Identifying competing endogenous RNA regulatory networks and hub genes in alcoholic liver disease for early diagnosis and potential therapeutic target insights.

Alcoholic liver disease (ALD) has a complex pathogenesis. Although early-stage ALD can be reversed by ceasing alcohol consumption, early symptoms are difficult to detect, and several factors contribute to making alcohol difficult to quit. Continued alcohol abuse worsens the condition, meaning it may gradually progress into alcoholic hepatitis and cirrhosis, ultimately, resulting in irreversible consequences. Therefore, effective treatments are urgently needed for early-stage ALD. Current research mainly focuses on preventing the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. However, challenges remain in identifying key therapeutic targets and understanding the molecular mechanisms that underlie the treatment of alcoholic hepatitis and cirrhosis, such as the limited discovery of effective therapeutic targets and treatments. Here, we downloaded ALD microarray data from Gene Expression Omnibus and used bioinformatics to compare and identify the hub genes involved in the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. We also predicted target miRNAs and long non-coding RNAs (lncRNAs) to elucidate the regulatory mechanisms (the mRNA-miRNA-lncRNA axis) underlying this progression, thereby building a competitive endogenous RNA (ceRNA) mechanism for lncRNA, miRNA, and mRNA. This study provides a theoretical basis for the early treatment of alcoholic hepatitis and cirrhosis and identifies potential therapeutic targets.

A tumor-microenvironment-activated nanoplatform of modified SnFe2O4 nanozyme in scaffold for enhanced PTT/PDT tumor therapy.

Phototherapy has attracted widespread attention for cancer treatment due to its noninvasiveness and high selectivity. However, severe hypoxia, overexpressed glutathione and high levels of hydrogen peroxide (H2O2) of tumor microenvironment limit the antitumor efficiency of phototherapy. Herein, inspired by the specific response of nanozymes to the tumor microenvironment, a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform is constructed. In this study, tin ferrite (SnFe2O4, SFO) nanozyme as a photosensitizer was surface modified with polydopamine (denoted as P-SFO) and incorporated into poly(l-lactide) to fabricate an antitumor scaffold fabricated by selective laser sintering. On one hand, SFO nanozyme could act as a photoabsorber to convert light energy into heat for photothermal therapy (PTT). On the other hand, it played a role of photosensitizer in transferring the photon energy to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). Importantly, its multivalent metal ions redox couples would decompose H2O2 into O2 for enhancing O2-dependent PDT and consume glutathione to relieve antioxidant capability of the tumors. Besides, polydopamine as a photothermal conversion agent further enhanced the photothermal performance of SFO. The results revealed the PLLA/P-SFO scaffold possessed a photothermal conversion efficiency of 43.52% for PTT and a high ROS generation capacity of highly toxic ·O2- and ·OH for PDT. Consequently, the scaffold displayed a prominent phototherapeutic effect with antitumor rate of 96.3%. In addition, the PLLA/P-SFO scaffolds possessed good biocompatibility for cell growth. These advantages endow PLLA/P-SFO scaffold with extensive applications in biomedical fields and opened up new avenue towards nanozyme-mediated synergistic phototherapy.

Bioinformatics Analysis of Novel Targets for Treating Cervical Cancer by Immunotherapy Based on Immune Escape.

BACKGROUND/AIM: Cervical cancer (CC) is a high-risk disease in women, and advanced CC can be difficult to treat even with surgery, radiotherapy, and chemotherapy. Hence, developing more effective treatment methods is imperative. Cancer cells undergo a renewal process to escape immune surveillance and then attack the immune system. However, the underlying mechanisms remain unclear. Currently, only one immunotherapy drug has been approved by the Food and Drug Administration for CC, thus indicating the need for and importance of identifying key targets related to immunotherapy. MATERIALS AND METHODS: Data on CC and normal cervical tissue samples were downloaded from the National Center for Biotechnology Information database. Transcriptome Analysis Console software was used to analyze differentially expressed genes (DEGs) in two sample groups. These DEGs were uploaded to the DAVID online analysis platform to analyze biological processes for which they were enriched. Finally, Cytoscape was used to map protein interaction and hub gene analyses. RESULTS: A total of 165 up-regulated and 362 down-regulated genes were identified. Among them, 13 hub genes were analyzed in a protein-protein interaction network using the Cytoscape software. The genes were screened out based on the betweenness centrality value and average degree of all nodes. The hub genes were as follows: ANXA1, APOE, AR, C1QC, CALML5, CD47, CTSZ, HSP90AA1, HSP90B1, NOD2, THY1, TLR4, and VIM. We identified the following 12 microRNAs (miRNAs) that target the hub genes: hsa-miR-2110, hsa-miR-92a-2-5p, hsa-miR-520d-5p, hsa-miR-4514, hsa-miR-4692, hsa-miR-499b-5p, hsa-miR-5011-5p, hsa-miR-6847-5p, hsa-miR-8054, hsa-miR-642a-5p, hsa-miR-940, and hsa-miR-6893-5p. CONCLUSION: Using bioinformatics, we identified potential miRNAs that regulated the cancer-related genes and long noncoding RNAs (lncRNAs) that regulated these miRNAs. We further elucidated the mutual regulation of mRNAs, miRNAs, and lncRNAs involved in CC occurrence and development. These findings may have major applications in the treatment of CC by immunotherapy and the development of drugs against CC.

Regulatory pathway underpinning the development of encephalitis after simian immunodeficiency virus infection in rhesus macaques (Macaca mulatta).

BACKGROUND: Simian immunodeficiency virus (SIV) infection in rhesus macaques (Macaca mulatta) can lead to the development of SIV encephalitis (SIVE), which is closely related to human immunodeficiency virus (HIV)-induced dementia. METHODS: This was done by analyzing SIV and SIVE encephalitis in infected M. mulatta hippocampus samples from two microarray data sets, identifying two groups of common differentially expressed genes and predicting associated protein interactions. RESULTS: We found that eight genes-MX1, B2M, IFIT1, TYMP, STAT1, IFI44, ISG15, and IFI27-affected the negative regulation of biological processes, hepatitis C and Epstein-Barr viral infection, and the toll-like receptor signaling pathway, which mediate the development of encephalitis after SIV infection. In particular, STAT1 played a central role in the process by regulating biopathological changes during the development of SIVE. CONCLUSION: These findings provide a new theoretical basis for the treatment of encephalopathy after HIV infection by targeting STAT1.

Targeting peroxisome proliferator-activated receptor γ proteasomal degradation by magnolol is a potential avenue for adipogenesis-mediated metabolic homeostasis.

OBJECTIVE: Adipogenesis has been recognized as an attractive avenue for maintaining systemic homeostasis, with peroxisome proliferator-activated receptor γ (PPARγ) showing predominant roles in this process. This study aims to identify promising drug candidates by targeting PPARγ for adipogenesis-based metabolic homeostasis and to clarify the detailed mechanisms. METHODS: Molecular events contributing to adipogenesis were screened, which identified PPARγ as having the predominant role. Promising agents of adipogenesis agonism were screened using a PPARγ-based luciferase reporter assay. The functional capacity and molecular mechanisms of magnolol were intensively examined using 3T3-L1 preadipocytes and dietary models. RESULTS: This study found that F-box only protein 9 (FBXO9)-mediated lysine 11 (K11)-linked ubiquitination and proteasomal degradation of PPARγ are critically required during adipogenesis and systemic homeostasis. Notably, magnolol was identified as a potent adipogenesis activator by stabilizing PPARγ. The pharmacological mechanisms investigations clarified that magnolol directly binds to PPARγ and markedly interrupts its interaction with FBXO9, leading to a decline in K11-linked ubiquitination and proteasomal degradation of PPARγ. Clinically important, magnolol treatment significantly facilitates adipogenesis in vitro and in vivo. CONCLUSIONS: The downregulation of K11-linked ubiquitination of PPARγ caused by FBOX9 is essentially required for adipogenesis, while targeting PPARγ-FBXO9 interaction provides a new avenue for the therapy of adipogenesis-related metabolic disorder.

Network-based analysis identifies key regulatory transcription factors involved in skin aging.

Skin aging is a complex process involving intricate genetic and environmental factors. In this study, we performed a comprehensive analysis of the transcriptional regulatory landscape of skin aging in canines. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify aging-related gene modules. We subsequently validated the expression changes of these module genes in single-cell RNA sequencing (scRNA-seq) data of human aging skin. Notably, basal cell (BC), spinous cell (SC), mitotic cell (MC), and fibroblast (FB) were identified as the cell types with the most significant gene expression changes during aging. By integrating GENIE3 and RcisTarget, we constructed gene regulation networks (GRNs) for aging-related modules and identified core transcription factors (TFs) by intersecting significantly enriched TFs within the GRNs with hub TFs from WGCNA analysis, revealing key regulators of skin aging. Furthermore, we demonstrated the conserved role of CTCF and RAD21 in skin aging using an H2O2-stimulated cell aging model in HaCaT cells. Our findings provide new insights into the transcriptional regulatory landscape of skin aging and unveil potential targets for future intervention strategies against age-related skin disorders in both canines and humans.

Effect of different dry matter content on fermentation characteristics and nutritional quality of Napier grass silage with novel lactic acid bacteria strains.

To investigate the characteristics of different LAB strains isolated from subtropics and their effects on Napier grass (Pennisetum purpureum Schum.) silage with two dry matter (DM) levels, sugar fermentation pattern, and growth profiles of three screened lactic acid bacteria (LAB) strains [Pediococcus pentosaceus (PP04), Weissella cibaria (WC10), and Lactobacillus plantarum (LP694)] were characterized, and then used either individually or in combination at 1.0 × 106 cfu g-1 fresh weight to inoculate grass having 15% or 25% DM. Treatments were applied: (1) no inoculant (control); (2) PP04; (3) WC10; (4) LP694; (5) M-1 (PP04: WC10 = 2:1); (6) M-2 (PP04: LP694 = 1:2); (7) M-3 (WC10: LP694 = 2:1); (8) M-4 (PP04: WC10: LP694 = 2:1:1). The results showed that all inoculations increased LAB, DM recovery, and lactic acid (LA) concentration, while decreasing pH, the ammonia nitrogen/total nitrogen (NH3-N/TN), and butyric acid (BA) concentration compared to control group in both DM. However, the effect of inoculations was very limited at 15% DM. Silages with inoculants achieved higher silage quality at 25% DM than 15% DM. The different LAB inoculants result in significant differences in silage quality, while W. cibaria decreased the pH and inhibited the growth of undesirable bacteria and those characteristics were not affected by the DM content.

A spatiotemporal drug release scaffold with antibiosis and bone regeneration for osteomyelitis.

INTRODUCTION: Scaffolds loaded with antibacterial agents and osteogenic drugs are considered essential tools for repairing bone defects caused by osteomyelitis. However, the simultaneous release of two drugs leads to premature osteogenesis and subsequent sequestrum formation in the pathological situation of unthorough antibiosis. OBJECTIVES: In this study, a spatiotemporal drug-release polydopamine-functionalized mesoporous silicon nanoparticle (MSN) core/shell drug delivery system loaded with antibacterial silver (Ag) nanoparticles and osteogenic dexamethasone (Dex) was constructed and introduced into a poly-l-lactic acid (PLLA) scaffold for osteomyelitis therapy. METHODS: MSNs formed the inner core and were loaded with Dex through electrostatic adsorption (MSNs@Dex), and then polydopamine was used to seal the core through the self-assembly of dopamine as the outer shell (pMSNs@Dex). Ag nanoparticles were embedded in the polydopamine shell via an in situ growth technique. Finally, the Ag-pMSNs@Dex nanoparticles were introduced into PLLA scaffolds (Ag-pMSNs@Dex/PLLA) constructed by selective laser sintering (SLS). RESULTS: The Ag-pMSNs@Dex/PLLA scaffold released Ag+ at the 12th hour, followed by the release of Dex starting on the fifth day. The experiments verified that the scaffold had excellent antibacterial performance against Escherichia coli and Staphylococcus aureus. Moreover, the scaffold significantly enhanced the osteogenic differentiation of mouse bone marrow mesenchymal stem cells. CONCLUSION: The findings suggested that this spatiotemporal drug release scaffold had promising potential for osteomyelitis therapy.

Hyaluronic acid encapsulated silver metal organic framework for the construction of a slow-controlled bifunctional nanostructure: Antibacterial and anti-inflammatory in intrauterine adhesion repair.

Intrauterine adhesion (IUA) is a common gynecological disease caused by endometrial injury, which might result in abnormal menstruation, miscarriage, and even fetal deaths. Nevertheless, existing treatment strategies such as intrauterine device and uterine cavity balloons only provide a physical barrier, and not circumvent inflammation of endometrial microenvironment and retrograde infection. In this study, a slow-controlled bifunctional nanostructure was developed via encapsulating hyaluronic acid (HA) on surface of silver-metal organic framework (Ag-MOF), and then loaded in poly lactic-co-glycolic acid scaffold to prevent IUA. In therapy, macro-molecule of HA provided anti-inflammatory function by the adjustment of signal transduction pathways of macrophage surface receptors, whereas Ag-MOF inactivated bacteria by destroying bacterial membrane and producing reactive oxygen. Significantly, the coated HA effectively avoided burst release of Ag+, thus achieving long-term antibacterial property and good biocompatibility. Antibacterial results showed antibacterial rate of the scaffold reached 87.8 % against staphylococcus aureus. Anti-inflammatory assays showed that the scaffold inhibited the release of inflammatory cytokines and promoted the release of anti-inflammatory cytokines. Moreover, in vitro cell tests revealed that the scaffold effectively inhibited fibroblast growth, indicating its good ability to prevent IUA. Taken together, the scaffold may be a promising candidate for IUA treatment.

Silicon dioxide nanoparticles decorated on graphene oxide nanosheets and their application in poly(l-lactic acid) scaffold.

INTRODUCTION: The aggregation of graphene oxide (GO) is considered as main challenge, although GO possesses excellent mechanical properties which arouses widespread attention as reinforcement for polymers. OBJECTIVES: In this study, silicon dioxide (SiO2) nanoparticles were decorated onto surface of GO nanosheets through in situ growth method for promoting dispersion of GO in poly(l-lactic acid) (PLLA) bone scaffold. METHODS: Hydroxyl and carboxyl functional groups of GO provided sites for SiO2 nucleation, and SiO2 grew with hydrolysis and polycondensation of tetraethyl orthosilicate (TEOS) and finally formed nanoparticles onto surface of GO with covalent bonds. Then, the GO@ SiO2 nanocomposite was blended with PLLA for the fabrication of bone scaffold by selective laser sintering (SLS). RESULT: The results indicated that the obtained SiO2 were distributed relatively uniformly on surface of GO under TEOS concentration of 0.10 mol/L (GO@SiO2-10), and the covering of SiO2 on GO could increase interlayer distance of GO nanosheets from 0.799 nm to 0.894 nm, thus reducing van der Waals forces between GO nanosheets and facilitating the dispersion. Tensile and compressive strength of scaffold containing GO@SiO2 hybrids were significantly enhanced, especially for the scaffold containing GO@SiO2-10 hybrids with enhancement of 30.95 % in tensile strength and 66.33 % in compressive strength compared with the scaffold containing GO. Additionally, cell adhesion and fluorescence experiments demonstrated excellent cytocompatibility of the scaffold. CONCLUSIONS: The good dispersion of GO@SiO2 enhances the mechanical properties and cytocompatibility of scaffold, making it a potential candidate for bone tissue engineering applications.

A bifunctional zoledronate sustained-release system in scaffold: Tumor therapy and bone repair.

It is of great challenges to repair bone defect and prevent tumor recurrence in bone tumors postoperative treatment. Bone scaffolds loaded with zoledronate (ZOL) are expected to solve these issues due to its osteogenesis and anti-tumor ability. Furthermore, ZOL needs to be sustained release to meet the requirement of long-term therapy. In this study, ZOL was loaded into amination functionalized mesoporous silicon (SBA15NH2), and then incorporated into poly (L-lactic acid) to prepare PLLA/SBA15NH2-ZOL scaffold via selective laser sintering technology. On one hand, ZOL of local release not only can inhibit growth and proliferation of bone tumor cells but also inhibit osteoclast differentiation through competitive binding of receptor activator of nuclear factor (NF)-kB (RANK) in osteoclast precursors. On the other hand, amination function could change the surface charge of mesoporous silica to positive charge to enhance the absorption of ZOL, mesoporous structure and abundant amino groups of SBA15NH2 play a barrier role and form hydrogen bond with phosphate groups of ZOL, respectively, thereby achieving its sustained release. The results showed that the loading amount of ZOL was 236.53 mg/g, and the scaffold could sustainedly release ZOL for more than 6 weeks. The scaffold inhibited proliferation of osteosarcoma cells through inducing apoptosis and cell cycle arrest. TRAP staining and F-actin ring formation experiment showed the scaffold inhibited differentiation and mature of osteoclast. Pit formation assay indicated that bone resorption activity was inhibited strongly.

Accelerated anode and cathode reaction due to direct electron uptake and consumption by manganese dioxide and titanium dioxide composite cathode in degradation of iron composite.

The movement towards the clinical application of iron (Fe) has been hindered by the slow degradation rate in physiological environments. Herein, manganese dioxide (MnO2) particles were compounded with titanium dioxide (TiO2) particles by mechanical ball milling, and then the mixed powders were incorporated into Fe and fabricated into an implant using selective laser melting. On the one hand, MnO2 had a higher work function (5.21 eV) than Fe (4.48 eV), which inclined electrons to transfer from Fe to MnO2 to accelerate the anode reaction. On the other hand, MnO2 catalysed the oxygen reduction reaction (ORR) through a four-step proton-electron-coupled reaction, which caused more oxygen to flow into the sample to improve the cathode performance. Besides, anatase TiO2 with high conductivity was compounded with MnO2 to construct a composite cathode, which facilitated electron transport from the cathode to the electrolyte, further consuming electrons and promoting cathode reaction. Results showed that Fe-MnO2-TiO2 had a high limiting current density of 5.32 mA·cm-2 and a large half-wave potential of -767.4 mV, indicating an enhanced ORR activity. More significantly, Fe-MnO2-TiO2 had a higher average electron transfer number (2.9) than Fe-MnO2 (2.5), demonstrating a faster electronic consumption reaction and higher cathode performance. In addition, the Fe-MnO2-TiO2 also exhibited fast instantaneous and long-term degradation rates (0.33 ± 0.03 and 0.19 ± 0.02 mm/year), suggesting a high anode dissolution rate. In conclusion, introducing the cathode with high work function and ORR activity provides novel pathways for accelerating the degradation rate of Fe-based implants.

Construction of magnetic nanochains to achieve magnetic energy coupling in scaffold.

BACKGROUND: Fe3O4 nanoparticles are highly desired for constructing endogenous magnetic microenvironment in scaffold to accelerate bone regeneration due to their superior magnetism. However, their random arrangement easily leads to mutual consumption of magnetic poles, thereby weakening the magnetic stimulation effect. METHODS: In this study, magnetic nanochains are synthesized by magnetic-field-guided interface co-assembly of Fe3O4 nanoparticles. In detail, multiple Fe3O4 nanoparticles are aligned along the direction of magnetic force lines and are connected in series to form nanochain structures under an external magnetic field. Subsequently, the nanochain structures are covered and fixed by depositing a thin layer of silica (SiO2), and consequently forming linear magnetic nanochains (Fe3O4@SiO2). The Fe3O4@SiO2 nanochains are then incorporated into poly l-lactic acid (PLLA) scaffold prepared by selective laser sintering technology. RESULTS: The results show that the Fe3O4@SiO2 nanochains with unique core-shell structure are successfully constructed. Meanwhile, the orderly assembly of nanoparticles in the Fe3O4@SiO2 nanochains enable to form magnetic energy coupling and obtain a highly magnetic micro-field. The in vitro tests indicate that the PLLA/Fe3O4@SiO2 scaffolds exhibit superior capacity in enhancing cell activity, improving osteogenesis-related gene expressions, and inducing cell mineralization compared with PLLA and PLLA/Fe3O4 scaffolds. CONCLUSION: In short, the Fe3O4@SiO2 nanochains endow scaffolds with good magnetism and cytocompatibility, which have great potential in accelerating bone repair.

Integrated Analysis of Single-Molecule Real-Time Sequencing and Next-Generation Sequencing Eveals Insights into Drought Tolerance Mechanism of Lolium multiflorum.

Lolium multiflorum is widely planted in temperate and subtropical regions globally, and it has high economic value owing to its use as forage grass for a wide variety of livestock and poultry. However, drought seriously restricts its yield and quality. At present, owing to the lack of available genomic resources, many types of basic research cannot be conducted, which severely limits the in-depth functional analysis of genes in L. multiflorum. Therefore, we used single-molecule real-time (SMRT) and next-generation sequencing (NGS) to sequence the complex transcriptome of L. multiflorum under drought. We identified 41,141 DEGs in leaves, 35,559 DEGs in roots, respectively. Moreover, we identified 1243 alternative splicing events under drought. LmPIP5K9 produced two different transcripts with opposite expression patterns, possibly through the phospholipid signaling pathway or the negatively regulated sugar-mediated root growth response to drought stress, respectively. Additionally, 13,079 transcription factors in 90 families were obtained. An in-depth analysis of R2R3-MYB gene family members was performed to preliminarily demonstrate their functions by utilizing subcellular localization and overexpression in yeast. Our data make a significant contribution to the genetics of L. multiflorum, offering a current understanding of plant adaptation to drought stress.

Efficacy of traditional Chinese medicine injections for treating idiopathic pulmonary fibrosis: A systematic review and network meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), acutely or slowly progressing into irreversible pulmonary disease, causes severe damage to patients' lung functions, as well as death. In China, Chinese medicine injections (CMIs) have been generally combined with Western medicine (WM) to treat IPF, which are safe and effective. This study aimed to systematically compare the efficacy of 14 CMIs combined with WM in the treatment of IPF based on a systematic review and network meta-analysis (NMA). MATERIAL AND METHODS: PubMed, Web of Science, Embase, Cochrane Library, MEDLINE, and Chinese databases, including the China National Knowledge Infrastructure, Wanfang Database, Scientific Journal Database, and China Biology Medicine Database were searched from inception to October 31, 2021. The inclusion criterion was randomized controlled trials (RCTs) on CMIs with WM for treating IPF. Reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.4 software and Stata software (version 16.0) were used for the data analysis. NMA were carried out for calculating the odd ratios (ORs) with 95% confidence intervals (CI), the surface under cumulative ranking curve (SUCRA) and the probabilities of being the best. RESULTS: A total of 63 eligible RCTs involving 14 CMIs were included in this NMA. More CMIs can significantly improve the clinical effectiveness rate (CER); Shuxuening injection (SXN)+WM (OR 8.91, 95% CI 3.81-20.83), Shuxuetong injection (SXT)+WM (OR 7.36, 95% CI 3.30-16.00), Shenxiong injection (SX)+WM (OR 5.42, 95% CI 2.90-10.13), Danhong injection (DH)+WM (OR 4.06, 95% CI 2.62-6.29), and Huangqi injection (HQ)+WM (OR 3.47, 95% CI 1.55-7.77) were the top five treatment strategies. Furthermore, DH +WM ranked relatively high in the SUCRA value of the nine outcome indicators, oxygen partial pressure (PaO2) (OR -13.39; 95% CI -14.90,-11.89; SUCRA 83.7%), carbon dioxide partial pressure (PaCO2) (OR -4.77; 95% CI -5.55,-3.99; SUCRA 83.3), orced vital capacity (FVC) (OR -1.42; 95% CI -2.47,-0.36; SUCRA 73.5%), total lung capacity (TLC) (OR 0.93; 95% CI 0.51,1.36; SUCRA 89.0%), forced expiratory volume 1/ forced vital capacity (FEV1/FVC%) (OR -10.30; 95% CI -12.98,-7.62; SUCRA 72.7%), type III collagen (IIIC) (OR 13.08; 95% CI 5.11,21.05; SUCRA 54.9%), and transforming growth factor (TGF) (OR -4.22; 95% CI -6.06,-2.37; SUCRA 85.7%) respectively, which seems to indicate that DH+WM had the highest likelihood of being the best treatment. CONCLUSIONS: This review specified several CMIs combined with WM in the treatment of IPF in China. In contrast to glucocorticoids or antioxidants, CMIs combined with WM delayed the decline in lung function, maintained oxygenation and quality of life in patients with IPF. The combined use of DH, SXN, SX, and safflower yellow sodium chloride injection (HHS) with WM exerted a more positive effect in treating IPF than WM alone. However, there were limitations to the conclusions of this study due to quality control differences in the included trials.

A rat study model of depression-driven chronic prostatitis by modulating the PI3K/Akt/mTOR network.

Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.

In Situ Growth of a Metal-Organic Framework on Graphene Oxide for the Chemo-Photothermal Therapy of Bacterial Infection in Bone Repair.

Bacterial infection with high morbidity (>30%) seriously affects the defect's healing after bone transplantation. To this end, chemotherapy and photothermal therapy have been utilized for antibacterial treatment owing to their high selectivity and minimal toxicity. However, they also face several dilemmas. For example, bacterial biofilms prevented the penetration of antibacterial agents and local temperatures (over 70 °C) caused by the photothermal therapy damaged normal tissue. Herein, a co-dispersion nanosystem with chemo-photothermal function was constructed via the in situ growth of zeolitic imidazolate framework-8 (ZIF-8) on graphene oxide (GO) nanosheets. In this nanosystem, GO generates a local temperature (∼50 °C) to increase the permeability of a bacterial biofilm under near-infrared laser irradiation. Then, Zn ions released by ZIF-8 seized this chance to react with the bacterial membrane and inactivate it, thus realizing efficient sterilization in a low-temperature environment. This antibacterial system was incorporated into a poly-l-lactic acid scaffold for bone repair. Results showed that the scaffold showed a high antibacterial rate of 85% against both Escherichia coli and Staphylococcus aureus. In vitro cell tests showed that the scaffold promoted cell proliferation.

Stress-Induced Dual-Phase Structure to Accelerate Degradation of the Fe Implant.

Fe is considered as a potential candidate for implant materials, but its application is impeded by the low degradation rate. Herein, a dual-phase Fe30Mn6Si alloy was prepared by mechanical alloying (MA). During MA, the motion of dislocations driven by the impact stress promoted the solid solution of Mn in Fe, which transformed α-ferrite into γ-austenite since Mn was an austenite-stabilizing element. Meanwhile, the incorporation of Si decreased the stacking fault energy inside austenite grains, which tangled dislocations into stacking faults and acted as nucleation sites for ε-martensite. Resultantly, Fe30Mn6Si powder had a dual-phase structure composed of 53% γ-austenite and 47% ε-martensite. Afterward, the powders were prepared into implants by selective laser melting. The Fe30Mn6Si alloy had a more negative corrosion potential of -0.76 ± 0.09 V and a higher corrosion current of 30.61 ± 0.41 µA/cm2 than Fe and Fe30Mn. Besides, the long-term weight loss tests also proved that Fe30Mn6Si had the optimal degradation rate (0.25 ± 0.02 mm/year).

Silver-decorated black phosphorus: a synergistic antibacterial strategy.

Black phosphorus (BP) exhibits great potential as antibacterial materials due to its unique photocatalytic activity. However, the unsatisfactory optical absorption and quick recombination of photoinduced electron-hole pairs restrain its photocatalytic antibacterial performance. In this work, silver nanoparticles (AgNPs) were decorated on BP to construct BP@AgNPs nanohybrids and then introduced into poly-l-lactic acid scaffold. Combining the tunable bandgap of BP and the LSPR effect of AgNPs, BP@AgNPs nanohybrids displayed the broaden visible light absorption. Furthermore, AgNPs acted as electron acceptors could accelerate charge transfer and suppress electron-hole recombination. Therefore, BP@AgNPs nanohybrids achieved synergistically enhanced photocatalytic antibacterial activity under visible light irradiation. Fluorescence probe experiment verified that BP@AgNPs promoted the generation of reactive oxygen species, which could disrupt bacteria membrane, damage DNA and oxide proteins, and finally lead to bacteria apoptosis. As a result, the scaffold possessed strong antibacterial efficiency with a bactericidal rate of 97% under light irradiation. Moreover, the scaffold also exhibited good cytocompatibility. This work highlighted a new strategy to develop photocatalytic antibacterial scaffold for bone implant application.

Genome-wide identification of C2H2-type zinc finger gene family members and their expression during abiotic stress responses in orchardgrass (Dactylis glomerata).

The C2H2-type zinc finger protein (ZFP) family is one of the largest transcription factor families in the plant kingdom and its members are involved in plant growth, development, and stress responses. As an economically valuable perennial graminaceous forage crop, orchardgrass (Dactylis glomerata) is an important feedstuff resource owing to its high yield and quality. In this study, 125 C2H2-type ZFPs in orchardgrass (Dg-ZFPs) were identified and further classified by phylogenetic analysis. The members with similar gene structures were generally clustered into the same groups, with proteins containing the conserved QALGGH motif being concentrated in groups VIII and IX. Gene ontology and miRNA target analyses indicated that Dg-ZFPs likely perform diverse biological functions through their gene interactions. The RNA-seq data revealed differentially expressed genes across tissues and development phases, suggesting that some Dg-ZFPs might participate in growth and development regulation. Abiotic stress responses of Dg-ZFP genes were verified by qPCR and Saccharomyces cerevisiae transformation, revealing that Dg-ZFP125 could enhance the tolerance of yeasts to osmotic and salt stresses. Our study performed a novel systematic analysis of Dg-ZFPs in orchardgrass, providing a reference for this gene family in other grasses and revealing new insights for enhancing gene utilization.