Developing hydrogels for gene therapy and tissue engineering.

Hydrogels are a class of highly absorbent and easily modified polymer materials suitable for use as slow-release carriers for drugs. Gene therapy is highly specific and can overcome the limitations of traditional tissue engineering techniques and has significant advantages in tissue repair. However, therapeutic genes are often affected by cellular barriers and enzyme sensitivity, and carrier loading of therapeutic genes is essential. Therapeutic gene hydrogels can well overcome these difficulties. Moreover, gene-therapeutic hydrogels have made considerable progress. This review summarizes the recent research on carrier gene hydrogels for the treatment of tissue damage through a summary of the most current research frontiers. We initially introduce the classification of hydrogels and their cross-linking methods, followed by a detailed overview of the types and modifications of therapeutic genes, a detailed discussion on the loading of therapeutic genes in hydrogels and their characterization features, a summary of the design of hydrogels for therapeutic gene release, and an overview of their applications in tissue engineering. Finally, we provide comments and look forward to the shortcomings and future directions of hydrogels for gene therapy. We hope that this article will provide researchers in related fields with more comprehensive and systematic strategies for tissue engineering repair and further promote the development of the field of hydrogels for gene therapy.

Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis.

Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.

Selection and Validation of Reference Genes in Sudan Grass (Sorghum sudanense (Piper) Stapf) under Various Abiotic Stresses by qRT-PCR.

Quantitative reverse transcription PCR (qRT-PCR) can screen applicable reference genes of species, and reference genes can be used to reduce experimental errors. Sudan grass (Sorghum sudanense (Piper) Stapf) is a high-yield, abiotic-tolerant annual high-quality forage with a wide range of uses. However, no studies have reported reference genes suitable for Sudan grass. Therefore, we found eight candidate reference genes, including UBQ10, HIS3, UBQ9, Isoform0012931, PP2A, ACP2, eIF4α, and Actin, under salt stress (NaCl), drought stress (DR), acid aluminum stress (AlCl3), and methyl jasmonate treatment (MeJA). By using geNorm, NormFinder, BestKeeper, and RefFinder, we ranked eight reference genes on the basis of their expression stabilities. The results indicated that the best reference gene was PP2A under all treatments. eIF4α can be used in CK, MeJA, NaCl, and DR. HIS3 can serve as the best reference gene in AlCl3. Two target genes (Isoform0007606 and Isoform0002387) belong to drought-stress-response genes, and they are highly expressed in Sudan grass according to transcriptome data. They were used to verify eight candidate reference genes under drought stress. The expression trends of the two most stable reference genes were similar, but the trend in expression for Actin showed a significant difference. The reference genes we screened provided valuable guidance for future research on Sudan grass.

Overexpression of Lolium multiflorum LmMYB1 Enhances Drought Tolerance in Transgenic Arabidopsis.

Lolium multiflorum is one of the world-famous forage grasses with rich biomass, fast growth rate and good nutritional quality. However, its growth and forage yield are often affected by drought, which is a major natural disaster all over the world. MYB transcription factors have some specific roles in response to drought stress, such as regulation of stomatal development and density, control of cell wall and root development. However, the biological function of MYB in L. multiflorum remains unclear. Previously, we elucidated the role of LmMYB1 in enhancing osmotic stress resistance in Saccharomyces cerevisiae. Here, this study elucidates the biological function of LmMYB1 in enhancing plant drought tolerance through an ABA-dependent pathway involving the regulation of cell wall development and stomatal density. After drought stress and ABA stress, the expression of LmMYB1 in L. multiflorum was significantly increased. Overexpression of LmMYB1 increased the survival rate of Arabidopsis thaliana under drought stress. Under drought conditions, expression levels of drought-responsive genes such as AtRD22, AtRAB and AtAREB were up-regulated in OE compared with those in WT. Further observation showed that the stomatal density of OE was reduced, which was associated with the up-regulated expression of cell wall-related pathway genes in the RNA-Seq results. In conclusion, this study confirmed the biological function of LmMYB1 in improving drought tolerance by mediating cell wall development through the ABA-dependent pathway and thereby affecting stomatal density.

Transcriptomic analysis of wheat reveals possible resistance mechanism mediated by Yr10 to stripe rust.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a catastrophic disease that threatens global wheat yield. Yr10 is a race-specific all-stage disease resistance gene in wheat. However, the resistance mechanism of Yr10 is poorly characterized. Therefore, to elucidate the potential molecular mechanism mediated by Yr10, transcriptomic sequencing was performed at 0, 18, and 48 h post-inoculation (hpi) of compatible wheat Avocet S (AvS) and incompatible near-isogenic line (NIL) AvS + Yr10 inoculated with Pst race CYR32. Respectively, 227, 208, and 4050 differentially expressed genes (DEGs) were identified at 0, 18, and 48 hpi between incompatible and compatible interaction. The response of Yr10 to stripe rust involved various processes and activities, as indicated by the results of Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Specifically, the response included photosynthesis, defense response to fungus, metabolic processes related to salicylic acid (SA) and jasmonic acid (JA), and activities related to reactive oxygen species (ROS). Ten candidate genes were selected for qRT-PCR verification and the results showed that the transcriptomic data was reliable. Through the functional analysis of candidate genes by the virus-induced gene silencing (VIGS) system, it was found that the gene TaHPPD (4-hydroxyphenylpyruvate dioxygenase) negatively regulated the resistance of wheat to stripe rust by affecting SA signaling, pathogenesis-related (PR) gene expression, and ROS clearance. Our study provides insight into Yr10-mediated resistance in wheat.

The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease.

Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum (C. butyricum) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1ß and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host's inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro, butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD.

Molecular Mechanism Underlying the Sorghum sudanense (Piper) Stapf. Response to Osmotic Stress Determined via Single-Molecule Real-Time Sequencing and Next-Generation Sequencing.

Drought, as a widespread environmental factor in nature, has become one of the most critical factors restricting the yield of forage grass. Sudangrass (Sorghum sudanense (Piper) Stapf.), as a tall and large grass, has a large biomass and is widely used as forage and biofuel. However, its growth and development are limited by drought stress. To obtain novel insight into the molecular mechanisms underlying the drought response and excavate drought tolerance genes in sudangrass, the first full-length transcriptome database of sudangrass under drought stress at different time points was constructed by combining single-molecule real-time sequencing (SMRT) and next-generation transcriptome sequencing (NGS). A total of 32.3 Gb of raw data was obtained, including 20,199 full-length transcripts with an average length of 1628 bp after assembly and correction. In total, 11,921 and 8559 up- and down-regulated differentially expressed genes were identified between the control group and plants subjected to drought stress. Additionally, 951 transcription factors belonging to 50 families and 358 alternative splicing events were found. A KEGG analysis of 158 core genes exhibiting continuous changes over time revealed that 'galactose metabolism' is a hub pathway and raffinose synthase 2 and ß-fructofuranosidase are key genes in the response to drought stress. This study revealed the molecular mechanism underlying drought tolerance in sudangrass. Furthermore, the genes identified in this study provide valuable resources for further research into the response to drought stress.

Ischemia/reperfusion-activated ferroptosis in the early stage triggers excessive inflammation to aggregate lung injury in rats.

Objective: Lung ischemia/reperfusion injury (LIRI) is a clinical syndrome of acute lung injury that occurs after lung transplantation or remote organ ischemia. Ferroptosis and inflammation are involved in the pathogenesis of LIRI according to the results of several studies on animal models. However, the interactive mechanisms between ferroptosis and inflammation contributing to LIRI remain unclear. Methods: HE staining and indicators of oxidative stress were used to evaluated the lung injury. The reactive oxygen species (ROS) level was examined by DHE staining. The quantitative Real-time PCR (qRT-PCR) and western blot analysis were employed to detect the level of inflammation and ferroptosis, and deferoxamine (DFO) was used to assess the importance of ferroptosis in LIRI and its effect on inflammation. Results: In the present study, the link of ferroptosis with inflammation was evaluated at reperfusion 30-, 60- and 180-minute time points, respectively. As the results at reperfusion 30-minute point shown, the pro-ferroptotic indicators, especially cyclooxygenase (COX)-2 and acyl-CoA synthetase long-chain family member 4 (ACSL4), were upregulated while the anti-ferroptotic factors glutathione peroxidase 4 (GPX4), cystine-glumate antiporter (XCT) and ferritin heavy chain (FTH1) were downregulated. Meanwhile, the increased level of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α) and IL-1ß were observed beginning at reperfusion 60-minute point but mostly activated at reperfusion 180-minute point. Furthermore, deferoxamine (DFO) was employed to block ferroptosis, which can alleviate lung injury. Expectedly, the survival rate of rats was increased and the lung injury was mitigated containing the improvement of type II alveolar cells ultrastructure and ROS production. In addition, at the reperfusion 180-minute point, the inflammation was observed to be dramatically inhibited after DFO administration as verified by IL-6, TNF-α and IL-1ß detection. Conclusion: These findings suggest that ischemia/reperfusion-activated ferroptosis plays an important role as the trigger for inflammation to further deteriorate lung damages. Inhibiting ferroptosis may have therapeutic potential for LIRI in clinical practice.

Butyrate inhibits the mitochondrial complex Ι to mediate mitochondria-dependent apoptosis of cervical cancer cells.

BACKGROUND: Cervical cancer (CC) is a common gynecological malignancy with high morbidity worldwide. Butyrate, a short-chain fatty acid produced by intestinal flora, has been reported to inhibit cervical carcinogenesis. This study aimed to investigate the pro-apoptotic effects of butyrate on CC and the underlying mechanisms. METHODS: Human HeLa and Ca Ski cells were used in this study. Cell proliferation, cell migration and invasion were detected by CCK-8 and EdU staining, transwell and wound healing assay, respectively. Cell cycle, mitochondrial membrane potential and apoptosis were evaluated by flow cytometry. Western blot and RT-qPCR were carried out to examine the related genes and proteins to the mitochondrial complex Ι and apoptosis. Metabolite changes were analyzed by energy metabolomics and assay kits. The association between G protein-coupled receptor 41, 43, 109a and CC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA). RESULTS: CCK-8 results showed significant inhibition of CC cell proliferation induced by butyrate treatment, which was confirmed by EdU staining and cell cycle detection. Data from the transwell and wound healing assay revealed that CC cell migration was dramatically reduced following butyrate treatment. Additionally, invasiveness was also decreased by butyrate. Western blot analysis showed that cleaved Caspase 3 and cleaved PARP, the enforcers of apoptosis, were increased by butyrate treatment. The results of Annexin V/PI staining and TUNEL also showed an increase in butyrate-induced apoptotic cells. Expression of Cytochrome C (Cytc), Caspase 9, Bax, but not Caspase 12 or 8, were up-regulated under butyrate exposure. Mechanistically, the decrease in mitochondrial NADH and NAD + levels after treatment with butyrate was observed by energy metabolomics and the NAD+/NADH Assay Kit, similar to the effects of the complex Ι inhibitor rotenone. Western blot results also demonstrated that the constituent proteins of mitochondrial complex Ι were reduced by butyrate. Furthermore, mitochondria-dependent apoptosis has been shown to be initiated by inhibition of the complex Ι. CONCLUSION: Collectively, our results revealed that butyrate inhibited the proliferation, migration and invasion of CC cells, and induced mitochondrial-dependent apoptosis by inhibiting mitochondrial complex Ι.

Berberine modulates gut microbiota to attenuate cerebral ferroptosis induced by ischemia-reperfusion in mice.

Ferroptosis was reported to be involved in cerebral ischemia-reperfusion injury (CIRI), on which the effects of berberine (BBR) remain unclear. Moreover, based on the critical role of gut microbiota in pleiotropic actions of BBR, we hypothesized that BBR can suppress CIRI-induced ferroptosis by modulating the gut microbiota. In this study, the results showed that BBR obviously attenuated the behavioral deficits of CIRI mice, accompanied with the improved survival rate and neuron damages, as phenocopied by dirty cage experiment. The typical morphological changes in ferroptotic cells and biomarkers of ferroptosis were attenuated in BBR- and its fecal microbiota-treated mice, accompanied by reduced malondialdehyde and reactive oxygen species, and the increased glutathione (GSH). BBR was found to alter the gut microbiota of CIRI mice with decreased abundance of Muribaculaceae, Erysipelotrichaceae, Helicobacteraceae, Streptococcaceae and Tannerellaceae, but elevated Bacteroidaceae and Enterobacteriaceae. KEGG analysis based on the 16S rRNA results indicated that multiple metabolic pathways including ferroptosis and GSH metabolism, were altered by BBR. Oppositely, the antibiotics administration counteracted the protective properties of BBR. Summarily, this study revealed the therapeutic potential of BBR on CIRI via inhibiting neuronal ferroptosis, in which upregulated glutathione peroxidase 1 (GPX1) was possibly involved. Moreover, the BBR-modulated gut microbiota was shown to play the critical role in the underlying mechanism.

Prevotella histicola suppresses ferroptosis to mitigate ethanol-induced gastric mucosal lesions in mice.

BACKGROUND: Ethanol-induced gastric mucosal lesions (EGML) is one of the most common digestive disorders for which current therapies have limited outcomes in clinical practice. Prevotella histicola (P. histicola) has shown probiotic efficacy against arthritis, multiple sclerosis and oestrogen deficiency-induced depression in mice; however, its role in EGML remains unclear in spite of its extensive colonisation of the stomach. Ferroptosis, which is characterised by lipid peroxidation, may be involved in EGML. Herein, we aimed to investigate the effects and underlying mechanism of action of P. histicola on EGML in the ferroptosis-dependent pathway. METHODS: P. histicola was intragastrically administered for a week, and deferoxamine (DFO), a ferroptosis inhibitor, was intraperitoneally injected prior to oral ethanol administration. The gastric mucosal lesions and ferroptosis were assessed via histopathological examinations, quantitative real-time PCR, Western blot, immunohistochemistry and immunofluorescence. RESULTS: P. histicola was originally found to attenuate EGML by reducing histopathological changes and lipid reactive oxygen species (ROS) accumulation. The pro-ferroptotic genes of Transferrin Receptor (TFR1), Solute Carrier Family 39 Member 14 (SLC39A14), Haem Oxygenase-1 (HMOX-1), Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4), Cyclooxygenase 2 (COX-2) and mitochondrial Voltage-dependent Anion Channels (VDACs) were up-regulated; the anti-ferroptotic System Xc-/Glutathione Peroxidase 4 (GPX4) axis was inhibited after ethanol administration. However, the changes of histopathology and ferroptosis-related parameters induced by ethanol were reversed by DFO. Furthermore, P. histicola treatment significantly downregulated the expression of ACSL4, HMOX-1 and COX-2, as well as TFR1 and SLC39A14, on mRNA or the protein level, while activating the System Xc-/GPX4 axis. CONCLUSIONS: We found that P. histicola reduces ferroptosis to attenuate EGML by inhibiting the ACSL4- and VDAC-dependent pro-ferroptotic pathways and activating the anti-ferroptotic System Xc-/GPX4 axis.

Butyrate Inhibits Gastric Cancer Cells by Inducing Mitochondriamediated Apoptosis.

BACKGROUND: Gastric cancer (GC) remains a common cause of cancer death in East Asia. Current treatment strategies for GC, including medical and surgical interventions, are suboptimal. Butyrate, a short-chain fatty acid produced by the intestinal flora, has been reported to be able to inhibit gastric carcinogenesis. This study aimed to investigate the effects of butyrate on human GC and its underlying mechanisms. MATERIALS AND METHODS: Human GC cell lines BGC-823 and SGC-7901, human GC tissues and adjacent normal tissues were used for this study. Cell proliferation was assessed using CCK-8 and EdU staining. TUNEL fluorescence and Annexin V/PI staining were adopted for qualitative and quantitative evaluation of cell apoptosis, respectively. Reactive oxygen species (ROS) assay was performed to analyse mitochondrial function. Real-time q-PCR and western blot were carried out to examine the expression of apoptosis-related genes and the synthesis of apoptosis-related proteins. The association between G protein-coupled receptor 109a (GPR109a) and GC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA). RESULTS: CCK-8 and EdU staining confirmed inhibitory activities of butyrate against human GC cells. Annexin V/PI staining and TUNEL fluorescence microscopy showed that butyrate promoted GC cell apoptosis. No difference in the expression of GPR109a was found between GC tissues and adjacent normal tissues, and no direct association between GPR109a and GC prognosis was discovered, suggesting that GPR109a may not be a key factor mediating the apoptosis of GC cells. Butyrate increased the synthesis of caspase 9 and decreased BCL-2, the well-known effector and regulator of mitochondria-mediated apoptosis, and significantly induced mitochondrial ROS. CONCLUSION: Collectively, our results suggest that butyrate is able to inhibit the proliferation of GC cells and induce GC apoptosis, possibly via a mitochondrial pathway.

Efficacy of probiotics against dental caries in children: a systematic review and meta-analysis.

Dental caries causes serious consequences and the financial burden of society especially in children with high morbidity rate. Here we carried out a meta-analysis to systematically evaluate the efficacy of probiotics against dental caries in children. Forty-three RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane and Web of Science from the inception through October 2021. Pooled estimates demonstrated that treatment with probiotics significantly reduced noncavitated (dicdas2-6mft) (SMD = -0.18, 95% CI: -0.3 to -0.06, p = 0.002) and cavitated (dicdas5-6mft) carious lesions in children (SMD = -0.32, 95% CI: -0.5 to 0.14, p = 0.0004). Probiotics also reduced prevalence of noncavitated (dicdas2-6mft) carious lesions (RR = 0.8, 95% CI: 0.67 to-0.97, p = 0.02). Salivary Streptococcus mutans was declined after intervention (SMD = -1.17, 95% CI: -1.85 to -0.5, p = 0.0007), while Lactobacillus counts were upregulated (SMD = 1.19, 95% CI: 0.46-1.92, p = 0.001). However, no significant effects in total bacteria counts and salivary pH were observed. Our findings suggest that probiotics especially Lactobacillus could be a promising therapeutic strategy for clinical applications in children dental caries.

Metformin: update on mechanisms of action on liver diseases.

Substantial attention has been paid to the various effects of metformin on liver diseases; the liver is the targeted organ where metformin exerts its antihyperglycemic properties. In non-alcoholic fatty liver disease (NAFLD), studies have shown that metformin affects the ATP/AMP ratio to activate AMPK, subsequently governing lipid metabolism. The latest research showed that low-dose metformin targets the lysosomal AMPK pathway to decrease hepatic triglyceride levels through the PEN2-ATP6AP1 axis in an AMP-independent manner. Metformin regulates caspase-3, eukaryotic initiation factor-2a (eIF2a), and insulin receptor substrate-1 (IRS-1) in palmitate-exposed HepG2 cells, alleviating endoplasmic reticulum (ER) stress. Recent observations highlighted the critical association with intestinal flora, as confirmed by the finding that metformin decreased the relative abundance of Bacteroides fragilis while increasing Akkermansia muciniphila and Bifidobacterium bifidum. The suppression of intestinal farnesoid X receptor (FXR) and the elevation of short-chain fatty acids resulted in the upregulation of tight junction protein and the alleviation of hepatic inflammation induced by lipopolysaccharide (LPS). Additionally, metformin delayed the progression of cirrhosis by regulating the activation and proliferation of hepatic stellate cells (HSCs) via the TGF-ß1/Smad3 and succinate-GPR91 pathways. In hepatocellular carcinoma (HCC), metformin impeded the cell cycle and enhanced the curative effect of antitumor medications. Moreover, metformin protects against chemical-induced and drug-induced liver injury (DILI) against hepatotoxic drugs. These findings suggest that metformin may have pharmacological efficacy against liver diseases.

Microbial treatment of alcoholic liver disease: A systematic review and meta-analysis.

Background and aims: Alcoholic liver disease (ALD) is characterized by impaired liver function due to chronic alcohol consumption, even fatal in severe cases. We performed a meta-analysis to determine whether microbial agents have therapeutic potential for ALD and elucidate the underlying mechanisms. Methods and results: Forty-one studies were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. The combined analysis showed that microbial therapy significantly decreased hepatic enzymatic parameters, including alanine transaminase [standardized mean difference (SMD): -2.70, 95% confidence interval (CI): -3.33 to -2.07], aspartate aminotransferase (SMD: -3.37, 95% CI: -4.25 to -2.49), γ-glutamyl transpeptidase (SMD: -2.07, 95% CI: -3.01 to -1.12), and alkaline phosphatase (SMD: -2.12, 95% CI: -3.32 to -0.92). Microbial agents endotoxin to enter the portal circulation and increasing reduced total cholesterol (SMD = -2.75, 95%CI -4.03 to -1.46) and triglycerides (SMD = -2.64, 95% CI: -3.22 to -2.06). Microbial agents increased amounts of the beneficial flora Lactobacillus (SMD: 4.40, 95% CI: 0.97-7.84) and Bifidobacteria (SMD: 3.84, 95% CI: 0.22-7.45), Bacteroidetes (SMD: 2.51, 95% CI: 0.29-4.72) and decreased harmful Proteobacteria (SMD: -4.18, 95% CI: -6.60 to -1.77), protecting the integrity of the intestinal epithelium and relieving endotoxin (SMD: -2.70, 95% CI: -3.52 to -2.17) into the portal vein, thereby reducing the production of inflammatory factors such as tumor necrosis factor-α (SMD: -3.35, 95% CI: -4.31 to -2.38), interleukin-6 (SMD: -4.28, 95% CI: -6.13 to -2.43), and interleukin-1ß (SMD: -4.28, 95% CI: -6.37 to -2.19). Oxidative stress was also relieved, as evidenced by decreased malondialdehyde levels (SMD: -4.70, 95% CI: -6.21 to -3.20). Superoxide dismutase (SMD: 2.65, 95% CI: 2.16-3.15) and glutathione levels (SMD: 3.80, 95% CI: 0.95-6.66) were elevated. Conclusion: Microbial agents can reverse dysbiosis in ALD, thus significantly interfering with lipid metabolism, relieving inflammatory response and inhibiting oxidative stress to improve liver function.

K3C6N7O3·2H2O: A Multifunctional Nonlinear Optical Cyamelurate Crystal with Colossal π-Conjugated Orbitals.

The delocalized π-conjugated units are considered as an advantageous gene for improving the optical nonlinearity of acentric crystals. For the first time, we synthesized a new acentric SHG-active metal cyamelurate crystal K3C6N7O3·2H2O (I) by a facile solution method, containing a colossal planar π-conjugated (C6N7O3)3- unit. It displays a strong second-order harmonic generation (SHG) of 4 × KDP and a giant anisotropic birefringence of 0.446 at 1064 nm. The theoretical calculations reveal that such substantial improvement is contributed from the strong molecular susceptibility of (C6N7O3)3- units and their near-perfect coplanar arrangement. Moreover, I exhibits a broadband ultraviolet photoluminescence at 366 nm, suggesting its multifunctional capacity and great potential for compact highly integrated optoelectronic devices.

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.

Enhanced Electron-Phonon Coupling Effect in Rare-Earth Borate Crystals Containing a "Quasi-Free-Oxygen" Motif.

Revealing the interaction between electrons and phonons, e.g., electron-phonon coupling or decoupling, is a great challenge for physics and functional material communities. For rare-earth single crystals, the electron-phonon coupling and fluorescence behaviors strongly depend on the crystal structure and constituent motifs. Here, we proposed a universal "quasi-free O" as an effective structural motif to enhance phonon-assisted electronic transitions and photoluminescence. Using Gd3+ ion as a probe, we studied Gd:La2CaB10O19 (Gd:LCB) and GdMgB5O10 (GdMB) crystals composed of double B-O layers and dangling "quasi-free O", respectively, which enable strengthened phonon-involved luminescence. Especially, a GdMB crystal features an infinite [O-Gd-O-Gd-O] chain (O represents quasi-free oxygen), thus greatly promoting the energy transfer and electron-phonon coupling effect. As a result, its Huang-Rhys S factor is two times larger than that of a Gd:LCB crystal under room temperature. These results put forward "quasi-free O" to improve the electron-phonon coupling intensity and allow LCB and GdMB crystals to serve as potential hosts for phonon-terminated vibronic lasers.

Detection of inflammatory bowel disease (IBD)-associated microRNAs by two color DNA-templated silver nanoclusters fluorescent probes.

Researches demonstrated that circulating miRNAs could be used as novel diagnostic and prognostic potential markers for patients with inflammatory bowel diseases (IBD). It is of great significance in clinical to develop rapid and specific detection methods for miRNAs. Herein, we established a fluorescent probe for ulcerative colitis (UC) activity-associated two serum biomarkers (miR-23a and miR-223) simultaneous detection, which used multi-color fluorescent DNA-stabilized silver nanoclusters (DNA-AgNC) illuminated by a close guanine (G)-rich sequence as a signal transducer and two split DNA probes as recognition units. In principle, the two DNA probe sequences containing AgNC nucleation sequence and G-rich sequence respectively, formed a ternary complex when in the presence of target miRNA through base pairing, so as to induce enhancement of fluorescence emission of AgNC by shortening the distance from G-rich sequence. The combined probes for miR-23a and miR-223 detection generated increased fluorescence signals at 460 nm ex/545 nm em and at 560 nm ex/630 nm em, respectively. With this technique, we successfully quantified the two target miRNAs with high selectivity. Furthermore, the potential clinic applicability of this method was verified by testing the spiked standard miRNAs in human serum. Thus, this one-step, low-cost, and homogenous method offers a great opportunity for disease-associated multiplex miRNAs simultaneous detection.

Anion-Centered Polyhedron Strategy for Strengthening Photon Emission Induced by Electron-Phonon Coupling.

Electron-phonon coupling emerges as a growing frontier in the heart of condensed matter from physical symmetry to the electronic quantum state, but its quantitative strength dependence on the chemical structure has not been assessed. Here, we originally proposed the anion-centered polyhedron (ACP) strategy for elaborating the electron-phonon coupling interaction in rare-earth (RE) materials comprising three chemical factors, RE-O bond length, the effective charge of the coordinated atom, and structural dimensionality. Using Gd3+ cation with 4f7 configuration as a fluorescence probe, we found that the "free-O"-centered polyhedron is the most crucial motif in strengthening the phonon-assisted energy transfer and photon emission. The temperature-dependent Huang-Rhys S factors were calculated to identify the electron-phonon coupling intensity based on the fluorescence spectrum quantitatively. Finally, beyond conventional wisdom, a series of structural criteria were presented, serving as useful guidelines for discovering strongly coupled rare-earth optical materials. Our study breaks the long-time "blind"-searching diagram and provides reliable principles for many functional materials associated with electron-phonon coupling, such as superconductors, multiferroics, and phosphors.