Pore Classification and Structural Characteristics of Oligocene-Pliocene Shale Reservoirs in the Western Qaidam Depression.

Oligocene-Pliocene shale reservoirs in the Western Qaidam Depression represent typical mixed shale deposits characterized by moderate organic matter (OM) abundance and sufficient OM maturity, indicating substantial shale-oil resource potential. Here, a comprehensive study was conducted to analyze the reservoir characteristics of different shale types, including the Upper Xiaganchaigou (late Oligocene), Shangganchaigou (Miocene), and Xiayoushashan (early Pliocene) Formations in the Western Qaidam Depression. Our analysis focused on the pore structural characteristics of shale reservoirs, employing X-ray diffraction, casting thin sections, scanning electron microscopy, low-temperature nitrogen adsorption, and nuclear magnetic resonance (NMR) as investigative techniques. Our results show that (1) the study area comprises five typical shale types: lime shale, argillaceous shale, limestone, argillaceous limestone, and mudstone. The best hydrocarbon source rock conditions are found in the lime shale and argillaceous shale. (2) Inorganic pores, including dissolution pores, intergranular pores, bedding fractures, structural fractures, and intraparticle pores in clay minerals, are the main pore types found in the studied samples and constitute the primary reservoir space for shale oil. On the basis of fractal dimensions obtained through NMR, the pores can be classified as micropores (<100 nm), mesopores (100-1000 nm), or macropores (>1000 nm). Mesopores are the main contributors to porosity. (3) The development of micropores is positively correlated with clay mineral content. The development of mesopores and macropores is influenced by the quartz, feldspar, dolomite, and calcite contents. Calcite content exhibits a negative correlation with porosity, suggesting that later-stage pore cementation hinders shale reservoir development. (4) The five typical shale reservoirs in the study area can be categorized into three types. Type I reservoir lithologies include lime shale and argillaceous shale; type II reservoir lithologies include limestone and argillaceous limestone; and type III reservoirs comprise mudstone. Type I and II reservoirs are of better quality than type III.

A Functional Switch Between Asperfumene and Fusicoccadiene Synthase and Entrance to Asperfumene Biosynthesis through a Vicinal Deprotonation-Reprotonation Process.

The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and - according to a structural model - active site architecture are highly similar to those of the fusicocca-2,10(14)-diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6-5-5-5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations. The reaction cascade proceeds in its initial steps through similar intermediates as for the PaFS cascade, but then diverges through an unusual vicinal deprotonation-reprotonation process that triggers a skeletal rearrangement at the entrance to the steps leading to the unique asperfumene skeleton. The structural model revealed only one major difference between the active sites: The PaFS residue F65 is substituted by I65 in AfAS. Intriguingly, site-directed mutagenesis experiments with both diterpene synthases revealed that position 65 serves as a bidirectional functional switch for the biosynthesis of tetracyclic asperfumene versus structurally less complex diterpenes.

The role of long non-coding RNA in Crohn's disease.

Emerging evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating immunological functions and autoimmune responses. In the context of Crohn's disease (CD), an array of novel lncRNAs has been identified in the plasma and intestinal tissues of afflicted individuals, suggesting a dualistic influence on the disease progression, either exacerbating or mitigating its course. Current research has demonstrated the involvement of lncRNAs in competitive endogenous RNA, the inflammation process, epithelial barrier function, gut microbiota imbalance, and epigenetic regulation. This review aims to encapsulate the current knowledge on the lncRNA contribution to CD and underscore potential avenues for future research. LncRNAs are increasingly recognized as significant biomarkers and potential therapeutic targets, holding a key position in the pathogenesis of CD. Furthermore, the unique attributes of circulating lncRNAs, such as minimal side effects, combinational therapy potential, and personalized medicine, render them as promising therapeutic tools for individual health management in CD.

Stroke volume variation induced by lung recruitment maneuver to predict fluid responsiveness in patients receiving mechanical ventilation: A systematic review and meta-analysis.

STUDY OBJECTIVE: The aim of this study was to evaluate the accuracy of lung recruitment maneuver induced stroke volume variation (ΔSVLRM) in predicting fluid responsiveness in mechanically ventilated adult patients by systematic review and meta-analysis. METHODS: A comprehensive electronic search of relevant literature was conducted in PubMed, Web of Science, Cochrane Library, Ovid Medline, Embase and Chinese databases (including China National Knowledge Infrastructure, Wanfang and VIP databases). Review Manager 5.4, Meta-DiSc 1.4 and STATA 16.0 were selected for data analysis, and QUADAS-2 tool was used for quality assessment. Data from selected studies were pooled to obtain sensitivity, specificity, diagnostic likelihood ratio (DLR) of positive and negative, diagnostic odds ratio (DOR), and summary receiver operating characteristic curve. RESULTS: A total of 6 studies with 256 patients were enrolled through March 2024. The risk of bias and applicability concerns for each included study were low, and there was no significant publication bias. There was moderate to substantial heterogeneity for the non-threshold effect, but not for the threshold effect. The combined sensitivity and specificity were 0.84 (95% CI, 0.77-0.90) and 0.79 (95% CI, 0.70-0.86), respectively. The DOR and the area under the curve (AUC) were 22.15 (95%CI, 7.62-64.34) and 0.90 (95% CI, 0.87-0.92), respectively. The positive and negative predictive values of DLR were 4.53 (95% CI, 2.50-8.18) and 0.19 (95% CI, 0.11-0.35), respectively. Fagan's nomogram showed that with a pre-test probability of 52%, the post-test probability reached 83% and 17% for the positive and negative tests, respectively. CONCLUSIONS: Based on the currently available evidence, ΔSVLRM has a good diagnostic value for predicting the fluid responsiveness in adult patients undergoing mechanical ventilation. Given the heterogeneity and limitations of the published data, further studies with large sample sizes and different clinical settings are needed to confirm the diagnostic value of ΔSVLRM in predicting fluid responsiveness. PROSPERO registration number: CRD42023490598.

Erythroid-intrinsic activation of TLR8 impairs erythropoiesis in inherited anemia.

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Selective fluorescence detection of acetylsalicylic acid, succinic acid and ascorbic acid based on a responsive lanthanide metal fluorescent coordination polymer.

A fluorescent sensor for highly selective and ultrasensitive detection of acetylsalicylic acid (ASA), succinic acid (SA), and ascorbic acid (AA) was reported. The water-soluble fluorescent ligand salicylic acid (Sal) was generated through catalyzing ASA by the hydrolase activity of zeolitic-imidazolate framework-8 (ZIF-8) or natural esterase (Est). The Sal can coordinate with 2-methylimidazole (2-MIm) and Ln(III) to form a fluorescent lanthanide coordination polymer (LCP), which has a fluorescence emission peak with the maximum wavelength at 412 nm (the excitation wavelength at 300 nm). Therefore, the detection of ASA can be achieved through the fluorescence intensity changes of LCPs in the system, which has comparable sensitivity and good selectivity (linear range of 0.031-1.00 mM and LODs of 11.72 and 3.22 µM) as compared to a direct reaction between Est/ZIF-8 and ASA for detecting ASA (linear range of 0.05-1.20 mM and limits of detection (LODs) of 4.43 and 4.58 µM). Furthermore, upon the addition of SA and AA, the fluorescence intensity of the reaction system can be enhanced and weakened through changing the energy resonance transfer pathways and affecting the enzymatic reaction process, respectively, realizing their sensitive and selective fluorescence detection. The established fluorescent sensors can work well in a wide linear range of SA concentrations from 0 to 2.50 mM (Est-based reaction system) and 0 to 1.50 mM (ZIF-8-based reaction system) with the LODs of 0.032 and 0.028 mM, respectively. The linear ranges of AA concentrations are from 0.0078 to 0.25 mM (Est-based reaction system) and 0.0078 to 0.13 mM (ZIF-8-based reaction system) with the LODs of 2.54 and 3.80 µM, respectively. The established sensors were successfully used in the detection of SA in rabbit plasma, with a recovery of 84.0%-98.7%. Additionally, the contents of ASA in Aspirin Enteric-Coated tablets and AA in vitamin C tablets were also determined by the developed methods.

The Garden of Forking Paths: Reinterpreting Haseman-Elston Regression for a Genotype-by-Environment Model.

Haseman-Elston regression (HE-reg) has been known as a classic tool for detecting an additive genetic variance component. However, in this study we find that HE-reg can capture GxE under certain conditions, so we derive and reinterpret the analytical solution of HE-reg. In the presence of GxE, it leads to a natural discrepancy between linkage and association results, the latter of which is not able to capture GxE if the environment is unknown. Considering linkage and association as symmetric designs, we investigate how the symmetry can and cannot hold in the absence and presence of GxE, and consequently we propose a pair of statistical tests, Symmetry Test I and Symmetry Test II, both of which can be tested using summary statistics. Test statistics, and their statistical power issues are also investigated for Symmetry Tests I and II. Increasing the number of sib pairs is important to improve statistical power for detecting GxE.

Study on the mechanism of quercetin in Sini Decoction Plus Ginseng Soup to inhibit liver cancer and HBV virus replication through CDK1.

BACKGROUND: To explore the anti-tumor and anti-virus key active ingredients of Sini Decoction Plus Ginseng Soup (SNRS) and their mechanisms. METHODS: The main ingredients of SNRS were analyzed by network pharmacology, and quercetin was identified as the key active ingredient. Then, we obtained the targets of quercetin by using Drugbank, PharmMapper, and SwissTargetPrediction databases. Then, the targets of HBV-related hepatocellular carcinoma (HBV-related HCC) were obtained by using Genecards database. In addition, using the gene expression profiles of HBV-related HCC patients in GEO database and the genes with the greatest survival difference in GEPIA 2 database identified the potential targets of quercetin. In addition, the mechanism of potential genes was studied through GO, KEGG analysis, and PPI network. Using AUC and survival analysis to evaluate the diagnostic and prognostic value of cyclin-dependent kinase 1 (CDK1) and CCNB1. Finally, the effects of quercetin on proliferation of Hep3B and HepG2215 cells and the level of CDK1 and CCNB1 were verified in vitro. ELISA was used to measure the expression levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) after the intervention by quercetin for 24 h and 48 h in HepG2215 cell. RESULTS: The first 10 key ingredients of SNRS were identified, and quercetin was the most key ingredient. The 101 potential quercetin targets were identified for the treatment of HBV-related HCC. GO and KEGG showed that 101 potential target enrichment in cancer and cell cycle regulation. By Venn analysis, CDK1 and CCNB1 were intersection targets, which could be used as potential targets for the action of quercetin on HBV-related HCC. Moreover, the expression of CDK1 and CCNB1 was highly expressed in the high-risk group, while the OS rate was low. The 1-year, 3-year and 5-year area under the curve (AUC) curves of CDK1 and CCNB1 were 0.724, 0.676, 0.622 and 0.745, 0.678, 0.634, respectively. Moreover, experimental results also showed that quercetin inhibited cell proliferation and reduced CDK1 expression in Hep3B and HepG2215 cells. The expressions of HBsAg and HBeAg in HepG2215 cell supernatant and cell gradually decreased with the increase of intervention time of quercetin and CDK1 inhibitor. CONCLUSIONS: Quercetin is a key ingredient of anti-HBV-related HCC activity and inhibits HBV replication in SNRS by inhibiting CDK1.

Drying kinetics and energy efficiency of soot ash of smelting silicon manganese alloys under microwave heating.

When smelting silicon manganese alloy in an industrial electric furnace, it will produce smoke and dust waste gas, which can be utilized again back to the furnace and improve the utilization rate of raw materials after a particular trapping device and collection treatment. However, at higher moisture levels, they are prone to explode. Effects of various initial masses, initial moisture contents, and microwave output powers on the soot ash of smelting silicon manganese alloy were studies. The findings indicate that the microwave drying rate increases with all three variables. The time for complete microwave drying is directly proportional to the sample's initial moisture content and the sample's initial mass, and the time for complete microwave drying is inversely proportional to the microwave output power. The results demonstrate that the Modified Page model can accurately describe the microwave drying process. The experimental data were fitted experimentally by drying kinetic models. Microscopic characterization of soot ash from refining silico­manganese alloys before and after drying was carried out using FTIR and SEM. Through FTIR characterization, the peak value of the -OH absorption peak decreases upon drying, and SEM results in no agglomeration caused by microwave drying and better dispersion of the soot ash of the dried smelted silica­manganese alloys, all of which proved that microwaves could effectively remove water. It was discovered that the diffusion coefficient increased gradually with increasing power when it was computed using Fick's second law. The diffusion coefficient increases and then decreases as the moisture content increases. The diffusion coefficient decreases as the initial mass increases. Activation energy of microwave drying of soot ash from the refining of silicomanganese alloys was calculated to be -1.4467 W/g. Its purpose is to offer a detailed guide for the industrial drying of soot ash from silicomanganese alloy refinement using microwave drying technology.

Cucurbit[7]uril as the host of adamantane-modified dyes for fluorescence enhancement in aqueous environments.

Taking advantage of the excellent host-guest complexation ability between an auxochrome (adamantane group) and CB[7], the fluorescence emission performance of dyes in water was effectively improved with the addition of two equivalents of CB[7], which provided an efficient method for increasing fluorescence intensity in aqueous environments. Furthermore, these dyes with the host were successfully used in cell imaging.

High-Precision Photoacoustic Neural Modulation Uses a Non-Thermal Mechanism.

Neuromodulation is a powerful tool for fundamental studies in neuroscience and potential treatments of neurological disorders. Both photoacoustic (PA) and photothermal (PT) effects are harnessed for non-genetic high-precision neural stimulation. Using a fiber-based device excitable by a nanosecond pulsed laser and a continuous wave laser for PA and PT stimulation, respectively, PA and PT neuromodulation is systematically investigated at the single neuron level. These results show that to achieve the same level of neuron activation recorded by Ca2+ imaging, the laser energy needed for PA stimulation is 1/40 of that needed for PT stimulation. The threshold energy for PA stimulation is found to be further reduced in neurons overexpressing mechano-sensitive channels, indicating direct involvement of mechano-sensitive channels in PA stimulation. Electrophysiology study of single neurons upon PA and PT stimulation is performed by patch clamp recordings. Electrophysiological features induced by PA are distinct from those by PT, confirming that PA and PT stimulation operate through different mechanisms. These insights offer a foundation for the rational design of more efficient and safer non-genetic neural modulation approaches.

Flow cytometry-based peripheral blood analysis as an easily friendly tool for prognostic monitoring of acute ischemic stroke: a multicenter study.

Background and objective: Acute ischemic stroke (AIS) is a leading cause of mortality, severe neurological and long-term disability world-wide. Blood-based indicators may provide valuable information on identified prognostic factors. However, currently, there is still a lack of peripheral blood indicators for the prognosis of AIS. We aimed to identify the most promising prognostic indicators and establish prognostic models for AIS. Methods: 484 subjects enrolled from four centers were analyzed immunophenotypic indicators of peripheral blood by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression was applied to minimize the potential collinearity and over-fitting of variables measured from the same subject and over-fitting of variables. Univariate and multivariable Cox survival analysis of differences between and within cohorts was performed by log-rank test. The areas under the receiving operating characteristic (ROC) curves were used to evaluate the selection accuracy of immunophenotypic indicators in identifying AIS subjects with survival risk. The prognostic model was constructed using a multivariate Cox model, consisting of 402 subjects as a training cohort and 82 subjects as a testing cohort. Results: In the prospective study, 7 immunophenotypic indicators of distinct significance were screened out of 72 peripheral blood immunophenotypic indicators by LASSO. In multivariate cox regression, CTL (%) [HR: 1.18, 95% CI: 1.03-1.33], monocytes/µl [HR: 1.13, 95% CI: 1.05-1.21], non-classical monocytes/µl [HR: 1.09, 95% CI: 1.02-1.16] and CD56high NK cells/µl [HR: 1.13, 95% CI: 1.05-1.21] were detected to decrease the survival probability of AIS, while Tregs/µl [HR:0.97, 95% CI: 0.95-0.99, p=0.004], BM/µl [HR:0.90, 95% CI: 0.85-0.95, p=0.023] and CD16+NK cells/µl [HR:0.93, 95% CI: 0.88-0.98, p=0.034] may have the protective effect. As for indicators' discriminative ability, the AUC for CD56highNK cells/µl attained the highest of 0.912. In stratification analysis, the survival probability for AIS subjects with a higher level of Tregs/µl, BM/µl, CD16+NK cells/µl, or lower levels of CD56highNK cells/µl, CTL (%), non-classical monocytes/µl, Monocytes/µl were more likely to survive after AIS. The multivariate Cox model showed an area under the curve (AUC) of 0.805, 0.781 and 0.819 and 0.961, 0.924 and 0.982 in the training and testing cohort, respectively. Conclusion: Our study identified 7 immunophenotypic indicators in peripheral blood may have great clinical significance in monitoring the prognosis of AIS and provide a convenient and valuable predictive model for AIS.

A novel role of the cotton calcium sensor CBL3 was involved in Verticillium wilt resistance in cotton.

BACKGROUND: Verticillium wilt, causes mainly by the soilborne pathogen Verticillium dahliae, is a devastated vascular disease resulting in huge financial losses in cotton, so research on improving V. dahliae stress tolerance in cotton is the utmost importance. Calcium as the second messenger acts as a crucial role in plant innate immunity. Cytosolic Ca2+during the pathogen infection is a significant increase in plant immune responses. Calcineurin B-like (CBL) proteins are widely known calcium sensors that regulate abiotic stress responses. However, the role of cotton CBLs in response to V. dahliae stress remains unclear. OBJECTIVE: To discover and utilize the gene to Verticillium wilt resistance and defense response mechanism of cotton. METHODS: Through screening the gene to Verticillium wilt resistance in cotton, four GhCBL3 copies were obtained from the current common cotton genome sequences. The protein domain and phylogenetic analyses of GhCBL3 were performed using NCBI Blast, DNAMAN, and MotifScan programs. Real-time RT-PCR was used to detect the expression of GhCBL3 gene in cotton seedlings under various stress treatments. The expression construct including GhCBL3 cDNA was transduced into Agrobacterium tumefaciens (GV3101) by heat shock method and transformed into cotton plants by Virus-Induced Gene Silencing (VIGS) method. The results of silencing of GhCBl3 on ROS accumulation and plant disease resistance in cotton plants were assessed. RESULTS: A member of calcineurin B-like proteins (defined as GhCBL3) in cotton was obtained. The expression of GhCBL3 was significantly induced and raised by various stressors, including dahliae, jasmonic acid (JA) and H2O2 stresses. Knockdown GhCBL3 in cotton by Virus-Induced Gene Silencing analysis enhanced Verticillium wilt tolerance and changed the occurrence of reactive oxygen species. Some disease-resistant genes were increased in GhCBL3-silencing cotton lines. CONCLUSION: GhCBL3 may function on regulating the Verticillium dahliae stress response of plants.

[Characterization of carbon and oxygen isotopes of plant on climate and plant physiology at the southeastern margin of Qinghai-Tibet Plateau, China]. / é’è—é«˜åŽŸä¸œå—ç¼˜æ¤ç‰©ç¢³æ°§åŒä½ç´ å¯¹æ°”å€™åŠæ¤ç‰©ç”Ÿç†çš„è¡¨å¾.

To investigate the correlation between carbon and oxygen isotope compositions of plant cellulose and climatic factors as well as plant physiological indices on the southeastern margin of the Qinghai-Tibet Plateau, we examined plant species in eight sampling sites with similar latitudes and different longitudes in this region. Through the characteristics of δ13C and δ18O values, fractionation values (Δ13C and Δ18O) in leaf cellulose, we discussed water use efficiency (WUE) and the environmental factors, the variation of carbon and oxygen isotopes in the southeastern margin of the Qinghai-Tibet Plateau with elevation and longitude, and revealed the indication degrees of isotopic signals to different environments and vegetation physiology. By using the semi-quantitative model of carbon and oxygen dual isotopes, we investigated the physiological adaptation mechanisms of plants to varying environmental conditions. The results demonstrated that both Δ13C and Δ18O of cellulose decreased with increasing elevation and longitude, and Δ13C was more influenced by longitude, while Δ18O was more susceptible to elevation variation. Additionally, Δ13C and Δ18O were significantly and positively correlated with temperature (TEM), precipitation (PRE), potential evapotranspiration (PET), and relative humidity (RH). PRE was the dominant meteorological factor driving the variation of Δ13C, while RH was the dominant meteorological factor influencing Δ18O variation. In contrast to Δ13C, WUE showed a stronger correlation with elevation than with longitude, which increased as elevation and longitude increased. According to the carbon-oxygen model, plant stomatal conductance (gs) and photosynthetic capacity (Amax) decreased with increasing precipitation and relative humidity, while the values increased with increasing elevation and longitude. The combined analysis of carbon and oxygen isotopes of organic matters would yield additional environmental and gas exchange information for studies on climate tracing and vegetation physiology studies on the southeastern margin of the Qinghai-Tibet Plateau.

Optimizing the Utilization of Steel Slag in Cement-Stabilized Base Layers: Insights from Freeze-Thaw and Fatigue Testing.

This paper presents a study on the mechanical properties of cement-stabilized steel-slag-based materials under freeze-thaw cycles for a highway project in Xinjiang. Using 3D scanning technology the specimen model conforming to the real steel slag shape was established. The objectives of the study are as follows: to explore the sensitivity between the macro- and micro-parameters of the specimen and to establish a non-linear regression equation; and to study the changes in mechanical properties of materials under freeze-thaw cycles, fatigue loading, and coupled freeze-thaw cycle-fatigue loading. The results show that there are three stages of compression damage of the specimen, namely, linear elasticity, peak plasticity, and post-peak decline. Maximum contact forces between cracks and particles occur mainly in the shear zone region within the specimen. The compression damage of the specimen is a mixed tensile-shear damage dominated by shear damage. When freeze-thaw cycles or fatigue loads are applied alone, the flexural strength and fatigue life of the specimens show a linear relationship of decline. The decrease in flexural modulus at low stress is divided into the following: a period of rapid decline, a relatively smooth period, and a period of fracture, with a tendency to change towards linear decay with increasing stress. In the case of freeze-thaw-fatigue coupling, the flexural modulus of the specimen decreases drastically by about 50% in the first 2 years, and then enters a period of steady decrease in flexural modulus in the 3rd-5th years.

The Characteristics of Compound Heterozygosity for Hemoglobin G-Makassar with Hb E in Malaysia.

Background: Human hemoglobin of G-Makassar and hemoglobin E (Hb E) are hemoglobin variants that affect Beta (ß) globin. Hb G-Makassar is a very rare variant while Hb E is estimated to affect at least one million people worldwide. Both Hb G-Makassar and Hb E can be inherited in the heterozygous, homozygous or compound heterozygous state. This case series describes the characteristics of four individuals with compound heterozygosity for Hb G-Makassar/Hb E cases in Malaysia. To the best of our knowledge, these are the only four individuals with this genotype reported in the literature. Case Series: We present four cases of compound heterozygosity for Hb G-Makassar/Hb E identified from October 2014 to January 2021. All the cases were incidental findings whereby the screening Hb analysis showed the presence of peaks in both Hb S and Hb E zones on capillary electrophoresis (CE) and cation-exchange high-performance liquid chromatography (HPLC). Molecular analysis confirmed the findings of compound heterozygous Hb G-Makassar/Hb E. Two cases had a history of anemia secondary to unrelated conditions that resolved with treatment of the underlying cause. The other two cases were asymptomatic individuals who were detected through Malaysia's National Thalassemia Screening program. On the last follow-up, all the individuals were well, non-transfusion dependent, and had no reported history of chronic anemia, bleeding, hemolysis or thromboembolism complications. Conclusion: The cases reported here highlight the possibilities for rare compound heterozygous states in multi-ethnicity populations such as Malaysia. Compound heterozygous Hb G-Makassar/Hb E individuals are clinically silent with laboratory values suggesting microcytic and hypochromic red blood cells. Further local epidemiology or population studies with genotyping tests are required for a better understanding of the diversity of its clinical phenotype.

POLR2J expression promotes glioblastoma malignancy by regulating oxidative stress and the STAT3 signaling pathway.

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

CCL22 Induces the Polarization of Immature Dendritic Cells into Tolerogenic Dendritic Cells in Radiation-Induced Lung Injury through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 Signaling Pathway.

Recruitment of immune cells to the injury site plays a pivotal role in the pathology of radiation-associated diseases. In this study, we investigated the impact of the chemokine CCL22 released from alveolar type II epithelial (AT2) cells after irradiation on the recruitment and functional changes of dendritic cells (DCs) in the development of radiation-induced lung injury (RILI). By examining changes in CCL22 protein levels in lung tissue of C57BL/6N mice with RILI, we discovered that ionizing radiation increased CCL22 expression in irradiated alveolar AT2 cells, as did MLE-12 cells after irradiation. A transwell migration assay revealed that CCL22 promoted the migration of CCR4-positive DCs to the injury site, which explained the migration of pulmonary CCR4-positive DCs in RILI mice in vivo. Coculture experiments demonstrated that, consistent with the response of regulatory T cells in the lung tissue of RILI mice, exogenous CCL22-induced DCs promoted regulatory T cell proliferation. Mechanistically, we demonstrated that Dectin2 and Nr4a2 are key targets in the CCL22 signaling pathway, which was confirmed in pulmonary DCs of RILI mice. As a result, CCL22 upregulated the expression of PD-L1, IL-6, and IL-10 in DCs. Consequently, we identified a mechanism in which CCL22 induced DC tolerance through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 pathway. Collectively, these findings demonstrated that ionizing radiation stimulates the expression of CCL22 in AT2 cells to recruit DCs to the injury site and further polarizes them into a tolerant subgroup of CCL22 DCs to regulate lung immunity, ultimately providing potential therapeutic targets for DC-mediated RILI.

Associations of computer gaming with incident dementia, cognitive functions, and brain structure: a prospective cohort study and Mendelian randomization analysis.

BACKGROUND: Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. METHODS: We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. RESULTS: High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). CONCLUSIONS: Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention.

A long-term growth stable Halomonas sp. deleted with multiple transposases guided by its metabolic network model Halo-ecGEM.

Microbial instability is a common problem during bio-production based on microbial hosts. Halomonas bluephagenesis has been developed as a chassis for next generation industrial biotechnology (NGIB) under open and unsterile conditions. However, the hidden genomic information and peculiar metabolism have significantly hampered its deep exploitation for cell-factory engineering. Based on the freshly completed genome sequence of H. bluephagenesis TD01, which reveals 1889 biological process-associated genes grouped into 84 GO-slim terms. An enzyme constrained genome-scale metabolic model Halo-ecGEM was constructed, which showed strong ability to simulate fed-batch fermentations. A visible salt-stress responsive landscape was achieved by combining GO-slim term enrichment and CVT-based omics profiling, demonstrating that cells deploy most of the protein resources by force to support the essential activity of translation and protein metabolism when exposed to salt stress. Under the guidance of Halo-ecGEM, eight transposases were deleted, leading to a significantly enhanced stability for its growth and bioproduction of various polyhydroxyalkanoates (PHA) including 3-hydroxybutyrate (3HB) homopolymer PHB, 3HB and 3-hydroxyvalerate (3HV) copolymer PHBV, as well as 3HB and 4-hydroxyvalerate (4HB) copolymer P34HB. This study sheds new light on the metabolic characteristics and stress-response landscape of H. bluephagenesis, achieving for the first time to construct a long-term growth stable chassis for industrial applications. For the first time, it was demonstrated that genome encoded transposons are the reason for microbial instability during growth in flasks and fermentors.