Marine heatwaves alter competition between the cultured macroalga Gracilariopsis lemaneiformis and the harmful bloom alga Skeletonema costatum.

Seaweed cultivation can inhibit the occurrence of red tides. However, how seaweed aquaculture interactions with harmful algal blooms will be affected by the increasing occurrence and intensity of marine heatwaves (MHWs) is unknown. In this study, we run both monoculture and coculture systems to investigate the effects of a simulated heatwave on the competition of the economically important macroalga Gracilariopsis lemaneiformis against the harmful bloom diatom Skeletonema costatum. Coculture with G. lemaneiformis led to a growth decrease in S. costatum. Growth and photosynthetic activity (Fv/Fm) of G. lemaneiformis was greatly reduced by the heatwave treatment, and did not recover even after one week. Growth and photosynthetic activity of S. costatum was also reduced by the heatwave in coculture, but returned to normal during the recovery period. S. costatum also responded to the stressful environment by forming aggregates. Metabolomic analysis suggests that the negative effects on S. costatum were related to an allelochemical release from G. lemaneiformis. These findings show that MHWs may enhance the competitive advantages of S. costatum against G. lemaneiformis, leading to more severe harmful algal blooms in future extreme weather scenarios.

Odontogenesis-Empowered Extracellular Vesicles Safeguard Donor-Recipient Stem Cell Interplay to Support Tooth Regeneration.

Harnessing the developmental events of mesenchymal condensation to direct postnatal dental stem cell aggregation represents a cutting-edge and promising approach to tooth regeneration. Tooth avulsion is among the most prevalent and serious dental injuries, and odontogenic aggregates assembled by stem cells from human exfoliated deciduous teeth (SHED) have proven effective in revitalizing avulsed teeth after replantation in the clinical trial. However, whether and how SHED aggregates (SA) communicate with recipient components and promote synergistic tissue regeneration to support replanted teeth remains elusive. Here, it is shown that SA-mediated avulsed tooth regeneration involves periodontal restoration and recovery of recipient Gli1+ stem cells, which are mobilized and necessarily contribute to the reestablishment of the tooth-periodontal ligament-bone interface. Mechanistically, the release of extracellular vesicles (EVs) is revealed indispensable for the implanted SA to mobilize recipient Gli1+ cells and regenerate avulsed teeth. Furthermore, SHED aggregates-released EVs (SA-EVs) are featured with odontogenic properties linked to tissue regeneration, which enhance migration, proliferation, and differentiation of Gli1+ cells. Importantly, local application of SA-EVs per se empowers recipient Gli1+ cells and safeguards regeneration of avulsed teeth. Collectively, the findings establish a paradigm in which odontogenesis-featured EVs govern donor-recipient stem cell interplay to achieve tooth regeneration, inspiring cell-free translational regenerative strategies.

Rhei Radix et Rhizoma and its anthraquinone derivatives: Potential candidates for pancreatitis treatment.

BACKGROUND: Pancreatitis is a common exocrine inflammatory disease of the pancreas and lacks specific medication currently. Rhei Radix et Rhizoma (RR) and its anthraquinone derivatives (AQs) have been successively reported for their pharmacological effects and molecular mechanisms in experimental and clinical pancreatitis. However, an overview of the anti-pancreatitis potential of RR and its AQs is limited. PURPOSE: To summarize and analyze the pharmacological effects of RR and its AQs on pancreatitis and the underlying mechanisms, and discuss their drug-like properties and future perspectives. METHODS: The articles related to RR and its AQs were collected from the Chinese National Knowledge Infrastructure, Wanfang data, PubMed, and the Web of Science using relevant keywords from the study's inception until April first, 2024. Studies involving RR or its AQs in cell or animal pancreatitis models as well as structure-activity relationship, pharmacokinetics, toxicology, and clinical trials were included. RESULTS: Most experimental studies are based on severe acute pancreatitis rat models and a few on chronic pancreatitis. Several bioactive anthraquinone derivatives of Rhei Radix et Rhizoma (RRAQs) exert local protective effects on the pancreas by maintaining pancreatic acinar cell homeostasis, inhibiting inflammatory signaling, and anti-fibrosis, and they improve systemic organ function by alleviating intestinal and lung injury. Pharmacokinetic and toxicity studies have revealed the low bioavailability and wide distribution of RRAQs, as well as hepatotoxicity and nephrotoxicity. However, there is insufficient research on the clinical application of RRAQs in pancreatitis. Furthermore, we propose effective strategies for subsequent improvement in terms of balancing effectiveness and safety. CONCLUSION: RRAQs can be developed as either candidate drugs or novel lead structures for pancreatitis treatment. The comprehensive review of RR and its AQs provides references for optimizing drugs, developing therapies, and conducting future studies on pancreatitis.

Mucus Impaction Related to Postoperative Anastomosis Site Obstruction: A Rare Case.

Anastomotic stricture has an incidence rate of 6-10% and typically manifests three to six months after colorectal surgery. Immediate postoperative stricture is exceedingly rare and underreported in the literature. The possible etiology includes poor circulation, leakage, local inflammation, or infection. We report a rare case of a patient with total obstruction by mucus on the anastomosis site on postoperation day two. We used a sigmoidoscope to remove mucus material, following which the patient recovered well.

Lactobacillus Reuteri Vesicles Regulate Mitochondrial Function of Macrophages to Promote Mucosal and Cutaneous Wound Healing.

The interplay between bacteria and their host influences the homeostasis of the human immune microenvironment, and this reciprocal interaction also affects the process of tissue damage repair. A variety of immunomodulatory commensal bacteria reside in the body, capable of delivering membrane vesicles (MVs) to host cells to regulate the local immune microenvironment. This research revealed, for the initial time, the significant enhancement of mucosal and cutaneous wound healing by MVs secreted by the human commensal Lactobacillus reuteri (RMVs) through modulation of the inflammatory environment in wound tissue. Local administration of RMVs reduces the proportion of pro-inflammatory macrophages in inflamed tissues and mitigates the level of local inflammation, thereby facilitating the healing of oral mucosa and cutaneous wounds. The elevated oxidative stress levels in activated pro-inflammatory macrophages can be modulated by RMVs, resulting in phenotypic transformation of macrophages. Furthermore, 3-hydroxypropionaldehyde present in RMVs can decrease the mitochondrial permeability of macrophages and stabilize the mitochondrial membrane potential, thereby promoting the conversion of macrophages to an anti-inflammatory phenotype. This study pioneers the significance of commensal bacterial MVs in tissue injury repair and presents a novel concept for the repair of tissue damage.

Dual Pd-Acid Sites Confined in a Hierarchical Core-Shell Structure for Hydrogenation of Nitrobenzene.

A core-shell structured Pd@TS-1@meso-SiO2 catalyst with confined Pd nanometals has been fabricated by one-pot synthesis, impregnation method and sol-gel method. With the promotion of acid sites and protection of mesoporous silica shell, Pd@TS-1@meso-SiO2 shows higher activity than commercial comparison and higher stability than sample without mesoporous silica shell in the hydrogenation of nitrobenzene. The schematic illustration of the synergy effect is also proposed.

Simulated upwelling and marine heatwave events promote similar growth rates but differential domoic acid toxicity in Pseudo-nitzschia australis.

Along the west coast of the United States, highly toxic Pseudo-nitzschia blooms have been associated with two contrasting regional phenomena: seasonal upwelling and marine heatwaves. While upwelling delivers cool water rich in pCO2 and an abundance of macronutrients to the upper water column, marine heatwaves instead lead to warmer surface waters, low pCO2, and reduced nutrient availability. Understanding Pseudo-nitzschia dynamics under these two conditions is important for bloom forecasting and coastal management, yet the mechanisms driving toxic bloom formation during contrasting upwelling vs. heatwave conditions remain poorly understood. To gain a better understanding of what drives Pseudo-nitzschia australis growth and toxicity during these events, multiple-driver scenario or 'cluster' experiments were conducted using temperature, pCO2, and nutrient levels reflecting conditions during upwelling (13 °C, 900 ppm pCO2, replete nutrients) and two intensities of marine heatwaves (19 °C or 20.5 °C, 250 ppm pCO2, reduced macronutrients). While P. australis grew equally well under both heatwave and upwelling conditions, similar to what has been observed in the natural environment, cells were only toxic in the upwelling treatment. We also conducted single-driver experiments to gain a mechanistic understanding of which drivers most impact P. australis growth and toxicity. These experiments indicated that nitrogen concentration and N:P ratio were likely the drivers that most influenced domoic acid production, while the impacts of temperature or pCO2 concentration were less pronounced. Together, these experiments may help to provide both mechanistic and holistic perspectives on toxic P. australis blooms in the dynamic and changing coastal ocean, where cells interact simultaneously with multiple altered environmental variables.

Tectorigenin: A Review of Its Sources, Pharmacology, Toxicity, and Pharmacokinetics.

Tectorigenin is a well-known natural flavonoid aglycone and an active component that exists in numerous plants. Growing evidence suggests that tectorigenin has multiple pharmacological effects, such as anticancer, antidiabetic, hepatoprotective, anti-inflammatory, antioxidative, antimicrobial, cardioprotective, and neuroprotective. These pharmacological properties provide the basis for the treatment of many kinds of illnesses, including several types of cancer, diabetes, hepatic fibrosis, osteoarthritis, Alzheimer's disease, etc. The purpose of this paper is to provide a comprehensive summary and review of the sources, extraction and synthesis, pharmacological effects, toxicity, pharmacokinetics, and delivery strategy aspects of tectorigenin. Tectorigenin may exert certain cytotoxicity, which is related to the administration time and concentration. Pharmacokinetic studies have demonstrated that the main metabolic pathways in rats for tectorigenin are glucuronidation, sulfation, demethylation and methoxylation, but that it exhibits poor bioavailability. From our perspective, further research on tectorigenin should cover: exploring the pharmacological targets and mechanisms of action; finding an appropriate concentration to balance pharmacological effects and toxicity; attempting diversified delivery strategies to improve the bioavailability; and structural modification to obtain tectorigenin derivatives with higher pharmacological activity.

Myofascial acupuncture versus routine acupuncture for mechanical neck pain: a protocol for a multicentre randomised controlled trial.

INTRODUCTION: Mechanical neck pain (MNP) is defined as pain in the area of the neck and/or neck-shoulder provoked by body mechanics and which adversely affects physical, psychological and social function. The treatments for MNP are limited. Previous studies and clinical experience have indicated that myofascial acupuncture might be a better treatment option for MNP, but the efficacy is controversial. Therefore, our aim is to compare the efficacy of myofascial acupuncture and routine acupuncture for MNP. METHODS AND ANALYSIS: The study is a multicentre, prospective randomised clinical trial. Patients will be recruited from four tertiary hospitals in China. A total of 438 participants with MNP will be randomly assigned into two groups, namely the 'Sancai-Tianbu' myofascial acupuncture group and the routine acupuncture group, at a ratio of 1:1. Each group will receive the acupuncture treatment twice a week for 21 days, totalling six sessions. The primary outcome will be the Visual Analogue Scale score. The secondary outcomes will be the Neck Disability Index, the cervical range of motion and the MOS 36-Item Short Form Health Survey. The assessments will be performed at baseline (immediately after allocation), pretreatment (5 min before every treatment), post-treatment (within 10 min after every treatment), postcourse (within 1 day after the course), and at 1, 3 and 6 months after the course. All patients will be included in the intent-to-treat analysis. Repeated-measure analysis of covariance will be used to determine the effects of the intervention on the outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from China Aerospace Science & Industry Corporation 731 Hospital, with permission number 2022-0204-01. Written informed consent will be obtained from the enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2200061453.

Quantitative evaluation of bone marrow characteristics in occult and subtle rib fractures by spectral CT.

PURPOSE: The present study aimed to determine whether the water content change in the medullary cavity of occult rib fractures by spectral computed tomography (CT). METHODS: The material decomposition (MD) images were reconstructed using the water-hydroxyapatite basis material pairs from spectral CT. The water contents of the medullary cavity in subtle or occult rib fractures and the symmetrical sites of the contralateral ribs were measured, and their difference was calculated. The absolute value of the water content difference was compared to patients without trauma. An independent samples t-test was adopted to compare the consistency of the water content in the medullary cavity of the normal ribs. Intergroup and pairwise comparisons were applied to the difference in water content among the subtle/occult fractures and normal ribs, followed by receiver operating characteristic curve calculations. p < 0.05 was considered to have a statistically significant difference. RESULTS: A total of 100 subtle fractures, 47 occult fractures, and 96 pairs of normal ribs were included in this study. The water content of the medullary cavity in the subtle and occult fractures was both higher than that in their symmetrical sites with the difference value of 31.06 ± 15.03 mg/cm3 and 27.83 ± 11.40 mg/cm3, respectively. These difference values between the subtle and occult fractures were not statistically significant (p = 0.497). For the normal ribs, the bilateral water contents were not statistically different (p > 0.05) with a difference value of 8.05 ± 6.13 mg/cm3. The increased water content of fractured ribs was higher than that of normal ribs (p < 0.001). According to the classification based on whether the ribs were fractured, the area under the curve was 0.94. CONCLUSIONS: The water content measured on MD images in spectral CT in the medullary cavity increased as a response to subtle/occult rib fractures.

Hierarchically Porous Few-Layer Carbon Nitride and Its High H+ Selectivity for Efficient Photocatalytic Seawater Splitting.

Photocatalysts for seawater splitting are severely restricted because of the presence of multiple types of ions in seawater that cause corrosion and deactivation. As a result, new materials that promote adsorption of H+ and hinder competing adsorption of metal cations should enhance utilization of photogenerated electrons on the catalyst surface for efficient H2 production. One strategy to design advanced photocatalysts involves introduction of hierarchical porous structures that enable fast mass transfer and creation of defect sites that promote selective hydrogen ion adsorption. Herein, we used a facile calcination method to fabricate the macro-mesoporous C3N4 derivative, VN-HCN, that contains multiple nitrogen vacancies. We demonstrated that VN-HCN has enhanced corrosion resistance and elevated photocatalytic H2 production performance in seawater. Experimental results and theoretical calculations reveal that enhanced mass and carrier transfer and selective adsorption of hydrogen ions are key features of VN-HCN that lead to its high seawater splitting activity.

Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice.

The COVID-19 pandemic continues to threaten human health worldwide as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around Y453 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values ranging from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on broadly neutralizing chimeric antibodies to create K-RBD-hAb-60 and -62, which still retain excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.

Construct ceRNA Network and Risk Model of Breast Cancer Using Machine Learning Methods under the Mechanism of Cuproptosis.

Breast cancer (BRCA) has an undesirable prognosis and is the second most common cancer among women after lung cancer. A novel mechanism of programmed cell death called cuproptosis is linked to the development and spread of tumor cells. However, the function of cuproptosis in BRCA remains unknown. To this date, no studies have used machine learning methods to screen for characteristic genes to explore the role of cuproptosis-related genes (CRGs) in breast cancer. Therefore, 14 cuproptosis-related characteristic genes (CRCGs) were discovered by the feature selection of 39 differentially expressed CRGs using the three machine learning methods LASSO, SVM-RFE, and random forest. Through the PPI network and immune infiltration analysis, we found that PRNP was the key CRCG. The miRTarBase, TargetScan, and miRDB databases were then used to identify hsa-miR-192-5p and hsa-miR-215-5p as the upstream miRNA of PRNP, and the upstream lncRNA, CARMN, was identified by the StarBase database. Thus, the mRNA PRNP/miRNA hsa-miR-192-5p and hsa-miR-215-5p/lncRNA CARMN ceRNA network was constructed. This ceRNA network, which has not been studied before, is extremely innovative. Furthermore, four cuproptosis-related lncRNAs (CRLs) were screened in TCGA-BRCA by univariate Cox, LASSO, and multivariate Cox regression analysis. The risk model was constructed by using these four CRLs, and the risk score = C9orf163 * (1.8365) + PHC2-AS1 * (-2.2985) + AC087741.1 * (-0.9504) + AL109824.1 * (0.6016). The ROC curve and C-index demonstrated the superior predictive capacity of the risk model, and the ROC curve demonstrated that the AUC of 1-, 3-, and 5-year OS in all samples was 0.721, 0.695, and 0.633, respectively. Finally, 50 prospective sensitive medicines were screened with the pRRophetic R package, among which 17-AAG may be a therapeutic agent for high-risk patients, while the other 49 medicines may be suitable for the treatment of low-risk patients. In conclusion, our study constructs a new ceRNA network and a novel risk model, which offer a theoretical foundation for the treatment of BRCA and will aid in improving the prognosis of BRCA.

Mesenchymal stem cells: Emerging concepts and recent advances in their roles in organismal homeostasis and therapy.

Stem cells play a crucial role in re-establishing homeostasis in the body, and the search for mechanisms by which they interact with the host to exert their therapeutic effects remains a key question currently being addressed. Considering their significant regenerative/therapeutic potential, research on mesenchymal stem cells (MSCs) has experienced an unprecedented advance in recent years, becoming the focus of extensive works worldwide to develop cell-based approaches for a variety of diseases. Initial evidence for the effectiveness of MSCs therapy comes from the restoration of dynamic microenvironmental homeostasis and endogenous stem cell function in recipient tissues by systemically delivered MSCs. The specific mechanisms by which the effects are exerted remain to be investigated in depth. Importantly, the profound cell-host interplay leaves persistent therapeutic benefits that remain detectable long after the disappearance of transplanted MSCs. In this review, we summarize recent advances on the role of MSCs in multiple disease models, provide insights into the mechanisms by which MSCs interact with endogenous stem cells to exert therapeutic effects, and refine the interconnections between MSCs and cells fused to damaged sites or differentiated into functional cells early in therapy.

Importance of mobile genetic element immunity in numerically abundant Trichodesmium clades.

The colony-forming cyanobacteria Trichodesmium spp. are considered one of the most important nitrogen-fixing genera in the warm, low nutrient ocean. Despite this central biogeochemical role, many questions about their evolution, physiology, and trophic interactions remain unanswered. To address these questions, we describe Trichodesmium pangenomic potential via significantly improved genomic assemblies from two isolates and 15 new >50% complete Trichodesmium metagenome-assembled genomes from hand-picked, Trichodesmium colonies spanning the Atlantic Ocean. Phylogenomics identified ~four N2 fixing clades of Trichodesmium across the transect, with T. thiebautii dominating the colony-specific reads. Pangenomic analyses showed that all T. thiebautii MAGs are enriched in COG defense mechanisms and encode a vertically inherited Type III-B Clustered Regularly Interspaced Short Palindromic Repeats and associated protein-based immunity system (CRISPR-Cas). Surprisingly, this CRISPR-Cas system was absent in all T. erythraeum genomes, vertically inherited by T. thiebautii, and correlated with increased signatures of horizontal gene transfer. Additionally, the system was expressed in metaproteomic and transcriptomic datasets and CRISPR spacer sequences with 100% identical hits to field-assembled, putative phage genome fragments were identified. While the currently CO2-limited T. erythraeum is expected to be a 'winner' of anthropogenic climate change, their genomic dearth of known phage resistance mechanisms, compared to T. thiebautii, could put this outcome in question. Thus, the clear demarcation of T. thiebautii maintaining CRISPR-Cas systems, while T. erythraeum does not, identifies Trichodesmium as an ecologically important CRISPR-Cas model system, and highlights the need for more research on phage-Trichodesmium interactions.

Plastic responses lead to increased neurotoxin production in the diatom Pseudo-nitzschia under ocean warming and acidification.

Ocean warming (OW) and acidification (OA) are recognized as two major climatic conditions influencing phytoplankton growth and nutritional or toxin content. However, there is limited knowledge on the responses of harmful algal bloom species that produce toxins. Here, the study provides quantitative and mechanistic understanding of the acclimation and adaptation responses of the domoic acid (DA) producing diatom Pseudo-nitzschia multiseries to rising temperature and pCO2 using both a one-year in situ bulk culture experiment, and an 800-day laboratory acclimation experiment. Ocean warming showed larger selective effects on growth and DA metabolism than ocean acidification. In a bulk culture experiment, increasing temperature +4 °C above ambient seawater temperature significantly increased DA concentration by up to 11-fold. In laboratory when the long-term warming acclimated samples were assayed under low temperatures, changes in growth rates and DA concentrations indicated that P. multiseries did not adapt to elevated temperature, but could instead rapidly and reversibly acclimate to temperature shifts. However, the warming-acclimated lines showed evidence of adaptation to elevated temperatures in the transcriptome data. Here the core gene expression was not reversed when warming-acclimated lines were moved back to the low temperature environment, which suggested that P. multiseries cells might adapt to rising temperature over longer timescales. The distinct strategies of phenotypic plasticity to rising temperature and pCO2 demonstrate a strong acclimation capacity for this bloom-forming toxic diatom in the future ocean.

Analysis of 12 Chemical Compounds And Pattern Recognition of Different Parts of Angelicae Sinensis Radix by Liquid Chromatography-Tandem Mass Spectrometry And Chemometrics Methods.

To evaluate the quality and quantify bioactive constituents in different parts of Angelicae Sinensis Radix, an efficient, high-speed, high-sensitivity high-performance liquid chromatography and triple quadrupole mass spectrometry method was used for simultaneous detection of 12 chemical compounds including L-tryptophan, chlorogenic acid, caffeic acid, ferulic acid, isoferulic acid, senkyunolide I, guanosine, proline, L-glutamine, γ-aminobutyric acid, glutamic acid, and arginine in 52 batches of Angelicae Sinensis Radix from Gansu, China. The established methods were validated by good linearity (R2≥0.9921), limits of detection (0.0001-0.0156 µg/mL), limits of quantitation (0.0006-0.0781 µg/mL), stability (RSD≤7.77%), repeatability (RSD≤6.79%), intra- and interday precisions (RSD≤6.00% and RSD≤6.39%, respectively) and recovery (90.90-107.16%). According to the quantitative results, the contents of the hydrophilic compounds were higher in the head, while the medium and weak polar components were mainly concentrated in the tail. Finally, principal component analysis results revealed that Angelicae Sinensis Radix could be divided into different medicinal sites based on polar components such as amino acids, nucleosides. The combination of liquid chromatography-tandem mass spectrometry and principal component analysis is a simple and reliable method for pattern recognition and quality evaluation of Angelicae Sinensis Radix.

Integrated effects of residual plastic films on soil-rhizosphere microbe-plant ecosystem.

Intensive application of low-density polyethylene mulch films has resulted in substantial accumulation of residual plastics in agricultural soil. Although considerable concerns have been raised on the residual plastic pollution, their impacts on the soil-rhizosphere microbe-plant ecosystem have not been fully elucidated. In this study, we used a pot experiment to determine the effects of residual plastic films with different sizes (La, Ma, Mi and Mx) on properties, enzyme systems and nutrients of soil, composition of rhizosphere microbial community, and physiology, growth and stress response of rice plants. Residual plastic films significantly decreased soil bulk density and increased soil porosity, leading to the alteration of extracellular enzyme activities, and accumulation of dissolved nitrogen (NO3-N + NH4-N). The structures of both bacterial and fungal communities were significantly changed by residual plastic films with rhizosphere microbes more sensitive to small-sized plastics. Plant growth was inhibited to different extents by residual plastic films with different sizes. The weighted gene co-expression network analysis (WGCNA) showed that photosynthesis and carbon fixation of rice plants were repressed by residual plastic films, due to the reduced chlorophyll content and rubisco activity. In addition, the endogenous jasmonic acid and antioxidant enzyme system were induced to activate tolerant responses in rice plants to the stress imposed by residual plastic films. The partial least squares path models (PLS-PMs) revealed that residual plastic films had direct and/or indirect effects on the soil-rhizosphere microbe-plant system.

Monoclonal antibodies against S2 subunit of spike protein exhibit broad reactivity toward SARS-CoV-2 variants.

BACKGROUND: The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) harbor diverse spike (S) protein sequences, which can greatly influence the efficacies of therapeutics. Therefore, it would be of great value to develop neutralizing monoclonal antibodies (mAbs) that can broadly recognize multiple variants. METHODS: Using an mRNA-LNP immunization strategy, we generated several mAbs that specifically target the conserved S2 subunit of SARS-CoV-2 (B-S2-mAbs). These mAbs were assessed for their neutralizing activity with pseudotyped viruses and binding ability for SARS-CoV-2 variants. RESULTS: Among these mAbs, five exhibited strong neutralizing ability toward the Gamma variant and also recognized viral S proteins from the Wuhan, Alpha, Beta, Gamma, Delta and Omicron (BA.1, BA.2 and BA.5) variants. Furthermore, we demonstrated the broad reactivities of these B-S2-mAbs in several different applications, including immunosorbent, immunofluorescence and immunoblotting assays. In particular, B-S2-mAb-2 exhibited potent neutralization of Gamma variant (IC50 = 0.048 µg/ml) in a pseudovirus neutralization assay. The neutralizing epitope of B-S2-mAb-2 was identified by phage display as amino acid residues 1146-1152 (DSFKEEL) in the S2 subunit HR2 domain of SARS-CoV-2. CONCLUSION: Since there are not many mAbs that can bind the S2 subunit of SARS-CoV-2 variants, our set of B-S2-mAbs may provide important materials for basic research and potential clinical applications. Importantly, our study results demonstrate that the viral S2 subunit can be targeted for the production of cross-reactive antibodies, which may be used for coronavirus detection and neutralization.

Omentin1 ameliorates myocardial ischemia-induced heart failure via SIRT3/FOXO3a-dependent mitochondrial dynamical homeostasis and mitophagy.

BACKGROUND: Adipose tissue-derived adipokines are involved in various crosstalk between adipose tissue and other organs. Omentin1, a novel adipokine, exerts vital roles in the maintenance of body metabolism, insulin resistance and the like. However, the protective effect of omentin1 in myocardial ischemia (MI)-induced heart failure (HF) and its specific mechanism remains unclear and to be elucidated. METHODS: The model of MI-induced HF mice and oxygen glucose deprivation (OGD)-injured cardiomyocytes were performed. Mice with overexpression of omentin1 were constructed by a fat-specific adeno-associated virus (AAV) vector system. RESULTS: We demonstrated that circulating omentin1 level diminished in HF patients compared with healthy subjects. Furthermore, the fat-specific overexpression of omentin1 ameliorated cardiac function, cardiac hypertrophy, infarct size and cardiac pathological features, and also enhanced SIRT3/FOXO3a signaling in HF mice. Additionally, administration with AAV-omentin1 increased mitochondrial fusion and decreased mitochondrial fission in HF mice, as evidenced by up-regulated expression of Mfn2 and OPA1, and downregulation of p-Drp1(Ser616). Then, it also promoted PINK1/Parkin-dependent mitophagy. Simultaneously, treatment with recombinant omentin1 strengthened OGD-injured cardiomyocyte viability, restrained LDH release, and enhanced the mitochondrial accumulation of SIRT3 and nucleus transduction of FOXO3a. Besides, omentin1 also ameliorated unbalanced mitochondrial fusion-fission dynamics and activated mitophagy, thereby, improving the damaged mitochondria morphology and controlling mitochondrial quality in OGD-injured cardiomyocytes. Interestingly, SIRT3 played an important role in the improvement effects of omentin1 on mitochondrial function, unbalanced mitochondrial fusion-fission dynamics and mitophagy. CONCLUSION: Omentin1 improves MI-induced HF and myocardial injury by maintaining mitochondrial dynamical homeostasis and activating mitophagy via upregulation of SIRT3/FOXO3a signaling. This study provides evidence for further application of omentin1 in cardiovascular diseases from the perspective of crosstalk between heart and adipose tissue.