Blood urea nitrogen to albumin ratio is a novel predictor of fatal outcome for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.

Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.

BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.

BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

Robust Cooperative Control for Heterogeneous Uncertain Nonlinear High-Order Fully Actuated Multiagent Systems.

This research is intended to address a robust cooperative control problem of heterogeneous uncertain nonlinear high-order fully actuated multiagent systems (HUN-HOFAMASs). A nonlinear HOFA system model is used to describe the multiagent systems (MASs) with heterogeneous uncertain nonlinear dynamics, which is called the HUN-HOFAMASs. A predictive terminal sliding-mode control-based robust cooperative control scheme is presented to address this problem. In this scheme, heterogeneous nonlinear dynamics of original system are offset to establish a linear constant HOFA system with the help of full actuation feature. Then, a terminal sliding-mode variable for enhancing the system robustness is introduced to handle the uncertainties. Furthermore, a linear incremental prediction model is developed in a HOFA form by means of a Diophantine equation. According to this model, the multistep terminal sliding-mode predictions are yielded to optimize the robust cooperative control performance and compensate for the network-induced communication constraints in the feedback and forward channels. Based on a linear matrix inequality (LMI) method, a necessary and sufficient criterion is derived to discuss the simultaneous consensus and stability of closed-loop HUN-HOFAMASs. The simulation and comparison results of cooperative flying around of multiple spacecraft system are shown to illustrate the capability and advantage of the presented predictive terminal sliding-mode control for robust cooperative control.

Liquid lens based holographic camera for real 3D scene hologram acquisition using end-to-end physical model-driven network.

With the development of artificial intelligence, neural network provides unique opportunities for holography, such as high fidelity and dynamic calculation. How to obtain real 3D scene and generate high fidelity hologram in real time is an urgent problem. Here, we propose a liquid lens based holographic camera for real 3D scene hologram acquisition using an end-to-end physical model-driven network (EEPMD-Net). As the core component of the liquid camera, the first 10 mm large aperture electrowetting-based liquid lens is proposed by using specially fabricated solution. The design of the liquid camera ensures that the multi-layers of the real 3D scene can be obtained quickly and with great imaging performance. The EEPMD-Net takes the information of real 3D scene as the input, and uses two new structures of encoder and decoder networks to realize low-noise phase generation. By comparing the intensity information between the reconstructed image after depth fusion and the target scene, the composite loss function is constructed for phase optimization, and the high-fidelity training of hologram with true depth of the 3D scene is realized for the first time. The holographic camera achieves the high-fidelity and fast generation of the hologram of the real 3D scene, and the reconstructed experiment proves that the holographic image has the advantage of low noise. The proposed holographic camera is unique and can be used in 3D display, measurement, encryption and other fields.

Observer-based HOFA predictive cooperative control for networked multi-agent systems under time-variant communication constraints.

This research focuses on a cooperative control problem for networked multi-agent systems (NMASs) under time-variant communication constraints (containing time-variant communication delays and time-variant data losses) in the forward and feedback channels. From the perspective of high-order fully actuated (HOFA) system theory, a HOFA system model is adopted to describe the NMAS, which is called the networked HOFA multi-agent system (NHOFAMAS). Because of complicated working scenarios over the network, the states of NMASs are immeasurable and the communication constraints are always present, such that an observer-based HOFA predictive control (OB-HOFAPC) method is designed to implement the cooperative control when existing the immeasurable states and time-variant communication constraints. In this method, a HOFA observer is established to estimate the immeasurable states for constructing a consensus control protocol. Then, an incremental prediction model (IPM) in a HOFA form is developed via a Diophantine equation to take the place of a reduced-order prediction model. Through this IPM, multi-step output ahead predictions are derived to optimize the cooperative control performance and compensate for time-variant communication constraints in real-time. The depth discussion gives a sufficient and necessary criterion to analyze the simultaneous consensus and stability for closed-loop NHOFAMASs. The capability and advantage of OB-HOFAPC method are illustrated via numerical simulation and experimental verification on a cooperative flying-around task of three air-bearing spacecraft simulators.

Secure Predictive Coordinated Control of High-Order Fully Actuated Networked Multiagent Systems Under Random DoS Attacks.

This research addresses a coordinated control problem for high-order fully actuated networked multiagent systems (HOFANMASs) under random denial-of-service (DoS) attacks. A type of Bernoulli processes is exploited to denote the successful rate of launching random DoS attacks happened to the forward and feedback channels. When acting these attacks successfully, random data losses and disorders are caused in the forward and feedback channels. A high-order fully actuated (HOFA) secure predictive coordinated control scheme is provided to achieve the security coordination. In this scheme, a dynamic model of networked multiagent system is established with the help of a HOFA system model, which is called the HOFANMAS. Then, a prediction model in an incremental HOFA (IHOFA) form is developed by means of a Diophantine equation, which aims at constructing the multistep ahead output predictions for the optimization of coordinated control performance and the compensation of random data losses and disorders. Furthermore, a necessary and sufficient condition is proposed to analyze the consensus and stability of closed-loop HOFANMASs. The effectiveness and superiority of HOFA secure predictive control scheme can be demonstrated via simulated and experimental results of formation control for three air-bearing spacecraft (ABS) simulators.

A low-cost and portable fluorometer based on an optical pick-up unit for chlorophyll-a detection.

Chlorophyll-a (Chl-a) fluorescence detection is an important technique for monitoring water quality. In this work, we proposed an approach that employs the mass-produced low-cost optical pick-up unit (OPU) extracted from the high-definition digital versatile disc (HD-DVD) drive as the key optical component for our chlorophyll-a fluorometer. The built-in blue-violet 405 nm laser diode of the OPU acts as the excitation light to perform laser-induced fluorescence (LIF). The laser driver and a series of intrinsic lenses within the OPU, such as an objective lens with a numerical aperture (NA) of 0.65 and a collimating lens, help reduce the size, cost, and system complexity of the fluorometer. By integrating off-the-shelf electronic components, miniaturized optical setups, and 3D-printed assemblies, we have developed a low-cost, easy-to-make, standalone, and portable fluorometer. Finally, we validated the performance of the device for chlorophyll-a fluorescence detection under laboratory and on-site conditions, which demonstrated its great potential in water monitoring applications. The limit of detection (LOD) for chlorophyll-a is 0.35 µg/L, the size of the device is 151 × 100 × 80 mm3, and the total cost of the proposed fluorometer is as low as 137.5 USD. © 2023 Elsevier Science. All rights reserved.

Characterization of genes involved in micronutrients and toxic metals detoxification in Brassica napus by genome-wide cDNA library screening.

Stresses caused by deficiency/excess of mineral nutrients or of pollution of toxic metals have already become a primary factor in limiting crop production worldwide. Genes involved in minerals and toxic metals accumulation/tolerance could be potential candidates for improving crop plants with enhanced nutritional efficiency and environmental adaptability. In this study, we first generated a high-quality yeast expression cDNA library of Brassica napus (Westar), and 46 genes mediating excess micronutrients and toxic metals detoxification were screened using the yeast genetic complementation system, including 11, 5, 6, 14, 6, and 5 genes involved in cadmium (Cd), zinc (Zn), iron (Fe), manganese (Mn), boron (B), and copper (Cu) tolerance, respectively. Characterization of genes mediating excess ions stress resistance in this study is beneficial for us to further understand ions homeostasis in B. napus.

Modulation of HIV-1 capsid multimerization by sennoside A and sennoside B via interaction with the NTD/CTD interface in capsid hexamer.

Small molecules that bind to the pocket targeted by a peptide, termed capsid assembly inhibitor (CAI), have shown antiviral effects with unique mechanisms of action. We report the discovery of two natural compounds, sennoside A (SA) and sennoside B (SB), derived from medicinal plants that bind to this pocket in the C-terminal domain of capsid (CA CTD). Both SA and SB were identified via a drug-screening campaign that utilized a time-resolved fluorescence resonance energy transfer assay. They inhibited the HIV-1 CA CTD/CAI interaction at sub-micromolar concentrations of 0.18 µM and 0.08 µM, respectively. Mutation of key residues (including Tyr 169, Leu 211, Asn 183, and Glu 187) in the CA CTD decreased their binding affinity to the CA monomer, from 1.35-fold to 4.17-fold. Furthermore, both compounds induced CA assembly in vitro and bound directly to the CA hexamer, suggesting that they interact with CA beyond the CA CTD. Molecular docking showed that both compounds were bound to the N-terminal domain (NTD)/CTD interface between adjacent protomers within the CA hexamer. SA established a hydrogen-bonding network with residues N57, V59, Q63, K70, and N74 of CA1-NTD and Q179 of CA2-CTD. SB formed hydrogen bonds with the N53, N70, and N74 residues of CA1-NTD, and the A177and Q179 residues of CA2-CTD. Both compounds, acting as glue, can bring αH4 in the NTD and αH9 in the CTD of the NTD/CTD interface close to each other. Collectively, our research indicates that SA and SB, which enhance CA assembly, could serve as novel chemical tools to identify agents that modulate HIV-1 CA assembly. These natural compounds may potentially lead to the development of new antiviral therapies with unique mechanisms of action.

Clinical features, microbial spectrum, and antibiotic susceptibility patterns of spontaneous bacterial peritonitis in cirrhotic patients.

BACKGROUND AND AIMS: The microbial spectrum and antimicrobial resistance patterns change over time and vary across regions in patients with spontaneous bacterial peritonitis (SBP). There is an urgent need to clarify the factors associated with in-hospital mortality in these patients. METHODS: In this study, 377 patients with SBP and 794 patients with bacterascites were analyzed for the microbial spectrum, antimicrobial resistance profiles, and laboratory findings. RESULTS: The most common pathogens were Escherichia coli (96, 25.5%), Staphylococcus epidermidis (55, 14.6%), and Enterococcus faecium (42, 11.1%). Multidrug-resistant (MDR) bacteria comprised 49.7% of gram-positive bacteria (GPB) and 48.8% of gram-negative bacteria (GNB). The most sensitive antibiotics were amikacin (91.5%), meropenem (89.8%) and piperacillin/tazobactam (87.6%). Extensively drug-resistant (XDR) (OR=51.457, p < 0.001), neutrophil count (OR=1.088, p < 0.001), and the model for end-stage liver disease (MELD) score (OR=1.124, p < 0.001) were independent predictive factors of in-hospital mortality in patients with SBP. CONCLUSION: MDR represented nearly half of the bacteria isolated from patients with SBP, of which the high prevalence of extended-spectrum ß-lactamase-producing and Carbapenem-resistant bacteria is concerning. The presence of XDR, higher MELD score, and neutrophil count were independent predictive factors associated with higher in-hospital mortality in patients with SBP, indicating that intensive care should be provided to these patients.

Molecular characterization and effects of the TGIF1 gene on proliferation and steroidogenesis in yak (Bos grunniens) granulosa cells.

TG interaction factor 1 (TGIF1) plays a major role in transcriptional inhibition and suppression of TGF-ß signaling, but its functional roles in granulosa cells (GCs) have not been elucidated; in particular, there is no information about the yak (Bos grunniens) TGIF1 gene. Therefore, the objectives of this study were to clone yak TGIF1 and investigate TGIF1 functions in yak GCs. RT‒PCR results showed that the coding region of yak TGIF1 is 759 bp and encodes 252 amino acids. Its nucleotide sequence showed 85.24-99.74% similarity to mouse, human, pig, goat and cattle homologous genes. To explore the functional roles of TGIF1, we studied proliferation, apoptosis, cell cycle progression, steroidogenesis and the expression levels of related genes in yak GCs transfected with small interfering RNA specific to TGIF1. The results showed that TGIF1 knockdown promoted proliferation and cell cycle progression and inhibited apoptosis and estradiol (E2) and progesterone (P4) production in cultured yak GCs. Conversely, TGIF1 overexpression inhibited proliferation and cell cycle progression and stimulated apoptosis and E2 and P4 production. In addition, these functional changes in yak GCs were observed parallel to the expression changes in genes involved in the cell cycle (PCNA, CDK2, CCND1, CCNE1, CDK4 and P53), apoptosis (BCL2, BAX and CASPASE3), and steroidogenesis (CYP11A1, 3ß-HSD and StAR). In conclusion, TGIF1 was relatively conserved in the course of animal evolution. TGIF1 inhibited GC viability and stimulated apoptosis and the secretion of E2 and P4 by yak GCs. Our results will help to reveal the mechanism underlying yak follicular development and improve the reproductive efficiency of female yaks.

Impact factors of Blastocystis hominis infection in persons living with human immunodeficiency virus: a large-scale, multi-center observational study from China.

BACKGROUND: Blastocystis hominis (Bh) is zoonotic parasitic pathogen with a high prevalent globally, causing opportunistic infections and diarrhea disease. Human immunodeficiency virus (HIV) infection disrupts the immune system by depleting CD4+ T lymphocyte (CD4+ T) cell counts, thereby increasing Bh infection risk among persons living with HIV (PLWH). However, the precise association between Bh infection risk and HIV-related biological markers and treatment processes remains poorly understood. Hence, the purpose of the study was to explore the association between Bh infection risk and CD4+ T cell counts, HIV viral load (VL), and duration of interruption in antiviral therapy among PLWH. METHODS: A large-scale multi-center cross-sectional study was conducted in China from June 2020 to December 2022. The genetic presence of Bh in fecal samples was detected by real-time fluorescence quantitative polymerase chain reaction, the CD4+ T cell counts in venous blood was measured using flowcytometry, and the HIV VL in serum was quantified using fluorescence-based instruments. Restricted cubic spline (RCS) was applied to assess the non-linear association between Bh infection risk and CD4+ T cell counts, HIV VL, and duration of interruption in highly active antiretroviral therapy (HARRT). RESULTS: A total of 1245 PLWH were enrolled in the study, the average age of PLWH was 43 years [interquartile range (IQR): 33, 52], with 452 (36.3%) being female, 50.4% (n = 628) had no immunosuppression (CD4+ T cell counts > 500 cells/µl), and 78.1% (n = 972) achieved full virological suppression (HIV VL < 50 copies/ml). Approximately 10.5% (n = 131) of PLWH had interruption. The prevalence of Bh was found to be 4.9% [95% confidence interval (CI): 3.8-6.4%] among PLWH. Significant nonlinear associations were observed between the Bh infection risk and CD4+ T cell counts (Pfor nonlinearity < 0.001, L-shaped), HIV VL (Pfor nonlinearity < 0.001, inverted U-shaped), and duration of interruption in HARRT (Pfor nonlinearity < 0.001, inverted U-shaped). CONCLUSIONS: The study revealed that VL was a better predictor of Bh infection than CD4+ T cell counts. It is crucial to consider the simultaneous surveillance of HIV VL and CD4+ T cell counts in PLWH in the regions with high level of socioeconomic development. The integrated approach can offer more comprehensive and accurate understanding in the aspects of Bh infection and other opportunistic infections, the efficacy of therapeutic drugs, and the assessment of preventive and control strategies.

Global, but not chondrocyte-specific, MT1-MMP deficiency in adult mice causes inflammatory arthritis.

Membrane-type I metalloproteinase (MT1-MMP/MMP14) plays a key role in various pathophysiological processes, indicating an unaddressed need for a targeted therapeutic approach. However, mice genetically deficient in Mmp14 show severe defects in development and growth. To investigate the possibility of MT1-MMP inhibition as a safe treatment in adults, we generated global Mmp14 tamoxifen-induced conditional knockout (Mmp14kd) mice and found that MT1-MMP deficiency in adult mice resulted in severe inflammatory arthritis. Mmp14kd mice started to show noticeably swollen joints two weeks after tamoxifen administration, which progressed rapidly. Mmp14kd mice reached a humane endpoint 6 to 8 weeks after tamoxifen administration due to severe arthritis. Plasma TNF-α levels were also significantly increased in Mmp14kd mice. Detailed analysis revealed chondrocyte hypertrophy, synovial fibrosis, and subchondral bone remodeling in the joints of Mmp14kd mice. However, global conditional knockout of MT1-MMP in adult mice did not affect body weight, blood glucose, or plasma cholesterol and triglyceride levels. Furthermore, we observed substantial expression of MT1-MMP in the articular cartilage of patients with osteoarthritis. We then developed chondrocyte-specific Mmp14 tamoxifen-induced conditional knockout (Mmp14chkd) mice. Chondrocyte MT1-MMP deficiency in adult mice also caused apparent chondrocyte hypertrophy. However, Mmp14chkd mice did not exhibit synovial hyperplasia or noticeable arthritis, suggesting that chondrocyte MT1-MMP is not solely responsible for the onset of severe arthritis observed in Mmp14kd mice. Our findings also suggest that highly cell-type specific inhibition of MT1-MMP is required for its potential therapeutic use.

The mitophagy pathway and its implications in human diseases.

Mitochondria are dynamic organelles with multiple functions. They participate in necrotic cell death and programmed apoptotic, and are crucial for cell metabolism and survival. Mitophagy serves as a cytoprotective mechanism to remove superfluous or dysfunctional mitochondria and maintain mitochondrial fine-tuning numbers to balance intracellular homeostasis. Growing evidences show that mitophagy, as an acute tissue stress response, plays an important role in maintaining the health of the mitochondrial network. Since the timely removal of abnormal mitochondria is essential for cell survival, cells have evolved a variety of mitophagy pathways to ensure that mitophagy can be activated in time under various environments. A better understanding of the mechanism of mitophagy in various diseases is crucial for the treatment of diseases and therapeutic target design. In this review, we summarize the molecular mechanisms of mitophagy-mediated mitochondrial elimination, how mitophagy maintains mitochondrial homeostasis at the system levels and organ, and what alterations in mitophagy are related to the development of diseases, including neurological, cardiovascular, pulmonary, hepatic, renal disease, etc., in recent advances. Finally, we summarize the potential clinical applications and outline the conditions for mitophagy regulators to enter clinical trials. Research advances in signaling transduction of mitophagy will have an important role in developing new therapeutic strategies for precision medicine.

Extracellular matrix turnover: phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis.

Extracellular matrix (ECM) resolution by matrix metalloproteinases (MMPs) is a well-documented mechanism. MMPs play a dual and complex role in modulating ECM degradation at different stages of liver fibrosis, depending on the timing and levels of their expression. Increased MMP-1 combats disease progression by cleaving the fibrillar ECM. Activated hepatic stellate cells (HSCs) increase expression of MMP-2, -9, and -13 in different chemicals-induced animal models, which may alleviate or worsen disease progression based on animal models and the stage of liver fibrosis. In the early stage, elevated expression of certain MMPs may damage surrounding tissue and activate HSCs, promoting fibrosis progression. At the later stage, downregulation of MMPs can facilitate ECM accumulation and disease progression. A number of phytochemicals modulate MMP activity and ECM turnover, alleviating disease progression. However, the effects of phytochemicals on the expression of different MMPs are variable and may depend on the disease models and stage, and the dosage, timing and duration of phytochemicals used in each study. Here, we review the most recent advances in the role of MMPs in the effects of phytochemicals on liver fibrogenesis, which indicates that further studies are warranted to confirm and define the potential clinical efficacy of these phytochemicals.

Differential Characteristics of Patients for Hospitalized Severe COVID-19 Infected by the Omicron Variants and Wild Type of SARS-CoV-2 in China.

Background: As multiple mutations of SARS-Cov-2 exist, there are now many viral variants with regional differences in distribution. The clinical characteristics of patients hospitalized with the virus also vary significantly, with those of the Omicron variants being strikingly different from those of the earliest wild-type variant. However, comprehensive data on this subject is lacking. It is therefore crucial to explore these differences to develop better clinical strategies for the management of COVID-19. Methods: A total of 554 confirmed COVID-19 cases in China were clinically classified as mild, moderate, severe, and critical according to their diagnoses and treatment plans. We compared the demographics and clinical characteristics of patients infected with the Omicron vs wild-type strains, between severe and non-severe cases. Bacterial co-infections with SARS-CoV-2 and correlation between inflammatory factors and T cells were analyzed. Results: Compared to the wild-type cases, the severe Omicron cases were older (median age 48.36 vs 73.24), and had more upper-respiratory symptoms and comorbidities. Decreased leukocyte counts were less pronounced, although more instances of significantly decreased CD4+ and CD8+ T-cell counts, elevated infection-related biomarkers (eg procalcitonin and C-reactive protein), and abnormal coagulation factors (including increased D-dimer and fibrinogen levels) were detected in the severe Omicron cases. The mean length of hospital stay was significantly shorter in the severe Omicron cases. CD4+ and CD8+ T cell numbers were negatively correlated with neutrophil-to-lymphocyte ratios, as well as serum interleukin-6, procalcitonin, and C-reactive protein levels. Conclusion: There were significant clinical differences between patients hospitalized with severe cases of Omicron- variant COVID-19 vs wild-type. The Omicron cases tended to be older and had more upper respiratory tract symptoms, comorbidities and bacterial co-infections. Elevated levels of inflammatory cytokines with T-cell depletion correlated with poor disease progression and prognosis. We hope these data provide a theoretical basis for future integrated prevention and control plans for COVID-19.

Exosome-derived circKIF20B suppresses gefitinib resistance and cell proliferation in non-small cell lung cancer.

BACKGROUND: The gefitinib resistance mechanism in non-small cell lung cancer (NSCLC) remains unclear, albeit exosomal circular RNA (circRNA) is known to possibly play a vital role in it. METHODS: We employed high-throughput sequencing techniques to detect the expressions of exosomal circRNA both in gefitinib-resistant and gefitinib-sensitive cells in this study. The circKIF20B expression was determined in serum exosomes and tissues of patients by qRT-PCR. The structure, stability, and intracellular localization of circKIF20B were verified by Sanger sequencing, Ribonuclease R (RNase R)/actinomycin D (ACTD) treatments, and Fluorescence in situ hybridization (FISH). The functions of circKIF20B were investigated by 5-Ethynyl-20-deoxyuridine (EdU), flow cytometry, Cell Counting Kit-8 (CCK-8), oxygen consumption rate (OCR), and xenograft model. Co-culture experiments were performed to explore the potential ability of exosomal circKIF20B in treating gefitinib resistance. The downstream targets of circKIF20B were determined by luciferase assay, RNA pulldown, and RNA immunoprecipitation (RIP). RESULTS: We found that circKIF20B was poorly expressed in the serum exosomes of gefitinib-resistant patients (n = 24) and the tumor tissues of patients with NSCLC (n = 85). CircKIF20B was negatively correlated with tumor size and tumor stage. Decreasing circKIF20B was found to promote gefitinib resistance by accelerating the cell cycle, inhibiting apoptosis, and enhancing mitochondrial oxidative phosphorylation (OXPHOS), whereas increasing circKIF20B was found to restore gefitinib sensitivity. Mechanistically, circKIF20B is bound to miR-615-3p for regulating the MEF2A and then altering the cell cycle, apoptosis, and mitochondrial OXPHOS. Overexpressing circKIF20B parental cells can restore sensitivity to gefitinib in the recipient cells by upregulating the exosomal circKIF20B expression. CONCLUSIONS: This study revealed a novel mechanism of circKIF20B/miR-615-3p/MEF2A signaling axis involving progression of gefitinib resistance in NSCLC. Exosomal circKIF20B is expected to be an easily accessible and alternative liquid biopsy candidate and potential therapeutic target in gefitinib-resistant NSCLC. The schematic diagram of mechanism in this study. Exosomal circKIF20B inhibits gefitinib resistance and cell proliferation by arresting the cell cycle, promoting apoptosis, and reducing OXPHOS via circKIF20B/miR-615-3p/MEF2A axis in NSCLC.

Five long-distance dispersals shaped the major intercontinental disjunctions in Tectariaceae s.l. (Polypodiales, Polypodiopsida).

Intercontinental disjunct distributions can arise either from vicariance, from long-distance dispersal, or through extinction of an ancestral population with a broader distribution. Tectariaceae s.l., a clade of ferns in Polypodiales with ca. 300 species mainly distributed in the tropics and subtropics, provide an excellent opportunity to investigate global distribution patterns. Here, we assembled a dataset of eight plastid markers and one nuclear marker of 636 (92% increase of the earlier largest sampling) accessions representing ca. 210 species of all eight genera in Tectariaceae s.l. (Arthropteridaceae, Pteridryaceae, and Tectariaceae s.s.) and 35 species of other families of eupolypods Ⅰ. A new phylogeny is reconstructed to study the biogeography and trait-associated diversification. Our major results include: (1) a distinct lineage of Tectaria sister to the rest of the American Tectaria is identified; (2) Tectariaceae s.l., and the three families: Arthropteridaceae (Arthropteris), Pteridryaceae (Draconopteris, Malaifilix, Polydictyum, Pteridrys), and Tectariaceae s.s. (Hypoderris, Tectaria, and Triplophyllum), might have all originated in late Cretaceous; (3) only five intercontinental dispersals occurred in Pteridryaceae and Tectariaceae s.s. giving rise to their current intercontinental disjunction; (4) we provide the second evidence in ferns that a long-distance dispersal between Malesia and Americas during the Paleocene to Eocene led to the establishment/origin of a new genus (Draconopteris); and (5) diversification rate of each state of leaf dissection is different, and the lowest is in the simple-leaved taxa.