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Abstract Background Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. Methods Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs’ gene and protein expression was conducted using human colon cancer cells. Results Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. Conclusion This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

Abstract Background The optimal fluid management strategy for patients undergoing cardiac surgery was controversial regarding fluid volume and intraoperative fluid types. This study aimed to assess the correlation between colloids and crystalloids used for perioperative fluid therapy in cardiac surgery patients and postoperative prognosis. Methods The Ovid MEDLINE(R) ALL, Embase, and Cochrane Central Register of Controlled Trials databases were searched for eligible studies on fluid management strategies using colloids and crystalloids for cardiac surgery patients published before August 25th, 2023. Results Ten randomized controlled trials met the eligibility criteria. Compared to the use of crystalloids, the use of colloids, including hydroxyethyl starch (HES), albumin, and gelatine, did not show any differences in mortality, transfusion, acute kidney injury, and atrial fibrillation rates, postoperative blood loss, the length of hospital stay, or the length of intensive care unit (ICU) stay. The results of this meta-analysis showed that the crystalloid group had significantly reduced postoperative chest tube output compared to the colloid group. In the subgroup analysis, the amount of fresh frozen plasma (FFP) infused was significantly lower when using fluid management in the ICU and when using isotonic crystalloids compared to the colloids. In addition, when using fluid management in the ICU, patients in the colloid group had a significant increase in urine volume 24 h after surgery. However, other related factors, including the type of crystalloid solution, type of colloidal solution, and timing of liquid management, did not affect most outcomes. Conclusion Both colloids and crystalloids could be used as alternatives for perioperative fluid management after cardiac surgery. The use of crystalloids significantly reduced the postoperative chest tube output, and the need for FFP infusion decreased significantly with the use of isotonic crystalloids or fluid management during the ICU stay. ICU patients in the colloid group had higher urine output 24 h after surgery. In addition, although the infusion method was not related to most outcomes, the rates of red blood cell and FFP transfusion and postoperative blood loss in the crystalloid group seemed to be lower, which needed to be further studied in high-quality and large-sample RCTs. Trial registration PROSPERO, CRD42023415234.

The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

Abstract Organic light-emitting diodes (OLEDs) offer the advantage of flexibility; however, the use of traditional transparent anode ITO limits further extension of their flexible characteristics. In this study, we propose employing an polymer polybenzodifuranedione (PBFDO) as a flexible transparent anode instead of the rigid ITO. To address the issue encountered during the PBFDO solution spin-coating process, we introduced n-butanol into the PBFDO conductive solution to reduce its viscosity and freezing point by modulating intermolecular hydrogen bonding interactions. Consequently, high-quality PBFDO films with high conductivity, superior transmittance, and low surface roughness were successfully obtained via spin-coating. Moreover, due to its proper work function, regular molecular stacking, and low refractive index properties, PBFDO electrode facilitate efficient carrier injection and transport as well as photon extraction. The resulting device utilizing a PBFDO anode combined with Super Yellow as the light-emitting layer exhibited excellent performance characteristics including a normal threshold voltage of 2.6 V and a maximum luminous efficiency of 12.8 cd A−1 comparable to that device based on the ITO electrode. Furthermore, flexible device also achieved satisfactory performance (7.7 cd A−1) when using the PEN substrate.

Influence maximization (IM) algorithms play a significant role in hypergraph analysis tasks, such as epidemic control analysis, viral marketing, and social influence analysis, and various IM algorithms have been proposed. The main challenge lies in IM algorithm evaluation, due to the complexity and diversity of the spreading processes of different IM algorithms in different hypergraphs. Existing evaluation methods mainly leverage statistical metrics, such as influence spread, to quantify overall performance, but do not fully unravel spreading characteristics and patterns. In this paper, we propose an exploratory visual analytics system, IMVis, to assist users in exploring and evaluating IM algorithms at the overview, pattern, and node levels. A spreading pattern mining method is first proposed to characterize spreading processes and extract important spreading patterns to facilitate efficient analysis and comparison of IM algorithms. Novel visualization glyphs are designed to comprehensively reveal both temporal and structural features of IM algorithms’ spreading processes in hypergraphs at multiple levels. The effectiveness and usefulness of IMVis are demonstrated through two case studies and expert interviews.

Abstract Background The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven’t been comprehensively described. Methods We searched the medical records of all the transplant recipients who attended the Children’s Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children. Results A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system. Conclusions Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern.

Abstract Nickel (Ni), a component of urease, is a micronutrient essential for plant growth and development, but excess Ni is toxic to plants. Tomato (Solanum lycopersicum L.) is one of the important vegetables worldwide. Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils, thus reducing yield and quality of tomatoes. However, the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated. Here, we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physio-biochemical, transcriptomic and molecular regulatory network analyses. Ni toxicity repressed photosynthesis, induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings. Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants. Furthermore, Ni toxicity reduced the phytohormone concentrations, including auxin, cytokinin and gibberellic acid, thereby retarding plant growth. Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways. Taken together, these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.

Recently, the construction of the trisubstituted olefin-type probe molecules has elicited the attention of many researchers. However, the synthesis of the trisubstituted olefin-type probes containing two N-heterocycles simultaneously has been rarely reported. In this study, starting from the inexpensive mucobromic acid 1 and N-heterocyclic compound 2, we first utilized a simple one-step reaction to synthesize a series of trisubstituted olefin-type compounds 3 simultaneously bearing with the structure of two N-heterocyclic rings in the absence of transition metal catalysts with a yield of 62–86%. The optimal reaction conditions were systematically explored, and the structure of the obtained compounds 3 were well characterized with 1H NMR, 13C NMR, X-ray single-crystal and HR-MS. The preliminary observation showed that, in the presence of base, mucobromic acid 1 reacts as its ring-opening structure, and the successive nucleophilic substitution reaction and Michael addition reaction can generate the target product 3. Considering that the aldehyde group in the molecular structure of the trisubstituted olefin-type compounds 3 may react with malononitrile, we carried out some relevant investigations so as to realize the visual detection of malononitrile. Interestingly, among the products, compounds 3a–3c can be prepared in portable test strips through a simple process and used to achieve the naked-eye detection of malononitrile in environmental systems as designed.

In order to solve the problem of roof water inrush risk during the mining of No. 9 coal seam in Longfeng Coal Mine, an LDA-RBF neural network model for predicting the development height of water-conduction fracture zone was constructed by linear discriminant analysis (LDA), and a CRITIC-AHP comprehensive weighting method was established based on the improved CRITIC evaluation method combined with analytic hierarchy method (AHP) to evaluate the risk of roof cracking and the water richness level of the aquifer in the mining area. Through ArcGis geographic information processing technology, the cracking risk zone and the water-rich zone are superimposed to obtain a comprehensive zoning map of the water inrush risk of the roof of No.9 coal seam. The results show that the LDA-RBF neural network prediction model has a simple structure and higher fitting accuracy, and the development prediction height of the No.9 coal seam water-conducting fracture zone is 50.4 m, which has exceeded the bottom boundary level of most aquifers in the area, indicating that there is a high risk of cracking in most areas. The improved comprehensive weighting method avoids the problem of excessive subjectivity and objectivity of the evaluation results, and the water-rich zoning results are consistent with the actual water inflow of the borehole. Finally, the water inrush danger zone is mainly distributed in strips in the central and northern parts of the mining area, which is the result of the combined effect of strong water richness and high cracking risk of the aquifer in this area, indicating that the above areas should be paid attention to in actual mining.

Abstract During the development of the vertebrate nervous system, 50% of the nerve cells undergo apoptosis shortly after formation. This process is important for sculpting tissue during morphogenesis and removing transiently functional cells that are no longer needed, ensuring the appropriate number of neurons in each region. Dysregulation of neuronal apoptosis can lead to neurodegenerative diseases. However, the molecular events involved in activating and regulating the neuronal apoptosis program are not fully understood. In this study, we identified several RB1 mutations in patients with neurodegenerative diseases. Then, we used a zebrafish model to investigate the role of Rb1 in neuronal apoptosis. We showed that Rb1-deficient mutants exhibit a significant hindbrain neuronal apoptosis, resulting in increased microglia infiltration. We further revealed that the apoptotic neurons in Rb1-deficient zebrafish were post-mitotic neurons, and Rb1 inhibits the apoptosis of these neurons by regulating bcl2/caspase through binding to Kmt5b. Moreover, using this zebrafish mutant, we verified the pathogenicity of the R621S and L819V mutations of human RB1 in neuronal apoptosis. Collectively, our data indicate that the Rb1-Kmt5b-caspase/bcl2 axis is crucial for protecting post-mitotic neurons from apoptosis and provides an explanation for the pathogenesis of clinically relevant mutations.

Abstract Aim To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). Methods The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. Results Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493–0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482–0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. Conclusions Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Abstract Background There have been no reports on the successful implementation of stellate ganglion block (SGB) in mice. Objectives This study aims to investigate a new method for implementing SGB in mice by placing them in a supine position with abducted upper limbs and touching the trachea and sternoclavicular joint with the hand. Methods Fifty BABL/C mice, 8–10 weeks, were selected and randomly divided into four groups: control group (n = 5); SGB-R group (n = 15); SGB-L group (n = 15); and SGB-L + R (group n = 15). SGB was administered with 0.15% ropivacaine solution in a volume of 0.1 mL. The control group received equal volumes of saline. Horner's syndrome, heart rate, and complications such as brachial plexus block, vascular injury, pneumothorax, local anesthetic toxicity, and death were observed. Results Horner's syndrome developed in 100% of SGB surviving mice; no difference was seen in the time to onset (100.4 ± 13.4 vs 96.7 ± 12.4, mean ± SD, seconds) and duration (264.1 ± 40.5 vs 296.3 ± 48.0, mean ± SD, min) of Horner's syndrome in the left and right SGB (P > 0.05). Compared with the control group (722 [708–726], median [IQR], bpm), the heart rate was significantly slowed down in the right SGB (475 [451.5–491], median [IQR], bpm) (P 0.05). The overall complication rate was 18.4%, with a brachial plexus block rate of 12.3%, a vascular injury rate of 4.6%, and a mortality rate of 1.5%, as well as no local anesthetic toxicity (includes bilateral implementation of SGB) or pneumothorax manifestations were found. Conclusions This method allows for the successful implementation of SGB in a mouse model.

Introduction Our goal was to systematically review the current evidence comparing the relative effectiveness of two maxillary sinus floor elevation (MSFE) approaches (internal and external) without bone grafts with that of conventional/grafted MSFE in patients undergoing implantation in the posterior maxilla. Material and Methods Medical databases (PubMed/Medline, Embase, Web of Science, and Cochrane Library) were searched for randomised controlled trials published between January 1980 and May 2023. A manual search of implant-related journals was also performed. Studies published in English that reported the clinical outcomes of MSFE with or without bone material were included. The risk of bias was assessed using the Cochrane Handbook Risk Assessment Tool. Meta-analyses and trial sequence analyses were performed on the included trials. Meta-regression analysis was performed using pre-selected covariates to account for substantial heterogeneity. The certainty of evidence for clinical outcomes was assessed using GRADEpro GDT online (Guideline Development Tool). Results Seventeen studies, including 547 sinuses and 696 implants, were pooled for the meta-analysis. The meta-analysis showed no statistically significant difference between MSFE without bone grafts and conventional MSFE in terms of the implant survival rate in the short term (n = 11, I2 = 0%, risk difference (RD): 0.03, 95% confidence intervals (CI): –0.01–0.07, p = 0.17, required information size (RIS) = 307). Although conventional MSFE had a higher endo-sinus bone gain (n = 13, I2 = 89%, weighted mean difference (WMD): –1.24, 95% CI: –1.91– –0.57, p = 0.0003, RIS = 461), this was not a determining factor in implant survival. No difference in perforation (n = 13, I2 = 0%, RD = 0.03, 95% CI: –0.02–0.09, p = 0.99, RIS = 223) and marginal bone loss (n = 4, I2 = 0%, WMD = 0.05, 95% CI: –0.14–0.23, p = 0.62, no RIS) was detected between the two groups using meta-analysis. The pooled results of the implant stability quotient between the two groups were not robust on sensitivity analysis. Because of the limited studies reporting on the visual analogue scale, surgical time, treatment costs, and bone density, qualitative analysis was conducted for these outcomes. Conclusions This systematic review revealed that both non-graft and grafted MSFE had high implant survival rates. Owing to the moderate strength of the evidence and short-term follow-up, the results should be interpreted with caution.

Abstract Charging behaviours of electric vehicles (EVs) exhibit substantial randomness, making accurate prediction or modelling challenging. Furthermore, as the number of EVs continues to increase, charging stations are diversifying their offerings to accommodate distinct charging characteristics, addressing a wide spectrum of EV charging needs. Previous research mostly focused on the randomness of EVs while neglecting the heterogeneity in charging infrastructure. Therefore, this paper introduces a decentralized collaborative optimal method for EV charging stations, taking into account the varying facility types and the power limitations. First, a decentralized collaborative framework is proposed. The energy boundary model and the average laxity of EVs contribute to transforming the optimization problem into a Markov Decision Process (MDP) with uncertain transitions. Then, multi‐agent deep deterministic policy gradient multi‐individuals (MADDPG‐MI) algorithm is developed to train several heterogeneous agents presenting different types of charging facilities. Each agent makes decisions for multiple homogenous charging piles. Numerous simulation studies validate that the proposed method can effectively reduce charging costs and manages in scenarios involving either homogeneous or multiple heterogeneous charging facilities. Moreover, the MADDPG‐MI algorithm demonstrates performance consistency among multiple decision‐making units while consuming lower training resources offering enhanced scalability.

Abstract Tumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free deoxy-ribonucleoside triphosphates (dNTPs). How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated. MYC family oncoproteins coordinate nucleotide synthesis and ROS generation to drive the development of numerous cancers. We herein perform a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based functional screen targeting metabolic genes and identified nudix hydrolase 1 (NUDT1) as a MYC-driven dependency. Mechanistically, MYC orchestrates the balance of two metabolic pathways that act in parallel, the NADPH oxidase 4 (NOX4)-ROS pathway and the Polo like kinase 1 (PLK1)-NUDT1 nucleotide-sanitizing pathway. We describe LC-1-40 as a potent, on-target degrader that depletes NUDT1 in vivo. Administration of LC-1-40 elicits excessive nucleotide oxidation, cytotoxicity and therapeutic responses in patient-derived xenografts. Thus, pharmacological targeting of NUDT1 represents an actionable MYC-driven metabolic liability.

Abstract Background Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin’s clinical application is limited due to its poor water solubility and low bioavailability. Results In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA——miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. Conclusion In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment. Graphical Abstract

Microorganisms play an important role in multi-factor synergistic corrosion. The synergistic effects of which are greatly stronger than elastic stress and alternative current. Changes of alternative current directly dominate the effect of microbial synergy. With increasing AC current density, corrosion rate of pipeline steel X80 increased first and then decreased, reaching a peak at 100 A m−2. Number of SRB cells vaired as a function of AC current density. Lower current density promoted SRB growth while high current density inhibited SRB growth. When sessile cells are more than 105 cell cm−2, the dominant role of microorganisms is strong, and corrosion rate increases with current density. The maximum value is reached at 100 A m−2. However, when the cells are less than 103 cell cm−2, the dominant effect is greatly reduced, leading to a reduction in the synergistic effect of the multi-factor, and finally reduced corrosion rate to 200 A m−2.

BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic, the infection of Mycoplasma pneumoniae (MP) decreased significantly. At the beginning of the summer of 2023, there was an increasing trend of MP infection in China and the MP pneumonia (MPP) is surging when it comes to the school season and lasts for several months which has attracted widespread attention.ObjectiveThis study aims to investigate the prevalent characteristics of the MP and the difference between the COVID-19 pandemic and the post in Shanghai, China.MethodsThe demographic information and the results of laboratory pathogen detection from July 2021 to May 2024 were collected and analyzed to find out the prevalent characteristics of MP. Two periods, during the COVID-19 pandemic and the post-pandemic, were divided and compared. The P1 genotyping and macrolide resistance-associated gene of 23 s rRNA were detected using the remaining MP-positive samples.ResultsDuring the COVID-19 pandemic, the prevalence of the MP has significantly decreased. Female children are more susceptible to MP infection than the male. The school-aged group (>6 years) had the highest infection rate. The rate of MP P1 genotype during post panel is higher than that during COVID-19 pandemic, which is dominant from July 2021 to May 2024, while the macrolide-resistant associated mutations (A2063G) keep high percentage during or post pandemic.ConclusionAfter the COVID-19 pandemic, an outbreak of MP infection occurred from summer onwards in 2023 with children in Shanghai, China. Immunity debt and high rate of macrolide-resistance may take effects in this MP epidemic. Continuous surveillance of MP is necessary to help to alert the prevalence of MPP.

BackgroundNumerous research studies have indicated a possible association between type 2 diabetes (T2DM) and gut microbiota. To explore specific metabolic pathways connecting gut microbiota and T2DM, we employed Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) techniques.MethodsThis research utilized data from genome-wide association studies (GWAS) that are publicly accessible. We evaluated the genetic correlation between gut microbiota and T2DM using LDSC. Causality was primarily determined through the inverse variance weighted (IVW) method. To verify the robustness of our results, we conducted sensitivity analyses using several approaches, including the weighted median, MR-Egger, and MR-PRESSO. We integrated summary effect estimates from LDSC, along with forward and reverse MR, into a meta-analysis for T2DM using various data sources. Additionally, mediation analysis was performed to explore the impact of plasma metabolites on the relationship between gut microbiota and T2DM.ResultsOur study indicated a significant genetic correlation between genus RuminococcaceaeUCG005 (Rg = −0.26, Rg_P = 2.07×10−4) and T2DM. Moreover, the forward MR analysis identified genus RuminococcaceaeUCG010 (OR = 0.857, 95% CI 0.795, 0.924; P = 6.33×10−5) and order Clostridiales (OR = 0.936, 95% CI 0.878, 0.997; P = 0.039) as being significantly associated with a decreased risk of T2DM. The analysis also highlighted several plasma metabolites as significant mediators in these relationships, with metabolites like octadecadienedioate (C18:2-DC) and branched chain 14:0 dicarboxylic acid being notably involved.ConclusionThe findings demonstrate a significant impact of gut microbiota on T2DM via plasma metabolites, suggesting potential metabolic pathways for therapeutic targeting. This study enhances our understanding of the microbiota’s role in T2DM pathogenesis and supports the development of microbiota-based interventions.

IntroductionCitrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a devastating disease worldwide. Previously, we successfully generated canker-resistant Citrus sinensis cv. Hamlin lines in the T0 generation. This was achieved through the transformation of embryogenic protoplasts using the ribonucleoprotein (RNP) containing Cas12a and one crRNA to edit the canker susceptibility gene, CsLOB1, which led to small indels.MethodsHere, we transformed embryogenic protoplasts of Hamlin with RNP containing Cas12a and three crRNAs.ResultsAmong the 10 transgene-free genome-edited lines, long deletions were obtained in five lines. Additionally, inversions were observed in three of the five edited lines with long deletions, but not in any edited lines with short indel mutations, suggesting long deletions maybe required for inversions. Biallelic mutations were observed for each of the three target sites in four of the 10 edited lines when three crRNAs were used, demonstrating that transformation of embryogenic citrus protoplasts with Cas12a and three crRNAs RNP can be very efficient for multiplex editing. Our analysis revealed the absence of off-target mutations in the edited lines. These cslob1 mutant lines were canker- resistant and no canker symptoms were observed after inoculation with Xcc and Xcc growth was significantly reduced in the cslob1 mutant lines compared to the wild type plants.DiscussionTaken together, RNP (Cas12a and three crRNAs) transformation of embryogenic protoplasts of citrus provides a promising solution for transgene-free multiplex genome editing with high efficiency and for deletion of long fragments.

IntroductionThe immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.MethodsHere, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).ResultsThe child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.ConclusionConclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19.

Background: Previous studies have shown that pyroptosis in hepatocyte is essential for the development of MAFLD. Growing evidence has shown that exosomal miRNAs-mediated communication between inflammatory cells and hepatocyte is an important link in MAFLD. In the present study, we aim to elucidate whether macrophage-derived exosomal miRNAs contribute to the hepatocyte pyroptosis in the pathophysiological process of MAFLD. Methods: The effects of hepatocyte pyroptosis were investigated in an HFD-induced MAFLD mouse model and in the liver tissues from patients with MAFLD using immunohistochemistry, real-time PCR, Western blotting, and luciferase reporter assay, among other techniques. MiR-155 inhibitor tail injections and AAV-FoxO3a-GFP were also administered to respectively inhibit or overexpress its expression in an HFD-induced MAFLD mouse model. Results: Hepatocyte pyroptosis was heightened in the liver tissue of patients with MAFLD or HFD-induced MAFLD mouse. Importantly, treatment with a caspase-1 inhibitor or overexpression of FoxO3a reversed this trend. Our study also demonstrated that miR-155 expression and the number of infiltrated macrophages were increased, and knockdown of miR-155 attenuated hepotocyte pyroptosis and liver fibrosis in HFD-induced mouse. In addition, we demonstrated that macrophage-derived exosomal miR-155 was transferred to hepatocytes, leading to hepatocyte pyroptosis in MAFLD mouse. Furthermore, blockade of exosome secretion improved hepotocyte pyroptosis and liver fibrosis in HFD-induced mouse. On the contrary, macrophage-derived exosomal miR-155 worsened hepotocyte pyroptosis. Moreover, we found that miR-155 promoted hepatocyte pyroptosis in MAFLD by down-regulating FoxO3a. Conclusions: Taken together, our results demonstrated that macrophage-derived exosomal miR-155 promotes hepatocyte pyroptosis and liver fibrosis in MAFLD.

Similar to the layout of an oscillating heat pipe (OHP), a quartz hybrid heat pipe (HHP) with an inner diameter of 5 mm, exceeding 59.7 % of the capillary threshold of OHP, was designed. The detailed thermal hydraulic behavior of fluid in the HHP has been revealed. It was found that the HHP undergoes a heat transfer mode transition from phase change to pulsating flow. It is also means that the liquid slugs can be dynamically and stably formed if the heat input is sufficient. The single bubble growth and the multi-bubble coalescence are two ways to form the intermittent flow. In addition, as the main flow pattern in low filling ratio (FR), the formation of annular flow is closely concerned in the behaviors of fluid. Moreover, the higher the FR is, the clearer the contour of slug flow is. At the same time, the oscillating motion can be formed easily at a high FR, resulting in a better performance of HHP in lower heat load. However, as the heat input increases, HHP with a 60 % filling ratio exhibits lower thermal resistance, achieving a minimum value of 0.08 °C/W at 100 W.

Severe COVID-19 cases often progress to life-threatening conditions such as acute respiratory distress syndrome (ARDS), sepsis, and multiple organ dysfunction syndrome (MODS). Gelsolin (GSN), an actin-binding protein with anti-inflammatory and immunomodulatory properties, is a promising therapeutic target for severe COVID-19. Plasma GSN levels are significantly decreased in critical illnesses, including COVID-19, correlating with dysregulated immune responses and poor outcomes. GSN supplementation may mitigate acute lung injury, ARDS, and sepsis, which share pathophysiological features with severe COVID-19, by scavenging actin, modulating cytokine production, enhancing macrophage phagocytosis, and stabilizing the alveolar-capillary barrier. Preliminary data indicate that recombinant human plasma GSN improves oxygenation and lung function in severe COVID-19 patients with ARDS. Although further research is needed to optimize GSN therapy, current evidence supports its potential to mitigate severe consequences of COVID-19 and improve patient outcomes. This review provides a comprehensive analysis of the biological characteristics, mechanisms, and therapeutic value of GSN in severe COVID-19.

IntroductionCitrus is one of the most important fruit crops worldwide, and the root-associated microbiota can have a profound impact on tree health and growth.MethodsIn a collaborative effort, the International Citrus Microbiome Consortium investigated the global citrus root microbiota with samples collected from nine citrus-producing countries across six continents. We analyzed 16S rDNA and ITS2 amplicon sequencing data to identify predominant prokaryotic and fungal taxa in citrus root samples. Comparative analyses were conducted between root-associated microbial communities and those from the corresponding rhizosphere and bulk soil samples. Additionally, genotype-based group-wise comparisons were performed to assess the impact of citrus genotype on root microbiota composition.ResultsTen predominant prokaryotic phyla, containing nine bacterial phyla including Proteobacteria, Actinobacteria, Acidobacteria, and Bacteroidetes and one archaeal phylum (Thaumarchaeota), and multiple fungal phyla including Ascomycota and Basidiomycota were identified in the citrus root samples. Compared with the microbial communities from the corresponding rhizosphere and bulk soil samples from the same trees, the prokaryotic and fungal communities in the roots exhibited lower diversity and complexity but greater modularity compared to those in the rhizosphere. In total, 30 root-enriched and 150 root-depleted genera in bacterial community were identified, whereas 21 fungal genera were enriched, and 147 fungal genera were depleted in the root niche compared with the rhizosphere. The citrus genotype significantly affected the root prokaryotic and fungal communities. In addition, we have identified the core root prokaryotic genera comprising Acidibacter, Allorhizobium, Bradyrhizobium, Chitinophaga, Cupriavidus, Devosia, Dongia, Niastella, Pseudomonas, Sphingobium, Steroidobacter and Streptomyces, and the core fungal genera including Acrocalymma, Cladosporium, Fusarium, Gibberella, Mortierella, Neocosmospora and Volutella. The potential functions of these core genera of root microbiota were predicted.ConclusionOverall, this study provides new insights into the assembly of microbial communities and identifies core members of citrus root microbiota across a wide geographic range. The findings offer valuable information for manipulating root microbiota to enhance plant growth and health.

Abstract Surface modification is frequently used to solve the problems of low combustion properties and agglomeration for aluminum‐based fuels. However, due to the intrinsic incompatibility between the aluminum powder and the organic modifiers, the surface coating is usually uneven and disordered, which significantly deteriorates the uniformity and performances of the Al‐based fuels. Herein, a new approach of monolayer nano‐vesicular self‐assembly is proposed to prepare high‐performance Al fuels. Triblock copolymer G‐F‐G is produced by glycidyl azide polymer (GAP) and 2,2′‐(2,2,3,3,4,5,5‐Octafluorohexane‐1,6‐diyl) bis (oxirane) (fluoride) ring‐open addition reaction. By utilizing G‐F‐G vesicular self‐assembly in a special solvent, the nano‐sized vesicles are firmly adhered to the surface of Al powder through the long‐range attraction between the fluorine segments and Al. Meanwhile, the electrostatic repulsion between vesicles ensures an extremely thin coating thickness (≈15 nm), maintaining the monolayer coating structure. Nice ignition, combustion, anti‐agglomeration, and water‐proof properties of Al@G‐F‐G(DMF) are achieved, which are superior among the existing Al‐based fuels. The derived Al‐based fuel has excellent comprehensive properties, which can not only inspire the development of new‐generation energetic materials but also provide facile but exquisite strategies for exquisite surface nanostructure construction via ordered self‐assembly for many other applications.

IntroductionThis study characterized Vibrio alginolyticus isolated from seafood and freshwater products in China (2020).Methods and ResultsIn total, 122 (95.31%) V. alginolyticus isolates were resistant to at least 1 antibiotic category, and 2 (1.56%) isolates were resistant to at least 3 antibiotic categories and belong to multi-drug resistance (MDR) isolates. A high prevalence rate was observed to be blaCARB (98.04%) encoding beta-lactam resistance, followed by tet (97.06%) encoding tetracycline resistance and fos (4.90%) encoding resistance to fosfomycin. Among the 57 V. alginolyticus isolates, the commonest virulence genes were type III secretion system translocated gene vopD, vopB, and vcrH (54.4%, 31/57), type III secretion system regulated gene tyeA (54.39%), followed by vscI and vscF (50.88%) encoded type III secretion system inner rod protein and needle protein, respectively. Multilocus sequence typing (MLST) showed considerable genetic diversity, with 34 distinct sequence types (STs) identified among 55 isolates. ST421 (n = 5), ST166 (n = 4), ST523 (n = 3), ST516 (n = 3), and ST507 (n = 3) were dominant STs among 55 V. alginolyticus isolates.DiscussionThese findings highlight the widespread occurrence of V. alginolyticus in both freshwater and seafood products, underscoring the critical need for vigilant monitoring of these bacteria. Such measures are essential for ensuring effective food safety management and safeguarding public health.

Currently, chemotherapy remains occupying a pivotal place in the treatment of pancreatic ductal adenocarcinoma (PDAC). Nonetheless, the emergence of drug resistance in recent years has limited the clinical efficacy of chemotherapeutic agents, especially gemcitabine (GEM). Through bioinformatics analysis, AT-rich Interactive Domain-containing Protein 3A (ARID3A), one of transcription factors, is discovered to possibly participate in this progress. This study thoroughly investigates the potential role of ARID3A in the malignant progression and GEM chemoresistance of PDAC and explores the underlying mechanisms. The results indicate that ARID3A knockdown suppresses tumor development and enhances the sensitivity of PDAC cells to GEM in vitro and vivo. Mechanically, CUT&Tag profiling sequencing, RNA‐sequencing and functional studies demonstrates that decreased ARID3A expression alleviates the transcriptional inhibition of phosphatase and tensin homolog (PTEN), consequently leading to glutathione peroxidase 4 (GPX4) depletion and increased lipid peroxidation levels. Activated ferroptosis induced by the inhibition of GPX4 subsequently restricts tumor progression and reduces GEM resistance in PDAC. This research identifies the ferroptosis regulatory pathway of ARID3A-PTEN-GPX4 axis and reveals its critical role in driving the progression and chemoresistance of pancreatic cancer. Notably, both inhibition of ARID3A and enhancement of ferroptosis can increase chemosensitivity to GEM, which offers a promising opportunity for developing therapeutic strategies to combat acquired chemotherapy resistance in pancreatic cancer.

A 54-year-old woman was admitted to the hospital with a left neck mass. Enhanced CT and ultrasound examinations revealed a lesion in the left sternocleidomastoid muscle. The patient undergone right thyroid lobe resection 8 years ago. Interestingly, the lesion on the sternocleidomastoid muscle, along with the left lobe of the patient’s thyroid, visually appears to form a displaced and complete thyroid in the early Tc-99m-MIBI parathyroid scintigraphy. Combined with Tc-99m-MIBI scintigraphy and abnormal PTH and blood calcium levels, the consideration was given to the lesion in the sternocleidomastoid muscle as an ectopic parathyroid adenoma. Subsequent surgical pathology confirmed this suspicion.

Styxl2, a poorly characterized pseudophosphatase, was identified as a transcriptional target of the Jak1-Stat1 pathway during myoblast differentiation in culture. Styxl2 is specifically expressed in vertebrate striated muscles. By gene knockdown in zebrafish or genetic knockout in mice, we found that Styxl2 plays an essential role in maintaining sarcomere integrity in developing muscles. To further reveal the functions of Styxl2 in adult muscles, we generated two inducible knockout mouse models: one with Styxl2 being deleted in mature myofibers to assess its role in sarcomere maintenance, and the other in adult muscle satellite cells (MuSCs) to assess its role in de novo sarcomere assembly. We find that Styxl2 is not required for sarcomere maintenance but functions in de novo sarcomere assembly during injury-induced muscle regeneration. Mechanistically, Styxl2 interacts with non-muscle myosin IIs, enhances their ubiquitination, and targets them for autophagy-dependent degradation. Without Styxl2, the degradation of non-muscle myosin IIs is delayed, which leads to defective sarcomere assembly and force generation. Thus, Styxl2 promotes de novo sarcomere assembly by interacting with non-muscle myosin IIs and facilitating their autophagic degradation.

In the context of today's information explosion, how to extract useful information from a large amount of image data and convey it to users is a challenging problem. Therefore, this study aims to achieve effective communication of image data by constructing a sensor network simulation and utilizing visual feature extraction methods. The study constructed a sensor network simulation to simulate the working principle of a biosensor system, thereby achieving perception and understanding of image data, and automatically obtaining and processing information from input images. Research on the use of visual feature extraction methods to extract features that describe the content and structure of images, and apply them to the results obtained from sensor network simulation to accurately capture important information in image data. The research aims to convey the extracted feature information to users through visual means, and present the extracted feature information to users in an intuitive graphical form, in order to gain a more intuitive understanding of the meaning and features of image data, improve the ability to understand data and analyze results. By constructing a sensor network to simulate the perception process of image data and using visual feature extraction methods to extract key feature information, this article can effectively convey this information to users through visualization methods. This method provides a new solution for the field of image data visualization communication, which helps to improve the efficiency and accuracy of data communication.