Effects of individualized positive end-expiratory pressure on intraoperative oxygenation and postoperative pulmonary complications in patients requiring pneumoperitoneum with Trendelenburg position: A systematic review and meta-analysis.

BACKGROUND: Whether individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and reduces postoperative pulmonary complications (PPCs) remains unclear. This systematic review and meta-analysis examined whether individualized PEEP is associated with improved intraoperative oxygenation and reduce PPCs for patients needing pneumoperitoneum with the Trendelenburg position during surgery. METHODS: Medline, Embase, the Cochrane Library, and www.clinicaltrials.gov were searched for randomized controlled trials evaluating the effects of individualized PEEP on intraoperative oxygenation and PPCs in patients who required Trendelenburg positioning with pneumoperitoneum. The primary outcome was the oxygenation (PaO2/FiO2) during the procedure. Secondary outcomes included PPCs, intraoperative respiratory mechanics (driving pressure, compliance), and vasopressor consumption. DerSimonian-Laird random effects models were used to calculate mean differences (MDs) and log risk ratios (log RRs) with 95% confidence intervals (CIs). The Cochrane Risk-of-Bias tool 2.0 was applied to assess the risk of bias in included studies. The protocol of this meta-analysis has been registered in PROSPERO. RESULTS: We included 14 studies (1121 patients) that employed different individualized PEEP strategies. Compared with control groups, individualized PEEP groups exhibited a significantly improved intraoperative PaO2/FiO2 (MD=56.52 mm Hg, 95% CI: [33.98, 79.06], P<0.001) and reduced incidence of PPCs (log RR=-0.50, 95% CI: [-0.84, -0.16], P=0.004). Individualized PEEP reduced driving pressure while improving respiratory compliance. Intraoperative vasopressor consumption was similar between both groups. The weighted mean PEEP in the individual PEEP groups was 13.2 [95% CI, 11.7, 14.6] cmH2O. No evidence indicated that one individualized PEEP strategy is superior to others. CONCLUSIONS: Individualized PEEP seems to work positively for lung protection in the Trendelenburg position and pneumoperitoneum in patients undergoing general anesthesia.

Dynamic histone modification signatures coordinate developmental programs in strawberry fruit ripening.

Chromatin structure plays a critical role in the regulation of dynamic gene expression in response to different developmental and environmental cues, but as yet their involvement in fruit ripening is not well understood. Here, we profile seven histone modifications in the woodland strawberry (Fragaria vesca) genome and analyze the histone modification signatures during ripening. Collectively, segments painted by the seven marks cover ~85% of the woodland strawberry genome. We report an eight-state chromatin structure model of the woodland strawberry based on the above histone marks, which reveals a diverse chromatin environment closely associated with transcriptional apparatus. Upon this model we build a chromatin-centric annotation to the strawberry genome. Expression of many genes essential for fruit ripening, such as abscisic acid catabolism, anthocyanin accumulation and fruit softening, are associated with shifts of active genic states and polycomb-associated chromatin states. Particularly, the expression levels of ripening-related genes are well correlated with histone acetylation, indicating a regulatory role of histone acetylation in strawberry ripening. Our identification of the chromatin states underpinning genome expression during fruit ripening not only elucidates the coordination of different pathways of morphological and metabolic development but also provides a framework to understand the signals that regulate fruit ripening.

Identification and validation of metastasis-related gene ZG16 in the prognosis and progression in colorectal cancer.

Background: Metastasis remains the leading cause of mortality among colorectal cancer (CRC) patients. Identification of new metastasis-related genes are critical to improve colorectal cancer prognosis. Methods: Data on mRNA expression in metastatic and primary CRC was obtained from the Gene Expression Omnibus (GEO) database, including GSE81986, GSE41568, GSE71222, GSE21510, and GSE14333. Additionally, data concerning mRNA expression in colon cancer (COAD) and adjacent normal tissues were acquired from The Cancer Genome Atlas (TCGA) database. Hub genes were identified by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Moreover, we assessed the impact of hub gene expression on both overall survival (OS) and disease-free survival (DFS) in patients and identified ZG16 as a potential target. We generated CRC cell lines transfected with lentivirus OE-ZG16 to investigate proliferation, invasion, and migration in vitro. To further elucidate the involvement of ZG16, we utilized gene set enrichment analysis (GSEA) to identify enriched pathways, which were subsequently validated via Western blot analysis. Results: Five datasets containing primary and metastatic CRC samples from GEO database and CRC samples from TCGA database were included in this study and 29 hub genes were identified by WGCNA and differentially expressed gene (DEG) analysis. Low expression of the hub genes (CLCA1 and ZG16) was associated with poor DFS and OS. We confirmed the low expression of ZG16 in CRC using external database and IHC analysis at both transcriptional and protein levels. In addition, the expression of ZG16 was notably elevated in NCM460 cells in comparison to CRC cell lines. The overexpression of ZG16 in CRC cells has been shown to inhibit the proliferation, invasion, and migration of CRC cells. Furthermore, the overexpression of ZG16 has been found to suppress the activation of the epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin signaling pathways in CRC. Conclusion: ZG16 may serve as a promising therapeutic target for metastatic CRC treatment.

Small molecular donor materials based on ß-ß-bridged BODIPY dimers with a triphenylamine or carbazole unit for efficient organic solar cells.

Herein, we have designed and synthesized two novel BODIPY dimer-based small molecules, denoted as ZMH-1 and ZMH-2, covalently linked and functionalized with triphenylamine (TPA) (ZMH-1) and carbazole (CZ) (ZMH-2) units as the electron donor at the 3- and 5-positions of the BODIPY core, respectively. Their optical and electrochemical properties were investigated. We have fabricated all small molecule bulk heterojunction organic solar cells using these BODIPY-based small molecules as electron donors along with fullerene derivative (PC71BM) and medium bandgap non-fullerene acceptor IDT-TC as electron acceptors. The optimized OSCs based on ZMH-1:PC71BM, ZMH-2:PC71BM, ZMH-1:IDT-IC, and ZMH-2:IDT-IC attain overall PCEs of 8.91%, 6.61%, 11.28%, and 5.48%, respectively. Moreover, when a small amount of PC71BM as guest acceptor is added to the binary host ZMH-1:IDT-TC and ZMH-2:IDT-TC, the ternary OSCs based on ZMH-1 and ZMH-2 reach PCEs of 13.70% and 12.71%, respectively.

Transcription factor MdbZIP44 targets the promoter of MdPPO2 to regulate browning in Malus domestica Borkh.

Apple (Malus domestica Borkh.) is among the most widely planted and economically valuable horticultural crops globally. Over time, the apple fruit's cut surface undergoes browning, and the degree of browning varies among different apple varieties. Browning not only affects the appearance of fruits but also adversely affects their taste and flavor. In the present study, we observed browning in different apple varieties over time and analyzed the expression of genes in the polyphenol oxidase gene family. The results indicated a strong correlation between the browning degree of the fruit and the relative expression of the polyphenol oxidase gene MdPPO2. With the MdPPO2 promoter as bait, the basic leucine zipper (bZIP) transcription factor MdbZIP44 was identified using the yeast single-hybrid screening method. Further investigation revealed that the overexpression of MdbZIP44 in 'Orin' callus could enhance the expression of MdPPO2 and promote browning of the callus. However, knocking out MdbZIP44 resulted in a callus with no apparent browning phenotype. In addition, our results confirmed the interaction between MdbZIP44 and MdbZIP11. In conclusion, the results indicated that MdbZIP44 can induce apple fruit browning by activating the MdPPO2 promoter. The results provide a theoretical basis for further clarifying the browning mechanism of apple fruit.

Immunogenic Treatment of Metastatic Breast Cancer Using Targeted Carbon Nanotube Mediated Photothermal Therapy in Combination with Anti-Programmed Cell Death Protein-1.

The high prevalence of breast cancer is a global health concern, compounded by the lack of safe or effective treatments for its advanced stages. These facts urge the development of novel treatment strategies. Annexin A5 (ANXA5) is a natural human protein that binds with high specificity to phosphatidylserine, a phospholipid tightly maintained in the inner leaflet of the cell membrane on most healthy cells but externalized in tumor cells and the tumor vasculature. Here, we have developed a targeted photosensitizer for photothermal therapy (PTT) of solid tumors through the functionalization of single-walled carbon nanotubes (SWCNTs) to ANXA5-the SWCNT-ANXA5 conjugate. The ablation of tumors through the SWCNT-ANXA5-mediated PTT synergizes with checkpoint inhibition, creating a systemic anticancer immune response. In vitro ablation of cells incubated with the conjugate promoted cell death in a dose-dependent and targeted manner. This treatment strategy was tested in vivo with the orthotopic EMT6 breast tumor model in female balb/cJ mice. Enhanced therapeutic effects were achieved by using intratumoral injection of the conjugate and treating tumors at a lower PTT temperature (45°C). Intratumoral injection prevented the accumulation of the SWCNTs in major clearance organs. When combined with checkpoint inhibition of anti-programmed cell death protein-1, SWCNT-ANXA5-mediated PTT increased survival and 80% of the mice survived for 100 days. Evidence of immune system activation by flow cytometry of splenic cells strengthens the hypothesis of an abscopal effect as a mechanism of prolonged survival. SIGNIFICANCE STATEMENT: This study demonstrated a relatively high survival rate (80% at 100 days) of mice with aggressive breast cancer when treated with photothermal therapy using the SWCNT-ANXA5 conjugate injected intratumorally and combined with immune stimulation using the anti-programmed cell death protein-1 checkpoint inhibitor. Photothermal therapy was accomplished by maintaining the tumor temperature at a relatively low level of 45°C and avoiding accumulation of the nanotubes in the clearance organs by using intratumoral administration.

Exercise Affects Mucosa-Associated Microbiota and Colonic Tumor Formation Induced by Azoxymethane in High-Fat-Diet-Induced Obese Mice.

The only reliable factor that reduces the risk of colorectal carcinogenesis is physical activity. However, the underlying mechanisms remain unclear. In this study, we examined the effects of physical activity against gut microbiota, including mucosa-associated microbiota (MAM) on azoxymethane-induced colorectal tumors in obese mice. We divided the subjects into four groups: normal diet (ND), high-fat diet (HFD), ND + exercise (Ex), and HFD + Ex groups. The Ex group performed treadmill exercise for 20 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiota analysis. DNA was collected from feces and colonic mucosa, and V3-V4 amplicon sequencing analysis of the 16SrRNA gene was performed using MiSeq. The HFD group had significantly more colonic polyps than the ND group (ND 6.5 ± 1.3, HFD 11.4 ± 1.5, p < 0.001), and the addition of Ex suppressed the number of colonic polyps in ND and HFD groups (ND 6.5 ± 1.3, ND + Ex 2.8 ± 2.5, p < 0.05). The HFD group showed significantly lower concentrations of succinic, acetic, butyric, and propionic acids (mg/g) in feces, compared with the ND group (succinic acid HFD 0.59, ND 0.17; acetic acid HFD 0.63, ND 2.41; propionic acid HFD 0.10, ND 0.47; and N-butyric acid HFD 0.31, ND 0.93). In the case of ND, succinic acid and butyric acid tended to decrease with Ex (succinic acid ND 0.17, ND + Ex 0.12; N-butyric acid ND 0.93, ND + Ex 0.74 0.74). Succinic acid, acetic acid, butyric acid, and propionic acid levels in feces were significantly lower in the HFD group than in the ND group; in both feces and mucus samples, Butyricicoccus and Lactobacillus levels were significantly lower in the HFD group. Akkermansia was significantly increased in ND + Ex and HFD + Ex groups. Diet and exercise affected the number of colorectal tumors. Furthermore, diet and exercise alter intestinal MAM, which may be involved in colorectal tumor development.

Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.

Differential microbiota shift on whole romaine lettuce subjected to source or forward processing and on fresh-cut products during cold storage.

Romaine lettuce in the U.S. is primarily grown in California or Arizona and either processed near the growing regions (source processing) or transported long distance for processing in facilities serving distant markets (forward processing). Recurring outbreaks of Escherichia coli O157:H7 implicating romaine lettuce in recent years, which sometimes exhibited patterns of case clustering in Northeast and Midwest, have raised industry concerns over the potential impact of forward processing on romaine lettuce food safety and quality. In this study, freshly harvested romaine lettuce from a commercial field destined for both forward and source processing channels was tracked from farm to processing facility in two separate trials. Whole-head romaine lettuce and packaged fresh-cut products were collected from both forward and source facilities for microbiological and product quality analyses. High-throughput amplicon sequencing targeting16S rRNA gene was performed to describe shifts in lettuce microbiota. Total aerobic bacteria and coliform counts on whole-head lettuce and on fresh-cut lettuce at different storage times were significantly (p < 0.05) higher for those from the forward processing facility than those from the source processing facility. Microbiota on whole-head lettuce and on fresh-cut lettuce showed differential shifting after lettuce being subjected to source or forward processing, and after product storage. Consistent with the length of pre-processing delays between harvest and processing, the lettuce quality scores of source-processed romaine lettuce, especially at late stages of 2-week storage, was significantly higher than of forward-processed product (p < 0.05).

Rapamycin functionalized carbon Dots: Target-oriented synthesis and suppression of vascular cell senescence.

Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 104 times higher than that of Rapa (2.6 × 10-4 g). The half maximal inhibitory concentration (IC50) of Rapa-CDs toward hydroxyl radical (•OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH•) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.

Extraction and application of extracellular polymeric substances from fungi.

Extracellular polymeric substances (EPS) are extracellular metabolites of microorganisms, highly associated with microbial function, adaptation, and growth. The main compounds in EPS have been revealed to be proteins, polysaccharides, nucleic acids, humic substances, lipids, etc. EPS are not only biomass, but also a biogenic material. EPS have high specific surface, abundant functional groups, and excellent degradability. In addition, they are more extensible to the environment than the microbial cells themselves, which exhibits their huge advantages. Therefore, they have been applied in many fields, such as the environment, ecosystem, basic commodities, and medicine. However, the functions of EPS highly depend on the suitable extraction process, as different extraction methods have different effects on their composition, structure, and function. There are many types of EPS extraction methods, in which physical and chemical methods have been widely utilized. This review summarizes the extraction methods and applications of EPS. In addition, it considers some important gaps in current knowledge, and indicates perspectives of EPS for their future study.