[Analysis on Spatial Variability of Hydrochemical Characteristics and Control Factors of Jinan Baotu Spring Area].

To understand the karst groundwater hydrochemical characteristics and ion sources of the Jinan Baotu Spring area, this study focused on the three functional zones as an indirect recharge area, direct recharge area, and discharge area. Through water sample collection and testing, the spatial variability of groundwater chemical characteristics in different functional zones and the formation mechanism were analyzed using hydrochemistry parameter statistics, multivariate statistics, self-organizing map, hydrochemistry graphical analysis, ion ratios, and other methods, guided by the theory of groundwater flow system and combined with regional physical geography and hydrogeological conditions. The results showed that： the groundwater of each functional zone was alkaline as is typical in the dissolution of carbonate minerals. Owing to the different groundwater runoff pathways, the variability of water chemistry parameters in different functional areas was obvious. The groundwater of the discharge area was recharged by both the direct recharge area and the indirect recharge area. The hydrochemistry type changed from HCO3-Ca type to HCO3·SO4-Ca type through the indirect recharge area to the discharge area. The presence of a small amount of gypsum dissolution within the aquifer generated Ca2+ and SO42-. The ions in groundwater mainly came from the dissolution and filtration of aquifer rock minerals, and at the same time, they were affected by cation exchange, mineral dissolution equilibrium, and the combined effects of human activities. The groundwater in the Baotu Spring area was greatly influenced by human activities, which to some extent affected the evolution of groundwater hydrochemistry in the spring area.

Identification and validation of Cystatin A as a novel promising therapeutic target for gastric cancer.

Background: The effect of pharmacological treatment of gastric cancer (GC) is limited, thus, it holds significant scientific importance to thoroughly investigate the molecular mechanisms underlying GC development and identify novel molecules capable of substantially extending patients' survival. This study utilized bioinformatics techniques to identify 11 genes associated with recurrence-free survival (RFS) in GC patients and investigated the potential biological functions of these genes through single-cell transcriptomic analysis. Subsequently, a single gene Cystatin A (CSTA) was selected for further analysis to explore its impact on signaling pathways and treatment. Methods: Differentially expressed genes (DEGs) were identified and overlapped in the analysis of RFS to identify potential prognostic genes for GC patients, based on data from the Cancer Genome Atlas-stomach adenocarcinoma (TCGA-STAD) and GSE54129. Subsequently, a prognostic model based on RFS in GC patients was established. Single-cell sequencing data were employed to explore the potential functions of these model genes. CSTA, one of the RFS-related genes, was further investigated using immunohistochemistry (IHC), Cell Counting Kit 8 (CCK-8), transwell, scratch, colony formation assays, flow cytometry, and Western blotting methods. Results: Through bioinformatics analysis, we identified 23 RFS-related genes in GC. Using the least absolute shrinkage and selection operator (LASSO)-Cox method, an RFS prognostic model was developed which pinpointed 11 GC prognosis-related (GPR) genes as significant factors influencing RFS in GC patients. The single-cell analysis revealed their potential role in affecting differentiation and maturation of pre-fibroblasts thereby impacting RFS in GC patients. CSTA exhibited low expression levels in GC tissues. Overexpression of CSTA promoted apoptosis in GC cells through the caspase-dependent apoptotic pathway and enhanced their response to cisplatin via this same pathway. Conclusions: The 11 GPR genes are primarily enriched within a specific type of stromal cell exhibiting heightened communication, metabolism, and differentiation levels. The gene signature of these stromal cells has implications for patient prognosis. Additionally, CSTA, a gene related to prognosis, has been shown to influence apoptosis levels in GC cells.

Reversed oxidative TCA (roTCA) for carbon fixation by an Acidimicrobiia strain from a saline lake.

Acidimicrobiia are widely distributed in nature and suggested to be autotrophic via the Calvin-Benson-Bassham (CBB) cycle. However, direct evidence of chemolithoautotrophy in Acidimicrobiia is lacking. Here, we report a chemolithoautotrophic enrichment from a saline lake, and the subsequent isolation and characterization of a chemolithoautotroph, Salinilacustristhrix flava EGI L10123T, which belongs to a new Acidimicrobiia family. Although strain EGI L10123T is autotrophic, neither its genome nor Acidimicrobiia metagenome-assembled genomes (MAGs) from the enrichment culture encode genes necessary for the CBB cycle. Instead, genomic, transcriptomic, enzymatic, and stable-isotope probing data hinted at the activity of the reversed oxidative TCA (roTCA) coupled with the oxidation of sulfide as the electron donor. Phylogenetic analysis and ancestral character reconstructions of Acidimicrobiia suggested that the essential CBB gene rbcL was acquired through multiple horizontal gene transfer events from diverse microbial taxa. In contrast, genes responsible for sulfide- or hydrogen-dependent roTCA carbon fixation were already present in the last common ancestor of extant Acidimicrobiia. These findings imply the possibility of roTCA carbon fixation in Acidimicrobiia and the ecological importance of Acidimicrobiia. Further research in the future is necessary to confirm whether these characteristics are truly widespread across the clade.

Tyrosine hydroxylase plays crucial roles in larval cuticle formation and larval-pupal tanning in the rice stem borer, Chilo suppressalis.

The striped stem borer, Chilo suppressalis (Walker), a notorious pest infesting rice, has evolved a high level of resistance to many commonly used insecticides. In this study, we investigate whether tyrosine hydroxylase (TH), which is required for larval development and cuticle tanning in many insects, could be a potential target for the control of C. suppressalis. We identified and characterized the full-length cDNA (CsTH) of C. suppressalis. The complete open reading frame of CsTH (MW690914) was 1683 bp in length, encoding a protein of 560 amino acids. Within the first to the sixth larval instars, CsTH was high in the first day just after molting, and lower in the ensuing days. From the wandering stage to the adult stage, levels of CSTH began to rise and reached a peak at the pupal stage. These patterns suggested a role for the gene in larval development and larval-pupal cuticle tanning. When we injected dsCsTH or 3-iodotyrosine (3-IT) as a TH inhibitor or fed a larva diet supplemented with 3-IT, there were significant impairments in larval development and larval-pupal cuticle tanning. Adult emergence was severely impaired, and most adults died. These results suggest that CsTH might play a critical role in larval development as well as larval-pupal tanning and immunity in C. suppressalis, and this gene could form a potential novel target for pest control.

Enhancing the Electrochemical Performances of Disordered Li1.23Ni0.3Nb0.3Fe0.16O0.85F0.15 Cathode Material for Lithium-Ion Batteries by LiNbOx Coating.

For the next generation of lithium-ion batteries (LIBs), it is primary to seek high capacity and long-lifetime electrode materials. Li-excess disordered rock-salt structure (DRS) cathodes have gained much attention due to their high specific capacity. However, Li-excess can lead to a decrease in the structural stability of an electrode material. A new Li-rich DRS oxyfluorides, Li1.23Ni0.3Nb0.3Fe0.16O0.85F0.15 (F0.15) with a series amounts of LiNbOx (LN) coating (0, 5, 10, and 15 wt % denoted as F0.15-LN0, F0.15-LN5, F0.15-LN10, and F0.15-LN15, respectively), are successfully synthesized and evaluated as cathode materials in LIBs. Among them, F0.15-LN10 exhibits the highest initial discharge specific capacity of 296.1 mAh g-1 (at a current density of 20 mA g-1) with the capacity retention rate of 14% higher than that of the uncoated F0.15 after 80 cycles. Even at 300 mA g-1, F0.15-LN10 still delivers the highest discharge specific capacity of 130 mAh g-1. After 20 cycles, the charge-transfer impedance of F0.15-LN10 remained the smallest. The characterizations indicate that LN coating reduces the surface polarization of the cathode materials, slows the interfacial side reactions between the electrolyte and the electrode, and speeds up the Li+ diffusion. These results demonstrate that LN coating is an effective strategy to improve the electrochemical performance.

PeNAC67-PeKAN2-PeSCL23 and B-class MADS-box transcription factors synergistically regulate the specialization process from petal to lip in Phalaenopsis equestris.

The molecular basis of orchid flower development involves a specific regulatory program in which MADS-box transcription factors play a central role. The recent 'perianth code' model hypothesizes that two types of higher-order heterotetrameric complexes, namely SP complex and L complex, play pivotal roles in the orchid perianth organ formation. Therefore, we explored their roles and searched for other components of the regulatory network.Through the combined analysis for transposase-accessible chromatin with high-throughput sequencing and RNA sequencing of the lip-like petal and lip from Phalaenopsis equestris var.trilip, transcription factor-(TF) genes involved in lip development were revealed. PeNAC67 encoding a NAC-type TF and PeSCL23 encoding a GRAS-type TF were differentially expressed between the lip-like petal and the lip. PeNAC67 interacted with and stabilized PeMADS3, which positively regulated the development of lip-like petal to lip. PeSCL23 and PeNAC67 competitively bound with PeKAN2 and positively regulated the development of lip-like petal to petal by affecting the level of PeMADS3. PeKAN2 as an important TF that interacts with PeMADS3 and PeMADS9 can promote lip development. These results extend the 'perianth code' model and shed light on the complex regulation of orchid flower development.

Biomarkers in the Severity of Necrotizing Enterocolitis in Preterm Infants: A Pilot Study.

Background: The occurrence of necrotizing enterocolitis (NEC) is a common and severe disease of the digestive system in neonates. This study aims to assess the value of the intestinal tissue oxygen saturation (rintSO2) combined with the levels of procalcitonin (PCT) and mean platelet volume (MPV) in predicting the severity of NEC in preterm infants. Methods: This experiment was a retrospective cohort study conducted in the Department of Pediatrics, Hongqi Hospital Affiliated to Mudanjiang Medical University between January 2017 and July 2022. Premature neonates with NEC were enrolled and divided into mild-moderate NEC group and severe NEC group according to Bell's stage. The general information data, rintSO2 and blood parameters such as the white blood cell (WBC) count, platelet count (PLT), PCT, MPV, red blood cell distribution width (RDW), hemoglobin (Hb), C-reactive protein (CRP) were compared between the two groups. Results: A total of 122 patients were enrolled, including 79 mild-moderate NEC and 43 severe NEC. The rintSO2 was lower in severe group than in mild-moderate group (P = 0.042), the PCT and MPV were both higher in severe group than in mild-moderate group (P = 0.048, P = 0.049). The results of logistic regression suggested that the rintSO2 (OR = 1.491, P = 0.003), PCT (OR = 3.071, P = 0.001) and MPV (OR = 4.027, P = 0.015) were independent predictive factors for severity of NEC. The area under the curve (AUC) of the rintSO2 combined with PCT and MPV showed good diagnostic ability in the severity of NEC. Conclusion: The rintSO2 combined with PCT and MPV may be considered as the early biomarkers in the severity of NEC and could help us to diagnose the case early with early treatment with better prognosis.

Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms.

In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response. Bone marrow samples of n = 12 low-risk MDS patients from the above referenced clinical trial were analyzed by serial deep whole exome sequencing in a total of n = 58 time points. We could distinguish a mean of 3.5 molecularly defined subclones per patient (range 2-6). We observed a molecular response defined as reductions of dominant clone sizes by a variant allele frequency (VAF) decrease of at least 10% (mean 20%, range: 10.5-39.2%) in dependency of Asunercept treatment in 9 of 12 (75%) patients. Most of this decline in clonal populations was observed after completion of 12 weeks treatment. Particularly early and pronounced reductions of clone sizes were found in subclones driven by mutations in genes involved in regulation of methylation (n = 1 DNMT3A, n = 1 IDH2, n = 1 TET2). Our results suggest that APG101 could be efficacious in reducing clone sizes of mutated hematopoietic cells in the bone marrow of Myelodysplastic Neoplasms, which warrants further investigation.

Comparison of the efficacy of steroid-free versus classic steroid-containing regimens in primary membranous nephropathy.

Objective: To compare the efficacy of a steroid-free regimen with steroid-based treatment in managing primary membranous nephropathy (PMN) and investigate the potential benefits of steroid-free regimens in PMN therapy. Methods: This was a single-centre prospective cohort study. A total of 81 patients were divided into two groups according to their medication regimen: a rituximab (RTX)/tacrolimus (TAC) group (low-dose RTX combined with low-dose TAC group, without steroids, n = 31) and a prednisone (P)/TAC group (P combined with TAC group, n = 61). The changes in 24-h urine protein quantification, levels of blood albumin, blood creatinine, total cholesterol, triglyceride and fasting blood glucose as well as anti-phospholipase A2 receptor antibody titres were observed in both groups before treatment and after 1, 3, 6 and 12 months of treatment. Clinical remission (complete and partial remission), serological remission and recurrence were assessed in both groups after treatment, and the occurrence of adverse reactions was observed. Results: 1) Before treatment, there was no significant difference in baseline values between the two groups (p > 0.05). 2) After 12 months of treatment, the 24-h proteinuria and total cholesterol levels in the RTX/TAC group were significantly lower than those in the P/TAC group (p < 0.05). 3) After 6 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). After 12 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). (4) After 3, 6 and 12 months of treatment, serological remission rates in the RTX/TAC group were significantly higher than those in the P/TAC group (p < 0.05). During treatment, the anti-PLA2R antibody titres in the RTX/TAC group remained lower than those in the P/TAC group (p < 0.05). Conclusion: The low-dose RTX combined with low-dose TAC steroid-free regimen induces serological remission in patients with PMN earlier than the classic regimen of P combined with TAC, and there was no significant difference in adverse effects between the two groups. Besides, the long-term clinical remission effect of low-dose RTX combined with low-dose TAC is better than that of P combined with TAC.

Hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors versus lenvatinib and PD-1 inhibitors for HCC refractory to TACE.

BACKGROUND AND AIM: The study aims to investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and immune checkpoint inhibitors (ICIs) versus lenvatinib and ICIs for hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) refractoriness. METHODS: Patients with intermediate or advanced TACE-refractory HCC who received lenvatinib and ICIs with or without HAIC between 2020 and 2022 were retrospectively reviewed. The tumor response, overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were evaluated and compared between the two groups. Factors affecting OS and PFS were identified with univariate and multivariate Cox regression analyses. RESULTS: A total of 121 patients were enrolled, with 58 patients assigned to the HAIC-Len-ICI group and 63 patients assigned to the Len-ICI group. A higher objective response rate and disease control rate were found in the HAIC-Len-ICI group than in the Len-ICI group (48.30% vs 23.80%, P = 0.005; 87.90% vs 69.80%, P = 0.02, respectively). The median OS was 24.0 months in the HAIC-Len-ICI group and 13.0 months in the Len-ICI group (P = 0.001). The median PFS was 13.0 months in the HAIC-Len-ICI group and 7.2 months in the Len-ICI group (P < 0.001). Multivariable analyses suggested that the presence of cirrhosis, Child-Pugh B stage, and HAIC-Len-ICI therapy option were prognostic factors for OS and PFS. The incidences of any grade and grade 3/4 TRAEs were both comparable between the two groups. CONCLUSIONS: HAIC combined with lenvatinib and ICIs yielded better OS, PFS, ORR, and DCR than lenvatinib-ICI therapy in patients with HCC refractory to TACE, with manageable adverse events.

A biocompatible chitosan-based fluorescent polymer for efficient H2O2 detection in living cells and water samples.

As a biomarker of oxidative stress, hydrogen peroxide (H2O2) plays a complex role in organisms, including regulating cell signaling, respiration, the immune system, and other life processes. Therefore, it is important to develop a tool that can simply and effectively monitor H2O2 levels in organisms and the environment. In this work, naphthalene fluorophores with a borate structure were introduced into chitosan (CTS) azide, and a CTS-based fluorescence sensor (CTS-HP) was designed for sensitive H2O2 detection. The biocompatibility and degradability of CTS endowed CTS-HP with reduced biotoxicity compared with organic fluorescent dyes, and the substitution degree of fluorophores on the CTS chains was 0.703. The randomly coiled chain structure of the CTS-HP probe enabled the boronic acid recognition sites on the fluorophores to achieve the enrichment of analyte H2O2 through a synergistic effect. Therefore, the probe CTS-HP (10 µg mL-1) exhibited a 21-fold fluorescence enhancement and good detection limit (LOD = 8.98 nM) in H2O2 solution, reaching the maximum fluorescence response faster (within 16 min). The probe also successfully achieved the fluorescence imaging of endogenous and exogenous H2O2 in zebrafish and living cells and labeled the recovery experiment of H2O2 in real water samples (recoveries rates of 90.93-102.9 % and RSD < 3.09 %).

ASXL1 mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic neoplasms.

Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMAs) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. Availability of biomarkers for response to the alvocidib + 5- AZA could also extend the rationale of this treatment concept to high-risk MDS. In this study, we performed a comprehensive in vitro assessment of alvocidib and 5-AZA effects in n=45 high-risk MDS patients. Our data revealed additive cytotoxic effects of the combination treatment. Mutational profiling of MDS samples identified ASXL1 mutations as predictors of response. Further, increased response rates were associated with higher gene-expression of the pro-apoptotic factor NOXA in ASXL1 mutated samples. The higher sensitivity of ASXL1 mutant cells to the combination treatment was confirmed in vivo in ASXL1Y588X transgenic mice. Overall, our study demonstrated augmented activity for the alvocidib + 5-AZA combination in higher-risk MDS and identified ASXL1 mutations as a biomarker of response for potential stratification studies.

SNHG25 promotes colorectal cancer metastasis by regulating MMP2.

LncRNA has been shown to play an important role in tumors, but the functions of most lncRNAs in colorectal cancer is not clear. By analyzing the transcriptome data of tumor tissues and adjacent tissues, we identified the lncRNA profiles that were abnormally expressed in colorectal cancer and selected the abnormally highly expressed lncRNA SNHG25 for further study. The functional assays showed that after knocking down SNHG25, the metastatic ability of colorectal cancer cells was significantly reduced. Western blot and immunofluorescence assays showed that inhibiting SNHG25 would affect the expression of Vimentin and E-Cadherin. In terms of mechanism, the results of RNA pull down assays, RNA immunoprecipitation (RIP) assays and dual luciferase reporter assays showed that SNHG25 could promote MMP2 expression by adsorbing miR-296-3p. In addition, chromatin immunoprecipitation (ChIP) assays and promoter luciferase reporter assays revealed that PAX5 could activate the transcription of SNHG25 in colorectal cancer cells. Our study proved that SNHG25 acts a pro-metastasis role in colorectal cancer, enriching the theory of the functions of lncRNA in colorectal cancer.

The prognostic value of systemic immune-inflammation index in patients with aneurysmal subarachnoid hemorrhage: a systematic review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating and life-threatening stroke subtype, that has a high disability and fatality rate. By the use of the systemic immune-inflammation index (SII), it is possible to understand the pathophysiology that underlies immune and inflammatory responses and anticipate consequences including delayed cerebral ischemia (DCI), delayed cerebral vasospasm, and functional outcome. A systematic search of the English-language literature in PubMed and Embase was performed to locate articles addressing the usage of SII in aSAH patients. The cutoff value, sensitivity, specificity, and area-under-the curve (AUC) of the receiver operating characteristic (ROC) curve were collected. Four publications were reviewed after applying the exclusion criteria from the 53 included articles. All the studies indicated that higher SII on admission was significantly associated with poor prognosis. The research examined in this paper provides the earliest indications that higher SII predicts DCI, delayed cerebral vasospasm, and functional outcome, even though other medical subspecialties have used this ratio for a long time to make such predictions.

A water-soluble and biocompatible chitosan-based fluorescent probe for real-time monitoring formaldehyde in living cells and zebrafish.

Formaldehyde (HCHO) is a common environmental toxicant that can harm the human respiratory tract and nervous system when exposed for long period of time. As a carcinogen, HCHO also increases the risk of cancer in humans. HCHO can be produced endogenously in living systems and plays an essential role in physiological and biochemical reactions and pathogenesis. Therefore, monitoring the level of HCHO in vivo and in vitro has become the focus of attention. The designed naphthalene fluorophore was introduced onto modified chitosan to prepare a chitosan-based fluorescent probe (CS-FA) for HCHO detection. Compared to other small-molecule probe analogs for the detection of HCHO, the randomly coiled polymer chain of chitosan enabled CS-FA to "enrich" HCHO using the synergistic binding of hydrazino-naphthalimide recognition sites. Thus, the reaction of the analyte with the recognition site was accelerated, resulting in a faster equilibrium fluorescence response (2-3 min) and high sensitivity. In addition, the introduction of biomass material chitosan also improved the biocompatibility of the probe. Then a series of composite materials (test strips and hydrogel) were prepared based on the probe to expand the application form of the probe.

Flexomagnetic Effect Enhanced Ferromagnetism and Magnetoelectrochemistry in Freestanding High-Entropy Alloy Films.

Freestanding thin films of functional materials enable the tuning of properties via strain and strain gradients, broadening their applications. Here, a systematic approach is proposed to fabricate freestanding CrMnFeCoNi high-entropy alloy (HEA) thin films by pulsed laser deposition using expansion-contraction of NaCl substrates and weak van der Waals interaction of the interface, which form wrinkles with inhomogeneous strain gradients when transferred to a viscous handle. We demonstrate that the nonuniform gradients of external strain (flexomagnetic effect) can induce the partial structural phase transition from FCC to BCC in the wrinkled HEA film, resulting in a 10-fold increase in its room-temperature saturation magnetization compared with the unstrained flat HEA film. Furthermore, after applying an external magnetic field, due to the different electron transfer behavior caused by the electron scattering in wrinkled and flat HEA films, their electrocatalytic magnetic responses showed a diametrically opposite picture. Our work provides a promising strategy for tuning physical and chemical properties via complex strained geometries.

CPEB2 Suppresses Hepatocellular Carcinoma Epithelial-Mesenchymal Transition and Metastasis through Regulating the HIF-1α/miR-210-3p/CPEB2 Axis.

Hepatocellular carcinoma (HCC) is a prevalent and high-mortality cancer worldwide, and its complexity necessitates novel strategies for drug selection and design. Current approaches primarily focus on reducing gene expression, while promoting gene overexpression remains a challenge. In this work, we studied the effect of cytoplasmic polyadenylation element binding protein 2 (CPEB2) in HCC by constructing tissue microarrays (TAMs) from 90 HCC cases and corresponding para-cancerous tissues. Our analysis showed that CPEB2 expression was significantly reduced in HCC tissues, and its low expression was associated with a higher recurrence risk and poorer prognosis in patients with head and neck cancer. CPEB2 was found to regulate HCC epithelial-mesenchymal transition (EMT) and metastasis through the HIF-1α/miR-210-3p/CPEB2 feedback circuit. Using the RNA binding protein immunoprecipitation (RIP) assay, we demonstrated that miR-210 directly governs the expression of CPEB2. The inverse relationship between CPEB2 expression and miR-210-3p in HCC tissues suggested that this regulatory mechanism is directly linked to HCC metastasis, EMT, and clinical outcomes. Moreover, utilizing the SM2miR database, we identified drugs that can decrease miR-210-3p expression, consequently increasing CPEB2 expression and providing new insights for drug development. In conclusion, our findings illustrated a novel HIF-1α/miR-210-3p/CPEB2 regulatory signaling pathway in HCC and highlighted the potential of enhancing CPEB2 expression through targeting miR-210-3p as a novel predictive biomarker and therapeutic strategy in HCC, as it is modulated by the HIF-1α/miR-210-3p/CPEB2 feedback circuit.

Significant improvement of bone marrow-derived MSC expansion from MDS patients by defined xeno-free medium.

BACKGROUND: Robust and reliable in vitro and in vivo models of primary cells are necessary to study the pathomechanisms of Myelodysplastic Neoplasms (MDS) and identify novel therapeutic strategies. MDS-derived hematopoietic stem and progenitor cells (HSPCs) are reliant on the support of bone marrow (BM) derived mesenchymal stroma cells (MSCs). Therefore, isolation and expansion of MCSs are essential for successfully modeling this disease. For the clinical use of healthy MSCs isolated from human BM, umbilical cord blood or adipose tissue, several studies showed that xeno-free (XF) culture conditions resulted in superior growth kinetics compared to MSCs cultured in the presence of fetal bovine serum (FBS). In this present study, we investigate, whether the replacement of a commercially available MSC expansion medium containing FBS with a XF medium is beneficial for the expansion of MSCs derived from BM of MDS patients which are often difficult to cultivate. METHODS: MSCs isolated from BM of MDS patients were cultured and expanded in MSC expansion medium with FBS or XF supplement. Subsequently, the impact of culture media on growth kinetics, morphology, immunophenotype, clonogenic potential, differentiation capacity, gene expression profiles and ability to engraft in immunodeficient mouse models was evaluated. RESULTS: Significant higher cell numbers with an increase in clonogenic potential were observed during culture of MDS MSCs with XF medium compared to medium containing FBS. Differential gene expression showed an increase in transcripts associated with MSC stemness after expansion with XF. Furthermore, immunophenotypes of the MSCs and their ability to differentiate into osteoblasts, adipocytes or chondroblasts remained stable. MSCs expanded with XF media were similarly supportive for creating MDS xenografts in vivo as MSCs expanded with FBS. CONCLUSION: Our data indicate that with XF media, higher cell numbers of MDS MSCs can be obtained with overall improved characteristics in in vitro and in vivo experimental models.

A highly sensitive and low toxicity cellulose-based fluorescent polymer for H2S detection in cells, zebrafish and food samples.

A cellulose based polymer probe (HC-HS) was prepared for the detection of H2S. HC-HS can be applied to fluorescence imaging of H2S in living cells and zebrafish, and HC-HS was made into test strips to detect H2S produced in the process of food corruption.

Rationally Improving Doramectin Production in Industrial Streptomyces avermitilis Strains.

Avermectins (AVMs), a family of 16-membered macrocyclic macrolides produced by Streptomyces avermitilis, have been the most successful microbial natural antiparasitic agents in recent decades. Doramectin, an AVM derivative produced by S. avermitilis bkd- mutants through cyclohexanecarboxylic acid (CHC) feeding, was commercialized as a veterinary antiparasitic drug by Pfizer Inc. Our previous results show that the production of avermectin and actinorhodin was affected by several other polyketide biosynthetic gene clusters in S. avermitilis and Streptomyces coelicolor, respectively. Thus, here, we propose a rational strategy to improve doramectin production via the termination of competing polyketide biosynthetic pathways combined with the overexpression of CoA ligase, providing precursors for polyketide biosynthesis. fadD17, an annotated putative cyclohex-1-ene-1-carboxylate:CoA ligase-encoding gene, was proven to be involved in the biosynthesis of doramectin. By sequentially removing three PKS (polyketide synthase) gene clusters and overexpressing FadD17 in the strain DM203, the resulting strain DM223 produced approximately 723 mg/L of doramectin in flasks, which was approximately 260% that of the original strain DM203 (approximately 280 mg/L). To summarize, our work demonstrates a novel viable approach to engineer doramectin overproducers, which might contribute to the reduction in the cost of this valuable compound in the future.