the midstream of the Heihe River in northwestern China’s arid region. Significant variations in species composition were observed across the upper, middle, and lower reaches of this midstream (adonis2 and anosim, p < 0.001). The lower reaches exhibited higher species diversity (Shannon index up to 2.12) compared to the other reaches. Gramineous plants, particularly Agropyron cristatum (L.) Gaertn. and Equisetum ramosissimum Desf., dominated all reaches, with relative abundances exceeding 50% in the upper reach sites. The soil ionic concentration showed distinct spatial heterogeneity, peaking at site 9 (upper reaches) and lowest at site 3 (lower reaches). Species diversity indices negatively correlated with SO42−, Mg2+, and Ca2+ concentrations, while salt-tolerant species like Agropyron cristatum (L.) Gaertn. and Phragmites australis Trin. positively correlated with Na+ and Cl− levels. Soil nutrients had weaker but notable effects on the distribution of Onopordum acanthium L. and Artemisia argyi H. Lév. and Vaniot. These findings suggest that riparian plant community distribution along the Heihe River is influenced by complex interactions between hydrological processes, salt dynamics, and soil physicochemical properties, such as anion and cation concentrations and electrical conductivity (EC). Our research provides valuable insights for understanding and managing riparian ecosystems in arid regions.

BackgroundExposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS) during pregnancy might affect thyroid-related hormone levels in pregnant women. However, most previous studies focused on the effects of PFAS containing 8-10 carbon atoms, and few studies have estimated the associations between PFAS with longer carbon chain and thyroid-related hormone levels. ObjectiveTo examine the associations between PFAS exposure and thyroid-related hormones in pregnant women. MethodsThe present study was based on the Jiashan Birth Cohort from September 2016 to April 2018. We analyzed 13 PFAS in maternal blood samples (n=781) by high-performance liquid chromatography-tandem mass spectrometry, as well as total triiodothyronine (T3), total thyroxine (T4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), and thyroid peroxidase antibody (TPOAb) by electrochemiluminescence immunoassay. PFAS were divided into three groups:low concentration, medium concentration and high concentration according to the tertile of their concentrations. We estimated the associations between PFAS concentrations and thyroid-related hormones in pregnant women by multiple linear regression. ResultsIn the multiple linear regression models, a change in perfluorododecanoic acid (PFDoA) concentrations from the low concentration group to the high concentration group was associated with a −0.10 (95%CI: −0.20, 0) nmol·L−1 change in T3, −0.15 (95%CI: −0.28, −0.02) pmol·L−1 change in FT3, and −3.02 (95%CI: −5.66, −0.39) pmol·L−1 change in FT4, respectively. A change in perfluorotridecanoic acid (PFTrDA) concentrations from the low concentration group to the high concentration group was associated with a −0.10 (95%CI: −0.20, 0) nmol·L−1 change in T3. Compared with the low concentration group, the concentration of T4 in the medium concentration group of perfluorohexane sulfonate (PFHxS) increased by 6.10 (95%CI: 0.44, 11.75) nmol·L−1. No statistically significant associations were found between PFAS and TSH concentration. The negative associations of PFAS with thyroid-related hormones were more pronounced in pregnant women with positive TG-Ab and/or TPOAb. ConclusionExposure to PFAS during pregnancy may affect thyroid-related hormone homeostasis in pregnant women, and the effect is stronger in TG-Ab and/or TPOAb-positive pregnant women.

Abstract Dermal fibroblasts and cutaneous nerves are important players in skin diseases, while their reciprocal roles during skin inflammation have not been characterized. Here we identify an inflammation-induced subset of papillary fibroblasts that promotes aberrant neurite outgrowth and psoriasiform skin inflammation by secreting the extracellular matrix protein tenascin-C (TNC). Single-cell analysis of fibroblast lineages reveals a Tnc + papillary fibroblast subset with pro-axonogenesis and neuro-regulation transcriptomic hallmarks. TNC overexpression in fibroblasts boosts neurite outgrowth in co-cultured neurons, while fibroblast-specific TNC ablation suppresses hyperinnervation and alleviates skin inflammation in male mice modeling psoriasis. Dermal γδT cells, the main producers of type 17 pathogenic cytokines, frequently contact nerve fibers in mouse psoriasiform lesions and are likely modulated by postsynaptic signals. Overall, our results highlight the role of an inflammation-responsive fibroblast subset in facilitating neuro-immune synapse formation and suggest potential avenues for future therapeutic research.

Camellia oleifera Abel, a woody oil plant, that is endemic to China. Tea oil, also referred to as “oriental olive oil,” is a superior quality plant-based cooking oil. The production of tea oil accounts for 8% of the total edible vegetable oil production in the country. Since 2022, the annual output value of C. oleifera industry has exceeded 100 billion yuan, making it one of the major economic contributors to China’s rural revitalization development strategy. In recent years, demand and production have grown in parallel. However, this has led to an increase in the incidence levels of pest and diseases. Pests and diseases significantly reduce the quality and yield of C. oleifera. C. oleifera diseases are mainly caused by pathogenic fungi. C. oleifera anthracnose, soft rot, leaf spot, coal stain, leaf gall disease, and root rot are the most important fungal diseases affecting the C. oleifera industry. However, the same disease may be caused by different pathogenic fungi. C. oleifera can be found in half of China and is found in several climatic zones. The geographical distribution of woody plant diseases is consistent with the distribution of the tree species and the ecology of the range, which also results in a highly complex distribution of fungal diseases of C. oleifera. The management of fungal diseases in C. oleifera is extremely challenging due to the variety of pathogenic fungal species, multiple routes of transmission, the lack of resistant plants, and the environmental safety of chemical measures. The optimal strategy for addressing fungal diseases in C. oleifera is to develop and apply an integrated disease management plan. This review provides a brief overview of the pathogenic species, pathogenesis, pathogenesis, geographical distribution, current management strategies, and potentially new methods of C. oleifera fungal diseases, to provide direction for the development of comprehensive management measures for C. oleifera fungal diseases in the future.

The microbial hybrid system modified by magnetic nanomaterials can enhance the interfacial electron transfer and energy conversion under the stimulation of a magnetic field. However, the bioelectrocatalytic performance of a hybrid system still needs to be improved, and the mechanism of magnetic field-induced bioelectrocatalytic enhancements is still unclear. In this work, γ-Fe2O3 magnetic nanoparticles were coated on a Shewanella putrefaciens CN32 cell surface and followed by placing in an electromagnetic field. The results showed that the electromagnetic field can greatly boost the extracellular electron transfer, and the oxidation peak current of CN32@γ-Fe2O3 increased to 2.24 times under an electromagnetic field. The enhancement mechanism is mainly due to the fact that the surface modified microorganism provides an elevated contact area for the high microbial catalytic activity of the outer cell membrane’s cytochrome, while the magnetic nanoparticles provide a networked interface between the cytoplasm and the outer membrane for boosting the fast multidimensional electron transport path in the magnetic field. This work sheds fresh scientific light on the rational design of magnetic-field-coupled electroactive microorganisms and the fundamentals of an optimal interfacial structure for a fast electron transfer process toward an efficient bioenergy conversion.

In this paper, a multi-physical field coupling curing experimental instrument was developed to study the effect of curing pressure on the stability of bottom cemented paste backfill (CPB) under two different barricades. The effect mechanism was analyzed by using 5TE, MPS-6 sensor, scanning electron microscope (SEM), and binary processing of SEM images. And then, the strength prediction model of CPB under different curing conditions was established. The findings show that the strength of CPB increases with curing pressure regardless of permeable or impermeable barricade, and the relationship between CPB strength and curing pressure conforms to the law of linear function, and the change law of strength grow rate can also be expressed by a linear function. The curing pressure will accelerate the hydration reaction rate and compress the internal pores of the CPB, making the structure of the CPB more denser, thus promoting the formation of strength. It is worth noting that after the curing pressure was increased to 600 kPa, the strength growth rate of CPB slowed down in the later period, and obvious cracks appeared in the bottom CPB during sampling. The results will be helpful to better consider setting different types of barricade at different stope heights

Psoriasis is an inflammatory disease which has proven difficult to cure. Prof. Honglin Wang’s team describes L-menthol for treating models of psoriasis and uncovers the dysfunctional HES1- IGBP1-PP6 axis in psoriasis pathology by using L-menthol as a probe.

Uniform magmatic crust formed at the Mid-Atlantic Ridge in the equatorial Atlantic Ocean reveals a two-dimensional mantle upwelling facilitated by the large transform faults and the high concentration of volatiles in the primitive melt in the mantle.

There is no doubt that the digital economy has brought much convenience to our work and life, improving productivity and optimising social service and government efficiency. However, there are also quite a few problems in the development of the digital economy, such as fake and even malicious information flooding the internet and new media, counterfeit e-commerce, and the shocks to the economy and society brought about by the extensively advanced development of internet technologies and fintech. People lack an understanding of the digital economy, leading to criminal offences and economic offences. This paper presents an accurate review of the development of the digital economy and its extensive effects on social economic growth. It begins with the introduction of the digital econ- omy, with a profound influence on human productivity and people’s lives, plus an essential literature review. It explains the research materials and methods, as well as the structure of the article. It then explores the development law of the digital economy and inteprets the essence of the accurate cognition of the digital economy. Further, it traces the impact of the digital economy on society and emphasises the normalisation of the development of the digital economy. This is followed by a deep assessment of the service efficiency of the digital economy and building a new area for attracting investment. It examines the importance of the information transmission mechanism in avoiding the overlapping of digital isolated islands. The paper concludes with the premise of precisely defining the development stage of the digital economy so as to stimulate the iterative innovation of social economic development.

BackgroundCurrent expectations are that surgeons should be technically proficient in minimally invasive low anterior resection (LAR)—both laparoscopic and robotic-assisted surgery. However, methods to effectively train surgeons for both approaches are under-explored. We aimed to compare two different training programs for minimally invasive LAR, focusing on the learning curve and perioperative outcomes of two trainee surgeons.MethodsWe reviewed 272 consecutive patients undergoing laparoscopic or robotic LAR by surgeons A and B, who were novices in conducting minimally invasive colorectal surgery. Surgeon A was trained by first operating on 80 cases by laparoscopy and then 56 cases by robotic-assisted surgery. Surgeon B was trained by simultaneously performing 80 cases by laparoscopy and 56 by robotic-assisted surgery. The cumulative sum (CUSUM) method was used to evaluate the learning curves of operative time and surgical failure.ResultsFor laparoscopic surgery, the CUSUM plots showed a longer learning process for surgeon A than surgeon B (47 vs. 32 cases) for operative time, but a similar trend in surgical failure (23 vs. 19 cases). For robotic surgery, the plots of the two surgeons showed similar trends for both operative times (23 vs. 25 cases) and surgical failure (17 vs. 19 cases). Therefore, the learning curves of surgeons A and B were respectively divided into two phases at the 47th and 32nd cases for laparoscopic surgery and at the 23rd and 25th cases for robotic surgery. The clinicopathological outcomes of the two surgeons were similar in each phase of the learning curve for each surgery.ConclusionsFor surgeons with rich experience in open colorectal resections, simultaneous training for laparoscopic and robotic-assisted LAR of rectal cancer is safe, effective, and associated with accelerated learning curves.

Growth-regulating factors (GRFs) are plant-specific transcription factors that contain two highly conserved QLQ and WRC domains, which control a range of biological functions, including leaf growth, floral organ development, and phytohormone signaling. However, knowledge of the evolutionary patterns and driving forces of GRFs in Gramineae crops is limited and poorly characterized. In this study, a total of 96 GRFs were identified from eight crops of Brachypodium distachyon, Hordeum vulgare, Oryza sativa L. ssp. indica, Oryza rufipogon, Oryza sativa L. ssp. japonica, Setaria italic, Sorghum bicolor and Zea mays. Based on their protein sequences, the GRFs were classified into three groups. Evolutionary analysis indicated that the whole-genome or segmental duplication plays an essential role in the GRFs expansion, and the GRFs were negatively selected during the evolution of Gramineae crops. The GRFs protein function as transcriptional activators with distinctive structural motifs in different groups. In addition, the expression of GRFs was induced under multiple hormonal stress, including IAA, BR, GA3, 6BA, ABA, and MeJ treatments. Specifically, OjGRF11 was significantly induced by IAA at 6 h after phytohormone treatment. Transgenic experiments showed that roots overexpressing OjGRF11 were more sensitive to IAA and affect root elongation. This study will broaden our insights into the origin and evolution of the GRF family in Gramineae crops and will facilitate further research on GRF function.

Regulatory T (Treg) cells constitute a dynamic population that is critical in autoimmunity. Treg cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities. However, recent studies demonstrated that certain inflammatory conditions induce Treg cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells. Therefore, the identification of novel targets crucial to both Treg cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity. In this study, we found that conditional Pp6 knockout (cKO) in Treg cells led to spontaneous autoinflammation, immune cell activation, and diminished levels of FoxP3 in CD4+ T cells in mice. Loss of Pp6 in Treg cells exacerbated two classical mouse models of Treg-related autoinflammation. Mechanistically, Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308, leading to impaired FoxP3 expression in Treg cells. In summary, our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling, thus maintaining Treg cell stability and preventing autoimmune diseases.

Through a case study to the gas pipeline network of Suzhou Industrial Park, a corrosion risk assessment model of gas pipeline network was established in combination with the risk assessment theory to assess the corrosion risk of the gas pipeline network in the industrial park. The assessment model adopted the fuzzy comprehensive evaluation method based on the improved AHP. By establishing the corrosion risk index system of gas pipeline network, the weight of each index was determined with the improved AHP method, the corrosion risk assessment level was established with the fuzzy comprehensive evaluation method, and finally the risk level of each pipeline section in the industrial park was solved. Excavation inspection was conducted for six gas pipelines in Suzhou Industrial Park randomly selected to judge the corrosion status of the pipeline, and the inspection results were compared with the evaluation results. The results show that the corrosion risk model can accurately assess the risk status of the gas pipeline network, and it is of some significance to improve the early warning and management level of the corrosion risk of city gas pipelines.

Abstract Instruction Lead (Pb) exposure is a risk factor for male infertility, but the epigenetic changes in sperm DNAattributable to lead exposure is poorly defined. Methods In this study, we investigated whether low Pb exposure ( 5 µg/dL or when predicting NP, no significant Pb–Ca interaction was observed. Discussion Overall, our results indicate that aberrant DNA methylation of the Ca homeostasis pathway, induced by low Pb exposure, is the potential cause for reduced sperm velocity.

Colletotrichum is widespread, and these pathogenic fungi can cause various plant diseases. Studies have shown that Colletotrichum fructicola cause oil-tea (Camellia oleifera) anthracnose and is widely distributed as a dominant fungus in all Ca. oleifera-producing regions. Real-time quantitative PCR(RT-qPCR) is considered the most reliable technique for simultaneously measuring relative gene expression levels in different tissues. Target genes are typically quantified using RT-qPCR to explore gene function, and reliable RT-qPCR results require data normalization using stable reference genes. No studies have reported a suitable reference gene in C. fructicola. This study has eight candidate reference genes (CfCk, CfRpp, CfUce, CfRrp, CfAdrh, CfDd, CfAct, and CfTub) which were selected from C. fructicola-Ca. oleifera transcriptome data and evaluated and sequenced using geNorm, NormFinder, and BestKeeper algorithms. The results showed that CfRrp had better stability in C. fructicola, both during the growth of pure pathogenic fungi and during the invasion of different oil-tea leaves. After normalization with CfRrp, the differentially expressed target genes were similar to the transcriptome. Our work provides suitable reference genes for future studies to quantify target gene expression levels in C. fructicola.

Anthracnose, caused by the fungus Collectotrichum fructicola (C. fructicola), is a major disease affecting the quality and yield of Camellia oleifera (C. oleifera); it reduces C. oleifera yield by 40%–80%. Bacillus subtilis (B. subtilis) YL13 is an antagonistic endophytic bacteria strain isolated from healthy C. oleifera leaves. This study was aimed at investigating the potential of YL13 for the biocontrol of C. oleifera anthracnose and the possible mechanisms involved. In in vitro assays, YL13 demonstrated remarkable antagonistic activity of C. fructicola. Its cell-free filtrates displayed antagonistic activity, which suggested that the metabolites of YL13 might play important roles. In vivo tests showed that the disease index of YL13-treated plants was obviously reduced under greenhouse conditions. YL13 secretes a variety of bioactive metabolites, including protease, cellulase, and siderophore, which might participate in the resistance to C. fructicola. In addition, C. oleifera treated with the fermentation broth of YL13 demonstrated different defense responses, e.g., accumulation of hydrogen peroxide (H2O2) and activation of the defense-related enzyme peroxidase (POD), which might contribute directly or indirectly to overcome external stresses. The significant biocontrol effect and host defense-induction activity of YL13 suggested that this B. subtilis strain as well as its metabolites have the potential to be exploited as microbial control agents for the efficient management of C. oleifera anthracnose.

Cyanobacteria bloom is a global aquatic ecological problem that seriously threatens human health and social development. The outbreak of cyanobacteria bloom is affected by various environmental factors, among which light dose is an essential factor. In this study, the growth changes of cyanobacteria under different amounts of natural light were studied by simulating different depths of Taihu Lake, and we used 16S rRNA and non-targeted metabolomics for sequencing to reveal the effects of light on the diversity of cyanobacteria and coexisting microorganisms, and to analyze the changes of related genes, functional structures and internal metabolism involved in nitrogen cycling. The result shows that excessive and insufficient light could limit the growth, photosynthesis, and EPS secretion of cyanobacteria, resulting in an antioxidant stress response. At the same time, the amount of natural light affects the vertical distribution of cyanobacteria, and under the condition of 1/3 natural light, cyanobacteria first appeared to float. In addition, the amount of natural light affects the diversity, abundance, and metabolites of cyanobacteria and coexisting microorganisms, and the expression of nifH, nirK, and nirS, three nitrogen-fixing genes, is significantly different in different genera. This study provides valuable information on the molecular mechanism of the effects of the amount of natural light on cyanobacteria bloom.

“Whale Fall” is a collective term for the whale carcass, the process of dead whale fall, and the formed deep-sea ecosystem. The whale fall process produces a lot of unstable organic matter that has a significant impact on deep-sea ecosystems. Scientists speculate that organic matter input is the source of energy and material for organisms in deep-sea ecosystems. In the seafloor of the North Pacific, whale fall supports the survival of at least 12,490 organisms of 43 species, contributing to the prosperity of deep-sea life. Due to the specificity of the time and space of the formation of whale fall, there are few studies on whale fall and its impact on the deep-sea ecosystem. This article summarizes and analyses the current research status on the distribution of whale fall and its impact on the deep-sea ecosystem at home and abroad. The results show that the current distribution of whale fall is mainly concentrated in the Pacific and Atlantic regions, and the research on the impact of whale fall on deep-sea ecosystems focuses on the formation process, degradation rate and impact on deep-sea biological systems. This article has some significance to the understanding of biodiversity and ecosystem succession in the deep-sea “desert area.”

The sluggish electron transfer at the interface of microorganisms and an electrode is a bottleneck of increasing the output power density of microbial fuel cells (MFCs). Mo-doped carbon nanofibers (Mo-CNFs) prepared with electrostatic spinning and high-temperature carbonization are used as an anode in MFCs here. Results clearly indicate that Mo2C nanoparticles uniformly anchored on carbon nanowire, and Mo-doped anodes could accelerate the electron transfer rate. The Mo-CNF ΙΙ anode delivered a maximal power density of 1287.38 mW m−2, which was twice that of the unmodified CNFs anode. This fantastic improvement mechanism is attributed to the fact that Mo doped on a unique nanofiber surface could enhance microbial colonization, electrocatalytic activity, and large reaction surface areas, which not only enable direct electron transfer, but also promote flavin-like mediated indirect electron transfer. This work provides new insights into the application of electrospinning technology in MFCs and the preparation of anode materials on a large scale.

Abstract Background MicroRNAs (miRNAs) are a class of noncoding small RNAs that play important roles in many physiological processes by regulating gene expression. Previous studies have shown that the expression levels of total miRNAs increase during mouse embryonic development, and some miRNAs control the regulatory network in development progression. However, few studies have focused on the effects of miRNAs on early human embryonic development. The relationship between miRNAs and early human embryogenesis is still unknown. Results In this study, RNA-seq data collected from sperm samples from 102 patients with a normal sperm index but treated with assisted reproductive technology (ART) were analyzed for the relationships between differentially expressed small RNAs and the fertilization rate (FR), blastocyst rate and high-quality embryo rate (HQER). The sperm samples with high hsa-mir-191 expression had a higher FR, effective embryo rate (EER) and HQER. hsa-mir-191 was used as a single indicator to predict the HQER. The receiver operating characteristic (ROC) curve had an area under the ROC curve (AUC) of 0.686. We also found that hsa-mir-191 expression is correlated with an abnormal sperm rate (cor = 0.29, p

Because of the limitation of the long-range detection capability of airborne sensors, it is very difficult for a single interceptor to achieve accurate mid-course guidance, especially for the long and medium range interceptors, and the maneuvering or invisible targets. As one of the solutions, the strategy of multi-interceptor cooperative intercepting can overcome the shortages of single-interceptor. Unfortunately, the existing mid-course guidance laws can't meet the requirements of cooperative intercepting strategy. To solve the problem, a novel cooperative mid-course guidance law is proposed in this paper by combining the traditional trajectory shaping guidance law and the cooperative parameter. Firstly, the cooperative mid-course guidance law is designed, and consensus of cooperative parameter characteristics is proved then. Secondly, the general expression of cooperative parameter and its convergence speed is analyzed. Finally, numeral simulations demonstrate the effectiveness and advantages of the proposed cooperative mid-course guidance law.

Multi-layered NiO nanowires linked with a nitrogen-doped carbon backbone grown directly on flexible carbon cloth (NiO/NCBN/CC) was successfully fabricated with a facile synthetic strategy. The NiO/NCBN/CC was further used as a binding-free electrode for flexible energy storage devices, showing a boosted performance including a high capacitance of 1039.4 F g−1 at 1 A g−1 and an 83.4% capacitance retention ratio. More importantly, after 1500 cycles, the capacitance retention can achieve 72.5% at a current density of 20 A g−1. The excellent electrochemical properties of the as-prepared NiO/NCBN/CC are not only attributed to the multi-layered structure that can help to tender unimpeded channels and accommodate the electrolyte ions around the electrode interface during the charge–discharge process, but is also due to the link between the NiO and N-doped carbon backbone and the nitrogen doping on the carbon substrate, which results in extra defects on the surface that could boost the interfacial electron transfer rate of the electrode.

Heading date, as one of the most important agronomic traits, is a fundamental factor determining crop yield. Although diverse genes related to heading date have already been reported in rice, the key gene that regulates heading date is still poorly understood. Here, we identified a heading date regulator, heading date 8 (OsHd8), which promoted the heading date under long-day conditions and encoded a putative HAP3 subunit of the CCAAT-box-binding transcription factor. It is localized in the nucleus and expressed in various tissues. Sequence analysis revealed that there were four SNPs and one InDel in the promoter region of OsHd8, which was involved in the regulation of some floral regulators including GHD7.1, SDG718, OsGI and HDT1. Further evolutionary analysis showed that OsHd8 presents divergence between indica and japonica, showing natural selection during the domestication of cultivated rice. These results indicate that OsHd8 plays an important role in the regulation of heading date, and may be an important target for rice breeding programs.

Background: Psoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets with therapeutic potentials. Acetyl-11-keto-β-boswellic acid (AKBA) is the most bioactive ingredient of boswellic acids, a group of compounds with anti-inflammatory and anti-cancer properties. Target identification of AKBA and metabolomics analysis of psoriasis helped to elucidate the molecular mechanism underlying its effect, and provide new target(s) to treat the disease. Methods: To explore the targets and molecular mechanism of AKBA, we performed affinity purification, metabolomics analysis of HaCaT cells treated with AKBA, and epidermis of imiquimod (IMQ) induced mouse model of psoriasis and psoriasis patients. Findings: AKBA directly interacts with methionine adenosyltransferase 2A (MAT2A), inhibited its enzyme activity, decreased level of S-adenosylmethionine (SAM) and SAM/SAH ratio, and reprogrammed one‑carbon metabolism in HaCaT cells. Untargeted metabolomics of epidermis showed one‑carbon metabolism was activated in psoriasis patients. Topical use of AKBA improved inflammatory phenotype of IMQ induced psoriasis-like mouse model. Molecular docking and site-directed mutagenesis revealed AKBA bound to an allosteric site at the interface of MAT2A dimer. Interpretation: Our study extends the molecular mechanism of AKBA by revealing a new interacting protein MAT2A. And this leads us to find out the dysregulated one‑carbon metabolism in psoriasis, which indicates the therapeutic potential of AKBA in psoriasis. Fund: The National Natural Science Foundation, the National Program on Key Basic Research Project, the Shanghai Municipal Commission, the Leading Academic Discipline Project of the Shanghai Municipal Education Commission. Keywords: Psoriasis, AKBA, Metabolomics, MAT2A, Methionine cycle, One‑carbon metabolism

Endophytes represent a ubiquitous and magical world in plants. Almost all plant species studied by different researchers have been found to harbor one or more endophytes, which protect host plants from pathogen invasion and from adverse environmental conditions. They produce various metabolites that can directly inhibit the growth of pathogens and even promote the growth and development of the host plants. In this review, we focus on the biological control of plant diseases, aiming to elucidate the contribution and key roles of endophytes and their metabolites in this field with the latest research information. Metabolites synthesized by endophytes are part of plant disease management, and the application of endophyte metabolites to induce plant resistance is very promising. Furthermore, multi-omics should be more fully utilized in plant–microbe research, especially in mining novel bioactive metabolites. We believe that the utilization of endophytes and their metabolites for plant disease management is a meaningful and promising research direction that can lead to new breakthroughs in the development of more effective and ecosystem-friendly insecticides and fungicides in modern agriculture.

In this paper, a new dynamic surrounding attack cooperative guidance law against highly maneuvering target based on decoupled model is proposed. First, a new dynamic surrounding guidance strategy is proposed, and virtual targets are introduced to establish the cooperative guidance model for dynamic surrounding attack. Second, a dynamic inverse method is used to decouple the cooperative guidance model, and extended state observers (ESOs) are introduced to estimate the disturbances caused by target maneuver. Then, the impact time and dynamic surrounding guidance (ITDSG) law against highly maneuvering target is designed based on a prescribed-time stable method and the decoupled model. Finally, numerical simulations are performed to illustrate the superiority and effectiveness of the proposed ITDSG.

In this study, we present a hybrid model coupled with two-set nodes Green element method (GEM) and embedded discrete fracture model (EDFM) for capturing the effect of transient flow in inhomogeneous fractured porous media. GEM is an excellent advanced algorithm, which can solve nonlinear problems in heterogeneous media. That is also an obvious advantage of GEM against the original boundary element method (BEM). The novel GEM has double nodes of pressure and flux and it is an improvement of classical GEM, which has a second-order precision and fits for triangle structured grids. In the place of adopting the linear flow approximation for original EDFM, the interflows between local triangle matrix grids and fracture elements are derived using the novel GEM, which has higher accuracy than those in previous EDFMs. Consequently, the modified hybrid model can indeed calculate the pressure and flux distribution of transient flow in multifracture porous media. Three numerical cases are presented to show the practicability of our novel model which include (i) multistage fractured horizontal well, (ii) heterogeneous fractured porous media, and (iii) complex fracture networks (CFNs) in an unconventional reservoir.

Melanoma is a life-threatening cancer with limited treatments. Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) crucial to RNA virus sensing, interferon production, and tumor suppression. Quercetin, a natural flavonoid, has particularly therapeutic interests to prevent and treat cancer, for its pharmacological effects against oxidant, inflammation, and angiogenesis. Quercetin was investigated for its anti-melanoma activity and potential mechanisms in this study. We found that quercetin inhibited mouse melanoma growth in vivo, and suppressed proliferation and promoted apoptosis of both B16 and A375 cells in vitro. Quercetin upregulated IFN-α and IFN-β expression through activating RIG-I promoter in B16 cells. The induction of IFN-α and IFN-β, which could be severely impaired by silencing RIG-I induced interferon stimulated genes (ISGs). Moreover, RIG-I likely amplifies antitumor effects by activating signal transduction and activator of transcription 1 (STAT1) in the IFN-JAK-STAT pathway in an autocrine and paracrine manner. Our study provided novel insights regarding biological and anti-proliferative activities of quercetin against melanoma, and we identified RIG-I as a potential target in anti-tumor therapies.