ATDC binds to KEAP1 to drive NRF2-mediated tumorigenesis and chemoresistance in pancreatic cancer.

Pancreatic ductal adenocarcinoma is a lethal disease characterized by late diagnosis, propensity for early metastasis and resistance to chemotherapy. Little is known about the mechanisms that drive innate therapeutic resistance in pancreatic cancer. The ataxia-telangiectasia group D-associated gene (ATDC) is overexpressed in pancreatic cancer and promotes tumor growth and metastasis. Our study reveals that increased ATDC levels protect cancer cells from reactive oxygen species (ROS) via stabilization of nuclear factor erythroid 2-related factor 2 (NRF2). Mechanistically, ATDC binds to Kelch-like ECH-associated protein 1 (KEAP1), the principal regulator of NRF2 degradation, and thereby prevents degradation of NRF2 resulting in activation of a NRF2-dependent transcriptional program, reduced intracellular ROS and enhanced chemoresistance. Our findings define a novel role of ATDC in regulating redox balance and chemotherapeutic resistance by modulating NRF2 activity.

ATDC is required for the initiation of KRAS-induced pancreatic tumorigenesis.

Pancreatic adenocarcinoma (PDA) is an aggressive disease driven by oncogenic KRAS and characterized by late diagnosis and therapeutic resistance. Here we show that deletion of the ataxia-telangiectasia group D-complementing (Atdc) gene, whose human homolog is up-regulated in the majority of pancreatic adenocarcinoma, completely prevents PDA development in the context of oncogenic KRAS. ATDC is required for KRAS-driven acinar-ductal metaplasia (ADM) and its progression to pancreatic intraepithelial neoplasia (PanIN). As a result, mice lacking ATDC are protected from developing PDA. Mechanistically, we show ATDC promotes ADM progression to PanIN through activation of ß-catenin signaling and subsequent SOX9 up-regulation. These results provide new insight into PDA initiation and reveal ATDC as a potential target for preventing early tumor-initiating events.

Coxiella burnetii inhibits host immunity by a protein phosphatase adapted from glycolysis.

Coxiella burnetii is a bacterial pathogen that replicates within host cells by establishing a membrane-bound niche called the Coxiella-containing vacuole. Biogenesis of this compartment requires effectors of its Dot/Icm type IV secretion system. A large cohort of such effectors has been identified, but the function of most of them remain elusive. Here, by a cell-based functional screening, we identified the effector Cbu0513 (designated as CinF) as an inhibitor of NF-κB signaling. CinF is highly similar to a fructose-1,6-bisphosphate (FBP) aldolase/phosphatase present in diverse bacteria. Further study reveals that unlike its ortholog from Sulfolobus tokodaii, CinF does not exhibit FBP phosphatase activity. Instead, it functions as a protein phosphatase that specifically dephosphorylates and stabilizes IκBα. The IκBα phosphatase activity is essential for the role of CinF in C. burnetii virulence. Our results establish that C. burnetii utilizes a protein adapted from sugar metabolism to subvert host immunity.

SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms.

Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.

GhVIM28, a negative regulator identified from VIM family genes, positively responds to salt stress in cotton.

The VIM (belonged to E3 ubiquitin ligase) gene family is crucial for plant growth, development, and stress responses, yet their role in salt stress remains unclear. We analyzed phylogenetic relationships, chromosomal localization, conserved motifs, gene structure, cis-acting elements, and gene expression patterns of the VIM gene family in four cotton varieties. Our findings reveal 29, 29, 17, and 14 members in Gossypium hirsutum (G.hirsutum), Gossypium barbadense (G.barbadense), Gossypium arboreum (G.arboreum), and Gossypium raimondii (G. raimondii), respectively, indicating the maturity and evolution of this gene family. motifs among GhVIMs genes were observed, along with the presence of stress-responsive, hormone-responsive, and growth-related elements in their promoter regions. Gene expression analysis showed varying patterns and tissue specificity of GhVIMs genes under abiotic stress. Silencing GhVIM28 via virus-induced gene silencing revealed its role as a salt-tolerant negative regulator. This work reveals a mechanism by which the VIM gene family in response to salt stress in cotton, identifying a potential negative regulator, GhVIM28, which could be targeted for enhancing salt tolerance in cotton. The objective of this study was to explore the evolutionary relationship of the VIM gene family and its potential function in salt stress tolerance, and provide important genetic resources for salt tolerance breeding of cotton.

Anionic Coordination Control in Building Cu-Based Electrocatalytic Materials for CO2 Reduction Reaction.

Renewable energy-driven conversion of CO2 to value-added fuels and chemicals via electrochemical CO2 reduction reaction (CO2RR) technology is regarded as a promising strategy with substantial environmental and economic benefits to achieve carbon neutrality. Because of its sluggish kinetics and complex reaction paths, developing robust catalytic materials with exceptional selectivity to the targeted products is one of the core issues, especially for extensively concerned Cu-based materials. Manipulating Cu species by anionic coordination is identified as an effective way to improve electrocatalytic performance, in terms of modulating active sites and regulating structural reconstruction. This review elaborates on recent discoveries and progress of Cu-based CO2RR catalytic materials enhanced by anionic coordination control, regarding reaction paths, functional mechanisms, and roles of different non-metallic anions in catalysis. Finally, the review concludes with some personal insights and provides challenges and perspectives on the utilization of this strategy to build desirable electrocatalysts.

Genome-wide association study of image-based trait reveals the genetic architecture of dark-induced leaf senescence in rice.

Darkness is often used as an effective measure to induce leaf senescence. Although many senescence-related genes in rice have been reported, the genome-wide genetic architecture underlying leaf senescence remains poorly understood. In our study, indica and japonica rice showed contrasting responses to dark-induced leaf senescence (DILS). Genome-wide association studies (GWAS) combined with transcriptomic analyses revealed 57, 97, and 48 loci involved in the regulation of the onset, progression, and ending of DILS, respectively. Haplotype analyses showed that the senescence-related loci differentially accumulated in indica and japonica accessions and functioned additively to regulate DILS. A total of 357 candidate genes were identified that are involved in various senescence-related processes such as lipid and amino acid catabolism, photosynthesis, response to reactive oxygen species, and regulation of defense response. In addition, functional analyses of the two candidate genes, OsMYB21 and OsSUB1B, revealed that OsMYB21 positively regulates the onset of DILS, while OsSUB1B negatively regulates its progression. Thus, our results provide new insights into the genetic regulation of DILS in rice.

Zero-Emission Cement Plants with Advanced Amine-Based CO2 Capture.

Decarbonization of the cement sector is essentially required to achieve carbon neutrality to combat climate change. Amine-based CO2 capture is a leading and practical technology to deeply remove CO2 from the cement industry, owing to its high retrofittability to existing cement plants and extensive engineering experience in industrial flue gas decarbonization. While research efforts have been made to achieve low-carbon cement with 90% CO2 removal, a net-zero-emission cement plant that will be required for a carbon neutrality society has not yet been investigated. The present study proposed an advanced amine-based CO2 capture system integrated with a cement plant to achieve net-zero CO2 emission by pushing the CO2 capture efficiency to 99.7%. Monoethanomaine (MEA) and piperazine/2-amino-2-methyl-1-propanol (PZ-AMP) amine systems, which are considered to be the first- and second-generation capture agents, respectively, were detailed investigated to deeply decarbonize the cement plant. Compared to MEA, the advanced PZ-AMP system exhibited excellent energy performance with a regeneration duty of ∼2.6 GJ/tonne CO2 at 99.7% capture, 39% lower than the MEA process. This enabled a low CO2 avoided cost of $72.0/tonne CO2, which was 18% lower than that of the MEA-based zero-emission process and even 16.2% lower than the standard 90% MEA process. Sensitivity analysis revealed that the zero-emission capture cost of the PZ-AMP system would be further reduced to below $56/tonne CO2 at a $4/GJ steam production cost, indicating its economic competitiveness among various CO2 capture technologies to achieve a zero-emission cement plant.

Sulfur Migration Enhanced Proton-Coupled Electron Transfer for Efficient CO2 Desorption with Core-Shelled C@Mn3O4.

Transforming hazardous species into active sites by ingenious material design was a promising and positive strategy to improve catalytic reactions in industrial applications. To synergistically address the issue of sluggish CO2 desorption kinetics and SO2-poisoning solvent of amine scrubbing, we propose a novel method for preparing a high-performance core-shell C@Mn3O4 catalyst for heterogeneous sulfur migration and in situ reconstruction to active -SO3H groups, and thus inducing an enhanced proton-coupled electron transfer (PCET) effect for CO2 desorption. As anticipated, the rate of CO2 desorption increases significantly, by 255%, when SO2 is introduced. On a bench scale, dynamic CO2 capture experiments reveal that the catalytic regeneration heat duty of SO2-poisoned solvent experiences a 32% reduction compared to the blank case, while the durability of the catalyst is confirmed. Thus, the enhanced PCET of C@Mn3O4, facilitated by sulfur migration and simultaneous transformation, effectively improves the SO2 resistance and regeneration efficiency of amine solvents, providing a novel route for pursuing cost-effective CO2 capture with an amine solvent.

Electrochemical Reduction of Flue Gas Denitrification Wastewater to Ammonia Using a Dual-Defective Cu2O@Cu Heterojunction Electrode.

Wet flue gas denitrification offers a new route to convert industrial nitrogen oxides (NOx) into highly concentrated nitrate wastewater, from which the nitrogen resource can be recovered to ammonia (NH3) via electrochemical nitrate reduction reactions (NITRRs). Low-cost, scalable, and efficient cathodic materials need to be developed to enhance the NH3 production rate. Here, in situ electrodeposition was adopted to fabricate a foamy Cu-based heterojunction electrode containing both Cu-defects and oxygen vacancy loaded Cu2O (OVs-Cu2O), which achieved an NH3 yield rate of 3.59 mmol h-1 cm-2, NH3 Faradaic efficiency of 99.5%, and NH3 selectivity of 100%. Characterizations and theoretical calculations unveiled that the Cu-defects and OVs-Cu2O heterojunction boosted the H* yield, suppressed the hydrogen evolution reaction (HER), and served as dual reaction sites to coherently match the tandem reactions kinetics of NO3-to-NO2 and NO2-to-NH3. An integrated system was further built to combine wet flue gas denitrification and desulfurization, simultaneously converting NO and SO2 to produce the (NH4)2SO4 fertilizer. This study offers new insights into the application of low-cost Cu-based cathode for electrochemically driven wet denitrification wastewater valorization.

Current trends in the detection and removal of heavy metal ions using functional materials.

The shortage of freshwater resources caused by heavy metal pollution is an acute global issue, which has a great impact on environmental protection and human health. Therefore, the exploitation of new strategies for designing and synthesizing green, efficient, and economical materials for the detection and removal of heavy metal ions is crucial. Among the various methods for the detection and removal of heavy ions, advanced functional systems including nanomaterials, polymers, porous materials, and biomaterials have attracted considerable attention over the past several years due to their capabilities of real-time detection, excellent removal efficiency, anti-interference, quick response, high selectivity, and low limit of detection. In this tutorial review, we review the general design principles underlying the aforementioned functional materials, and in particular highlight the fundamental mechanisms and specific examples of detecting and removing heavy metal ions. Additionally, the methods which enhance water purification quality using these functional materials have been reviewed, also current challenges and opportunities in this exciting field have been highlighted, including the fabrication, subsequent treatment, and potential future applications of such functional materials. We envision that this tutorial review will provide invaluable guidance for the design of functional materials tailored towards the detection and removal of heavy metals, thereby expediting the development of high-performance materials and fostering the development of more efficient approaches to water pollution remediation.

A Note on Stronger Forms of Sensitivity for Non-Autonomous Dynamical Systems on Uniform Spaces.

This paper introduces the notion of multi-sensitivity with respect to a vector within the context of non-autonomous dynamical systems on uniform spaces and provides insightful results regarding N-sensitivity and strongly multi-sensitivity, along with their behaviors under various conditions. The main results established are as follows: (1) For a k-periodic nonautonomous dynamical system on a Hausdorff uniform space (S,U), the system (S,fk∘⋯∘f1) exhibits N-sensitivity (or strongly multi-sensitivity) if and only if the system (S,f1,∞) displays N-sensitivity (or strongly multi-sensitivity). (2) Consider a finitely generated family of surjective maps on uniform space (S,U). If the system (S,f1,∞) is N-sensitive, then the system (S,fk,∞) is also N-sensitive. When the family f1,∞ is feebly open, the converse statement holds true as well. (3) Within a finitely generated family on uniform space (S,U), N-sensitivity (and strongly multi-sensitivity) persists under iteration. (4) We present a sufficient condition under which an nonautonomous dynamical system on infinite Hausdorff uniform space demonstrates N-sensitivity.

Impact of Combined Modulation of Two Potassium Ion Currents on Spiral Waves and Turbulent States in the Heart.

In the realm of cardiac research, the control of spiral waves and turbulent states has been a persistent focus for scholars. Among various avenues of investigation, the modulation of ion currents represents a crucial direction. It has been proved that the methods involving combined control of currents are superior to singular approaches. While previous studies have proposed some combination strategies, further reinforcement and supplementation are required, particularly in the context of controlling arrhythmias through the combined regulation of two potassium ion currents. This study employs the Luo-Rudy phase I cardiac model, modulating the maximum conductance of the time-dependent potassium current and the time-independent potassium current, to investigate the effects of this combined modulation on spiral waves and turbulent states. Numerical simulation results indicate that, compared to modulating a single current, combining reductions in the conductance of two potassium ion currents can rapidly control spiral waves and turbulent states in a short duration. This implies that employing blockers for both potassium ion currents concurrently represents a more efficient control strategy. The control outcomes of this study represent a novel and effective combination for antiarrhythmic interventions, offering potential avenues for new antiarrhythmic drug targets.

Genetic diversity and structure of mongolian gazelle (Procapra gutturosa) populations in fragmented habitats.

BACKGROUND: The Mongolian gazelle (Procapra gutturosa) population has shown a considerable range of contractions and local extinctions over the last century, owing to habitat fragmentation and poaching. A thorough understanding of the genetic diversity and structure of Mongolian gazelle populations in fragmented habitats is critical for planning effective conservation strategies. RESULT: In this study, we used eight microsatellite loci and mitochondrial cytochrome b (Cytb) to compare the levels of genetic diversity and genetic structure of Mongolian gazelle populations in the Hulun Lake National Nature Reserve (HLH) with those in the China-Mongolia border area (BJ). The results showed that the nucleotide diversity and observed heterozygosity of the HLH population were lower than those of the BJ population. Moreover, the HLH and BJ populations showed genetic differentiation. We concluded that the HLH population had lower genetic diversity and a distinct genetic structure compared with the BJ population. CONCLUSION: The genetic diversity of fragmented Mongolian gazelle populations, can be improved by protecting these populations while reinforcing their gene exchange with other populations. For example, attempts can be made to introduce new individuals with higher genetic diversity from other populations to reduce inbreeding.

Optimizing the Spatial Density of Single Co Sites via Molecular Spacing for Facilitating Sustainable Water Oxidation.

Advances in single-atom (-site) catalysts (SACs) provide a new solution of atomic economy and accuracy for designing efficient electrocatalysts. In addition to a precise local coordination environment, controllable spatial active structure and tolerance under harsh operating conditions remain great challenges in the development of SACs. Here, we show a series of molecule-spaced SACs (msSACs) using different acid anhydrides to regulate the spatial density of discrete metal phthalocyanines with single Co sites, which significantly improve the effective active-site numbers and mass transfer, enabling one of the msSACs connected by pyromellitic dianhydride to exhibit an outstanding mass activity of (1.63 ± 0.01) × 105 A·g-1 and TOFbulk of 27.66 ± 1.59 s-1 at 1.58 V (vs RHE) and long-term durability at an ultrahigh current density of 2.0 A·cm-2 under industrial conditions for oxygen evolution reaction. This study demonstrates that the accessible spatial density of single atom sites can be another important parameter to enhance the overall performance of catalysts.

Comprehensive analysis of immune-related lncRNAs and their clinical relevance in gastric adenocarcinoma.

Increasing evidence has demonstrated that lncRNA plays a significant role in the immunity regulation of gastric adenocarcinoma. However, the immune-related lncRNAs and the prognostic value in immunotherapies remain largely unexplored. We collected immune-related lncRNA and the associated pathways of gastric cancer from the ImmLnc database. The cox regression model is used to analyze the prognostic value of these lncRNAs. Gastric cancer is further divided into different subtypes based on these lncRNAs. Tumor microenvironment analysis, functional enrichment analysis, and genomic alteration analysis are performed for different subtypes. Furthermore, chemotherapeutic and immunotherapeutic sensitivity are also analyzed among different subtypes. Nine lncRNAs are identified as significant regulators of the immune pathway of gastric cancer. Gastric cancer can be classified into 5 subtypes based on these lncRNAs. Tumor microenvironment analysis shows that cluster C3 has the highest immune score and C5 has the lowest score. Functional analysis shows that these subtypes are enriched with distinct biological processes. Genomic analysis shows that LAMA2 mutation is a protective factor in C3 but a risk factor in C5. Furthermore, these subtypes are found to respond distinctly to the same chemotherapeutic and immunotherapeutic drugs. In this study, we analyzed the immune-related lncRNA and identified the crucial role in the regulation of immune properties, biological processes, and immunotherapeutic sensitivity. These findings can improve our understanding of the epigenetic immunoregulation of lncRNA and advance the research of immunotherapy.

Progranulin promoted the proliferation, metastasis, and suppressed apoptosis via JAK2-STAT3/4 signaling pathway in papillary thyroid carcinoma.

BACKGROUND: Progranulin (PGRN), a glycoprotein secreted by a wide range of epithelial cells and plays an important role in inflammatory mechanisms and tumor progression. In this study, the expression, and functions of PGRN in papillary thyroid carcinoma (PTC) was examined to explore the potential pathogenesis of PTC. METHODS: Western blotting and qRT-PCR were used to detect the relationship between PGRN expression and clinicopathological characteristics of patients with PTC. PTC cell lines with PGRN overexpression and with PGRN knockdown were established to explore their effects on the biological behavior. Western blotting was used to detect the changes of relevant molecules and JAK2-STAT3/4 signaling pathway. Moreover, rescue experiments validated the involvement of the JAK2-STAT3/4 signaling pathway. And statistical analyses were analyzed using SPASS 21.0 and graph generation were performed using GraphPad Prism 8.0. RESULTS: PGRN was overexpressed in PTC tissue and increased by 75% at mRNA level and 161% at relative protein level in the patients with lymph node metastasis compared to without lymph node metastasis. Besides, PGRN regulated and promoted PTC cell proliferation, migration, invasion, and inhibited cell apoptosis. With PGRN overexpressed, relevant molecules including the expression of BCL2/BAX, BCL2/BAD, CyclinD1, MMP2, vimentin and N-cadherin were increased, the expression level of E-cadherin was decreased, and the phosphorylation of JAK2 and STAT3/4 were increased. JAK inhibitor (JSI-124) rescued these changes of PTC cells induced by overexpressed PGRN. CONCLUSIONS: These findings revealed that PGRN promote the progression of PTC through the JAK2-STAT3/4 pathway, and PGRN could be served as a potential therapeutic target for PTC.

Genomic architecture of leaf senescence in sorghum (Sorghum bicolor).

KEY MESSAGE: Leaf senescence in sorghum is primarily controlled by the progression, but not by the onset of senescence. The senescence-delaying haplotypes of 45 key genes accentuated from landraces to improved lines. Leaf senescence is a genetically programmed developmental process and plays a central role for plant survival and crop production by remobilising nutrients accumulated in senescent leaves. In theory, the ultimate outcome of leaf senescence is determined by the onset and progression of senescence, but how these two processes contribute to senescence is not fully illustrated in crops and the genetic basis for them is not well understood. Sorghum (Sorghum bicolor), which is known for the remarkable stay-green trait, is ideal for dissecting the genomic architecture underlying the regulation of senescence. In this study, a diverse panel of 333 sorghum lines was explored for the onset and progression of leaf senescence. Trait correlation analysis showed that the progression of leaf senescence, rather than the onset of leaf senescence, significantly correlated with variations of the final leaf greenness. This notion was further supported by GWAS, which identified 31 senescence-associated genomic regions containing 148 genes, of which 124 were related to the progression of leaf senescence. The senescence-delaying haplotypes of 45 key candidate genes were enriched in lines with extremely prolonged senescence duration, while senescence-promoting haplotypes in those with extremely accelerated senescence. Haplotype combinations of these genes could well explain the segregation of the senescence trait in a recombinant inbred population. We also demonstrated that senescence-delaying haplotypes of candidate genes were under strong selection during sorghum domestication and genetic improvement. Together, this research advanced our understanding of crop leaf senescence and provided a suite of candidate genes for functional genomics and molecular breeding.

Self-Supporting Co/CeO2 Heterostructures for Ampere-Level Current Density Alkaline Water Electrolysis.

Remodeling the active surface through fabricating heterostructures can substantially enhance alkaline water electrolysis driven by renewable electrical energy. However, there are still great challenges in the synthesis of highly reactive and robust heterostructures to achieve both ampere-level current density hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Herein, we report a new Co/CeO2 heterojunction self-supported electrode for sustainable overall water splitting. The self-supporting Co/CeO2 heterostructures required only low overpotentials of 31.9 ± 2.2, 253.3 ± 2.7, and 316.7 ± 3 mV for HER and 214.1 ± 1.4, 362.3 ± 1.9, and 400.3 ± 3.7 mV for OER at 0.01, 0.5, and 1.0 A·cm-2, respectively, being one of the best Co-based bifunctional electrodes. Electrolyzer constructed from this electrode acting as an anode and cathode merely required cell voltages of 1.92 ± 0.02 V at 1.0 A·cm-2 for overall water splitting. Multiple characterization techniques combined with density functional theory calculations disclosed the different active sites on the anode and cathode, and the charge redistributions on the heterointerfaces that can optimize the adsorption of H and oxygen-containing intermediates, respectively. This study presents the tremendous prospective of self-supporting heterostructures for effective and economical overall water splitting.

Use of La-Co@NPC for Sulfite Oxidation and Arsenic Detoxification Removal for High-Quality Sulfur Resources Recovery in Desulfurization Process.

Ammonia desulfurization is a typical resource-recovery-type wet desulfurization process that is widely used in coal-fired industrial boilers. However, the sulfur recovery is limited by the low oxidation rate of byproduct (ammonium sulfite), leading to secondary SO2 pollution due to its easy decomposability. In addition, the high toxic arsenic trace substances coexisting in desulfurization liquids also reduce the quality of the final sulfate product, facing with high environmental toxicity. In this study, nitrogen-doped porous carbon coembedded with lanthanum and cobalt (La-Co@NPC) was fabricated with heterologous catalytic active sites (Co0) and adsorption sites (LaOCl) to achieve sulfite oxidation and the efficient removal of high toxic trace arsenic for the recovery of high-value ammonium sulfate from the desulfurization liquid. The La-Co@NPC/S(IV) catalytic system can generate numerous strongly oxidizing free radicals (·SO5- and ·O2-) for the sulfite oxidation on the Co0 site, as well as oxidative detoxification of As(III) into As(V). Subsequently, arsenic can be removed through chemical adsorption on LaOCl adsorption sites. By using the dual-functional La-Co@NPC at a concentration of 0.25 g/L, the rate of ammonium sulfite oxidation reached 0.107 mmol/L·s-1, the arsenic (1 mg/L) removal efficiency reached 92%, and the maximum adsorption capacity of As reached up to 123 mg/g. This study can give certain guiding significance to the functional material design and the coordinated control of multiple coal-fired pollutants in desulfurization for high-value recovery of sulfur resources.