Marine anoxia linked to abrupt global warming during Earth's penultimate icehouse.

Piecing together the history of carbon (C) perturbation events throughout Earth's history has provided key insights into how the Earth system responds to abrupt warming. Previous studies, however, focused on short-term warming events that were superimposed on longer-term greenhouse climate states. Here, we present an integrated proxy (C and uranium [U] isotopes and paleo CO2) and multicomponent modeling approach to investigate an abrupt C perturbation and global warming event (∼304 Ma) that occurred during a paleo-glacial state. We report pronounced negative C and U isotopic excursions coincident with a doubling of atmospheric CO2 partial pressure and a biodiversity nadir. The isotopic excursions can be linked to an injection of ∼9,000 Gt of organic matter­derived C over ∼300 kyr and to near 20% of areal extent of seafloor anoxia. Earth system modeling indicates that widespread anoxic conditions can be linked to enhanced thermocline stratification and increased nutrient fluxes during this global warming within an icehouse.

TMEM44 as a Novel Prognostic Marker for Kidney Renal Clear Cell Carcinoma is Associated with Tumor Invasion, Migration and Immune Infiltration.

Transmembrane (TMEM) proteins are integral membrane proteins that traverse biological membranes. Several members of the TMEM family have been linked to the development and progression of various tumors. However, the specific role and mechanism of TMEM44 in tumor biology remain largely unexplored. In this study, we initially conducted an extensive analysis using the TCGA database to investigate the expression patterns and survival associations of TMEM44 across various human tumors. Subsequently, we focused on KIRC and found a significant correlation between TMEM44 expression and this particular cancer type. To validate our findings, we performed western blot and quantitative polymerase chain reaction (qPCR) assays to confirm the expression levels of TMEM44 in KIRC. Following this, we employed a series of functional assays, including CCK8 viability assay, EDU incorporation assay, wound healing assay, and transwell migration assay, to investigate the biological role of TMEM44 in KIRC. We observed a significant upregulation of TMEM44 expression in KIRC, indicating its potential involvement in the pathogenesis of this cancer. We intervened in the expression of TMEM44 in KIRC cells and found significant inhibitory effects on cell proliferation, migration, and invasion in KIRC cells. Furthermore, our findings indicated that TMEM44 could serve as an independent prognostic factor in KIRC, highlighting its potential clinical significance. Consequently, TMEM44 holds promise as both a prognostic biomarker and a prospective therapeutic target for KIRC.

Metal Halides for High-Capacity Energy Storage.

High-capacity electrochemical energy storage systems are more urgently needed than ever before with the rapid development of electric vehicles and the smart grid. The most efficient way to increase capacity is to develop electrode materials with low molecular weights. The low-cost metal halides are theoretically ideal cathode materials due to their advantages of high capacity and redox potential. However, their cubic structure and large energy barrier for deionization impede their rechargeability. Here, the reversibility of potassium halides, lithium halides, sodium halides, and zinc halides is achieved through decreasing their dimensionality by the strong π-cation interactions between metal cations and reduced graphene oxide (rGO). Especially, the energy densities of KI-, KBr-, and KCl-based materials are 722.2, 635.0, and 739.4 Wh kg-1 , respectively, which are higher than those of other cathode materials for potassium-ion batteries. In addition, the full-cell with 2D KI/rGO as cathode and graphite as anode demonstrates a lifespan of over 150 cycles with a considerable capacity retention of 57.5%. The metal halides-based electrode materials possess promising application prospects and are worthy of more in-depth researches.

Identification of surrogate prognostic biomarkers for allergic asthma in nasal epithelial brushing samples by WGCNA.

BACKGROUND: Allergic asthma is a lower respiratory tract disease of Th2 inflammation with multiple molecular mechanisms. The upper and lower airways can be unified by the concept of a united airway and, as such, gene expression studies of upper epithelial cells may provide effective surrogate biomarkers for the prognostic study of allergic asthma. OBJECTIVE: To identify surrogate biomarkers in upper airway epithelial cells for the prognostic study of allergic asthma. METHODS: Nasal epithelial cell gene expression in 40 asthmatic and 17 healthy control subjects were analyzed by weighted gene coexpression network analysis (WGCNA) to identify gene network modules and profiles in allergic asthma. Functional enrichment analysis was performed on the coexpression genes in certain highlighted modules. RESULTS: A total of 13 coexpression modules were constructed by WGCNA from 2804 genes in nasal epithelial brushing samples of the 40 asthmatic and 17 healthy subjects. The number of genes in these modules ranged from 1086 (Turquoise module) to 45 (Salmon). Eight coexpression modules were found to be significantly correlated (P < 0.05) with two clinic traits, namely disease status, and severity. Four modules were positively correlated ( P < 0.05) with the traits and these, therefore, contained genes that are mostly overexpressed in asthma. Contrastingly, the four other modules were found to be negatively correlated with the clinic traits. Functional enrichment analysis of the positively correlated modules showed that one (Magenta) was mainly enriched in mast cell activation and degranulation; another (Pink) was largely involved in immune cell response; the third (Yellow) was predominantly enriched in transmembrane signal pathways; and the last (Blue) was mainly enriched in substructure components of the cells. The hub genes in the modules were KIT, KITLG, GATA2, CD44, PTPRC, and CFTR, and these were confirmed as having significantly higher expression in the nasal epithelial cells. Combining the six hub genes enabled a relatively high capacity for discrimination between asthmatics and healthy subjects with an area under the receiver operating characteristic (ROC) curve of 0.924. CONCLUSIONS: Our findings provide a framework of coexpression gene modules from nasal epithelial brushing samples that could be used for the prognostic study of allergic asthma.

A large lung gene expression study identifying IL1B as a novel player in airway inflammation in COPD airway epithelial cells.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic and progressive lung disease characterized by a mixture of small airway disease and lung tissue parenchymal destruction. Abnormal inflammatory responses to cigarette smoking and other noxious particles are generally thought to be responsible for causing of COPD. Since airway inflammation is a key factor in COPD progress, it is crucial to unravel its underlying molecular mechanisms. Unbiased analysis of genome-wide gene expression profiles in lung small airway epithelial cells provides a powerful tool to investigate this. METHODS: Gene expression data of GSE611906, GSE20257, GSE8545 were downloaded from GEO database. All 288 lung small airway samples in these cohorts, including donors with (n = 61) and without (n = 227) COPD, were chosen for differential gene expression analysis. The gene ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses, gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were performed. Subsequently, the analyses of IL1B expression level, the Pearson correlation between IL1B and several COPD biomarkers were performed using other cohorts to validate our main findings. RESULTS: With a change ≥ twofold and P value < 0.05 cutoff, we found 38 genes were up-regulated and 114 genes were down-regulated in patients with COPD compared with health controls, while using cutoff fold change 1.5 and P value < 0.05, there were 318 genes up-regulated and 333 genes down-regulated. Among the most up-regulated genes were IL1B, CCL2, CCL23, and CXCL14, all implicated in inflammation triggering. GO, KEGG and WGCNA analysis all disclosed IL1B was highly correlated to COPD disease trait. The expression profile of IL1B was further validated using independent cohorts from COPD airway epithelium, lung tissue, sputum, and blood. We demonstrated higher IL1B gene expression in COPD small airway epithelial cells, but not in COPD lung tissue, sputum, and blood. Strong co-expression of IL1B with COPD biomarkers, such as DUOX2, MMP12, CCL2, and CXCL14, were validated in silico analysis. Finally, PPI network analysis using enriched data showed IL1B, CCL2, CCL7 and BMP7 were in the same hub node with high degrees. CONCLUSIONS: We identified IL1B was significantly up-regulated in COPD small airway epithelial cells and propose IL1B as a novel player in airway inflammation in COPD.

Improved performance of lateral flow immunoassays for alpha-fetoprotein and vanillin by using silica shell-stabilized gold nanoparticles.

The sensitivity of lateral flow assays (LFA) was increased 30-fold by making use of spherical core-shell gold-silica nanoparticles (AuNP@SiO2 NPs). They can be prepared by silylation of surfactant stabilized AuNPs. The AuNP@SiO2 NPs are highly stable and can be used to label antibodies at virtually any concentration. The detection limit of an LFA for alpha-fetoprotein (AFP) can be decreased from 10 ng·mL-1 to 300 pg·mL-1 which makes it comparable to an enzyme-linked immunosorbent assay. To demonstrate the applicability to an immunoassay, a sandwich assay was developed for vanillin by covalent modification of the AuNP@SiO2 NPs with antibody. By using the method, vanillin can be detected visually in milk powder samples in concentrations as low as 100 ng·g-1. With unique optical property and great stability, this AuNP@SiO2 endows great potential in biosensing applications. Graphical abstract Controlled growth of AuNP@SiO2. The newly prepared AuNP has a negative hydration layer. This layer is further surrounded by a bilayer of CTAB through electrostatic attraction. The hydrophobic inner layer enables the access and assembling of APTES and MTTS. After the hydrolysis of siloxane, a thin layer of silica shell is formed around AuNP.

Engineering Fast Ion Conduction and Selective Cation Channels for a High-Rate and High-Voltage Hybrid Aqueous Battery.

The rechargeable aqueous metal-ion battery (RAMB) has attracted considerable attention due to its safety, low costs, and environmental friendliness. Yet the poor-performance electrode materials lead to a low feasibility of practical application. A hybrid aqueous battery (HAB) built from electrode materials with selective cation channels could increase the electrode applicability and thus enlarge the application of RAMB. Herein, we construct a high-voltage K-Na HAB based on K2 FeFe(CN)6 cathode and carbon-coated NaTi2 (PO4 )3 (NTP/C) anode. Due to the unique cation selectivity of both materials and ultrafast ion conduction of NTP/C, the hybrid battery delivers a high capacity of 160 mAh g-1 at a 0.5 C rate. Considerable capacity retention of 94.3 % is also obtained after 1000 cycles at even 60 C rate. Meanwhile, high energy density of 69.6 Wh kg-1 based on the total mass of active electrode materials is obtained, which is comparable and even superior to that of the lead acid, Ni/Cd, and Ni/MH batteries.

Slurryless Li2S/reduced graphene oxide cathode paper for high-performance lithium sulfur battery.

Lithium sulfide (Li2S) is a promising cathode material for Li-S batteries with high capacity (theoretically 1166 mAh g(-1)) and can be paired with nonlithium-metal anodes to avoid potential safety issues. However, the cycle life of coarse Li2S particles suffers from poor electronic conductivity and polysulfide shuttling. Here, we develop a flexible slurryless nano-Li2S/reduced graphene oxide cathode paper (nano-Li2S/rGO paper) by simple drop-coating. The Li2S/rGO paper can be directly used as a free-standing and binder-free cathode without metal substrate, which leads to significant weight savings. It shows excellent rate capability (up to 7 C) and cycle life in coin cell tests due to the high electron conductivity, flexibility, and strong solvent absorbency of rGO paper. The Li2S particles that precipitate out of the solvent on rGO have diameters 25-50 nm, which is in contrast to the 3-5 µm coarse Li2S particles without rGO.

Methylene blue as a G-quadruplex binding probe for label-free homogeneous electrochemical biosensing.

Herein, G-quadruplex sequence was found to significantly decrease the diffusion current of methylene blue (MB) in homogeneous solution for the first time. Electrochemical methods combined with circular dichroism spectroscopy and UV-vis spectroscopy were utilized to systematically explore the interaction between MB and an artificial G-quadruplex sequence, EAD2. The interaction of MB and EAD2 (the binding constant, K ≈ 1.3 × 10(6) M(-1)) was stronger than that of MB and double-stranded DNA (dsDNA) (K ≈ 2.2 × 10(5) M(-1)), and the binding stoichiometry (n) of EAD2/MB complex was calculated to be 1.0 according to the electrochemical titration curve combined with Scatchard analysis. MB was proved to stabilize the G-quadruplex structure of EAD2 and showed a competitive binding to G-quadruplex in the presence of hemin. EAD2 might mainly interact with MB, a positive ligand of G-quadruplex, through the end-stacking with π-system of the guanine quartet, which was quite different from the binding mechanism of dsDNA with MB by intercalation. A novel signal read-out mode based on the strong affinity between G-quadruplex and MB coupling with aptamer/G-quadruplex hairpin structure was successfully implemented in cocaine detection with high specificity. G-quadruplex/MB complex will function as a promising electrochemical indicator for constructing homogeneous label-free electrochemical biosensors, especially in the field of simple, rapid, and noninvasive biochemical assays.

Biochar-enhanced three-dimensional conductive network thick electrodes for efficient lithium extraction from salt lake brines with high Magnesia-lithium ratios.

Enhancing the kinetic performance of thick electrodes is essential for improving the efficiency of lithium extraction processes. Biochar, known for its affordability and unique three-dimensional (3D) structure, is utilized across various applications. In this study, we developed a biochar-based, 3D-conductive network thick electrode (∼20 mg cm-2) by in-situ deposition of LiFePO4 (LFP) onto watermelon peel biomass (WB). Utilizing Density Functional Theory (DFT) calculations complemented by experimental data, we confirmed that this The thick electrode exhibits outstanding kinetic properties and a high capacity for lithium intercalation in brines, even in environments where the Magnesia-lithium ratios are significantly high. The electrode showed an impressive intercalation capacity of 30.67 mg g-1 within 10 min in a pure lithium solution. It also maintained high intercalation performance (31.17 mg g-1) in simulated brines with high Magnesia-lithium ratios. Moreover, in actual brine, it demonstrated a significant extraction capacity (23.87 mg g-1), effectively lowering the Magnesia-lithium ratio from 65 to 0.50. This breakthrough in high-conductivity thick electrode design offers new perspectives for lithium extraction technologies.

Directing silicon-graphene self-assembly as a core/shell anode for high-performance lithium-ion batteries.

There is great interest in utilization of silicon-containing nanostructures as anode materials for lithium-ion batteries but usually limited by manufacturing cost, their intrinsic low electric conductivity, and large volume changes during cycling. Here we present a facile process to fabricate graphene-wrapped silicon nanowires (GNS@Si NWs) directed by electrostatic self-assembly. The highly conductive and mechanical flexible graphene could partially accommodate the large volume change associated with the conversion reaction and also contributed to the enhanced electronic conductivity. The as-prepared GNS@Si NWs delivered a reversible capacity of 1648 mAh·g(-1) with an initial Coulombic efficiency as high as 80%. Moreover, capacity remained 1335 mAh·g(-1) after 80 cycles at a current of 200 mA·g(-1), showing significantly improved electrochemical performance in terms of rate capability and cycling performance.

Ultrahigh-rate and ultralong-life aqueous batteries enabled by special pair-dancing proton transfer.

The design of Faradaic battery electrodes with high rate capability and long cycle life comparable to those of supercapacitors is a grand challenge. Here, we bridge this performance gap by taking advantage of a unique ultrafast proton conduction mechanism in vanadium oxide electrode, developing an aqueous battery with untrahigh rate capability up to 1000 C (400 A g-1) and extremely long life of 0.2 million cycles. The mechanism is elucidated by comprehensive experimental and theoretical results. Instead of slow individual Zn2+ transfer or Grotthuss chain transfer of confined H+, the ultrafast kinetics and excellent cyclic stability are enabled by rapid 3D proton transfer in vanadium oxide via the special pair dance switching between Eigen and Zundel configurations with little constraint and low energy barriers. This work provides insight into developing high-power and long-life electrochemical energy storage devices with nonmetal ion transfer through special pair dance topochemistry dictated by hydrogen bond.

Regulating the Electrical Double Layer with Supramolecular Cyclodextrin Anions for Dendrite-Free Zinc Electrodeposition.

The interfacial stability of a Zn battery is dependent on the electrical double layer (EDL) that forms at the interface between the electrolyte and the Zn metal anode. A fundamental understanding of the regulation of the EDL structure and stability on the Zn surface is highly desirable for practical applications of aqueous batteries. Herein, the interfacial chemistry of the EDL is regulated by the adsorption of supramolecular cyclodextrin anions in the inner Helmholtz plane (IHP). The nucleation overpotential and the charge transfer activation energy for Zn2+ to go through the OHP (Ea1) and IHP (Ea2) are increased, leading to slower Zn2+ transfer kinetics. The electric field distribution and Zn2+ flux in the proximity of the Zn metal surface are homogenized, thus suppressing the growth of dendrites. The mechanism is supported with theoretical and experimental analyses. Consequently, a Zn||Zn symmetric cell achieves an ultrahigh cumulative capacity of 10000 and 4250 mAh cm-2 at a respective current density of 10 and 50 mA cm-2, and an average Coulombic efficiency of 99.5% over 1000 cycles under harsh conditions (at a high current density of 10 mA cm-2 with a high capacity of 10 mAh cm-2). This work provides insight into the introduction of supramolecular anions to regulate the electrical double layer EDL structure and improve the interfacial stability.

SOX family transcription factors as therapeutic targets in wound healing: A comprehensive review.

The SOX family plays a vital role in determining the fate of cells and has garnered attention in the fields of cancer research and regenerative medicine. It also shows promise in the study of wound healing, as it actively participates in the healing processes of various tissues such as skin, fractures, tendons, and the cornea. However, our understanding of the mechanisms behind the SOX family's involvement in wound healing is limited compared to its role in cancer. Gaining insight into its role, distribution, interaction with other factors, and modifications in traumatized tissues could provide valuable new knowledge about wound healing. Based on current research, SOX2, SOX7, and SOX9 are the most promising members of the SOX family for future interventions in wound healing. SOX2 and SOX9 promote the renewal of cells, while SOX7 enhances the microvascular environment. The SOX family holds significant potential for advancing wound healing research. This article provides a comprehensive review of the latest research advancements and therapeutic tools related to the SOX family in wound healing, as well as the potential benefits and challenges of targeting the SOX family for wound treatment.

Piezo1 in skin wound healing and related diseases: Mechanotransduction and therapeutic implications.

Skin wound healing is a multifaceted and intricate process involving inflammation, tissue proliferation, and scar formation, all of which are accompanied by the continuous application of mechanical forces. Mechanotransduction is the mechanism by which the skin receives and reacts to physical signals from the internal and external environment, converting them into intracellular biochemical signals. This intricate process relies on specialized proteins known as mechanotransducers, with Piezo1 being a critical mechanosensitive ion channel that plays a central role in this process. This article provides an overview of the structural characteristics of Piezo1 and summarizes its effects on corresponding cells or tissues at different stages of skin trauma, including how it regulates skin sensation and skin-related diseases. The aim is to reveal the potential diagnostic and therapeutic value of Piezo1 in skin trauma and skin-related diseases. Piezo1 has been reported to be a vital mediator of mechanosensation and transduction in various organs and tissues. Given its high expression in the skin, Piezo1, as a significant cell membrane ion channel, is essential in activating intracellular signaling cascades that trigger several cellular physiological functions, including cell migration and muscle contraction. These functions contribute to the regulation and improvement of wound healing.

Neuropeptide substance P: A promising regulator of wound healing in diabetic foot ulcers.

In the past, neuropeptide substance P (SP) was predominantly recognized as a neuroinflammatory factor, while its potent healing activity was overlooked. This paper aims to review the regulatory characteristics of neuropeptide SP in both normal and diabetic wound healing. SP actively in the regulation of wound healing-related cells directly and indirectly, exhibiting robust inflammatory properties, promoting cell proliferation and migration and restoring the activity and paracrine ability of skin cells under diabetic conditions. Furthermore, SP not only regulates healing-related cells but also orchestrates the immune environment, thereby presenting unique and promising application prospects in wound intervention. As new SP-based preparations are being explored, SP-related drugs are poised to become an effective therapeutic intervention for diabetic foot ulcers (DFU).

Mercury isotopes show vascular plants had colonized land extensively by the early Silurian.

The colonization and expansion of plants on land is considered one of the most profound ecological revolutions, yet the precise timing remains controversial. Because land vegetation can enhance weathering intensity and affect terrigenous input to the ocean, changes in terrestrial plant biomass with distinct negative Δ199Hg and Δ200Hg signatures may overwrite the positive Hg isotope signatures commonly found in marine sediments. By investigating secular Hg isotopic variations in the Paleozoic marine sediments from South China and peripheral paleocontinents, we highlight distinct negative excursions in both Δ199Hg and Δ200Hg at Stage level starting in the early Silurian and again in the Carboniferous. These geochemical signatures were driven by increased terrestrial contribution of Hg due to the rapid expansion of vascular plants. These excursions broadly coincide with rising atmospheric oxygen concentrations and global cooling. Therefore, vascular plants were widely distributed on land during the Ordovician-Silurian transition (~444 million years), long before the earliest reported vascular plant fossil, Cooksonia (~430 million years).

A CE-LIF method to monitor autophagy by directly detecting LC3 proteins in HeLa cells.

A fast, simple and quantitative approach was established for monitoring autophagy in HeLa cells by directly detecting the conversion of green fluorescent protein (GFP) labelled autophagy markers, GFP-LC3-I to GFP-LC3-II, in crude cellular extract using capillary electrophoresis (CE) with laser-induced fluorescence (LIF). Compared with the traditional methods, this proposed method is simpler and more reliable. Moreover, high sensitivity, with a limit of detection (LOD) of 0.48 ppt (bovine serum albumin as standard protein), was obtained by an in-capillary derivatization method coupled with a field-enhanced sample injection (FESI) technique, this may allow the success of this technique in the detection of endogenous markers of autophagy in cells.

Mercury oxidation and adsorption characteristics of potassium permanganate modified lignite semi-coke.

The adsorption characteristics of virgin and potassium permanganate modified lignite semi-coke (SC) for gaseous Hg0 were investigated in an attempt to produce more effective and lower price adsorbents for the control of elemental mercury emission. Brunauer-Emmett-Teller (BET) measurements, X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) were used to analyze the surface physical and chemical properties of SC, Mn-SC and Mn-H-SC before and after mercury adsorption. The results indicated that potassium permanganate modification had significant influence on the properties of semi-coke, such as the specific surface area, pore structure and surface chemical functional groups. The mercury adsorption efficiency of modified semi-coke was lower than that of SC at low temperature, but much higher at high temperature. Amorphous Mn7+, Mn6+ and Mn4+ on the surface of Mn-SC and Mn-H-SC were the active sites for oxidation and adsorption of gaseous Hg0, which oxidized the elemental mercury into Hg2+ and captured it. Thermal treatment reduced the average oxidation degree of Mn(x+) on the surface of Mn-SC from 3.80 to 3.46. However, due to the formation of amorphous MnOx, the surface oxidation active sites for gaseous Hg0 increased, which gave Mn-H-SC higher mercury adsorption efficiency than that of Mn-SC at high temperature.

Laparoscopic bladder diverticulectomy in a child with situs inversus totalis: A case report and literature review.

Situs inversus totalis (SIT) is a rare internal laterality disorder characterized by the mirror arrangement of organs. Multiple gene mutations and maternal environmental factors are thought to cause this variation. It is usually challenging to perform laparoscopic surgery in these cases. Bladder diverticulum is uncommon in children, with an incidence of 1.7%. We report a 14-year-old male patient who was admitted to our department because of lower abdominal pain and frequent urination. A series of examinations confirmed the rare combination of giant bladder diverticulum and SIT. After extensive preoperative discussion, we performed laparoscopic bladder diverticulectomy. The operation was successful. To the best of our knowledge, this is the first report of successful laparoscopic bladder surgery on a case of SIT. This article summarizes the key technical points and the difficulties of performing this kind of operation. In addition, during the process of reviewing the literature, we found that SIT often coexists with some high-risk factors for bladder diverticulum in some rare syndromes. It is helpful to further understand and provide experience in the diagnosis and treatment of the rare combination of bladder diverticulum and SIT in children.