Two maize homologs of mammalian proton-coupled folate transporter, ZmMFS_1-62 and ZmMFS_1-73, are essential to salt and drought tolerance.

Folates are essential to the maintenance of normal life activities in almost all organisms. Proton-coupled folate transporter (PCFT), belonging to the major facilitator superfamily, is one of the three major folate transporter types widely studied in mammals. However, information about plant PCFTs is limited. Here, a genome-wide identification of maize PCFTs was performed, and two PCFTs, ZmMFS_1-62 and ZmMFS_1-73, were functionally investigated. Both proteins contained the typical 12 transmembrane helixes with N- and C-termini located in the cytoplasm, and were localized in the plasma membrane. Molecular docking analysis indicated their binding activity with folates via hydrogen bonding. Interference with ZmMFS_1-62 and ZmMFS_1-73 in maize seedlings through virus-induced gene silencing disrupted folate homeostasis, mainly in the roots, and reduced tolerance to drought and salt stresses. Moreover, a molecular chaperone protein, ZmHSP20, was found to interact with ZmMFS_1-62 and ZmMFS_1-73, and interference with ZmHSP20 in maize seedlings also led to folate disruption and increased sensitivity to drought and salt stresses. Overall, this is the first report of functional identification of maize PCFTs, which play essential roles in salt and drought stress tolerance, thereby linking folate metabolism with abiotic stress responses in maize.

An abdominal vibration combined with walking exercise (AVCWE) program for older patients with constipation: Development and feasibility study.

BACKGROUND: Older patients with constipation are at higher risk for inadequate bowel preparation, but there are currently no targeted strategies. This study aims to develop an abdominal vibration combined with walking exercise (AVCWE) program and assess its feasibility among older patients with constipation. METHODS: Phase I: Using the Delphi technique, eight experts across three professional fields were consulted to develop the AVCWE program. The experts evaluated and provided recommendations on demonstration videos and detailed descriptions of the preliminary protocol. Phase II: A single-arm feasibility study of the AVCWE program was conducted on 30 older patients with constipation undergoing colonoscopy at a tertiary hospital in China. A 10-point exercise program evaluation form and several open-ended questions were used to gather feedback from participants regarding the program. In both phases, content analysis was used to critically analyze and summarize qualitative suggestions for protocol modifications. RESULTS: Based on feedback from the expert panel, the AVCWE program developed in Phase I included two procedures during laxative ingestion: at least 5,500 steps of walking exercise and two cycles of moderate-intensity abdominal vibration (each cycle consisted of 10 min of vibration and 10 min of rest). The feasibility study in Phase II showed high positive patient feedback scores for the program, ranging from 9.07 ± 0.74 to 9.73 ± 0.52. CONCLUSION: The AVCWE program was developed by eight multidisciplinary experts and was well accepted by 30 older patients with constipation. Study participants believed that this program was simple, safe, appropriate, and helpful for their bowel preparation. The findings of this study may provide valuable information for optimizing bowel preparation in older patients with constipation.

[Energy-saving and Emission Reduction Path for Road Traffic in Key Coastal Cities of Guangdong, Fujian and Zhejiang].

The rapid development of society and economy has resulted in a substantial increase in energy consumption, consequently exacerbating pollution issues. Current research predominantly focuses on energy-saving and emission reduction in road transportation within individual cities or the three major economic regions of China:the Yangtze River Delta, the Pearl River Delta, and the Beijing-Tianjin-Hebei Region. However, there is a dearth of studies addressing the southeastern coastal economic region. Located at the heart of China's southeastern coastal economic development, the provinces of Guangdong, Fujian, and Zhejiang unavoidably face challenges associated with energy consumption and emissions while pursuing economic growth. To address these challenges, this study employed a LEAP model to construct various scenarios for road transportation in the key coastal cities of Guangdong, Fujian, and Zhejiang from 2015 to 2035. These scenarios included a baseline scenario (BAU), an existing policy scenario (EPS), and an improved policy scenario (MPS). The MPS and EPS encompassed vehicle structure optimization (VSO), improved fuel economy (IFE), and reduced annual average mileage (RDM). By simulating and evaluating these scenarios, the energy-saving and emission reduction potentials of road transportation in the key coastal cities were assessed. The results indicated that, in the primary scenario, the MPS exhibited the most significant improvements in energy-saving, carbon reduction, and pollutant reduction effects. By 2035, the MPS achieved a remarkable 75% energy-saving rate compared to that in the baseline scenario, accompanied by reductions of 68%, 59%, 66%, 70%, and 64% in CO2, CO, NOx, PM2.5, and SO2 emissions, respectively. In the secondary scenario, the improved scenario of enhancing fuel economy achieved a notable 30% reduction in energy consumption. Additionally, the scenarios involving vehicle structure adjustment (yielding reductions of 36%, 30%, 36%, 26%, and 40%) and annual average mileage reduction (resulting in reductions of 37%, 37%, 36%, 37%, and 36%) demonstrated significant reductions in CO2, CO, NOx, PM2.5, and SO2 emissions.

[Clinical remission and transmural healing of ustekinumab in patients with Crohn's disease].

OBJECTIVE: To treat the Crohn's disease (CD) patients with ustekinumab (UST), to eva-luate their clinical and endoscopic remission, and to evaluate their transmural response (TR) and transmural healing (TH) condition using intestinal ultrasonography (IUS). METHODS: Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to August 2022, who were treated with UST for remission induction and maintenance therapy. All the patients were evaluated on both week 8 and week 16/20 after treatment, including clinical, biochemical indicators, colonoscopy and IUS examination. RESULTS: A total of 13 patients were enrolled in this study, including 11 males and 2 females. The minimum age was 23 years, the maximum age was 73 years and the mean age was 36.92 years. All the patients were in the active stage of disease before treatment, and the average Best Crohn's disease activity index (Best CDAI) score was 270.12±105.55. In week 8, the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66 (t=4.977, P < 0.001). Eight patients achieved clinical remission while 5 patients remained in the active stage. Nine patients underwent colonoscopy evaluation. The average simple endoscopic score for Crohn's disease (SES-CD) score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483, P=0.048) in week 16/20. Four patients achieved endoscopic remission while 5 patients did not. In week 8, 5 patients achieved TR, 2 patients achieved TH, the other 6 patients did not get TR or TH. In week 16/20, 6 patients achieved TR, 3 patients achieved TH while the other 4 patients did not get TR or TH. There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions (Fisher test, P > 0.999). The rate of UST transmural response in the patients who had had previous biological agent therapy was lower than those with no previous biological agent therapy, but there was no significant statistical difference (Fisher test, P=0.491). CONCLUSION: After treatment of UST, the clinical and endoscopic conditions of the CD patients had been improved, and some patients could achieve clinical remission and endoscopic remission. UST had good TR and TH effects on CD. TR might appear in week 8, and the TR effect increased in week 16/20. There was no significant statistical difference in the TR effect between small intestine and colon lesions. TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents, but the result had no significant statistical difference.

Based on the prognosis model of immunogenes, the prognosis model was constructed to predict the invasion of immune genes and immune cells related to primary liver cancer and its experimental validation.

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

Morus alba L. (Sangzhi) alkaloids mitigate atherosclerosis by regulating M1/M2 macrophage polarization.

BACKGROUND: Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the pivotal involvement of macrophages in arterial inflammation, participating in its formation and progression. Sangzhi alkaloid (SZ-A) is a novel natural alkaloid extracted from the mulberry branches, has extensive pharmacological effects and stable pharmacokinetic characteristics. However, the effects and mechanisms of SZ-A on AS remain unclear. PURPOSE: To explore the effect and underlying mechanisms of SZ-A on inflammation mediated by macrophages and its role in AS development. METHODS: Atherosclerosis was induced in vivo in apolipoprotein E-deficient mice through a high-fat and high-choline diet. We utilized macrophages and vascular endothelial cells to investigate the effects of SZ-A on macrophage polarization and its anti-inflammatory properties on endothelial cells in vitro. The transcriptomic analyses were used to investigate the major molecule that mediates cell-cell interactions and the antiatherogenic mechanisms of SZ-A based on AS, subsequently validated in vivo and in vitro. RESULTS: SZ-A demonstrated a significant inhibition in vascular inflammation and alleviation of AS severity by mitigating macrophage infiltration and modulating M1/M2 macrophage polarization in vitro and in vivo. Moreover, SZ-A effectively reduced the release of the proinflammatory mediator C-X-C motif chemokine ligand (CXCL)-10, predominantly secreted by M1 macrophages. This reduction in CXCL-10 contributed to improved endothelial cell function, reduced recruitment of additional macrophages, and inhibited the inflammatory amplification effect. This ultimately led to the suppression of atherogenesis. CONCLUSION: SZ-A exhibited potent anti-inflammatory effects by inhibiting macrophage-mediated inflammation, providing a new therapeutic avenue against AS. This is the first study demonstrating the efficacy of SZ-A in alleviating AS severity and offers novel insights into its anti-inflammatory mechanism.

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Enhanced protein-metabolite correlation analysis: To investigate the association between Staphylococcus aureus mastitis and metabolic immune pathways.

Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut-metabolism-mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum. Plasma analysis revealed significantly higher levels of L-isoleucine and cholic acid along with 7-ketodeoxycholic acid. Mammary tissue showed elevated levels of arachidonic acid metabolites and norlithocholic acid. Proteomic analysis showed increased levels of IFIH1, Tnfaip8l2, IRGM, and IRF5 in mastitis rats, which suggests that mastitis triggers an inflammatory response and immune stress. Follistatin (Fst) and progesterone receptor (Pgr) were significantly downregulated, raising the risk of breast cancer. Extracellular matrix (ECM) receptors and focal adhesion signaling pathways were downregulated, while blood-milk barrier integrity was disrupted. Analysis of protein-metabolic network regulation revealed that necroptosis, protein digestion and absorption, and arachidonic acid metabolism were the principal regulatory pathways involved in the development of mastitis. In short, the onset of mastitis leads to changes in the microbiota and alterations in the metabolic profiles of various biological samples, including colonic contents, plasma, and mammary tissue. Key manifestations include disturbances in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism. At the same time, the integrity of the blood-milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.

Transcriptomic responses of rabbits to infections by precocious line and wild-type Eimeria media: revealing molecular signatures and pathway differences in liver and duodenum during the peak and terminal phases of oocyst production.

Eimeria media is a principal pathogen responsible for rabbit coccidiosis, targeting the rabbit's intestinal epithelial cells. This parasitism damages the intestinal mucosal barrier, initiating a systemic immune and inflammatory response that jeopardizes the sustainable growth of rabbit farming. To understand the implications of infection on the host's immune and metabolic responses, we employed RNA-Seq to analyze RNA from the liver and duodenum tissues of post-infected rabbits infected with both the precocious line and wild-type strain of E.media. Comprehensive transcriptomic analysis revealed that the two parasites exhibit divergent transcriptomic imprints on host tissues. While the precocious line predominantly modulates immune-centric pathways with significant differential gene enrichment, wild-type strain favors pathways that affect metabolism. In addition, our study pinpointed a set of genes that undergo significant modifications in response to these effects. These revelations grant a fresh avenue to probe deeper into the symbiotic intricacies of the E.media and its rabbit host.

Comparison of Ba-Hao burn ointment gauze and petrolatum gauze in split graft donor site healing: A randomized, prospective, and self-control study.

Background and Aims: To assess patient comfort, wound healing, and scarring at the 6-month follow-up of split-skin graft donor sites treated with Ba-Hao burn ointment (BHBO) gauze, a compound preparation of traditional Chinese medicine since 1970s, compared with petrolatum gauze. Methods: Thirty patients admitted to the Department of Burns of the First Affiliated Hospital of Anhui Medical University between September 2021 and September 2022 participated in this randomized, prospective, self-control clinical study. After harvesting the split skin, donor sites were divided into two parts along the midline. BHBO gauze was applied to half of the donor wounds, and petrolatum gauze was applied to the other half. The wound healing time, pain scores on the postoperative Days 3, 6, and 9, and Vancouver Scar Scale (VSS) score at the 6-month follow-up were assessed. Results: The wound healing time was significantly shorter in the BHBO group than in the control group (10.07 ± 1.48 days vs. 11.50 ± 1.74 days, p < 0.001). On postoperative Days 3 and 6, the pain scores quantified by visual analog scores were significantly lower in the BHBO group than in the control group (5.33 ± 1.54 and 4.17 ± 1.51, respectively vs. 7.57 ± 1.41 and 5.20 ± 1.47, respectively). The difference in the visual analog scale score on postoperative Day 9 between the groups was not significant (p > 0.05). Microbiological assessment revealed the absence of bacterial contamination in both groups. At the 6-month follow up, the VSS score was significantly lower in the BHBO group (6.67 ± 1.92) than in the control group (9.57 ± 1.55). Conclusion: BHBO resulted in faster donor-site healing, reduced postoperative pain, and improved scar quality at the 6-month follow-up than petrolatum gauze alone.

Development and evaluation of a text analytics algorithm for automated application of national COVID-19 shielding criteria in rheumatology patients.

INTRODUCTION: At the beginning of the COVID-19 pandemic, the UK's Scientific Committee issued extreme social distancing measures, termed 'shielding', aimed at a subpopulation deemed extremely clinically vulnerable to infection. National guidance for risk stratification was based on patients' age, comorbidities and immunosuppressive therapies, including biologics that are not captured in primary care records. This process required considerable clinician time to manually review outpatient letters. Our aim was to develop and evaluate an automated shielding algorithm by text-mining outpatient letter diagnoses and medications, reducing the need for future manual review. METHODS: Rheumatology outpatient letters from a large UK foundation trust were retrieved. Free-text diagnoses were processed using Intelligent Medical Objects software (Concept Tagger), which used interface terminology for each condition mapped to Systematized Medical Nomenclature for Medicine-Clinical Terminology (SNOMED-CT) codes. We developed the Medication Concept Recognition tool (Named Entity Recognition) to retrieve medications' type, dose, duration and status (active/past) at the time of the letter. Age, diagnosis and medication variables were then combined to calculate a shielding score based on the most recent letter. The algorithm's performance was evaluated using clinical review as the gold standard. The time taken to deploy the developed algorithm on a larger patient subset was measured. RESULTS: In total, 5942 free-text diagnoses were extracted and mapped to SNOMED-CT, with 13 665 free-text medications (n=803 patients). The automated algorithm demonstrated a sensitivity of 80% (95% CI: 75%, 85%) and specificity of 92% (95% CI: 90%, 94%). Positive likelihood ratio was 10 (95% CI: 8, 14), negative likelihood ratio was 0.21 (95% CI: 0.16, 0.28) and F1 score was 0.81. Evaluation of mismatches revealed that the algorithm performed correctly against the gold standard in most cases. The developed algorithm was then deployed on records from an additional 15 865 patients, which took 18 hours for data extraction and 1 hour to deploy. DISCUSSION: An automated algorithm for risk stratification has several advantages including reducing clinician time for manual review to allow more time for direct care, improving efficiency and increasing transparency in individual patient communication. It has the potential to be adapted for future public health initiatives that require prompt automated review of hospital outpatient letters.

Extracellular CIRP co-stimulated T cells through IL6R/STAT3 in pediatric IgA vasculitis.

Immunoglobulin A vasculitis (IgAV) is the most common vasculitis of childhood. Disordered immune responses play important roles in its pathogenesis, but the comprehensive immune profile of the disease and the underlying mechanisms are still largely unknown. Here we found a potential disease biomarker cold inducible RNA binding protein (CIRP) in our pediatric IgAV cohort. Serum CIRP level in these patients were elevated and positively correlated with the increased early memory (CD45RA+CD62L+CD95+) T cells revealed using multicolor flow cytometry. Immune phenotyping of the patients showed they had more activated T cells with higher IL6Ra expression. T cell culture experiment showed CIRP further activated both human CD4+ and CD8+ T cells as indicated by increased perforin secretion and phosphorylation of STAT3. Blockade of IL6Rα attenuated CIRP-induced T cell toxicity in vitro. RNA-sequencing data further supported CIRP stimulation promoted human T cell activation and migration, fueled inflammation through the JAK-STAT signaling pathway. Therefore, IL6Ra-mediated T cell activation by extracellular CIRP may contribute to pathogenesis of IgAV in children, both CIRP and IL6Ra could be new therapeutic targets for IgAV.

Perception, practice, and barriers toward research among pediatric undergraduates: a cross-sectional questionnaire-based survey.

BACKGROUND: Scientific research activities are crucial for the development of clinician-scientists. However, few people pay attention to the current situation of medical research in pediatric medical students in China. This study aims to assess the perceptions, practices and barriers toward medical research of pediatric undergraduates. METHODS: This cross-sectional study was conducted among third-year, fourth-year and fifth-year pediatric students from Zhejiang University School of Medicine in China via an anonymous online questionnaire. The questionnaires were also received from fifth-year students majoring in other medicine programs [clinical medicine ("5 + 3") and clinical medicine (5-year)]. RESULTS: The response rate of pediatric undergraduates was 88.3% (68/77). The total sample of students enrolled in the study was 124, including 36 students majoring in clinical medicine ("5 + 3") and 20 students majoring in clinical medicine (5-year). Most students from pediatrics ("5 + 3") recognized that research was important. Practices in scientific research activities are not satisfactory. A total of 51.5%, 35.3% and 36.8% of the pediatric students participated in research training, research projects and scientific article writing, respectively. Only 4.4% of the pediatric students contributed to publishing a scientific article, and 14.7% had attended medical congresses. None of them had given a presentation at a congress. When compared with fifth-year students in the other medicine program, the frequency of practices toward research projects and training was lower in the pediatric fifth-year students. Lack of time, lack of guidance and lack of training were perceived as the main barriers to scientific work. Limited English was another obvious barrier for pediatric undergraduates. Pediatric undergraduates preferred to participate in clinical research (80.9%) rather than basic research. CONCLUSIONS: Although pediatric undergraduates recognized the importance of medical research, interest and practices in research still require improvement. Lack of time, lack of guidance, lack of training and limited English were the common barriers to scientific work. Therefore, research training and English improvement were recommended for pediatric undergraduates.

Adapt-On-Demand: A Novel Strategy for Personalized Adaptive Radiotherapy for Locally Advance Lung Cancer.

PURPOSE: Real time adaptation of thoracic radiation plans is compelling because offline adaptive experiences show that tumor volumes and lung anatomy can change during therapy. We present and analyze a novel adaptive-on-demand (AOD) workflow combining online adaptive radiotherapy (ART) on the ETHOS system with image-guided radiotherapy (IGRT) delivery on a Halcyon unit for conventional fractionated radiotherapy of locally advanced lung cancer (LALC). METHOD: We analyzed 26 LALC patients treated with the AOD workflow, adapting weekly. We timed segments of the workflow to evaluate efficiency in a real world clinic. Target coverage and OAR doses were compared between adapted plans (ADP) and scheduled plans without adaptation (SCH). Planning robustness was evaluated by the frequency of preplanning goals being achieved in ADP plans, stratified by tumor volume change. RESULTS: The AOD workflow was achievable within 30 min for most radiation fractions. Over the course of therapy we observed an average 26.6% ± 23.3% reduction in ITV volumes. Despite these changes, with online adaptive radiation therapy (o-ART), ITV and PTV coverage (V100%) was 99.2% and 93.9% for all members of the cohort. This represented a 2.9% and 6.8% improvement over non-adapted plans (p<0.05). For tumors that grew > 10%, V100% was 93.1% for o-ART, while it was 76.4% for non-adaptive plans, representing a median 17.2% improvement in the PTV coverage (p < 0.05). In these plans, critical OAR constraints were met 94.1% of the time, whereas in non-adapted plans it was 81.9%. This represented reductions of 1.32 Gy, 1.34 Gy, or 1.75 Gy in heart, esophagus, and lung, respectively. The effect was larger when tumors had shrunk more than 10%. Regardless of tumor volume alterations, the PTV/ITV coverage was achieved for all adaptive plans. Exceptional cases, where dose constraints were not met, were due to large initial tumor volumes or tumor growth. CONCLUSION: The AOD workflow is efficient and robust in responding to anatomical changes in LALC patients, providing dosimetric advantages over standard therapy. Weekly adaptation was adequate to keep pace with changes. This approach is a feasible alternative to conventional offline replanning workflows for managing anatomy changes in LALC radiotherapy.

Structures of human γδ T cell receptor-CD3 complex.

Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology1-3. The γδ T cell receptor (TCR), generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex2. The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy4. Here, we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes5,6, unveiling two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ/TCRδ extracellular domain (ECD) and connecting peptides (CPs). The length of CPs regulates the ligand association and T cell activation. Additionally, a cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signaling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, where two protomers nestle back-to-back via their Vγ5 domains of TCR ECDs. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the γδ TCR unique properties and facilitating immunotherapeutic interventions.

Colonization of Piriformospora indica enhances rice resistance against the brown planthopper Nilaparvata lugens.

BACKGROUND: Piriformospora indica is an endophytic fungus that can promote the growth and confer the resistance against diverse stresses in host plants by root colonization. However, the effects of P. indica colonization on improving plant resistance to insect pests are still less explored. The brown planthopper (BPH) Nilaparvata lugens is a serious monophagous pest that causes extensive damage to rice plants. Here, we aimed to evaluate the effects of P. indica colonization on rice resistance against BPH. RESULTS: The colonization of P. indica in the rice roots resisted the damage from BPH. The age-stage, two-sex life table analyses showed that feeding on P. indica-colonized rice plants affected BPH's female adult longevity, oviposition period, fecundity, population parameters and population size. BPH female adults feeding on P. indica-colonized plants excreted less honeydew. P. indica colonization remarkably increased the duration of np, N2, and N3 waveform, as well as the occurrences of N1 and N2, and decreased the duration of N4-b for BPH on rice plants. Meanwhile, the weight of BPH on the colonized plants was significantly lower than the control. In addition, the feeding and oviposition preferences of BPH to P. indica-colonized plants were reduced. qRT-RCR analyses revealed that P. indica colonization induced the expressions of jasmonic acid (JA)- and salicylic acid (SA)-related genes in rice plants. CONCLUSION: P. indica colonization can reduce BPH performance on rice plants with potentially inhibitory effects on population growth. Collectively, these results support the potential for endophytically colonized P. indica as an effective strategy to improve insect resistance of crops. This article is protected by copyright. All rights reserved.

Exosomes From Human Umbilical Cord Stem Cells Suppress Macrophage-to-myofibroblast Transition, Alleviating Renal Fibrosis.

Renal fibrosis, a progressive scarring of the kidney, lacks effective treatment. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exos) hold promise for treating kidney diseases due to their anti-inflammatory properties. This study investigates their potential to lessen renal fibrosis by targeting macrophage-to-myofibroblast transformation (MMT), a key driver of fibrosis. We employed a mouse model of unilateral ureteral obstruction (UUO) and cultured cells exposed to transforming growth factor-ß (TGF-ß) to mimic MMT. HucMSC-Exos were administered to UUO mice, and their effects on kidney function and fibrosis were assessed. Additionally, RNA sequencing and cellular analysis were performed to elucidate the mechanisms by which HucMSC-Exos inhibit MMT. HucMSC-Exos treatment significantly reduced kidney damage and fibrosis in UUO mice. They downregulated markers of fibrosis (Collagen I, vimentin, alpha-smooth muscle actin) and suppressed MMT (α-SMA + F4/80 + cells). Furthermore, ARNTL, a specific molecule, emerged as a potential target of HucMSC-Exos in hindering MMT and consequently preventing fibrosis. HucMSC-Exos effectively lessen renal fibrosis by suppressing MMT, suggesting a novel therapeutic strategy for managing kidney damage and fibrosis.

Effects of responsive breastfeeding intervention on breastfeeding and infant growth in China: A randomised controlled trial.

Responsive feeding serves as an important protective factor for infant growth and overall health development. This study based on self-determination theory (SDT) aimed to assess the effects of a responsive breastfeeding (RBF) intervention programme on maternal breastfeeding and infant growth and development. A total of 110 mother-infant pairs were recruited and randomly divided into an intervention group (n = 55) and a control group (n = 55). The primary outcomes were breastfeeding motivation score, breastfeeding self-efficacy (BSE) and exclusive breastfeeding rate; the secondary outcomes were infant physical development at 6 weeks and 3 months. A repeated measures ANOVA indicated that the intervention group had significantly higher Enjoyment scores compared to the control group at three time points: at discharge (MD: 5.28; 95% CI: 3.68 to 6.89; p < 0.001), 6 weeks post-partum (MD: 5.06; 95% CI: 3.80 to 6.31; p < 0.001) and 3 months post-partum (MD: 5.24; 95% CI: 4.12 to 6.35; p < 0.001). Similarly, the intervention group reported significantly higher connection and mother's self-perception scores at discharge (MD: 4.31; 95% CI: 3.07 to 5.56; p < 0.001), 6 weeks post-partum (MD: 4.69; 95% CI: 3.71 to 5.68; p < 0.001) and 3 months post-partum (MD: 4.93; 95% CI: 4.14 to 5.72; p < 0.001), compared to the control group. In contrast, the pressure from significant others scores were higher in the control group relative to the intervention group at discharge (MD: -2.09; 95% CI: -2.88 to -1.31; p < 0.001), 6 weeks post-partum (MD: -4.35; 95% CI: -5.20 to -3.49; p < 0.001) and 3 months (MD: -4.89; 95% CI: -5.70 to -4.08; p < 0.001). Finally, the intervention group also reported higher Instrumental Needs scores at all three time points: at discharge (MD: 1.96; 95% CI: 1.35 to 2.58; p < 0.001), 6 weeks post-partum (MD: 3.58; 95% CI: 3.05 to 4.11; p < 0.001) and 3 months post-partum (MD: 1.18; 95% CI: 0.68 to 1.69; p < 0.001). BSE scores were significantly higher in the intervention group compared to the control group at discharge (MD: 14.29; 95% CI: 10.38 to 18.21; p < 0.001), 6 weeks post-partum (MD: 14.04; 95% CI: 11.05 to 17.02; p < 0.001) and 3 months post-partum (MD: 6.80; 95% CI: 4.66 to 8.94; p < 0.001). The rates of exclusive breastfeeding were higher in the intervention group than in the control group at each stage of the intervention (p < 0.01). At 6 weeks post-partum, the intervention group's infants showed slower weight (t = -0.90, p = 0.371) and length (t = -0.69, p = 0.495) growth compared to the control group, though not significantly. By 3 months post-partum, there was a significant difference in both weight (t = -3.46, p = 0.001) and length (t = -2.95, p = 0.004) between the groups. The findings in this study suggest that the RBF intervention programme based on SDT may be effective in improving mothers' motivation to breastfeed, building breastfeeding self-confidence and increasing the rate of exclusive breastfeeding. The effects of the intervention on infant physical development will need to be verified with longer follow-up in future research.

A comprehensive review for artificial intelligence on neuroimaging in rehabilitation of ischemic stroke.

Stroke is the second leading cause of death worldwide, with ischemic stroke accounting for a significant proportion of morbidity and mortality among stroke patients. Ischemic stroke often causes disability and cognitive impairment in patients, which seriously affects the quality of life of patients. Therefore, how to predict the recovery of patients can provide support for clinical intervention in advance and improve the enthusiasm of patients for rehabilitation treatment. With the popularization of imaging technology, the diagnosis and treatment of ischemic stroke patients are often accompanied by a large number of imaging data. Through machine learning and Deep Learning, information from imaging data can be used more effectively. In this review, we discuss recent advances in neuroimaging, machine learning, and Deep Learning in the rehabilitation of ischemic stroke.