Risk factors and clinical outcomes of pulmonary hypertension associated with bronchopulmonary dysplasia in extremely premature infants: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the risk factors for bronchopulmonary dysplasia associated pulmonary hypertension (BPD-PH) in extremely premature infants (gestational age < 32 weeks) and its impact on outcomes. A computerized search of eight databases was performed, from the time of library construction to February 2024. The quality of the included studies was assessed with the Newcastle‒Ottawa scale. Statistical analyses were performed using RevMan 5.4.1 and Stata 16.0 software. Meta-analysis of 2137 extremely premature infants revealed that oligohydramnios (OR = 2.21, 95% CI 1.06-4.61), low gestational age (SMD = -0.36, 95% CI -0.47 to -0.24), low birth weight (SMD = -0.54, 95% CI -0.74 to -0.35), small for gestational age (OR = 1.61, 95% CI 1.06-2.44), neonatal respiratory distress syndrome (OR = 2.05, 95% CI 1.45-2.91), grade III bronchopulmonary dysplasia (OR = 4.67, 95% CI 1.34-16.30), and sepsis (OR = 2.25, 95% CI 1.69-4.66) were risk factors for BPD-PH, whereas antenatal steroids (OR = 0.66, 95% CI 0.49-0.88) were protective factors. BPD-PH led to the extension of oxygen therapy (SMD = 0.67, 95% CI 0.42-0.92) and hospital stay (SMD = 0.77, 95% CI 0.14-1.40), and elevated the risk of discharged on oxygen (OR = 2.77, 95% CI 1.35-5.70) and death (OR = 4.38, 95% CI 2.21-8.69). BPD-PH is a multifactorial disease. In this study, a total of seven risk factors, and one protective factor for BPD-PH were identified in extremely premature infants. By managing and mitigating these factors, it is possible to decrease the occurrence of BPD-PH. Furthermore, BPD-PH may increase the risk of a poor prognosis in extremely premature infants.

[Effects of Different Microbial Fertilizers on Soil Quality and Maize Yield in Coastal Saline Soil].

Microbial fertilizers have the characteristics of high efficiency and environmental protection in improving saline soils, and the application of functional microbial fertilizers is of great significance for the green abatement of saline barriers and the improvement of soil quality in coastal areas. The experiment was based on moderately saline soil in the coastal area of Hebei Province, with corn as the indicator crop, on the basis of conventional chemical fertilizer application. Different microbial fertilizer treatments, namely, T1 （conventional chemical fertilizer 750 kg·hm-2 + compound microbial agent 75 kg·hm-2）, T2 （conventional chemical fertilizer 750 kg·hm-2 + Bacillus megaterium 300 kg·hm-2）, T3 （conventional chemical fertilizer 750 kg·hm-2 + B. mucilaginosus 300 kg·hm-2）, T4 （conventional chemical fertilizer 750 kg·hm-2 + organic silicon fertilizer 600 kg·hm-2）, T5 （conventional chemical fertilizer 750 kg·hm-2 + bio-organic fertilizer 600 kg·hm-2）, T6 （conventional fertilizer 750 kg·hm-2 + active microalgae 15 kg·hm-2）, and CK （only fertilizer 750 kg·hm-2）, were used for these seven treatments, to study the effects of different microbial fertilizers on soil nutrients, salinity, bacterial community, and corn yield and economic efficiency during two critical periods （V12 stage and maturity stage） of corn. The results showed that compared with that in CK, T1 significantly increased soil total nitrogen （TN） and available phosphorus （AP） contents during the whole growth period. Over the whole reproductive period, soil organic matter （OM） at maturity increased by 10.35% over the V12 stage compared to that in CK, but there was no significant difference between treatments. Compared with that in CK, T5 and T6 significantly reduced soil total salinity and Ca2+ content during the whole growth period by an average of 14.51%-18.48% and 24.25%-25.51%. T1 significantly increased the bacterial diversity index over the whole growth period by 45.16% compared to that in CK. The dominant soil phyla were Actinobacteria, Proteobacteria, Acidobacteria, and Chloroflexi, and the dominant genera were Bacillus and Geminicoccaceae. The most abundant functions of the bacterial community in the study area were chemoheterotrophy and aerobic chemoheterotrophy, with average relative abundances of 28.89% and 27.11%, and T3 and T6 significantly improved soil N cycling function. The results of redundancy analysis （RDA） indicated that Na+, SO42-, pH, and EC were important factors driving the structure of the bacterial community, and correlation heatmaps showed that Na+, SO42-, pH, and EC were significantly and positively correlated mainly with the phylum Planctomycetota, whereas soil OM and TN were significantly and positively correlated with Cyanobacteria. Compared with that in CK, T6 increased the relative abundance of Cyanobacteria and optimized the bacterial community structure during the whole growth period. Using recommended dosages of bacterial fertilizers T1 and T6 increased maize yield by 7.31%-24.83% and economic efficiency by 9.05%-23.23%, respectively. The preliminary results of soil chemical properties and yield correlation analysis revealed that EC, AP, HCO3-, and Mg2+ were the obstacle factors limiting soil productivity in coastal areas. In conclusion, the use of the compound bacterial agent （T1） and active microalgae （T6） at the recommended dosage can significantly enhance soil nutrients, reduce salinity, and improve the structural diversity of soil bacterial communities, which not only ensures the increase in maize yield and efficiency but also realizes the efficient use of microbial fertilizers and the improvement of soil quality.

KMT2D-mediated H3K4me1 recruits YBX1 to facilitate triple-negative breast cancer progression through epigenetic activation of c-Myc.

BACKGROUND: Lysine methyltransferase 2D (KMT2D) mediates mono-methylation of histone H3 lysine 4 (H3K4me1) in mammals. H3K4me1 mark is involved in establishing an active chromatin structure to promote gene transcription. However, the precise molecular mechanism underlying the KMT2D-mediated H3K4me1 mark modulates gene expression in triple-negative breast cancer (TNBC) progression is unresolved. METHODS AND RESULTS: We recognized Y-box-binding protein 1 (YBX1) as a "reader" of the H3K4me1 mark, and a point mutation of YBX1 (E121A) disrupted this interaction. We found that KMT2D and YBX1 cooperatively promoted cell growth and metastasis of TNBC cells in vitro and in vivo. The expression levels of KMT2D and YBX1 were both upregulated in tumour tissues and correlated with poor prognosis for breast cancer patients. Combined analyses of ChIP-seq and RNA-seq data indicated that YBX1 was co-localized with KMT2D-mediated H3K4me1 in the promoter regions of c-Myc and SENP1, thereby activating their expressions in TNBC cells. Moreover, we demonstrated that YBX1 activated the expressions of c-Myc and SENP1 in a KMT2D-dependent manner. CONCLUSION: Our results suggest that KMT2D-mediated H3K4me1 recruits YBX1 to facilitate TNBC progression through epigenetic activation of c-Myc and SENP1. These results together unveil a crucial interplay between histone mark and gene regulation in TNBC progression, thus providing novel insights into targeting the KMT2D-H3K4me1-YBX1 axis for TNBC treatment. HIGHLIGHTS: YBX1 is a KMT2D-mediated H3K4me1-binding effector protein and mutation of YBX1 (E121A) disrupts its binding to H3K4me1. KMT2D and YBX1 cooperatively promote TNBC proliferation and metastasis by activating c-Myc and SENP1 expression in vitro and in vivo. YBX1 is colocalized with H3K4me1 in the c-Myc and SENP1 promoter regions in TNBC cells and increased YBX1 expression predicts a poor prognosis in breast cancer patients.

ECM1 and ANXA1 in urinary extracellular vesicles serve as biomarkers for breast cancer.

Objective: Although urinary extracellular vesicles (uEVs) have been extensively studied in various cancers, their involvement in breast cancer (BC) remains largely unexplored. The non-invasive nature of urine as a biofluid and its abundant protein content offer considerable potential for the early detection of breast cancer. Methods: This study analyzed the proteomic profiles of uEVs from BC patients and healthy controls (HC). The dysregulation of ECM1 and ANXA1 in the uEVs was validated in a larger cohort of 128 BC patients, 25 HC and 25 benign breast nodules (BBN) by chemiluminescence assay (CLIA). The expression levels of ECM1 and ANXA1 were also confirmed in the uEVs of MMTV-PyMT transgenic breast cancer mouse models. Results: LC-MS/MS analysis identified 571 dysregulated proteins in the uEVs of BC patients. ECM1 and ANXA1 were selected for validation in 128 BC patients, 25 HC and 25 BBN using CLIA, as their fold change showed a significant difference of more than 10 with p-value<0.05. Protein levels of ECM1 and ANXA1 in uEVs were significantly increased in BC patients. In addition, the protein levels of ECM1 and ANXA1 in the uEVs of MMTV-PyMT transgenic mice were observed to increase progressively with the progression of breast cancer. Conclusion: We developed a simple and purification-free assay platform to isolate uEVs and quantitatively detect ECM1 and ANXA1 in uEVs by WGA-coupled magnetic beads and CLIA. Our results suggest that ECM1 and ANXA1 in uEVs could potentially serve as diagnostic biomarkers for breast cancer.

Unveiling a novel entry gate: Insect foregut as an alternative infection route for fungal entomopathogens.

Insects and their natural microbial pathogens are intertwined in constant arms races, with pathogens continually seeking entry into susceptible hosts through distinct routes. Entomopathogenic fungi are primarily believed to infect host insects through external cuticle penetration. Here, we report a new variety, Beauveria bassiana var. majus (Bbm), that can infect insects through the previously unrecognized foregut. Dual routes of infection significantly accelerate insect mortality. The pH-responsive transcription factor PacC in Bbm exhibits rapid upregulation and efficient proteolytic processing via PalC for alkaline adaptation in the foregut. Expression of PalC is regulated by the adjacent downstream gene Aia. Compared to non-enteropathogenic strains such as ARSEF252, Aia in Bbm lacks a 249-bp fragment, resulting in its enhanced alkaline-induced expression. This induction promotes PalC upregulation and facilitates PacC activation. Expressing the active form of BbmPacC in ARSEF252 enables intestinal infection. This study uncovers the pH-responsive Aia-PalC-PacC cascade enhancing fungal alkaline tolerance for intestinal infection, laying the foundation for developing a new generation of fungal insecticides to control destructive insect pests.

Efficacy of Lenvatinib Combined with Anti-PD-1 Antibodies plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-PD-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07-34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The two-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Rapid identification of lactic acid bacteria at species/subspecies level via ensemble learning of Ramanomes.

Rapid and accurate identification of lactic acid bacteria (LAB) species would greatly improve the screening rate for functional LAB. Although many conventional and molecular methods have proven efficient and reliable, LAB identification using these methods has generally been slow and tedious. Single-cell Raman spectroscopy (SCRS) provides the phenotypic profile of a single cell and can be performed by Raman spectroscopy (which directly detects vibrations of chemical bonds through inelastic scattering by a laser light) using an individual live cell. Recently, owing to its affordability, non-invasiveness, and label-free features, the Ramanome has emerged as a potential technique for fast bacterial detection. Here, we established a reference Ramanome database consisting of SCRS data from 1,650 cells from nine LAB species/subspecies and conducted further analysis using machine learning approaches, which have high efficiency and accuracy. We chose the ensemble meta-classifier (EMC), which is suitable for solving multi-classification problems, to perform in-depth mining and analysis of the Ramanome data. To optimize the accuracy and efficiency of the machine learning algorithm, we compared nine classifiers: LDA, SVM, RF, XGBoost, KNN, PLS-DA, CNN, LSTM, and EMC. EMC achieved the highest average prediction accuracy of 97.3% for recognizing LAB at the species/subspecies level. In summary, Ramanomes, with the integration of EMC, have promising potential for fast LAB species/subspecies identification in laboratories and may thus be further developed and sharpened for the direct identification and prediction of LAB species from fermented food.

A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects.

PURPOSE: This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects. METHODS: Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct three-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean and standard deviation and compared using independent sample t-tests. RESULTS: In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment. CONCLUSION: Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

Blockade of pan-viral propagation by inhibition of host cell PNPT1.

For successful viral propagation within infected cells, the virus needs to overcome the cellular integrated stress response (ISR), triggered during viral infection, which, in turn, inhibits general protein translation. This paper reports a tactic employed by viruses to suppress the ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus and hepatovirus within their respective host cells induces PNPT1 expression. Notably, when PNPT1 is knocked down, the propagation of all three viruses is prevented. Mechanistically, the inhibition of PNPT1 facilitates the relocation of mitochondrial double-stranded RNAs (mt-dsRNAs) to the cytoplasm, where they activate RNA-activated protein kinase (PKR). This activation leads to eukaryotic initiation factor 2α (eIF2α) phosphorylation, resulting in the suppression of translation. Furthermore, by scrutinizing the PNPT1 recognition element and screening 17,728 drugs and bioactive compounds approved by the US Food and Drug Administration, lanatoside C was identified as a potent PNPT1 inhibitor. This compound impedes the propagation of adenovirus, murine cytomegalovirus and hepatovirus, and suppresses production of the severe acute respiratory syndrome coronavirus-2 spike protein. These discoveries shed light on a novel strategy to impede pan-viral propagation by activating the host cell mt-dsRNA-PKR-eIF2α signalling axis.

A multifunctional composite nanoparticle with antibacterial activities, anti-inflammatory, and angiogenesis for diabetic wound healing.

The treatment of chronic diabetic wounds remains challenging due to the rapid bacterial infection, severe inflammation, and insufficient angiogenesis. To address these challenges, a novel multifunctional composite nanoparticle is developed by co-assembling antisolvent-induced co-assembling silk-fibroin ε-poly-l-Lysine nanoparticles (nSF-EPL) and further assembling nSF-EPL with polydeoxyribonucleotide (PDRN) and exosome derived from human umbilical mesenchymal stem cells (Exo). Owing to the modification of EPL, PDRN and Exo, composite nanoparticles exhibited synergistic antibacterial action, anti-inflammatory and angiogenesis, which can significantly benefit for promoting wound healing. Release results show that the composite nanoparticles exhibit long-term sustained PDRN and Exo release profiles as well as outstanding release efficiency. Furthermore, in vitro studies show that the composite nanoparticles exhibit effective antibacterial activity, thus inducing an anti-inflammatory M2 macrophages phenotype and promoting angiogenesis. In vivo research results of investigations pertaining to diabetic wound healing show that the composite nanoparticles have good anti-inflammatory and angiogenesis capabilities, which can promote granulation tissue formation, collagen deposition, wound tissue epithelialization, and significantly accelerate skin healing. This study presents a promising strategy for the clinical treatment of chronic diabetic wounds.