Plastic film mulching application improves potato yields, reduces ammonia emissions, but boosts the greenhouse gas emissions in China.

With global population growth and climate change, food security and global warming have emerged as two major challenges to agricultural development. Plastic film mulching (PM) has long been used to improve yields in rain-fed agricultural systems, but few studies have focused on soil gas emissions from mulched rainfed potatoes on a long-term and regional scale. This study integrated field data with the Denitrification-Decomposition (DNDC) model to evaluate the impacts of PM on potato yields, greenhouse gas (GHG) and ammonia (NH3) emissions in rainfed agricultural systems in China. We found that PM increased potato yield by 39.7 % (1505 kg ha-1), carbon dioxide (CO2) emissions by 15.4 % (123 kg CO2 eq ha-1), nitrous oxide (N2O) emissions by 47.8 % (1016 kg CO2 eq ha-1), and global warming potential (GWP) by 38.9 % (1030 kg CO2 eq ha-1), while NH3 volatilization decreased by 33.9 % (8.4 kg NH3 ha-1), and methane (CH4) emissions were little changed compared to CK. Specifically, the yield after PM significantly increased in South China (SC), North China (NC), and Northwest China (NWC), with increases of 66.1 % (2429 kg ha-1), 44.1 % (1173 kg ha-1), and 43.6 % (956 kg ha-1) compared to CK, respectively. The increase in GWP and greenhouse gas emission intensity (GHGI) under PM was more pronounced in the Northeast China (NEC) and NWC regions, with respective increases of 57.1 % and 60.2 % in GWP, 16.9 % and 10.3 % in GHGI. While in the Middle and Lower reaches of the Yangtze River (MLYR) and SC, PM decreased GHGI with 10.2 % and 31.1 %, respectively. PM significantly reduced NH3 emissions in all regions and these reductions were most significant in Southwest China (SWC), SCand MLYR, which were 41 %, 38.0 %, and 38.0 % lower than CK, respectively. In addition, climatic and edaphic variables were the main contributors to GHG and NH3 emissions. In conclusion, it is appropriate to promote the use of PM in the MLYR and SC regions, because of the ability to increase yields while reducing environmental impacts (lower GHGI and NH3 emissions). The findings provide a theoretical basis for sustainable agricultural production of PM potatoes.

[Zuogui Jiangtang Qinggan Formula improves glucolipid metabolism in type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease by regulating FoxO1/MTP/APOB signaling pathway].

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.

SYT-SSX1 enhances the invasiveness and maintains stem-like cell properties in synovial sarcoma via induction of TGF-ß1/Smad signaling.

BACKGROUND: Synovial sarcoma (SS) is a type of soft tissue sarcoma (STS) of undetermined tissue origin, which is characterized by the recurrent pathognomonic chromosomal translocation t (X;18)(p11.2; q11.2). Studies have shown that SS is a malignant tumor originating from cancer stem cells or pluripotent mesenchymal stem cells and may be related to fusion genes. In addition, some studies have indicated that the induction of epithelial-mesenchymal transition (EMT) via the TGF-ß1/Smad signaling pathway leads to SS metastasis. METHODS: We analyzed the effects of SYT-SSX1 on the stemness of SS cells via TGF-ß1/Smad signaling in vitro. The SYT-SSX1 fusion gene high expression cell was constructed by lentiviral stable transfer technology. SYT-SSX1 and SW982 cells were cultured and tested for sphere-forming ability. The transwell migration assay and flow cytometry were used to assess the migration ability of the sphere cells as well as the expression of CSC-related markers. We treated SYT-SSX1 cells with rhTGF-ß1 (a recombinant agent of the TGF-ß1 signaling pathway) and SB431542 and observed morphological changes. A CCK-8 experiment and a western blot (WB) experiment were conducted to detect the expression of TGF-ß1 signaling pathway- and EMT-related proteins after treatment. The SYT-SSX1 cells were then cultured and their ability to form spheres was tested. Flow cytometry, WB, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of CSC surface markers on SYT-SSX1 sphere cells. RESULTS: It was found that SYT-SSX1 has stronger sphere-forming ability, migration ability, and higher expression of CSC-related molecules than SW982 cells. Through treating SYT-SSX1 and SW982 cells with rhTGF-ß1 and SB431542, we found that TGF-ß1 enhanced the proliferation of cells, induced EMT, and that TGF-ß1 enhanced the characteristics of tumor stem cells. CONCLUSIONS: Our results suggest that SYT-SSX1 enhances invasiveness and maintains stemness in SS cells via TGF-ß1/Smad signaling. These findings reveal an effective way to potentially improve the prognosis of patients with SS by eliminating the characteristics of cancer stem cells (CSCs) during treatment.

Insight into the capacity decay mechanism of cycled LiNi0.5Co0.2Mn0.3O2cathodes viain situx-ray diffraction.

Layered LiNixCoyMn1-x-yO2(NCM) is expected to dominate the future cathode technology of the automotive industry, due to its high energy density and low cost. Despite its excellent prospects, however, the severe capacity decay of NCM cathodes has prevented this promising material from achieving further success. The mechanism underlying this phenomenon is controversial and has been generally understood as arising from the complex structural changes that take place upon Li-(de)intercalation. However, deeper insight has not been available due to unclear structural kinetics, in particular, in cycled NCM cathodes. For this study, we conductedin situhigh-energy synchrotron x-ray diffraction (XRD) measurements on a typical LiNi0.5Co0.2Mn0.3O2(NCM523) cathode that had been operated for 90 cycles, then compared the results with those collected from a fresh NCM532 electrode. It was revealed that the H1-H2 phase transition that only occurs at the first cycle is irreversible. Remarkably, thec-contraction triggered by the H2-H3 transition, which is expected to be the major cause of intergranular cracks in electrodes, became even more profound after cycling. Combining the above results with electrochemical testing and microscopic imaging, we discuss the interplay between structural dynamics and performance degradation in NCM532 in detail. This study provides key evidence for a mechanically induced capacity decay mechanism, which is expected to be extended to NCM materials with various compositions.

Ultralow Volume Change of P2-Type Layered Oxide Cathode for Na-Ion Batteries with Controlled Phase Transition by Regulating Distribution of Na.

Most P2-type layered oxides exhibit a large volume change when they are charged into high voltage, and it further leads to bad structural stability. In fact, high voltage is not the reason which causes the irreversible phase transition. There are two internal factors which affect structural evolution: the amount and distribution of Na ions retained in the lattice. Hereon, a series of layered oxides Na2/3 Mnx Nix-1/3 Co4/3-2x O2 (1/3≤x≤2/3) were synthesized. It is observed that different components have different structural evolutions during the charge/discharge processes, and further researches find that the distribution of Na ions in layers is the main factor. By controlling the distribution of Na ions, the phase transition process can be well controlled. As the referential component, P2-Na2/3 Mn1/2 Ni1/6 Co1/3 O2 cathode with uniform distribution of Na ions is cycled at the voltage window of 1.5-4.5 V, which exhibits a volume change as low as 1.9 %. Such a low strain is beneficial for cycling stability. The current work provides a new and effective route to regulate the structural evolution of the promising P2-type layered cathode for sodium ion batteries.

Assembly and Degradation of Inorganic Nanoparticles in Biological Environments.

In solution, nanoparticles may be conceptually compartmentalized into cores and engineered surface coatings. Recent advances allow for simple and accurate characterization of nanoparticle cores and surface shells. After introduction into a complex biological environment, adsorption of biological molecules to the nanoparticle surface as well as a loss of original surface components occur. Thus, colloidal nanoparticles in the context of the biological environment are hybrid materials with complex structure, which may result in different chemical, physical, and biological outcomes as compared to the original engineered nanoparticles. In this review, we will discuss building up an engineered inorganic nanoparticle from its inside core to its outside surface and following its degradation in a biological environment from its outside to its inside. This will involve the way to synthesize selected inorganic nanoparticles. Then, we will discuss the environmental changes upon exposure of these nanoparticles to biological media and their uptake by cells. Next, the intracellular fate of nanoparticles and their degradation will be discussed. Based on these examples, the need to see nanoparticles in the context of the biological environment as dynamic hybrid materials will be highlighted.

Short-Chain Fatty Acids Manifest Stimulative and Protective Effects on Intestinal Barrier Function Through the Inhibition of NLRP3 Inflammasome and Autophagy.

BACKGROUND/AIMS: Short-chain fatty acids (SCFAs) are the major energy resources of intestinal epithelial cells. It has been reported that SCFAs can repair the dysfunction of intestinal barrier, however, the underlying mechanisms are still not fully understood. Here, we investigated the stimulative and protective effects of SCFAs on intestinal barrier function and the possible mechanisms. METHODS: To investigate the effects of SCFAs on intestinal barrier function, the Caco-2 monolayers were exposed to acetate, propionate, butyrate respectively or simultaneously without or with lipopolysaccharide (LPS). Next, Caco-2 cells were treated with trichostatin A and etomoxir to identify whether SCFAs act as HDAC inhibitors or energy substances. To activate NLRP3 inflammasome and autophagy, Caco-2 cells were treated with LPS+ATP and rapamycin respectively without or with SCFAs. The transepithelial electrical resistance (TER) and paracellular permeability were respectively detected with a Millicell-ERS voltohmmeter and fluorescein isothiocyanate-labeled dextran. Immunoblotting and immunofluorescence were applied to analyze the expression and distribution of tight junction proteins, and the activation of NLRP3 inflammasome and autophagy. RESULTS: Acetate (0.5mM), propionate(0.01mM) and butyrate (0.01mM) alone or in combination significantly increased TER, and stimulated the formation of tight junction. SCFAs also dramatically attenuated the LPS-induced TER reduction and paracellular permeability increase, accompanying significantly alleviated morphological disruption of ZO-1 and occludin. Meanwhile, the activation of NLRP3 inflammasome and autophagy induced by LPS were significantly inhibited by SCFAs. Trichostatin A imitated the inhibiting action of SCFAs on NLRP3 inflammasome, whereas etomoxir blocked the action of SCFAs on protecting intestinal barrier and inhibiting autophagy. In addition, the activation of autophagy and NLRP3 inflammasome by rapamycin and LPS+ATP resulted in TER reduction, paracellular permeability increase and morphological disruption of both ZO-1 and occludin, which was alleviated by SCFAs. CONCLUSION: It is suggested that SCFAs stimulate the formation of intestinal barrier, and protect the intestinal barrier from the disruption of LPS through inhibiting NLRP3 inflammasome and autophagy. In addition, SCFAs act as energy substances to protect intestinal barrier and inhibit autophagy, but act as HDAC inhibitors to suppress NLRP3 inflammasome. Furthermore, the mutual promoting action between NLRP3 inflammasome and autophagy would destroy intestinal barrier function, which could be alleviated by SCFAs.

Differences in genome characters and cell tropisms between two chikungunya isolates of Asian lineage and Indian Ocean lineage.

BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus within the family Togaviridae, which has attracted global attention due to its recent re-emergence. In one of our previous studies, we successfully isolated two CHIKV virus strains, SZ1050 and SZ1239, from the serum samples of two imported patients in 2010 and 2012, respectively. However, the differences in their genome characters and cell tropisms remain undefined. METHODS: We extracted the RNA of two CHIKV isolates and performed PCR to determine the sequence of the whole viral genomes. The genotypes were classified by phylogenetic analysis using the Mega 6.0 software. Furthermore, the cell tropisms of the two CHIKV isolates were evaluated in 13 cell lines. RESULTS: The lengths of the whole genomes for SZ1050 and SZ1239 were 11,844 nt and 12,000 nt, respectively. Phylogenetic analysis indicated that SZ1050 belonged to the Indian Ocean lineage (IOL), while SZ1239 was of the Asian lineage. Comparing to the prototype strain S27, a gap of 7 aa in the nsP3 gene and missing of one repeated sequence element (RSE) in the 3' UTR were observed in SZ1239. The E1-A226V mutation was not detected in both strains. SZ1050 and SZ1239 could infect most of the evaluated mammalian epithelial cells. The K562 cells were permissive for both SZ1050 and SZ1239 while the U937 cells were refractory to both viruses. For Aedes cell lines C6/36 and Aag-2, both SZ1050 and SZ1239 were able to infect and replicate efficiently. CONCLUSIONS: Compared to the prototype S27 virus, some deletions and mutations were found in the genomes of SZ1050 and SZ1239. Both viruses were susceptible to most evaluated epithelia or fibroblast cells and Aedes cell lines including C6/36 and Aag-2 in spite of marginal difference.

Selenoprotein K modulate intracellular free Ca2+ by regulating expression of calcium homoeostasis endoplasmic reticulum protein.

Selenoprotein K (SelK) is an 11-kDa selenoprotein, which may be involved in the regulation of oxidative stress, endoplasmic reticulum (ER) stress and immune response. To explore the function of SelK in the process of immune response, several short-hairpin RNAs (shRNA) were designed for the construction of recombinant plasmids to down-regulate the expression of SelK gene in vitro. These shRNAs specifically and efficiently interfered with the expression of SelK at both mRNA and protein levels. The expression of calcium homoeostasis endoplasmic reticulum protein (CHERP) and the intracellular free Ca2+ concentration were significantly down-regulated in anti-CD3 stimulated SelK-knockdown cells. The expression of Interleukin 2 receptor alpha chain (IL-2Rα) and the secretion of Interleukin 4 (IL-4), which play a significant role in the process of T cell activation and proliferation, were also reduced in SelK-knockdown cells. Selenomethionine (Se-Met) at an optimum concentration of 5 µM could up-regulate SelK expression and reverse the change of the expression of CHERP and the intracellular free calcium caused by SelK-knockdown. These results hereby imply SelK may regulate the release of Ca2+ by CHERP and play an important role in the proliferation and differentiation of T cell by TCR stimulation.

Prognostic value of the MicroRNA-29 family in multiple human cancers: A meta-analysis and systematic review.

MicroRNAs (miRNAs) in cancer development have attracted much attention in recent years. miR-29 is known to critically affect cancer progression by functioning as a tumor suppressor. However, it may also act as an oncogene under certain situations. The prognostic value of the miR-29 family in cancer progression is still under debate and reported results are inconsistent. Therefore, we reported here a meta-analysis and systematic review to analyze the prognostic role of the miR-29 family in cancer. We screened 20 published studies and calculated pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS) or disease-free survival/recurrence-free survival (DFS/RFS). Our results showed that a low or absent expression of miR-29 family was significantly associated with poor OS (HR, 1.57; 95%CI, 1.18-2.08), and inferior to 5-year DFS/RFS (HR, 1.89; 95%CI, 1.47-2.44). Analysis of individual miR-29 subtypes indicated that the low expression of miR-29a/b/c subtypes correlated with poor 5-year OS (miR-29a: HR, 1.99; 95%CI, 1.41-2.80; miR-29b: HR, 1.60; 95%CI, 1.18-2.17; miR-29c: HR, 1.69; 95%CI, 1.00-2.86), as well as poor 5-year DFS/RFS (miR-29b: HR, 1.70; 95%CI, 1.27-2.27). Ethnicity analysis demonstrated Asian patients with low expression of miR-29 were significantly correlated with poor OS (HR, 1.61; 95%CI, 1.16-2.23) and 5-year DFS/RFS (HR, 2.03; 95%CI, 1.50-2.74). Taken together, our analysis indicates that the low expression of miR-29 is associated with aggressiveness and poor prognosis of malignant neoplasms. More importantly, miR-29 might serve as a key biomarker for predicting the recurrence and progression of human cancers.

Dual N-linked glycosylation at residues 133 and 158 in the hemagglutinin are essential for the efficacy of H7N9 avian influenza virus like particle vaccine in chickens and mice.

H7N9 subtype avian influenza virus (AIV) poses a great challenge to poultry industry. Virus-like particle (VLP) is a prospective alternative for the traditional egg-based influenza vaccines. N-linked glycosylation (NLG) regulates the efficacy of influenza vaccines, whereas the impact of NLG modifications on the efficacy of influenza VLP vaccines remains unclear. Here, H7N9 VLPs were assembled in insect cells through co-infection with the baculoviruses expressing the NLG-modified hemagglutinin (HA), neuraminidase and matrix proteins, and the VLP vaccines were assessed in chickens and mice. NLG modifications significantly enhanced hemagglutination-inhibition and virus neutralization antibody responses in mice, rather than in chickens, because different immunization strategies were used in these animal models. The presence of dual NLG at residues 133 and 158 significantly elevated HA-binding IgG titers in chickens and mice. The VLP vaccines conferred complete protection and significantly suppressed virus replication and lung pathology post challenge with H7N9 viruses in chickens and mice. VLP immunization activated T cell immunity-related cytokine response and inhibited inflammatory cytokine response in mouse lung. Of note, the presence of dual NLG at residues 133 and 158 optimized the capacity of the VLP vaccine to stimulate interleukin-4 expression, inhibit virus shedding or alleviate lung pathology in chickens or mice. Intriguingly, the VLP vaccine with NLG addition at residue 133 provided partial cross-protection against the H5Nx subtype AIVs in chickens and mice. In conclusion, dual NLG at residues 133 and 158 in HA can be potentially used to enhance the efficacy of H7N9 VLP vaccines in chickens and mammals.

Knowledge, attitudes, and current practices toward lung cancer palliative care management in China: a national survey.

Scope: The present investigation seeks to illuminate the current state and disparities in the knowledge, attitudes, and practices (KAP) among healthcare professionals regarding the management of lung cancer palliative care (LCPC) in China, while simultaneously assessing the prevalence and context of patient-controlled analgesia (PCA) usage in the management of cancer-related pain. Methods: A total of 2093 healthcare practitioners from 706 hospitals across China completed a structured questionnaire that probed various facets of LCPC management. The questionnaire consisted of seven thematic sections, incorporating chi-square tests and Fisher's exact probabilities to statistically assess the discrepancies in KAP among healthcare professionals across different hospital grades. Ordered data distributions among hospital grades were compared using non-parametric Kruskal-Wallis H and Mann-Whitney U tests. Multiple-choice items were subjected to multiple-response cross-tabulation analysis, while the Spearman rank-order correlation coefficient was employed to gauge potential associations among variables. Results: Around 84.2% of the respondents perceived anti-tumor therapy to be of equal importance to palliative care. Statistically significant differences (χ² = 27.402, P = 0.002) in satisfaction levels were observed, with participants from Tertiary hospitals demonstrating higher satisfaction compared to those from Secondary and Primary hospitals. Pain emerged as the most prevalent symptom necessitating LCPC. Major impediments to LCPC adoption included patients' and families' concerns about the safety of long-term palliative care-related drug use. 31.1% of the respondents cited the most frequent rationale for PCA use as cases involving patients who required systemic administration of large opioid doses or exhibited intolerable adverse reactions to opioids. The principal deterrents against the use of PCA for cancer pain management were (1): apprehension about adverse drug reactions due to overdose (2), concern about the potential for opioid addiction, and (3) the anticipated increase in patients' economic burdens. Over the preceding 24-month period, 33.9% of the surveyed healthcare practitioners reported no engagement in either online or offline LCPC-related training initiatives. Conclusion: This study emphasizes the pressing need for comprehensive training in LCPC among Chinese health personnels, particularly focusing on the effective management of cancer pain symptoms.

Ultrasound image-guided cancer gene therapy using iRGD dual-targeted magnetic cationic microbubbles.

The gene therapy attracted more and more attention for the tumor therapy. To obtain a safe gene therapy system, the new gene vectors beyond the virus were developed for a high gene therapy efficiency. The ultrasound mediated gene therapy was safer and the plasmid DNA could be delivered by the microbubbles and combined with the ultrasound to increase the gene transfection efficiency. In this work, the cationic microbubbles decorated with Cyclo(Cys-Arg-Gly-Asp-Lys-Gly-Pro-AspCys) (iRGD peptides) and magnetic Fe3O4 nanoparticles (MBiM) was designed for targeted ultrasound contrast imaging guided gene therapy of tumors. The ultrasound image intensity was dramatically enhanced at the tumor site that received MBiM with the magnet applied, compared to those administrated the non-targeted microbubbles (MBb) or the microbubbles with only one target material on the surface (MBM and MBbi). The pGPU6/GFP/Neo-shAKT2 was used as a sample gene, which down regulate the AKT2 protein expression for the cancer therapy. It illustrated that MBiM/AKT2 had the highest gene transfection efficiency in the studied microbubbles mediated by the ultrasound, leading to the AKT2 protein expression downregulation and the strongest tumor killing effect in vitro and in vivo. In summary, a novel and biocompatible gene delivery platform via MBiM with both the endogenous and external targeting effects for breast cancer theranostics was developed.

Zuogui Jiangtang Shuxin formula Ameliorates diabetic cardiomyopathy mice via modulating gut-heart axis.

Background: There is growing evidence demonstrating that the gut microbiota plays a crucial role in multiple endocrine disorders, including diabetic cardiomyopathy (DCM). Research shows that the Chinese herb reduces disease occurrence by regulating gut microbiota. Zuogui Jiangtang Shuxin formula (ZGJTSXF), a Chinese medicinal formula, has been clinically used for treatment of DCM for many years. However, there is still no clear understanding of how ZGJTSXF treatment contributes to the prevention and treatment of DCM through its interaction with gut microbiota and metabolism. Methods: In this study, mice models of DCM were established, and ZGJTSXF's therapeutic effects were assessed. Specifically, serum glycolipid, echocardiography, histological staining, myocardial apoptosis rate were assessed. Using 16s rRNA sequencing and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), we determined the impact of ZGJTSXF on the structure of gut microbiota and content of its metabolite TMAO. The mechanism of ZGJTSXF action on DCM was analyzed using quantitative real-time PCR and western blots. Results: We found that ZGJTSXF significantly ameliorated DCM mice by modulating gut-heart axis: ZGJTSXF administration improved glycolipid levels, heart function, cardiac morphological changes, inhibited cardiomyocytes apoptosis, and regulate the gut microbiota in DCM mice. Specifically, ZGJTSXF treatment reverse the significant changes in the abundance of certain genera closely related to DCM phenotype, including Lactobacillus, Alloprevotella and Alistipes. Furthermore, ZGJTSXF alleviated DCM in mice by blunting TMAO/PERK/FoxO1 signaling pathway genes and proteins. Conclusion: ZGJTSXF administration could ameliorate DCM mice by remodeling gut microbiota structure, reducing serum TMAO generation and suppressing TMAO/PERK/FoxO1 signaling pathway.

An Integrative Pharmacology-Based Strategy to Uncover the Mechanism of Zuogui Jiangtang Shuxin Formula in Diabetic Cardiomyopathy.

Purpose: This study aimed to explore the mechanism of Zuogui Jiangtang Shuxin formula (ZGJTSXF) in the treatment of diabetic cardiomyopathy (DCM) by an integrative strategy combining serum pharmacochemistry, network pharmacology analysis, and experimental validation. Methods: An Ultra high performance liquid chromatography-high resolution mass spectrometry (UPLC-Q-Exactive-Orbitrap-MS) method was constructed to identify compounds in rat serum after oral administration of ZGJTSXF. A component-target network between the targets of ZGJTSXF ingredients and DCM was established using Cytoscape. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to deduce ZGJTSXF-associated targets and pathways. The DCM model mice were treated with ZGJTSXF, and the predicted important signaling pathways were verified using quantitative PCR and Western blot. Results: We identified 78 compounds in serum of medicated rats, which mainly included flavonoids, small peptides, nucleosides, organic acids, phenylpropanoids, alkaloids, phenanthrenequinones, iridoids, phenols, and saponins. Network pharmacology analysis revealed that ZGJTSXF may regulate targets including ALB, TNF, AKT1, GAPDH, VEGFA, EGFR, SRC, CASP3, MAPK3, JUN, and PI3K/AKT signaling pathway in the treatment of DCM. ZGJTSXF administration improved blood sugar levels, heart function, and cardiac morphological changes in DCM mice. Notably, ZGJTSXF inhibited cardiomyocytes apoptosis, which was associated with restored PI3K/Akt signaling and upregulated Bcl-2 and Bcl-xL proteins expression. Conclusion: Our preliminary results proposed the material basis and possible mechanisms of ZGJTSXF in treating DCM, which is related to the activation of the PI3K/AKT signaling pathway and apoptosis inhibition. These findings shed new light in developing ZGJTSXF-based therapeutics in treating DCM.

Direct mass spectrometry analysis of biological tissue for diagnosis of thyroid cancer using wooden-tip electrospray ionization.

Direct mass spectrometry (MS) analysis of human tissue at the molecular level could gain insight into biomarker discovery and disease diagnosis. Detecting metabolite profiles of tissue sample play an important role in understanding the pathological properties of disease development. Because the complex matrices in tissue samples, complicated and time-consuming sample preparation processes are usually required by conventional biological and clinical MS methods. Direct MS with ambient ionization technique is a new analytical strategy for direct sample analysis with little sample preparation, and has been proven to be a simple, rapid, and effective analytical tools for direct analysis of biological tissues. In this work, we applied a simple, low-cost, disposable wooden tip (WT) for loading tiny thyroid tissue, and then loading organic solvents to extract biomarkers under electrospray ionization (ESI) condition. Under such WT-ESI, the extract of thyroid was directly sprayed out from wooden tip to MS inlet. In this work, thyroid tissue from normal and cancer parts were analyzed by the established WT-ESI-MS, showing lipids were mainly detectable compounds in thyroid tissue. The MS data of lipids obtained from thyroid tissues were further analyzed with MS/MS experiment and multivariate variable analysis, and the biomarkers of thyroid cancer were also investigated.

Plasmonic hot carrier injection from single gold nanoparticles into topological insulator Bi2Se3 nanoribbons.

Plasmonic gold nanoparticles injecting hot carriers into the topological insulator (TI) interface of Bi2Se3 nanoribbons are studied by resonant Raman spectroscopy. We resolve the impact of individual gold particles with sizes ranging from 140 nm down to less than 40 nm on the topological surface states of the nanoribbons. In resonance at 1.96 eV (633 nm), we find distinct phonon renormalization in the Eg2- and A1g2-modes that can be associated with plasmonic hot carrier injection. The phonon modes are strongly enhanced by a factor of 350 when tuning the excitation wavelengths into interband transition and in resonance with the surface plasmon of gold nanoparticles. At 633 nm wavelength, a plasmonic enhancement factor of 18 is observed indicating a contribution of hot carriers injected from the gold nanoparticles into the TI interface. Raman studies as a function of gold nanoparticle size reveal the strongest hot carrier injection for particles with size of 108 nm in agreement with the resonance energy of its surface plasmon. Hot carrier injection opens the opportunity to locally control the electronic properties of the TI by metal nanoparticles attached to the surface of nanoribbons.

Repurposing CRISPR/Cas to Discover SARS-CoV-2 Detecting and Neutralizing Aptamers.

RNA aptamers provide useful biological probes and therapeutic agents. New methodologies to screen RNA aptamers will be valuable by complementing the traditional Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Meanwhile, repurposing clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated systems (Cas) has expanded their utility far beyond their native nuclease function. Here, CRISmers, a CRISPR/Cas-based novel screening system for RNA aptamers based on binding to a chosen protein of interest in a cellular context, is presented. Using CRISmers, aptamers are identified specifically targeting the receptor binding domain (RBD) of the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two aptamer leads enable sensitive detection and potent neutralization of SARS-CoV-2 Delta and Omicron variants in vitro. Intranasal administration of one aptamer, further modified with 2'-fluoro pyrimidines (2'-F), 2'-O-methyl purines (2'-O), and conjugation with both cholesterol and polyethylene glycol of 40 kDa (PEG40K), achieves effective prophylactic and therapeutic antiviral activity against live Omicron BA.2 variants in vivo. The study concludes by demonstrating the robustness, consistency, and potential broad utility of CRISmers using two newly identified aptamers but switching CRISPR, selection marker, and host species.

An Innovative Insight into Performance Degradation of NCM111 Cathode Induced by Suspension of Operation.

The lifespan of lithium-ion batteries varies enormously from fundamental study to practical applications. This big difference has been typically ascribed to the high degree of uncertainty in unpredictable and complicated operation conditions in real-life applications. Here, we report that the pause of the charging-discharging process, which is frequently operated in practice but rarely studied in academics, is an important reason for the performance degradation of the NCM111 cathode. It is found that the pause during cycling could trigger a remarkable drop in capacity, giving rise to ∼30% more capacity decay compared with the continuously cycled sample. In situ synchrotron X-ray diffraction analysis reveals that the harmful H1-H2 phase transition, which typically appears in the initial cycle but disappears in subsequent cycles, is reactivated by the pausing process. The anisotropic lattice strains that occur during the H1-H2 transition result in mechanical fractures that terminate with an inert NiO-type rock-salt phase on the surface of particles. The present study indicates that the discontinuous usage of rechargeable batteries is also a key factor for cycle life, which might provide a distinct perspective on the performance decay in practical applications.

Exploring biomarkers and transcriptional factors in type 2 diabetes by comprehensive bioinformatics analysis on RNA-Seq and scRNA-Seq data.

Background: Type 2 diabetes (T2D) is a prevalent chronic disease with elusive. Combining transcriptome and single-cell sequencing data to explore biomarkers of T2D could provide new insights into the in-depth understanding of the molecular mechanisms and diagnosis of T2D. Methods: The GSE41762 dataset including RNA-seq data for healthy and T2D patients, was obtained from the Gene Expression Omnibus (GEO) database. The potential functions of the differentially expressed genes (DEGs) were revealed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Moreover, biomarkers were screened out by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and receiver operating characteristic (ROC) analysis. Furthermore, single-cell RNA (sc-RNA)-seq data in the "E-MTAB-5061" dataset was downloaded from the ArrayExpress (European Bioinformatics Institute, EBI) database. Principal components analysis (PCA) and t-distributed stochastic neighbor embedding (tSNE) were used for dimensionality reduction analysis and cell clustering. The FindAllMarkers function was used annotate different cell clusters, and key cell clusters were screened by the expression levels of the biomarkers. Finally, the transcription factors (TFs) of the biomarkers were recognized. Results: A total of 111 DEGs were screened in the GSE41762 dataset, which were mainly related to hormone secretion, specialized postsynaptic membrane, pancreatic secretion, JAK-STAT signaling pathway, and Ras signaling pathway. In addition, SLC2A2, SERPINF1, RASGRP1, and CHL1 were screened out as biomarkers of T2D, which possessed potential diagnostic value as AUC value greater than 0.8. A total of 1,515 T2D group cells and 1,817 healthy cohort cells were screened as core cells in the "E-MTAB-5061" dataset. Following tSNE dimensionality reduction cluster analysis, the core cells were divided into 13 cell clusters. According to the marker genes, the 13 cell clusters were annotated into six types of cells. Notably, SERPINF1 was highly expressed in fibroblasts and might be regulated by NR2F2 (nuclear receptor subfamily2, group F, and member 2). Conclusions: This study identified four biomarkers (SLC2A2, SERPINF1, RASGRP1, and CHL1) for T2D, which provided new markers for the clinical diagnosis of T2D. Among them, SERPINF1 might be regulated by NR2F2, which provides valuable insight into the pathogensis of T2D.