Printing of 3D photonic crystals in titania with complete bandgap across the visible spectrum.

A photonic bandgap is a range of wavelengths wherein light is forbidden from entering a photonic crystal, similar to the electronic bandgap in semiconductors. Fabricating photonic crystals with a complete photonic bandgap in the visible spectrum presents at least two important challenges: achieving a material refractive index > ~2 and a three-dimensional patterning resolution better than ~280 nm (lattice constant of 400 nm). Here we show an approach to overcome such limitations using additive manufacturing, thus realizing high-quality, high-refractive index photonic crystals with size-tunable bandgaps across the visible spectrum. We develop a titanium ion-doped resin (Ti-Nano) for high-resolution printing by two-photon polymerization lithography. After printing, the structures are heat-treated in air to induce lattice shrinkage and produce titania nanostructures. We attain three-dimensional photonic crystals with patterning resolution as high as 180 nm and refractive index of 2.4-2.6. Optical characterization reveals ~100% reflectance within the photonic crystal bandgap in the visible range. Finally, we show capabilities in defining local defects and demonstrate proof-of-principle applications in spectrally selective perfect reflectors and chiral light discriminators.

Out-of-sync evolutionary patterns and mutual interplay of major and minor capsid proteins in norovirus GII.2.

Human noroviruses are the most common cause of viral gastroenteritis, resulting annually in 219 000 deaths and a societal cost of $60 billion, and no antivirals or vaccines are available. The minor capsid protein may play a significant role in the evolution of norovirus. GII.4 is the predominant genotype of norovirus, and its VP2 undergoes epochal co-evolution with the major capsid protein VP1. Since the sudden emergence of norovirus GII.2[P16] in 2016, it has consistently remained a significant epidemic strain in recent years. In the construction of phylogenetic trees, the phylogenetic trees of VP2 closely parallel those of VP1 due to the shared tree topology of both proteins. To investigate the interaction patterns between the major and minor capsid proteins of norovirus GII.2, we chose five representative strains of GII.2 norovirus and investigated their evolutionary patterns using a yeast two-hybrid experiment. Our study shows VP1-VP2 interaction in GII.2, with critical interaction sites at 167-178 and 184-186 in the highly variable region. In the intra-within GII.2, we observed no temporal co-evolution between VP1 and VP2 of GII.2. Notable distinctions were observed in the interaction intensity of VP2 among inter-genotype (P<0.05), highlighting the divergent evolutionary patterns of VP2 within different norovirus genotypes. In summary, the interactions between VP2 and VP1 of GII.2 norovirus exhibit out-of-sync evolutionary patterns. This study offered valuable insights for further understanding and completing the evolutionary mechanism of norovirus.

Highly selective fluorescent probe for cysteine via a tandem reaction and its bioimaging application in HeLa cells.

Cysteine, as a vital endogenous small molecule mercaptan, plays a crucial role in various physiological processes. The high sensitivity and selectivity of fluorescent probes provide a method to monitor cysteine, which is helpful to understand the mechanism of cysteine in physiological processes more comprehensively. However, the detection of cysteine can be interfered by other small molecule biothiols. Therefore, the design of fluorescent probe based on the structural characteristics and reactivity of cysteine has become research focus currently. Given the biological compatibilities, biological targets, the metabolic pathway of 3-hydoxythalidomide, and its unique fluorescent properties, herein, we have designed a chemodosimeter, 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl acrylate, for the detection of cysteine based on a tandem reaction of thiol-ene click chemistry and aminolysis involving 3-hydroxythalidomide as a parent compound. Experimental data exhibited that the probe showed unique selectivity and sensitivity for cysteine over other amino acid and biothiols. In addition, the fluorescent intensity at 511 nm increased linearly as a function of cysteine concentration in the range of 0-6 × 10-7 M (regression factor, R2 = 0.999), with a limit of detection of 6.1 nM. The sensing mechanism was confirmed through 1H NMR titration and density functional theory calculations. Additionally, the probe was also successfully utilized for the detection of cysteine in sewage and for bioimaging in HeLa cells.

High-Precision Measurement of Microscales Based on Optoelectronics and Image Integration Method.

Currently, there are various types of microscales and the conventional line detection system usually has only one detection method, which is difficult to adapt to the diverse calibration needs of microscales. This article investigates the high-precision measurement method of a microscale based on optoelectronics and the image integration method to solve the diversified calibration needs of microscales. The automatic measurement and processing system integrates two methods: the photoelectric signal measurement method and the photoelectric image measurement method. This article studies the smooth motion method based on ordinary linear guides, investigates the method of reducing the cosine error of a small-range interference length measurement, proposes an image-based line positioning method, and studies the edge and center recognition algorithms of the line. According to the experimental data, the system's measurement accuracy was analyzed using the photoelectric signal measurement method to measure the 1 mm microscale, the maximum difference from the reference value was 0.105 µm, the standard uncertainty was 0.068 µm, and the absolute value of normalized error was less than 1. The accuracy of the image measurement method to measure the 1 mm microscale was consistent with that of the photoelectric signal method. The results show good consistency in the measurement results between the two methods of the integrated measurement system. The photoelectric signal method has the technical characteristics of high measurement efficiency and high accuracy, while the pixel-based measurement of the image method has two-dimensional measurement characteristics, which can realize measurements that cannot be realized by the photoelectric signal method; therefore, the measurement system of optoelectronics and image integration is characterized by high precision and a wide range of measurement adaptations.

Discovery of novel nitrofuran PROTAC-like compounds as dual inhibitors and degraders targeting STING.

Aberrant activation of the innate immune molecule STING can initiate inflammation and autoimmune diseases. Small molecule inhibitors targeting STING have demonstrated therapeutic efficacy against these conditions. Moreover, employing degradants to target STING represents a novel approach to drug design strategy. Consequently, we have designed and synthesized a series of covalent degradants targeting STING. Among them, compound P8 exhibited the highest degradation capacity, with a 24-h DC50 of 2.58 µM in THP-1 cells. In THP-1 cells, P8 specifically degraded STING proteins through the lysosomal pathway, acting as dual a degrader and inhibitor to manifest anti-inflammatory effects. Conversely, in RAW264.7 cells, P8 solely acted as an inhibitor without exhibiting degradative capacity towards the STING protein level. Additionally, P8 displayed renal-protective properties in a cisplatin-induced acute kidney injury model. These results highlight the significant potential of further investigating compound P8.

Proteomic Differences in Colonic Epithelial Cells in Ulcerative Colitis Have an Epigenetic Basis.

Background and Aims: The colonic epithelium serves as both a barrier to lumenal contents and a gatekeeper of inflammatory responses. In ulcerative colitis (UC), epithelial dysfunction is a core feature, but little is known about the cellular changes that may underlie disease pathology. We therefore evaluated how the chromatin epigenetics and proteome of epithelial cells differs between health and UC. Methods: We sorted live CD326+ epithelial cells from colon biopsies of healthy control (HC) screening colonoscopy recipients and from inflamed or uninflamed colon segments of UC patients on no biologic nor immunomodulator therapy (n = 5-7 subjects per group). Cell lysates were analyzed by proteomic evaluation and nuclei were analyzed for open chromatin with assay for transposase-accessible chromatin using sequencing. Results: Proteins most highly elevated in inflamed UC biopsies relative to HC were those encoded by the HLA-DRA (P = 3.1 × 10-33) and CD74 (P = 1.6 × 10-27), genes associated with antigen presentation, and the antimicrobial dual oxidase 2 (DUOX2) (P = 3.2 × 10-28) and lipocalin-2 (P = 2.2 × 10-26) genes. Conversely, the water channel aquaporin 8 was strikingly less common with inflammation (P = 1.9 × 10-18). Assay for transposase-accessible chromatin using sequencing revealed more open chromatin around the aquaporin 8 gene in HCs (P = 2.0 × 10-2) and more around the DUOX2/DUOXA2 locus in inflamed UC colon (P = 5.7 × 10-4), suggesting an epigenetic basis for differential protein expression by epithelial cells in health and disease. Conclusion: Numerous differences exist between the proteome and chromatin of colonic epithelial cells in UC patients and HCs, some of which correlate to suggest specific epigenetic mechanisms regulating the epithelial proteome.

Synergistic Intramolecular Non-Covalent Interactions Enable Robust Pure-Blue TADF Emitters.

Stability-issues of organic light-emitting diodes (OLEDs) employing thermally activated delayed fluorescence (TADF) require further advancements, especially in pure-blue range of CIEy < 0.20, existing a dilemma between color purity and device lifetime. Though improving bond-dissociation-energy (BDE) can effectively improve material intrinsic stability, strategies to simultaneously improve BDE and photophysical performances are still lacking. Herein, it is disclosed that synergistic intramolecular non-covalent interactions (Intra-NI) can achieve not only the highest C─N BDE among blue TADF materials, but enhanced molecular-rigidity, near-unity photoluminescent quantum yields and short delayed lifetime. Pure-blue TADF-OLEDs based on proof-of-concept TADF material realize high external-quantum-efficiency and record-high LT80@500 cd m-2 of 109 h with CIEy = 0.16. Furthermore, deep-blue TADF-sensitized devices exhibit high LT80@500 cd m-2 of 81 h with CIEy = 0.10. The findings provide new insight into the critical role of Intra-NI in OLED materials and open the way to tackling vexing stability issues for developing robust pure-blue organic emitters and other functional materials.

[Effect of Pterostilbene Regulating Nuclear Factor E2-Related Factor 2 on Apoptosis of Colon Cancer Cells in Vitro].

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2 (Nrf2) in the process of pterostilbene acting on LoVo cells. Methods LoVo cells were treated with different concentrations (5,10,20,40,60,80,100 µmol/L) of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Transwell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochondrial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlorofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic proteins (Bcl2 and Bax) were determined by Western blotting.In addition,cell viability,Nrf2 expression,and apoptosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane. Results Compared with the control group,40,60,80,100 µmol/L pterostilbene reduced the viability of LoVo cells (P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 µmol/L did not show effects on cell viability but inhibited cell migration (P=0.008,P<0.001,P<0.001) and invasion (all P<0.001).Pterostilbene at 40,60,80 µmol/L increased apoptosis (P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization (P=0.026,P<0.001,P<0.001) and reactive oxygen species accumulation (all P<0.001),and down-regulated the expression of phosphorylated Nrf2 (P=0.030,P<0.001,P<0.001),heme oxygenase 1 (P=0.015,P<0.001,P<0.001),and Bcl2 (P=0.039,P<0.001,P<0.001) in LoVo cells.Pterostilbene at 60,80 µmol/L down-regulated Nrf2 expression (P=0.001,P<0.001) and up-regulated Bax expression (both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability (P<0.001),apoptosis (P<0.001),and Nrf2 expression (P=0.022). Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

[Application of ARHGAP8 in Predicting the Efficacy of Neoadjuvant Chemotherapy for Locally Advanced Mid-Low Rectal Cancer].

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer. Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were selected.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARHGAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the patients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expression.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups. Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue (P<0.001).The expression level of ARHGAP8 was correlated with tumor stage (P=0.024),lymph node metastasis (P=0.007),and age (P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P<0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P=0.011).The expression of ARHGAP8 was correlated with tumor size (P=0.010) and pathological stage (P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 patients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91% (29/44) patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy (P<0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that (53.33%) in the patients with high protein level of ARHGAP8 (P=0.033). Conclusion ARHGAP8 is highly expressed in the rectal cancer tissue.The patients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and development of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.

Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.

Thermodynamically spontaneously intercalated H3O+ enables LiMn2O4 with enhanced proton tolerance in aqueous batteries.

LiMn2O4 (LMO) is an attractive positive electrode material for aqueous lithium-ion batteries (ALIBs), but its inferior cycle performance limits the practical application. The degradation mechanism of LMO in ALIBs is still unclear, resulting in inability to predictably improve its structural stability. The electrode/electrolyte interface is believed to play an important role in electrode degradation. However, the interactions of the water-containing electrode/electrolyte interface of LMO are underexplored. In this work, we demonstrate the insertion of H3O+ into LMO during cycling in aqueous electrolyte and elucidate the paradoxical effects of H3O+. The crystal H3O+ enhances the structural stability of LMO by forming a gradient Mn4+-rich protective shell, but an excess amount of crystal H3O+ leads to poor Li+ conductivity, resulting in rapid capacity fading. Combining electrochemical analyses, structural characterizations, and first-principles calculations, we reveal the intercalation of H3O+ into LMO and its associated mechanism on the structural evolution of LMO. Furthermore, we regulate the crystal H3O+ content in LMO by modifying the hydrogen bond networks of aqueous electrolyte to restrict H2O molecule activity. This approach utilizes an appropriate amount of crystal H3O+ to enhance the structural stability of LMO while maintaining sufficient Li+ diffusion.

[Distribution Characteristics and Ecological Risk Assessment of Heavy Metals in Roadside Soil of Important National Highways on the Qinghai-Xizang Plateau].

To clarify the impact of transportation on the sensitive and fragile ecosystems of the Qinghai Tibet Plateau and major ecological safety barrier functions, soil samples within 0-25 m on the roadside were collected from sections of national highways such as G214, G213, G345, G109, G316, and G317, and the contents of six heavy metals were analyzed. Then, the degree of heavy metal pollution and the risk of ecological hazards were evaluated using the single-factor pollution index method （Pi）, Nemero comprehensive index method （PN）, and potential ecological risk index method （RI）. The results showed that the heavy metal contents of As, Cd, Hg, Ni, Pb, and Zn in the soil of important transportation national roads on the Qinghai Tibet Plateau ranged from 5.65 to 176.00, 0.04 to 0.27, 0.01 to 0.14, 9.52 to 113.00, 9.16 to 54.50, and 24.70 to 109.00 mg·kg-1, respectively, showing high variability. In some sections of the soil, the values of the elements As, Cd, and Hg were higher than the local soil background values. The single-factor pollution index of heavy metals in roadside soil was Pi （As） > Pi （Hg） > Pi（Cd） > Pi （Pb） > Pi （Ni） > Pi （Zn）. The Nemero comprehensive pollution index ranged from 0.41 to 9.20, with an average value of 1.53, indicating clean and mild pollution. Some areas showed a moderate or severe pollution. The average potential ecological risk index of the research section was 106.2, and the soil was generally in a state of no pollution and light pollution. Only two road sections had soil heavy metal enrichment reaching moderate and strong ecological hazards. The comprehensive potential risk of the G213a road section indicated moderate to severe ecological risk, mainly contributed by Hg, As, and Cd. The comprehensive pollution risk of the G317 road section indicated mild to moderate ecological risk, mainly contributed by Hg and Cd. The heavy metal content in the soil of the Qinghai Tibet Plateau road area was not significantly correlated with the roadside distance and soil depth but was significantly positively correlated with the annual average temperature （P < 0.05）. In all, there was a trend of heavy metal input into the soil environment in areas with intense human activities and high traffic flow during road construction on the Qinghai Tibet Plateau.

Main group metal elements enhance electrochemical nitrogen reduction reaction of vanadium-based single atom catalysts through d-p orbital hybridization.

Developing active sites with flexibility and diversity is crucial for single atom catalysts (SACs) towards sustainable nitrogen fixation at ambient conditions. Herein, the effects of doping main group metal elements (MGM) on the stability, catalytic activity, and selectivity of vanadium-based SACs is systematically investigated based on density functional theory calculations. It is found that the catalytic activity of V site can be significantly enhanced by the synergistic effect between MGM and vanadium atoms. More importantly, a volcano curve between the catalytic activity and the adsorption free energy of NNH* can be established, in which V-Pb dimer embedded on N-coordinated graphene (VPb-NG) exhibits optimal NRR activity due to its location at the top of volcano. Further analysis of electronic structures reveals that the unoccupancy ratio (eg/t2g) of V site is dramatically increased by the strong d-p orbital hybridization between V and Pb atoms, subsequently, N2 is activated to a larger extent. These interesting findings may provide a new path for designing active sites in SACs with excellent performance.

[Study on related influencing factors on the occurrence of redundant sign in the cauda equina in lumbar spinal stenosis].

OBJECTIVE: To analyze the relational factors influencing the formation of cauda equina redundant nerve roots (RNRs) of the lumbar spinal stenosis. METHODS: Clinical data of 116 patients with lumbar spinal stenosis treated from January 2016 to June 2019 were retrospectively analyzed. The patients were divided into redundant nerve roots(RNRs) group and non-RNRs group based on the presence or absence of RNRs on sagittal T2-weighted MRI. In the non-RNRs group, there were 74 patients, including 38 males and 36 females with an average age of (62.00±10.41) years old, the body mass index (BMI) was (23.09±2.22) kg·m-2;the maximum stenosis segment was L2-L3 in 12 cases, L3-L4 in 38, L4-L5 in 20, and L5S1 in 4, respectively. In the RNRs group, there were 42 patients, including 18 males and 24 females with an average age of (63.36±8.73) years old, the BMI was (22.63±2.60) kg·m-2;the maximum stenosis segment was L2-L3 in 3 cases, L3-L4 in 9, L4-L5 in 27 and L5S1 in 3, respectively. MRI was performed in the supine position to observe the conshape and morphology of the redundant nerve in the sagittal position. The preoperative low back and leg pain visual analogue scale(VAS), and preoperative Oswestry disability index(ODI) were analyzed, and the rate of spondylolisthesis and ligamentum flavum hypertrophy were compared. Simultaneously, the inter-vertebral height, intervertebral foramen height, inter-vertebral height+vertebral height, median sagittal diameter at the inter-vertebral space level(DIW-MSD), median sagittal diameter at the pedicel level(DV-MSD), range of motion(ROM) of the stenotic segment were measured and analyzed. RESULTS: Among the 116 patients with lumbar spinal stenosis, 42 patients developed RNRs, with an incidence of 36.2%. There were no significant differences in gender, age, BMI, preoperative VAS for lumbar and leg pain and ODI between two groups(P>0.05). There were statistically significant differences regard to the duration of symptoms and the rate of spondylolisthesis and ligamentum flavum hypertrophy (P<0.05);the inter-vertebral height, intervertebral foramen height, inter-vertebral height+vertebral height, DIW-MSD, ROM of the stenotic segment were also significantly different between two groups(P<0.05). However, there was no significant difference in DV-MSD between two groups(P>0.05). CONCLUSION: The inter-vertebral height, inter-vertebral foramen height, inter-vertebral height+vertebral height, DIW-MSD and ROM of the stenotic segment were the crucial factors related to RNRs in lumbar spinal stenosis.

Plant traits regulated metal(loid)s in dominant herbs in an antimony mining area of the karst zone, China.

Understanding how plant functional traits respond to mining activities and impact metal(loid)s accumulation in dominant species is crucial for exploring the driving mechanisms behind plant community succession and predicting the ecological restoration potential of these plants. In this study, we investigated four dominant herbaceous species (Artemisia argyi, Miscanthus sinensis, Ficus tikoua, and Ageratina adenophora) growing on antimony (Sb) mining sites (MS) with high Sb and arsenic (As) levels, as well as non-mining sites (NMS). The aim was to analyze the variations in functional traits and their contribution to Sb and As concentrations in plants. Our results indicate that mining activities enhanced soil nitrogen (N) limitation and phosphorus (P) enrichment, while significantly reducing the plant height of three species, except for F. tikoua. The four species absorbed more calcium (Ca) to ensure higher tolerance to Sb and As levels, which is related to the activation of Ca signaling pathways and defense mechanisms. Furthermore, plant Sb and As concentrations were dependent on soil metal(loid) levels and plant element stoichiometry. Overall, these findings highlight the regulatory role of plant element traits in metal(loid) concentrations, warranting widespread attention and further study in the future.

A Probe-Free Occupancy Assay to Assess a Targeted Covalent Inhibitor of Receptor Tyrosine-Protein Kinase erbB-2.

Establishing target engagement is fundamental to effective target-based drug development. It paves the way for efficient medicinal chemistry design and definitive answers about target validation in the clinic. For irreversible targeted covalent inhibitor (TCI) drugs, there is a unique opportunity to establish and quantify the target engagement or occupancy. This is typically accomplished by using a covalent molecular probe, often a TCI analogue, derivatized to allow unoccupied target sites to be tracked; the difference of total sites minus unoccupied sites yields the occupied sites. When such probes are not available or the target is not readily accessible to covalent probes, another approach is needed. Receptor tyrosine-protein kinase erbB-2 (HER2) occupancy by afatinib presents such a case. Available HER2 covalent probes were unable to consistently modify HER2 after sample preparation, resulting in inadequate data. We demonstrate an alternative quantitative probe-free occupancy (PFO) method. It employs the immunoprecipitation of HER2 and direct mass spectrometer analysis of the cysteine-containing peptide that is targeted and covalently occupied by afatinib. Nontarget HER2 peptides provide normalization to the total protein. We show that HER2 occupancy by afatinib correlates directly to the inhibition of the receptor tyrosine kinase activity in NCI-N87 cells in culture and in vivo using those cells in a mouse tumor xenograft mode.

Characterization of the stem cell landscape and identification of a stemness-associated prognostic signature in bladder cancer.

It is accepted that cancer stem cells (CSCs) are key to the occurrence, progression, drug resistance, and recurrence of bladder cancer (BLCA). Here, we aimed to characterize the landscapes of CSCs and investigate the biological and clinical signatures based on a prognostic model constructed by genes associated with CSCs. The malignant epithelial cells were discovered and sorted into six clusters through single cell analysis. C2 was identified as the CSCs. The signaling involved in the interactions between C2, cancer-associated fibroblasts (CAFs), and immune cells mainly consisted of MK, THBS, ANGPTL, VISFATIN, JAM, and ncWNT pathways. The CSC-like prognostic index (CSCLPI) constructed by the random survival forest was a reliable risk factor for BLCA and had a stable and powerful effect on predicting the overall survival of patients with BLCA. The level of CAFs was higher among patients with higher CSCLPI scores, suggesting that CAFs play a significant role in regulating biological characteristics. The CSCLPI-developed survival prediction nomogram has the potential to be applied clinically to predict the 1-, 2-, 3-, and 5-year overall survival of patients with BLCA. The CSCLPI can be used for prognostic prediction and drug treatment evaluation in the clinic.

Lactate regulates pathological cardiac hypertrophy via histone lactylation modification.

Under the long-term pressure overload stimulation, the heart experiences embryonic gene activation, leading to myocardial hypertrophy and ventricular remodelling, which can ultimately result in the development of heart failure. Identifying effective therapeutic targets is crucial for the prevention and treatment of myocardial hypertrophy. Histone lysine lactylation (HKla) is a novel post-translational modification that connects cellular metabolism with epigenetic regulation. However, the specific role of HKla in pathological cardiac hypertrophy remains unclear. Our study aims to investigate whether HKla modification plays a pathogenic role in the development of cardiac hypertrophy. The results demonstrate significant expression of HKla in cardiomyocytes derived from an animal model of cardiac hypertrophy induced by transverse aortic constriction surgery, and in neonatal mouse cardiomyocytes stimulated by Ang II. Furthermore, research indicates that HKla is influenced by glucose metabolism and lactate generation, exhibiting significant phenotypic variability in response to various environmental stimuli. In vitro experiments reveal that exogenous lactate and glucose can upregulate the expression of HKla and promote cardiac hypertrophy. Conversely, inhibition of lactate production using glycolysis inhibitor (2-DG), LDH inhibitor (oxamate) and LDHA inhibitor (GNE-140) reduces HKla levels and inhibits the development of cardiac hypertrophy. Collectively, these findings establish a pivotal role for H3K18la in pathological cardiac hypertrophy, offering a novel target for the treatment of this condition.

Underestimation of calcium carbonate saturation state in marginal seas due to the disregard of calcium ion addition: A case study of the Bohai sea, China.

Seawater calcium ion (Ca2+) concentration was investigated based on the potentiometric titration method during the summer of 2018 in the Bohai Sea, China. The measured Ca2+ concentration ranged from 7760 to 9739 µmol kg-1 and deviated from the theoretical Ca2+ values, which were estimated from the calcium/salinity ratio. The excess calcium (Ca2+excess) ranged from 186 to 1229 µmol kg-1, showing a decreasing trend from the estuary to the nearshore, and then the offshore areas. Riverine input was an important source of seawater Ca2+excess in the Bohai Sea. Biological activity was another factor in regulating seawater Ca2+excess by precipitation in the Yellow River estuary and dissolution in other area of the Bohai Sea. Furthermore, the aragonite saturation state (Ωarag) values calculated from the measured Ca2+ concentrations showed a significant deviation from the values calculated from the theoretical Ca2+ concentrations, especially in the estuarine area with a maximum difference of 18.5%. Therefore, the disregard of the calcium addition would lead to an underestimation of the calcium carbonate saturation state and a deviation in the assessment of ocean acidification in marginal seas.

Sea surface carbon dioxide during early summer at the Tuandao nearshore time series site.

To investigate air-sea CO2 flux at the Qingdao nearshore site and its temporal variations, a high-resolution continuous observation of surface carbon dioxide partial pressure (pCO2) was carried out at Zhongyuan Pier near Tuandao from May 25 to July 8, 2019. It was observed that during this period, surface pCO2 varied between ∼490 and ∼690 µatm, mainly associated with sea surface temperature. Surface pCO2 also displayed substantial diurnal variations, with an average amplitude of 64 ± 21 µatm, largely dominated by biological activities. During the observational period, this site acted as a source of atmospheric CO2, releasing 361 mmol CO2 m-2. The notable diurnal variations in air-sea CO2 flux, such as the observed average amplitude of 10.9 mmol m-2 d-1 in this study, pose a challenge for accurately estimating the air-sea CO2 flux in coastal regions without high-resolution observations.