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Abstract Influenza remains a severe respiratory illness that poses significant global health threats. Recent studies have identified distinct microbial communities within the respiratory tract, from nostrils to alveoli. This research explores specific anti-influenza respiratory microbes using a mouse model supported by 16S rDNA sequencing and untargeted metabolomics. The study found that transferring respiratory microbes from mice that survived H9N2 influenza to antibiotic-treated mice enhanced infection resistance. Notably, the levels of Aeromicrobium were significantly higher in the surviving mice. Mice pre-treated with antibiotics and then inoculated with Aeromicrobium camelliae showed reduced infection severity, as evidenced by decreased weight loss, higher survival rates, and lower lung viral titres. Metabolomic analysis revealed elevated LysoPE (16:0) levels in mildly infected mice. In vivo and in vitro experiments indicated that LysoPE (16:0) suppresses inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX2) expression, enhancing anti-influenza defences. Our findings suggest that Aeromicrobium camelliae could serve as a potential agent for influenza prevention and a prognostic marker for influenza outcomes.

Abstract Background Backfat serves as a vital fat reservoir in pigs, and its excessive accumulation will adversely impact pig growth performance, farming efficiency, and pork quality. The aim of this research is to integrate assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) to explore the molecular mechanisms underlying porcine backfat deposition. Results ATAC-seq analysis identified 568 genes originating from 698 regions exhibiting differential accessibility, which were significantly enriched in pathways pertinent to adipocyte differentiation and lipid metabolism. Besides, a total of 283 transcription factors (TFs) were identified by motif analysis. RNA-seq analysis revealed 978 differentially expressed genes (DEGs), which were enriched in pathways related to energy metabolism, cell cycle and signal transduction. The integration of ATAC-seq and RNA-seq data indicates that DEG expression levels are associated with chromatin accessibility. This comprehensive study highlights the involvement of critical pathways, including the Wnt signaling pathway, Jak-STAT signaling pathway, and fatty acid degradation, in the regulation of backfat deposition. Through rigorous analysis, we identified several candidate genes (LEP, CTBP2, EHHADH, OSMR, TCF7L2, BCL2, FGF1, UCP2, CCND1, TIMP1, and VDR) as potentially significant contributors to backfat deposition. Additionally, we constructed TF-TF and TF-target gene regulatory networks and identified a series of potential TFs related to backfat deposition (FOS, STAT3, SMAD3, and ESR1). Conclusions This study represents the first application of ATAC-seq and RNA-seq, affording a novel perspective into the mechanisms underlying backfat deposition and providing invaluable resources for the enhancement of pig breeding programs.

Abstract Background The novel anti-HER2 antibody drug conjugates (ADCs) can effectively improve the long-term survival of patients with HER2-low expression breast cancer. However, pathological responses to neoadjuvant therapy (NAT) within HER2-low expression breast cancer, the relationship between pathological response and prognosis and the transformation of HER2 status are all now poorly understood. Methods The patients with HER2-0 and HER2-low expression breast cancer receiving NAT at Harbin Medical University Cancer Hospital between Jan. 2014 and Nov. 2018 were retrospectively explored. HER2 low expression refers to the IHC 1 + or 2 + and FISH negative. The Kappa test was utilized for analyzing the consistency rate of HER2 expression. To evaluate disease-free survival (DFS) and overall survival (OS), this research employed both the Kaplan-Meier analysis and the Cox regression. Results In this study, 178 patients with HER2-0 and 344 patients with HER2-low expression breast cancer were included. In comparison with the HER2-0 group, it is shown that patients in the HER2-low group have more possibility to be younger compared to those 50 years old (P

Abstract Pyroelectric (PE) detection technologies have attracted extensive attention due to the cooling-free, bias-free, and broadband properties. However, the PE signals are generated by the continuous energy conversion processes from light, heat, to electricity, normally leading to very slow response speeds. Herein, we design and fabricate a PE detector which shows extremely fast response in near-infrared (NIR) band by combining with the inhomogeneous plasmonic metasurface. The plasmonic effect dramatically accelerates the light-heat conversion process, unprecedentedly improving the NIR response speed by 2−4 orders of magnitude to 22 μs, faster than any reported infrared (IR) PE detector. We also innovatively introduce the concept of time resolution into the field of PE detection, which represents the detector’s ability to distinguish multiple fast-moving targets. Furthermore, the spatially inhomogeneous design overcomes the traditional narrowband constraint of plasmonic systems and thus ensures a wideband response from visible to NIR. This study provides a promising approach to develop next-generation IR PE detectors with ultrafast and broadband responses.

Abstract Spinal cord injury (SCI) compromises the blood-spinal cord barrier (BSCB) and induces neuroinflammation, potentially exacerbating neuronal damage. This underscores the importance of maintaining BSCB integrity and mitigating neuroinflammation in SCI treatment. Our study explores an innovative approach to treating SCI by utilizing platelet-rich plasma-derived exosomes (PRP-Exos) to stabilize BSCB function and alleviate neuroinflammation. We successfully isolated exosomes from platelet-rich plasma and conducted both in vivo and in vitro experiments to assess the therapeutic effects of PRP-Exos and explore their potential mechanisms in stabilizing the BSCB, reducing neuroinflammation, and promoting neural functional recovery.In vitro results demonstrate that PRP-Exos significantly reduce the permeability of bEnd.3 cells under hypoxic-hypoglycemic conditions, thereby restoring the integrity of tight junctions. Additionally, our study elucidates the critical role of the NF-κB signaling pathway in the amelioration of neuroinflammation by PRP-Exos. In the SCI model, local injection of hydrogel-encapsulated PRP-Exos reduced Evans blue dye leakage, enhanced the expression of tight junction proteins, alleviated the inflammatory environment in the damaged area, and improved neural functional recovery. In conclusion, PRP-Exos presents a promising and effective treatment option for SCI.

IntroductionThe influenza virus is recognized as the primary cause of human respiratory diseases, with the current influenza vaccine primarily offering strain-specific immunity and limited protection against drifting strains. Considering this, the development of a broad-spectrum influenza vaccine capable of inducing effective immunity is considered the future direction in combating influenza.MethodsThe present study proposes a novel mRNA-based multi-epitope influenza vaccine, which combines three conserved antigens derived from the influenza A virus. The antigens consist of M2 ion channel’s extracellular domain (M2e), the conserved epitope of located in HA2 of hemagglutinin (H1, H3, B), and HA1 of hemagglutinin. At the same time, trimeric sequences and ferritin were conjugated separately to investigate the immune effects of antigen multivalent presentation.ResultsImmunization studies conducted on C57BL/6 mice with these vaccines revealed that they can elicit both humoral immunity and CD4+ and CD8+ T cell responses, which collectively contribute to enhancing cross-protective effects. The virus challenge results showed that vaccinated groups had significantly reduced lung damage, lower viral loads in the lungs, nasal turbinates, and trachea, as well as decreased levels of pro-inflammatory cytokines.ConclusionThese findings clearly demonstrate the wide range of protective effects provided by these vaccines against H1N1 and B influenza viruses. The present finding highlights the potential of mRNA-based influenza vaccines encoding conserved proteins as a promising strategy for eliciting broad-spectrum protective humoral and cellular immunity against H1N1 and B influenza viruses.

Bioprinting is a groundbreaking technology that enables precise distribution of cell-containing bioinks to construct organoid models that accurately reflect the characteristics of tumors in vivo. By incorporating different types of tumor cells into the bioink, the heterogeneity of tumors can be replicated, enabling studies to simulate real-life situations closely. Precise reproduction of the arrangement and interactions of tumor cells using bioprinting methods provides a more realistic representation of the tumor microenvironment. By mimicking the complexity of the tumor microenvironment, the growth patterns and diffusion of tumors can be demonstrated. This approach can also be used to evaluate the response of tumors to drugs, including drug permeability and cytotoxicity, and other characteristics. Therefore, organoid models can provide a more accurate oncology research and treatment simulation platform. This review summarizes the latest advancements in bioprinting to construct tumor organoid models. First, we describe the bioink used for tumor organoid model construction, followed by an introduction to various bioprinting methods for tumor model formation. Subsequently, we provide an overview of existing bioprinted tumor organoid models.

CONTEXT: NL003 is a plasmid engineered to simultaneously express two isoforms of hepatocyte growth factor. The Phase II clinical trial shows that intramuscular injection of NL003 in the affected limb of patients with critical limb ischemia (CLI) is safe and could alleviate pain and promote ulcer healing. The purpose of this study was to evaluate the long-term safety and efficacy of NL003. METHODS: A total of 108 participants were evaluated: 32 in the placebo group and 76 in the NL003 group. The primary endpoint was 5-year amputation-free survival and the secondary endpoints were pain, ulcer, and adverse reactions. RESULTS: During a mean follow-up period of 10.4 years, the 5-year amputation-free survival rate was 67.1% (51/76) in the NL003 group and 37.5% (12/32) in the placebo group (P < 0.05). The median amputation-free survival was 9.53 years in the NL003 group and 4.51 years in the placebo group. There was no significant difference in the rates of major amputation between the two groups (21.1% vs. 21.9%). Pain relief and ulcer healing tended to favor the NL003 group. No serious adverse reactions such as gene integration and tumor were found during the follow-up. CONCLUSIONS: NL003 has a favorable long-term safety profile and may provide long-term benefit for patients with CLI.

Increasing the soybean-planting area and increasing the soybean yield per unit area are two effective solutions to improve the overall soybean yield. Northeast China has a large saline soil area, and if soybeans could be grown there with the help of isolated saline-tolerant rhizobia, the soybean cultivation area in China could be effectively expanded. In this study, soybeans were planted in soils at different latitudes in China, and four strains of rhizobia were isolated and identified from the soybean nodules. According to the latitudes of the soil-sampling sites from high to low, the four isolated strains were identified as HLNEAU1, HLNEAU2, HLNEAU3, and HLNEAU4. In this study, the isolated strains were identified for their resistances, and their acid and saline tolerances and nitrogen fixation capacities were preliminarily identified. Ten representative soybean germplasm resources in Northeast China were inoculated with these four strains, and the compatibilities of these four rhizobium strains with the soybean germplasm resources were analyzed. All four isolates were able to establish different extents of compatibility with 10 soybean resources. Hefeng 50 had good compatibility with the four isolated strains, while Suinong 14 showed the best compatibility with HLNEAU2. The isolated rhizobacteria could successfully establish symbiosis with the soybeans, but host specificity was also present. This study was a preliminary exploration of the use of salinity-tolerant rhizobacteria to help the soybean nitrogen fixation in saline soils in order to increase the soybean acreage, and it provides a valuable theoretical basis for the application of saline-tolerant rhizobia.

Abstract The global steel industry is integral to the development of modern infrastructure, yet it stands as one of the most significant contributors to greenhouse gas (GHG) emissions worldwide. This dichotomy brings forth the imperative for an in-depth analysis of GHG inventory practices and the pursuit of sustainable production methods. This mini-review paper addresses the current methodologies for GHG accounting within the steel sector, emphasizing the critical role of accurate and transparent emissions data as the basis for effective climate change mitigation strategies. Evaluating the prevalent carbon-intensive blast furnace-basic oxygen furnace (BF-BOF) production route, this paper contrasts traditional practices with innovative reduction initiatives, particularly those aligned with the emergence of green steel. We delve into the advancements in electric arc furnace (EAF) technology, direct reduced iron (DRI) processes utilizing green hydrogen, and the potential of carbon capture, utilization, and storage (CCUS) systems. The analysis extends to a critical examination of the challenges and opportunities these technologies face, including economic viability, scalability, and the readiness of energy infrastructure to support such a transition. Further, this review highlights the significance of verification and validation in reinforcing the credibility of GHG inventories. We scrutinize the materiality of reported emissions in the context of evolving regulatory frameworks and stakeholder expectations, stressing the need for standardized and rigorous assurance practices. Graphical Abstract

Abstract Neurotrauma, encompassing traumatic brain injuries (TBI) and spinal cord injuries (SCI) impacts a significant portion of the global population. While spontaneous recovery post-TBI or SCI is possible, recent advancements in cell-based therapies aim to bolster these natural reparative mechanisms. Emerging research indicates that the beneficial outcomes of such therapies might be largely mediated by exosomes secreted from the administered cells. While stem cells have garnered much attention, exosomes derived from non-stem cells, including neurons, Schwann cells, microglia, and vascular endothelial cells, have shown notable therapeutic potential. These exosomes contribute to angiogenesis, neurogenesis, and axon remodeling, and display anti-inflammatory properties, marking them as promising agents for neurorestorative treatments. This review provides an in-depth exploration of the current methodologies, challenges, and future directions regarding the therapeutic role of non-stem cell-derived exosomes in neurotrauma.

IntroductionHydrothermal vents, rich in heavy metals, provided a unique niche for heavy metal resistant microbes. However, knowledge about copper resistant microbes in deep sea hydrothermal vents is still limited.MethodsThe copper-resistant bacteria were isolated from deep-sea hydrothermal vent samples and conducted thorough physical, phylogenetic, and genomic analyses to elucidate their copper resistance capability and related genes.ResultsTwelve highly copper-resistant bacteria (up to 6-10 mM) were isolated from deep sea hydrothermal fields They were affiliated with the Pseudoalteromonas (4), Marinobacter (3), Halomonas (2), Psychrobacter (1), and Pseudomonas (1) genus in the α-Proteobacteria, and the Sphingomonas (1) genus in the β-Proteobacteria. The presence of copper in the medium obviously induced the amount of polysaccharides and proteins in the crude extracellular polymeric substances (EPS) produced by Halomonas sp. CuT 3-1, Pseudoalteromonas sp. CuT 4-3 and Marinobacter metalliresistant CuT 6, which could absorb 40 to 50 mg•g−1 copper. We further described a novel species, Marinobacter metalliresistant sp. nov. CuT 6T, which exhibited a higher copper resistance and encoded more heavy metal resistance-related genes than other Marinobacter species.DiscussionIt revealed that the copper resistance capability exhibited by these strains in hydrothermal fields is likely attributed to the production of exopolymeric substances, such as polysaccharides and proteins, as well as active transport or efflux mechanisms for heavy metals.

Metallic screws are one of the most common implants in orthopedics. However, the solid design of the screw has often resulted in stress shielding and postoperative loosening, substantially impacting its long-term fixation effect after surgery. Four additive manufacturing porous structures (Fischer-Koch S, Octet, Diamond, and Double Gyroid) are now introduced into the screw to fix those issues. Upon applying the four porous structures, elastic modulus in the screw decreased about 2∼15 times to reduce the occurrence of stress shielding, and bone regeneration effect on the screw surface increased about 1∼50 times to improve bone tissue regrowing. With more bone tissue regrowing on the inner surface of porous screw, a stiffer integration between screw and bone tissue will be achieved, which improves the long-term fixation of the screw tremendously. The biofunctions of the four topologies on osteogenesis have been fully explored, which provides an advanced topology optimization scheme for the screw utilized in orthopedic fixation.

Background Observational studies highlight the association between gut microbiota (GM) composition and depression; however, evidence for the causal relationship between GM and specific depressive symptoms remains lacking.Aims We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index (BMI).Methods We performed a two-sample Mendelian randomisation (MR) analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies. The mediating role of BMI was subsequently explored using mediation analysis via two-step MR.Results MR evidence suggested the Bifidobacterium genus (β=–0.03; 95% CI –0.05 to –0.02; p

BackgroundThe global COVID-19 pandemic has resulted in over seven million deaths, and IFI can further complicate the clinical course of COVID-19. Coinfection of COVID-19 and IFI (secondary IFI) pose significant threats not only to healthcare systems but also to patient lives. After the control measures for COVID-19 were lifted in China, we observed a substantial number of ICU patients developing COVID-19-associated IFI. This creates an urgent need for predictive assessment of COVID-19 patients in the ICU environment for early detection of suspected fungal infection cases.MethodsThis study is a single-center, retrospective research endeavor. We conducted a case-control study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. The cases consisted of patients who developed any secondary IFI during their ICU stay at Jilin University China-Japan Union Hospital in Changchun, Jilin Province, China, from December 1st, 2022, to August 31st, 2023. The control group consisted of SARS-CoV-2 positive patients without secondary IFI. Descriptive and comparative analyses were performed, and a logistic regression prediction model for secondary IFI in COVID-19 patients was established. Additionally, we observed an increased incidence of COVID-19-associated pulmonary aspergillosis (CAPA) during this pandemic. Therefore, we conducted a univariate subgroup analysis on top of IFI, using non-CAPA patients as the control subgroup.ResultsFrom multivariate analysis, the prediction model identified 6 factors that are significantly associated with IFI, including the use of broad-spectrum antibiotics for more than 2 weeks (aOR=4.14, 95% CI 2.03-8.67), fever (aOR=2.3, 95%CI 1.16-4.55), elevated log IL-6 levels (aOR=1.22, 95% CI 1.04-1.43) and prone position ventilation (aOR=2.38, 95%CI 1.15-4.97) as independent risk factors for COVID-19 secondary IFI. High BMI (BMI ≥ 28 kg/m2) (aOR=0.85, 95% CI 0.75-0.94) and the use of COVID-19 immunoglobulin (aOR=0.45, 95% CI 0.2-0.97) were identified as independent protective factors against COVID-19 secondary IFI. The Receiver Operating Curve (ROC) area under the curve (AUC) of this model was 0.81, indicating good classification.ConclusionWe recommend paying special attention for the occurrence of secondary IFI in COVID-19 patients with low BMI (BMI < 28 kg/m2), elevated log IL-6 levels and fever. Additionally, during the treatment of COVID-19 patients, we emphasize the importance of minimizing the duration of broad-spectrum antibiotic use and highlight the potential of immunoglobulin application in reducing the incidence of IFI.

Abstract Objective To investigate the clinical features, treatment strategies, and prognosis of neuroblastoma with bilateral blindness. Methods The clinical data of five patients with bilateral blindness neuroblastoma admitted to Beijing Children’s Hospital from April 2018 to September 2020 were retrospectively collected to summarize their clinical characteristics. Results All patients were female and the median age at presentation was 25 (23, 41) months. The median intervention time from the onset of symptoms of bilateral blindness to the start of treatment was 10 (10, 12) days. All five cases were staged as stage M and grouped as high risk. Four cases were MYCN gene amplification and one case was MYCN acquisition. Five children were treated according to a high-risk neuroblastoma treatment protocol. Four children did not recover their vision after treatment, and one case improved to have light perception. All patients were effectively followed up for a median of 20 (12, 31) months, with three deaths, one tumor-free survival, and one recurrent tumor-bearing survival. Conclusion Neuroblastoma with bilateral blindness is rare in the clinic, mostly in children of young age, and is often associated with MYCN amplification and multiple metastases. Early hormone shock therapy and optic nerve decompression are beneficial for preserving the child’s vision. A joint multi-disciplinary treatment may help in the formulation of treatment decisions. Achieving a balance between good visual preservation and survival within the short optic nerve neurotherapeutic window is extremely challenging.

Abstract Background The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics. Results Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids’ deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. Conclusions Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract

The preparation of novel sludge-based biochar and its application as soil amendments are considered as an environmentally friendly way to realize sludge recycling. In this study, a novel sludge-based biochar (RBC) was prepared by residual sludge after extracellular polymers (EPS) extraction, and the effect of RBC as soil amendment on the ryegrass germination in sandy soil was explored. The results indicated that the biochar yield by residual sludge after EPS extraction was higher than that by raw sludge. Compared with the raw sludge-based biochar (SBC), a variety of new functional groups and crystalline structures were formed in RBC, and the specific surface area and pore volume were significantly increased. Furthermore, a largest NH4+-N adsorption capacity of 7.6 mg/g was achieved by HNO3 modified RBC (MRBC) under an optimum pH of 7. Moreover, the ryegrass germination rate and ryegrass height were increased by 52.0 % and 213.4 % in sandy soil with MRBC adsorbed with NH4+-N as soil amendment compared with that in sandy soil with SBC addition. Accordingly, RBC has great potential for the preparation of novel sludge-based biochar and plays a prominent role as a soil amendment in enhancing plant growth in sandy soil. The above research will provide a new direction for the advanced resource utilization of sewage sludge.

Abstract Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30–150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.

Abstract Background Infertility affects many couples globally, causing physical, emotional, and financial burdens. While observational studies suggest a link between psychiatric disorders and female infertility, causal relationships remain uncertain. Mendelian randomization analysis, using genome-wide association studies data, minimizes confounding factors and reverse causation, providing valuable insights into causal associations. Methods We conducted Mendelian randomization analysis to explore the potential causal relationship between female infertility and psychiatric disorders. Genome-wide association studies summary data for female infertility (112,105 individuals of European ancestry, comprising 11,442 cases and 100,663 controls), depression (807,553 individuals of European ancestry, comprising 246,363 cases and 561,190 controls), anxiety (21,763 individuals of European ancestry, comprising 7,016 cases and 14,745 controls), bipolar disorder (51,710 individuals of European ancestry, comprising 20,352 cases and 31,358 controls), and eating disorders (72,517 individuals of European ancestry, comprising 16,992 cases and 55,525 controls) were utilized. Instrumental variables were selected based on significant single nucleotide polymorphisms associated with each phenotype. We assessed instrumental variable strength, examined confounding factors, and employed inverse variance weighting, weighted median, and MR-Egger approaches for analysis. Results Our analysis included 85 single nucleotide polymorphisms for female infertility and 62 single nucleotide polymorphisms for psychiatric disorders. Results suggest a potential causal relationship between depression and female infertility, with both inverse variance weighting and weighted median methods showing increased infertility risk in depressed patients. Evidence is weak regarding bipolar disorder not increasing female infertility risk. We found no evidence supporting causal links between anxiety, eating disorders, and female infertility. Similarly, no causal relationship was found between female infertility and psychiatric disorders in the opposite direction. Sensitivity analyses and tests for heterogeneity and polymorphism supported result robustness. Conclusions This analysis provides evidence for a potential causal relationship between depression and female infertility. Addressing depression in infertile women may improve fertility outcomes. Further research is needed to explore underlying mechanisms and potential interventions for improving fertility outcomes in women with psychiatric disorders.

Currently, numerous studies have reported that the invasion of Cassytha filiformis has affected both above and below ground communities, resulting in difficulties in the growth of original vegetation. Meanwhile, Cassytha filiformis was observed on the Xisha Islands in recent years which brings up the importance of monitoring its invasion to protect the biodiversity of the island. Nonetheless, to effectively monitor Cassytha filiformis at finer regional scales, there is a pressing need for centimeter-level resolution, a level of precision that current satellite sensors find challenging to attain in a consistent manner. Therefore, we adopted a DJI Phantom 4 unmanned aerial vehicle with five multispectral bands and centimeter-level spatial resolution to overcome this problem. An advanced deep learning network is employed to identify the invasion in Xisha Islands for three different time periods. Results show that the area of Cassytha filiformis on Bei Island increased from 211.8 m2 in April 2020 to 458.6 m2 in April 2021, and dropped to 112.8 m2 in July 2021, while that on Ganquan Island changed from 1996.9 m2 in April 2021 (dry season) to 1275.9 m2 in July 2021 (wet season). By incorporating climatic indicators, we further found that Cassytha filiformis in both Bei Island and Ganquan Island favors dry climate and its large area invasion in 2021 was possibly caused by a drought event.

Abstract We report two children with hepatoblastoma (HB) with a history of neonatal necrotizing enterocolitis (NEC). Case 1 was diagnosed with HB at 5 months of age. Liver enlargement was found during the NEC operation at 3 months of age and then was clinically diagnosed by imaging. After six chemotherapy courses, a partial hepatectomy was performed. Three months after ceasing the chemotherapy, a chest computed tomography scan suggested that distant metastasis of the tumor should be considered, and the lesion was removed. However, 9 months after the operation, alpha‐fetoprotein concentrations were increased, and abdominal imaging showed a recurrence of the tumor in situ, resulting in a hepatectomy. Case 2 was diagnosed with NEC shortly after birth and underwent an intestinal resection and anastomosis 1 month later. He was diagnosed with HB at 3 years of age. Hepatectomy was performed after five courses of chemotherapy. Chemotherapy was stopped after 10 courses, and alpha‐fetoprotein concentrations were normal. At present, both children have survived and are in a healthy condition. Physicians should be aware of the possibility of HB and a history of NEC in children. Premature birth and low birth weight are common factors leading to the pathogenesis of HB and NEC. The association between these two diseases requires further study.

Trace minerals are essential for biological processes, including enzyme function, immune response, and hormone synthesis. The study assessed the effects of different dietary trace minerals on the gut health, microbiota composition, and immune function of cats. Eighteen adult British Shorthair cats were divided into three groups receiving inorganic trace minerals (ITM), a 50/50 mix of inorganic and organic trace minerals (ITM + OTM), or organic trace minerals (OTM) for 28 days. The OTM showed enhanced immune capacities, reduced intestinal barrier function, and lower inflammation condition. The OTM altered gut microbiota diversity, with a lower Simpson index and higher Shannon index (p < 0.05). Specifically, the abundance of Bacteroidota, Lachnospiraceae, and Prevotella in the OTM group were higher than the ITM group (p < 0.05). Metabolomic analysis identified 504 differential metabolites between the OTM and ITM groups (p < 0.05, VIP-pred-OPLS-DA > 1), affecting pathways related to steroid hormone biosynthesis and glycerophospholipid metabolism (p < 0.05, VIP-pred-OPLS-DA > 2). Additionally, there was a significant correlation between intestinal microbiota and differential metabolites. To conclude, dietary OTM can modulate the gut metabolite and microbiota composition, enhance immune and intestinal barrier function, and mitigate inflammation in cats, highlighting the benefit of using OTM in feline diet to promote the intestinal and overall health.

Abstract Ammonia, a vital component in the synthesis of fertilizers, plastics, and explosives, is traditionally produced via the energy‐intensive and environmentally detrimental Haber–Bosch process. Given its considerable energy consumption and significant greenhouse gas emissions, there is a growing shift toward electrocatalytic ammonia synthesis as an eco‐friendly alternative. However, developing efficient electrocatalysts capable of achieving high selectivity, Faraday efficiency, and yield under ambient conditions remains a significant challenge. This review delves into the decades‐long research into electrocatalytic ammonia synthesis, highlighting the evolution of fundamental principles, theoretical descriptors, and reaction mechanisms. An in‐depth analysis of the nitrogen reduction reaction (NRR) and nitrate reduction reaction (NitRR) is provided, with a focus on their electrocatalysts. Additionally, the theories behind electrocatalyst design for ammonia synthesis are examined, including the Gibbs free energy approach, Sabatier principle, d‐band center theory, and orbital spin states. The review culminates in a comprehensive overview of the current challenges and prospective future directions in electrocatalyst development for NRR and NitRR, paving the way for more sustainable methods of ammonia production.

Abstract Senile plaque, composed of amyloid β protein (Aβ) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aβ aggregates exert age‐dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age‐gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of β‐amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age‐dependent Aβ deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age‐dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age‐dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age‐gradient changes in the autophagy–lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

Summary: Stephania japonica is an early-diverging eudicotyledon plant with high levels of cepharanthine, proven to be effective in curing coronavirus infections. Here, we report a high-quality S. japonica genome. The genome size is 688.52 Mb, and 97.37% sequences anchor to 11 chromosomes. The genome comprises 67.46% repetitive sequences and 21,036 genes. It is closely related to two Ranunculaceae species, which diverged from their common ancestor 55.90–71.02 million years ago (Mya) with a whole-genome duplication 85.59–96.75 Mya. We further reconstruct ancestral karyotype of Ranunculales. Several cepharanthine biosynthesis genes are identified and verified by western blot. Two genes (Sja03G0243 and Sja03G0241) exhibit catalytic activity as shown by liquid chromatography-mass spectrometry. Then, cepharanthine biosynthesis genes, transcription factors, and CYP450 family genes are used to construct a comprehensive network. Finally, we construct an early-diverging eudicotyledonous genome resources (EEGR) database. As the first genome of the Menispermaceae family to be released, this study provides rich resources for genomic studies.

Abstract Lung adenocarcinoma (LUAD) is a common type of malignant tumor with poor prognosis and high mortality. In our previous studies, we found that estrogen is an important risk factor for LUAD, and different estrogen statuses can predict different prognoses. Therefore, in this study, we constructed a prognostic signature related to estrogen reactivity to determine the relationship between different estrogen reactivities and prognosis. We downloaded the LUAD dataset from The Cancer Genome Atlas (TCGA) database, calculated the estrogen reactivity of each sample, and divided them into a high-estrogen reactivity group and a low-estrogen reactivity group. The difference in overall survival between the groups was significant. We also analyzed the status of immune cell infiltration and immune checkpoint expression between the groups. We analyzed the differential gene expression between the groups and screened four key prognostic factors by the least absolute shrinkage and selection operator (LASSO) regression and univariable and multivariable Cox regression. Based on the four genes, a risk signature was established. To a certain extent, the receiver operating characteristic (ROC) curve showed the predictive ability of the risk signature, which was further verified using the GSE31210 dataset. We also determined the role of estrogen in LUAD using an orthotopic mouse model. Additionally, we developed a predictive nomogram combining the risk signature with other clinical characteristics. In conclusion, our four-gene prognostic signature based on estrogen reactivity had prognostic value and can provide new insights into the development of treatment strategies for LUAD.

Abstract Objective To summarize the clinical characteristics of children with adrenocortical carcinoma (ACC) and preliminarily explore the indications for and efficacy of neoadjuvant chemotherapy in certain patients. Methods The data of 49 children with adrenocortical tumors (ACT) in the past 15 years were retrospectively analyzed, and after pathology assessment using Weiss system grading, 40 children diagnosed with ACC were included. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and three-dimensional (3D) reconstruction of contrast-enhanced computed tomography data were used to evaluate the response to neoadjuvant chemotherapy. Results Forty patients (17 males, 23 females) with ACC were enrolled. Abnormal hormone levels were common in children with ACC (n = 31), and in terms of clinical presentation, sexual precocity was the most common (n = 14, 35.0%), followed by Cushing’s syndrome (n = 12, 30.0%). Seven of 40 children received neoadjuvant chemotherapy due to a maximum lesion diameter greater than 10 cm (n = 4), invasion of surrounding tissues (n = 2), intravenous tumor thrombus (n = 2), and/or distant metastasis (n = 2); 2 patients achieved partial response, and 5 had stable disease according to the RECIST 1.1 standard. Furthermore, 3D tumor volume reconstruction was performed in 5 children before and after neoadjuvant chemotherapy. Tumor volumes were significantly reduced in all 5 children, with a median volume reduction of 270 (interquartile range, IQR 83, 293) (range: 49–413) ml. After surgery with/without chemotherapy, the 5-year overall survival rate for all children was 90.0% (95% CI-confidence interval 80.0–100.0%), and the 5-year event-free survival rate was 81.5% (95% CI 68.0–97.7%). Conclusion In the diagnosis and treatment of pediatric ACC, a comprehensive endocrine evaluation is necessary to facilitate early diagnosis. Surgery and chemotherapy are important components of ACC treatment, and neoadjuvant chemotherapy should be considered for children with ACC who meet certain criteria, such as a large tumor, distant metastases, or poor general condition.

Abstract In this commentary, we briefly introduce the importance of metabolic reprogramming in non‐small celllung cancer (NSCLC) and the role of aberrant glycolysis processes intumorigenesis and metastasis. We further summarize the regulation of deubiquitylation modification on glycolysis‐related kinases in this system. Andwe discusse the major discovery the research by He Yuanming et al. published in Clinical and Translational Medicine.Their study demonstrates targeting the USP7‐c‐Abl‐HK2 axis represents a promising therapeutic strategt for NSCLC.

Abstract Objectives Systemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease characterised by persistent inflammation. Hydroxychloroquine (HCQ) and glucocorticoids (GCs) are the primary agents commonly used in combination as the first‐line treatment for SLE. Nevertheless, the specific mechanisms responsible for the effectiveness of this combined therapy with HCQ and GCs have not been fully elucidated. This study aimed to reveal the mechanism behind combined HCQ and GC treatment in lupus. Methods An SLE IgG‐induced inflammation model was used to investigate the anti‐inflammatory effects of HCQ and dexamethasone (DXM). A glucocorticoid‐induced osteoporosis (GIOP) model was used to investigate the inhibitory effect of HCQ on osteoclastogenesis. Inflammation was assessed by haematoxylin and eosin staining. Bone metabolism was determined structurally via microcomputer tomography and in bone marrow‐derived osteoclast cultures. Results An SLE IgG‐induced inflammation model demonstrated that HCQ could not ameliorate inflammation alone but could enhance the anti‐inflammatory effect of GCs by decreasing the expression of FcγRI on macrophages. HCQ inhibited osteoclastogenesis induced by GCs and RANKL by upregulating nuclear factor erythroid 2‐related factor 2 and limiting reactive oxygen species formation, which mitigated GC‐induced bone loss. Conclusion The results indicate that HCQ improved the anti‐inflammatory effects of GCs and inhibits the osteoclastogenesis in experimental lupus. This study offers valuable insights into the mechanisms underlying the combined treatment of lupus with HCQ and GCs.

Port accessibility is an important factor in the efficiency of a port collection and distribution systems. And the carbon emission of the collection and transportation system is large, which is an important factor that cannot be ignored when constructing the collection and transportation system. In order to analyze the carbon emission characteristics of the port collection and distribution system, the paper incorporates the carbon emission factor into the accessibility measurement of the port collection and distribution system. To solve the problem of unbalanced demand of each logistics node, the distribution of logistics demand in the system is realized by the method based on the appropriate freight volume. The carbon emission cost factor is introduced, and the accessibility measurement model based on the generalized cost impedance function is constructed. Taking the collection and distribution system of Douala Port in West Africa as an example to verify, the results show that, after adding the carbon emission factor, the accessibility of each logistics node shows different degrees of decline which shows that the addition of the carbon emission factor can be more comprehensive and can reflect the accessibility of the system.

Acute lung injury (ALI) is a progressive inflammatory injury, and mesenchymal stem cells (MSCs) can be used to treat ALI. MSC-conditioned medium (MSC-CM) contains many cytokines, in which keratinocyte growth factor (KGF) is a soluble factor that plays a role in lung development. We aim to explore the protective effects of MSCs secreted KGF on ALI, and investigate the involvement of epithelial sodium channel (ENaC), which are important in alveolar fluid reabsorption. Both lipopolysaccharides (LPS)-induced mouse and alveolar organoid ALI models were established to confirm the potential therapeutic effect of MSCs secreted KGF. Meanwhile, the expression and regulation of ENaC were determined in alveolar type II epithelial (ATII) cells. The results demonstrated that MSC-CM and KGF could alleviate the extent of inflammation-related pulmonary edema in ALI mice, which was abrogated by a KGF neutralizing antibody. In an alveolar organoid ALI model, KGF in MSC-CM could improve the proliferation and decrease the differentiation of ATII cells. At the cellular level, the LPS-inhibited protein expression of ENaC could be reversed by KGF in MSC-CM. In addition, bioinformatics analysis and our experimental data provided the evidence that the NF-κB signaling pathway may be involved in the regulation of ENaC. Our research confirmed that the therapeutic effect of MSC-CM on edematous ALI was closely related to KGF, which may be involved in the proliferation and differentiation of ATII cells, as well as the upregulation of ENaC expression by the inhibition of NF-κB signaling pathway.

Abstract Cardiac hypertrophy is a common structural remodeling in many cardiovascular diseases. Recently, long non-coding RNAs (LncRNAs) were found to be involved in the physiological and pathological processes of cardiac hypertrophy. In this study, we found that LncRNA KCND1 (LncKCND1) was downregulated in both transverse aortic constriction (TAC)-induced hypertrophic mouse hearts and Angiotensin II (Ang II)-induced neonatal mouse cardiomyocytes. Further analyses showed that the knockdown of LncKCND1 impaired cardiac mitochondrial function and led to hypertrophic changes in cardiomyocytes. In contrast, overexpression of LncKCND1 inhibited Ang II-induced cardiomyocyte hypertrophic changes. Importantly, enhanced expression of LncKCND1 protected the heart from TAC-induced pathological cardiac hypertrophy and improved heart function in TAC mice. Subsequent analyses involving mass spectrometry and RNA immunoprecipitation assays showed that LncKCND1 directly binds to YBX1. Furthermore, overexpression of LncKCND1 upregulated the expression level of YBX1, while silencing LncKCND1 had the opposite effect. Furthermore, YBX1 was downregulated during cardiac hypertrophy, whereas overexpression of YBX1 inhibited Ang II-induced cardiomyocyte hypertrophy. Moreover, silencing YBX1 reversed the effect of LncKCND1 on cardiomyocyte mitochondrial function and its protective role in cardiac hypertrophy, suggesting that YBX1 is a downstream target of LncKCND1 in regulating cardiac hypertrophy. In conclusion, our study provides mechanistic insights into the functioning of LncKCND1 and supports LncKCND1 as a potential therapeutic target for pathological cardiac hypertrophy.

Abstract Background Hypoxia is associated with many respiratory diseases, partly due to the accumulation of edema fluid and mucus on the surface of alveolar epithelial cell (AEC), which forms oxygen delivery barriers and is responsible for the disruption of ion transport. Epithelial sodium channel (ENaC) on the apical side of AEC plays a crucial role to maintain the electrochemical gradient of Na+ and water reabsorption, thus becomes the key point for edema fluid removal under hypoxia. Here we sought to explore the effects of hypoxia on ENaC expression and the further mechanism related, which may provide a possible treatment strategy in edema related pulmonary diseases. Methods Excess volume of culture medium was added on the surface of AEC to simulate the hypoxic environment of alveoli in the state of pulmonary edema, supported by the evidence of increased hypoxia-inducible factor-1 expression. The protein/mRNA expressions of ENaC were detected, and extracellular signal-regulated kinase (ERK)/nuclear factor κB (NF-κB) inhibitor was applied to explore the detailed mechanism about the effects of hypoxia on epithelial ion transport in AEC. Meanwhile, mice were placed in chambers with normoxic or hypoxic (8%) condition for 24 h, respectively. The effects of hypoxia and NF-κB were assessed through alveolar fluid clearance and ENaC function by Ussing chamber assay. Results Hypoxia (submersion culture mode) induced the reduction of protein/mRNA expression of ENaC, whereas increased the activation of ERK/NF-κB signaling pathway in parallel experiments using human A549 and mouse alveolar type 2 cells, respectively. Moreover, the inhibition of ERK (PD98059, 10 µM) alleviated the phosphorylation of IκB and p65, implying NF-κB as a downstream pathway involved with ERK regulation. Intriguingly, the expression of α-ENaC could be reversed by either ERK or NF-κB inhibitor (QNZ, 100 nM) under hypoxia. The alleviation of pulmonary edema was evidenced by the administration of NF-κB inhibitor, and enhancement of ENaC function was supported by recording amiloride-sensitive short-circuit currents. Conclusions The expression of ENaC was downregulated under hypoxia induced by submersion culture, which may be mediated by ERK/NF-κB signaling pathway.

Abstract Background Age at puberty is an important factor affecting goat fertility, with endocrine and genetic factors playing a crucial role in the onset of puberty. To better understand the relationship between endocrine and genetic factors and mechanisms underlying puberty onset in goats, reproductive hormone levels were analyzed by ELISA and ultraperformance liquid chromatography–multiple reaction monitoring–multistage/mass spectrometry and RNA sequencing was performed to analyze ovarian genes. Results Serum follicle stimulating hormone, luteinizing hormone, estradiol, 11-deoxycortisol, 11-deoxycorticosterone, corticosterone, cortisone, and cortisol levels were found to be higher but progesterone were lower in pubertal goats as compared to those in prepubertal goats (P

The semi-circular breakwater (SBW) has been implemented at numerous global locations due to its outstanding wave dissipation effectiveness and high structural performance. This study extends prior research by investigating the seabed dynamic response and hydrodynamic response characteristics around perforated SBWs. A coupled numerical model is developed to integrate waves, a semi-circular breakwater, and a sandy seabed. Wave behavior is simulated using Reynolds-averaged Navier–Stokes equations with a k-ε turbulence closure scheme, and the seabed response is numerically simulated using Biot’s full-dynamic (u-w) equations. After verifying computational accuracy, a series of tests is conducted to explore the effects of marine environments and SBW characteristics. Test results reveal a positive correlation between seabed response and wave height, wave period, and perforation number, while showing a negative correlation between seabed response and water depth and perforation rate. The basic perforation type is more effective than front and rear perforation types in maintaining a stable flow field and seabed response. These findings provide insights for designing SBWs for effective wave dissipation and seabed stability in complex marine environments, offering valuable recommendations for future designs.

Alfalfa is one of the most widely cultivated perennial legume crops used as feedstock for animals. Efficiently estimating alfalfa yield and quality traits before harvesting is critical for the decision-making process regarding precision management activities and harvesting time to ensure high profitability. Satellite-based radar is a powerful tool in remote sensing for crop monitoring because it provides high-quality data regardless of weather conditions. Therefore, this study aims to investigate the potential use of satellite radar features and environmental factors in estimating alfalfa yield and quality. Alfalfa yield and quality traits, including dry matter yield (DMY), crude protein (CP), neutral detergent fiber (NDF), NDF digestibility (NDFD), and acid detergent fiber (ADF), were collected over 16 alfalfa fields from 2016 to 2021, leading to 126 samples in total. Sentinel-1 radar backscattering coefficients and environmental factors were collected for all the fields across all growing seasons. Five commonly used machine learning models were established to estimate each alfalfa trait separately. The results show that the Extreme Gradient Boosting model consistently performed the best for all alfalfa traits. The accuracy of the DMY estimates is acceptable, with an average R2 of 0.67 and an RMSE of 0.68 tons/ha. The best result for estimating CP was an average R2 of 0.70 and an RMSE of 1.63% DM. In estimating alfalfa fiber indicators (i.e., ADF, NDF, and NDFD), we achieved the highest average R2 values of 0.54, 0.62, and 0.56, respectively. Overall, this study demonstrated the potential use of environmental factors for alfalfa yield and quality estimation in-field before harvesting. However, the Sentinel-1 radar backscattering coefficients did not make significant contributions to improving the estimation performance, compared to the environmental factors.

Poly (ADP-ribose) polymerase inhibitors (PARPis) are approved for cancer therapy according to their synthetic lethal interactions, and clinical trials have been applied in non–small cell lung cancer. However, the therapeutic efficacy of PARPis in lung adenocarcinoma (LUAD) is still unknown. We explored the effect of a mutated retinoblastoma gene (RB1) on PARPi sensitivity in LUAD. Bioinformatic screening was performed to identify PARPi-sensitive biomarkers. Here, we showed that viability of LUAD cell lines with mutated RB1 was significantly decreased by PARPis (niraparib, rucaparib, and olaparib). RB1 deficiency induced genomic instability, prompted cytosolic double-stranded DNA (dsDNA) formation, activated the cGAS/STING pathway, and upregulated downstream chemokines CCL5 and CXCL10, triggering immune cell infiltration. Xenograft experiments indicated that PARPi treatment reduced tumorigenesis in RB1-KO mice. Additionally, single-cell RNA sequencing analysis showed that malignant cells with downregulated expression of RB1 had more communications with other cell types, exhibiting activation of specific signaling such as GAS, IFN response, and antigen-presenting and cytokine activities. Our findings suggest that RB1 mutation mediates the sensitivity to PARPis through a synthetic lethal effect by triggering the cGAS/STING pathway and upregulation of immune infiltration in LUAD, which may be a potential therapeutic strategy.

BackgroundRecent studies have reported better predictive performance of triglyceride glucose (TyG) index for cardiovascular events in women, however, whether this association persists in postmenopausal women is inconclusive. We investigated the association between TyG index and H-type hypertension (HHT) in postmenopausal women.Methods1,301 eligible women with hypertension were included in this cross-sectional study. Concomitant homocysteine levels >10 μmol/L were defined as H-type hypertension. The TyG index was calculated as ln [triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Multivariable logistic regression models and restricted cubic spline models were used to assess the association between TyG index and H-type hypertension in postmenopausal women, and subgroup analyses were performed for potential confounders.ResultsOf the 1,301 hypertensive patients, 634 (48.7%) participants had H-type hypertension. In each adjusted model, TyG index was significantly associated with the risk of H-type hypertension. each 1-unit increase in TyG index was associated with an increased risk of H-type hypertension in all participants (OR = 1.6; 95% CI, 1.3–2.0; P

Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and summarize the approaches for improving the characteristics of bone cement. Finally, we review the types and clinical efficacy of new vertebral implants. This review may provide valuable insights into newer strategies and methods for future research; it may also improve understanding on the application of minimally invasive materials for the treatment of vertebral compression fractures.

Abstract Myocardial fibrosis post myocardial infarction (MI) is characterized by abnormal extracellular matrix (ECM) deposition and cardiac dysfunction could finally develop into serious heart disease, like heart failure. Lots of regulating factors involved in this pathological process have been reported while the specific mediators and underlying mechanisms remain to need to be further investigated. As part of the NAP1 family, Nucleosome assembly protein 1 like 1 (NAP1L1) is expressed in a wide variety of tissues. Here, we report that NAP1L1 is a significant regulator of cardiac fibrosis and is upregulated in ischemic cardiomyopathy patient hearts. Enhanced expression of NAP1L1 can promote cardiac fibroblasts (CFs) proliferation, migration, and differentiation into myofibroblasts. In contrast, loss of NAP1L1 decreased fibrosis‐related mRNA and protein levels, inhibited the trans‐differentiation, and blunted migration and proliferation of CFs after Transforming Growth Factorβ1（TGF‐β1）stimulation. In vivo, NAP1L1 knockout mice enhanced cardiac function and reduced fibrosis area in response to MI stimuli. Mechanically, NAP1L1 binding to Yes‐associated protein 1 (YAP1) protein influences its stability, and silencing NAP1L1 can inhibit YAP1 expression by promoting its ubiquitination and degradation in CFs. Collectively, NAP1L1 could potentially be a new therapeutic target for various cardiac disorders, including myocardial fibrosis.

Summary: This study found that the level of neuroepithelial cell-transforming gene 1 protein (NET1) was significantly increased in a mouse cardiac fibrosis model. Moreover, the expression level of NET1 was increased in cardiac fibrosis induced by TGF-β1, suggesting that NET1 was involved in the pathological process of cardiac fibrosis. Overexpression of NET1 promoted β-catenin expression in the nucleus and significantly increased the proliferation and migration of cardiac fibroblasts. NET1 may form a complex with β-catenin through GSK3β. Knockdown of β-catenin alleviated the effects of NET1 overexpression on collagen production and cell migration. In the heart of NET1 knockout mice, NET1 knockout can reduce the expression of β-catenin, α-SMA, and collagen content induced by MI. In conclusion, NET1 may regulate the activation of Wnt/β-catenin and TGF/Smads signaling pathway, promote collagen synthesis in fibroblasts, and participate in cardiac fibrosis. Thus, NET1 may be a potential therapeutic target in cardiac fibrosis.

Summary: Glucocorticoid-induced osteoporosis (GIOP) is a severe and common complication of long-term usage of glucocorticoids (GCs) and lacks of efficient therapy. Here, we investigated the mechanism of anti-inflammation effect and osteoclastogenesis side effect of GCs and immunoglobulin G (IgG) treatment against GIOP. GCs inhibited SLE IgG-induced inflammation, while IgG inhibited GCs-induced osteoclastogenesis. FcγRI and glucocorticoid receptor (GR) were found directly interacted with each other. GCs and IgG could reduce the expression of FcγRI on macrophages. The deficiency of FcγRI affected osteoclastogenesis by GCs and systemic lupus erythematosus (SLE) IgG-induced inflammation. Also, IgG efficiently reduced GIOP in mice. These data showed that GCs could induce osteoporosis and inhibit IgG-induced inflammation through FcγRI while IgG efficiently suppressed osteoporosis induced by GCs through FcγRI. Hence, our findings may help in developing a feasible therapeutic strategy against osteoporosis, such as GIOP.

ABSTRACT: Aberrant epigenetic nuclear reprogramming, especially imprinting pattern disorders, is one of the major causes of failure of clone development from somatic cell nuclear transfer (SCNT). Previous studies showed that ZFP57 is a key protein required for imprint maintenance after fertilization. In this study, we found that imprinting control regions in several imprinted genes were significantly hypomethylated in cloned embryos compared with in vitro fertilization embryos, indicating a loss of imprinted gene methylation. The ZFP57 expression was capable of maintaining the correct degree of methylation at several imprinting control regions and correcting abnormal hypomethylation. Moreover, we successfully obtained bovine fetal fibroblasts overexpressing ZFP57, which were used as donors for SCNT. Our results demonstrated that overexpression of ZFP57 increased total and trophectoderm cell numbers and the ratio of inner cell mass to total cells, reduced the apoptosis rate and significantly enhanced the development of SCNT blastocysts in vitro, ultimately achieving a degree of methylation similar to that in in vitro fertilization embryos. We concluded that overexpression of ZFP57 in donor cells provided an effective method for enhancing nuclear reprogramming and developmental potential in SCNT embryos. The ZFP57 protein played a key role in maintaining the methylation of imprinted genes during early embryonic development, which may be effective for enhanced SCNT in cattle.

Purpose This study aimed to calculate and analyze the differences in electroencephalogram (EEG) between major depression disorder (MDD) patients and healthy controls using the method of brainwave music to provide evidence of physiological parameters for clinical diagnosis of MDD. Methods We translated the 5-minute resting EEG data of 20 MDD patients and 20 healthy controls, which were collected by Peking University Sixth Hospital, into brainwave music; and calculated the pitch, volume, duration and corresponding scaling exponents to analyze the differences between MDD patients and healthy people. Then combined the analysis methods of nonlinear dynamics and brain network structure to verify the validity of the proposed method. Results The pitch, volume, and Lemple-Ziv complexity (LZC) in the frontal lobe of MDD patients were higher than those of healthy people. In the central, occipital, and temporal regions of the left hemisphere, the scaling exponents, degrees, and clustering coefficient of MDD patients were lower than those of healthy people (P

Chlorine disinfection has been reported to be ineffective in controlling RO membrane biofouling in some projects. Feed water temperature is a crucial factor in the formation of RO membrane biofouling. It has a positive impact on the wide application of the RO process to ascertain whether chlorine disinfection can alleviate the membrane biofouling at low temperatures. In this study, the effects of chlorination on the RO membrane biofouling at low feed water temperature (10 °C) were investigated by a lab-scale RO apparatus. The final normalized flux was 0.33 and 0.29 with and without chlorination, respectively. According to the normalized flux decline curve, chlorination could not alleviate the RO membrane fouling at low temperature. Based on the intermediate blocking model, chlorination increased the membrane fouling potential of the feed water. At low temperature, the biofilm on the membrane with chlorination was thinner and denser than that without chlorination. In addition, the membrane with chlorination contained more foulants and dissolved organic matter than that without chlorination. Chlorination failed to continuously prevent bacteria accumulation on RO membrane at low temperature, but screened out bacteria that were potentially more suitable for the low-temperature membrane environment. HIGHLIGHTS Effects of chlorination on RO membrane biofouling at low temperature were studied.; Chlorine disinfection could not alleviate the RO membrane fouling at low temperature.; The biofilm with chlorination was thinner but had more foulants at low temperature.; Chlorine disinfection failed to prevent bacterial accumulation at low temperature.; Chlorination changed the microbial community structure at low temperature.;

Abstract IN the trend of energy revolution, power data becomes one of the key elements of the power grid. And an advance power system with "electric power + computing power" as the core has become an inevitable choice. However, the traditional search approach based on directory query is commonly used for power grid operation data in domestic and international. The approach fails to effectively meet the user's need for fast, accurate and personalized retrieval of useful information from the vast amount of power grid data. It seriously affects the real-time availability of data and the efficiency of business-critical analytical decisions. For this reason, an intelligent retrieval approach for power grid operation data based on improved SimHash and multi-attribute decision making is proposed in this paper. This method elaborates the properties of SimHash and multi-attribute decision making algorithms. And an intelligent parallel retrieval algorithm MR-ST based on MapReduce model is designed. Finally, real time grid operation data from multiple sources are analyzed on the cloud platform for example. The experimental results show the effectiveness and precision of the method. Compared with traditional methods, the search accuracy rate, search completion rate and search time are significantly improved. Experiments show that the method can be applied to intelligent retrieval of power grid operation data.

Cucurbitaceae is one of the most important plant families distributed worldwide. Transcription factors (TFs) regulate plant growth at the transcription level. Here, we performed a systematic analysis of 42 641 TFs from 63 families in 14 Cucurbitaceae and 10 non-cucurbit species. Whole-genome duplication (WGD) was the dominant event type in almost all Cucurbitaceae plants. The TF families were divided into 1 210 orthogroups (OGs), of which, 112 were unique to Cucurbitaceae. Although the loss of several gene families was detected in Cucurbitaceae, the gene families expanded in five species that experienced a WGD event comparing with grape. Our findings revealed that the recent WGD events that had occurred in Cucurbitaceae played important roles in the expansion of most TF families. The functional enrichment analysis of the genes that significantly expanded or contracted uncovered five gene families, AUX/IAA, NAC, NBS, HB, and NF-YB. Finally, we conducted a comprehensive analysis of the TCP gene family and identified 16 tendril-related (TEN) genes in 11 Cucurbitaceae species. Interestingly, the characteristic sequence changed from CNNFYFP to CNNFYLP in the TEN gene (Bhi06M000087) of Benincasa hispida. Furthermore, we identified a new characteristic sequence, YNN, which could be used for TEN gene exploitation in Cucurbitaceae. In conclusion, this study will serve as a reference for studying the relationship between gene family evolution and genome duplication. Moreover, it will provide rich genetic resources for functional Cucurbitaceae studies in the future.

ObjectivePost-thrombotic syndrome (PTS) is the most common long-term complication in patients with deep venous thrombosis, and the prevention of PTS remains a major challenge in clinical practice. Some studies have explored early predictors and constructed corresponding prediction models, whereas their specific application and predictive value are controversial. Therefore, we conducted this systematic evaluation and meta-analysis to investigate the incidence of PTS and the feasibility of early prediction.MethodsWe systematically searched databases of PubMed, Embase, Cochrane and Web of Science up to April 7, 2023. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included articles, and the OR values of the predictors in multi-factor logistic regression were pooled to assess whether they could be used as effective independent predictors.ResultsWe systematically included 20 articles involving 8,512 subjects, with a predominant onset of PTS between 6 and 72 months, with a 2-year incidence of 37.5% (95% CI: 27.8–47.7%). The results for the early predictors were as follows: old age OR = 1.840 (95% CI: 1.410–2.402), obesity or overweight OR = 1.721 (95% CI: 1.245–2.378), proximal deep vein thrombosis OR = 2.335 (95% CI: 1.855–2.938), history of venous thromboembolism OR = 3.593 (95% CI: 1.738–7.240), history of smoking OR = 2.051 (95% CI: 1.305–3.224), varicose veins OR = 2.405 (95% CI: 1.344–4.304), and baseline Villalta score OR = 1.095(95% CI: 1.056–1.135). Meanwhile, gender, unprovoked DVT and insufficient anticoagulation were not independent predictors. Seven studies constructed risk prediction models. In the training set, the c-index of the prediction models was 0.77 (95% CI: 0.74–0.80) with a sensitivity of 0.75 (95% CI: 0.68–0.81) and specificity of 0.69 (95% CI: 0.60–0.77). In the validation set, the c-index, sensitivity and specificity of the prediction models were 0.74(95% CI: 0.69–0.79), 0.71(95% CI: 0.64–0.78) and 0.72(95% CI: 0.67–0.76), respectively.ConclusionsWith a high incidence after venous thrombosis, PTS is a complication that cannot be ignored in patients with venous thrombosis. Risk prediction scoring based on early model construction is a feasible option, which helps to identify the patient's condition and develop an individualized prevention program to reduce the risk of PTS.