Restoring Treg/Th17 cell balance in ulcerative colitis through HRas silencing and MAPK pathway inhibition.

This study investigates HRas-dependent mechanisms in the disruption of regulatory T (Treg) cells and T helper 17 (Th17) cells balance in ulcerative colitis (UC). Comprehensive RNA sequencing and bioinformatics analyses revealed elevated HRas and MAPK pathway-related protein expression in UC samples. Using a murine UC model induced by dextran sulfate sodium (DSS), HRas silencing was found to promote Treg cell differentiation and suppress Th17 cell production, effectively restoring balance. Inactivation of the MAPK pathway played a pivotal role in this rebalancing effect. In vivo experiments further confirmed that HRas silencing mitigated colon tissue damage in DSS-induced mice, emphasizing its potential as a therapeutic strategy for UC.

Efficacy and safety of tongxinluo capsule for angina pectoris of coronary heart disease: an overview of systematic reviews and meta-analysis.

Background: Tongxinluo capsule (TXLC) is a common drug for treating angina pectoris of coronary heart disease (CHD). In recent years, many systematic reviews (SRs) and meta-analyses (MAs) have reported the efficacy and safety of TXLC for improving angina symptoms in patients with CHD. We aimed to comprehensively evaluate the existing SRs and MAs of TXLC in treating angina pectoris of CHD, summarize the evidence quality, and provide scientific evidence and recommendations. Methods: We searched seven databases for relevant SRs/MAs published up to 1 June 2023. Two reviewers independently completed the literature retrieval, screening, and data extraction. We used A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality, the Risk of Bias in Systematic Reviews (ROBIS) to assess the risk of bias, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to determine the strength of the evidence. RevMan 5.3 was used to synthesize data. Results: We identified 15 SRs/MAs, including 329 RCTs and 33,417 patients. According to the evaluation results of AMSTAR-2, only one SR was of high methodological quality, the others were very low. ROBIS assessment showed that one SR (6.67%) had a low risk, 3 SRs (20%) had an unclear risk, and 11 SRs (73.33%) had a high risk. We assessed 42 outcomes by the GRADE, 10 (23.81%) for moderate-quality evidence, 17 (40.48%) for low-quality evidence, and 15 (35.71%) for very-low-quality evidence. Mate-analysis showed that TXLC combined with conventional western medications improved electrocardiogram efficacy (RR = 1.38, 95% CI: 1.23-1.43, P < 0.001) and angina efficacy (OR = 3.58, 95% CI: 3.02-4.24, P < 0.001), reduced angina attack frequency (SMD = -0.54, 95% CI: -0.64 to -0.44, P < 0.001) and angina duration (SMD = -0.42, 95% CI: -0.57 to -0.28, P < 0.001), with general heterogeneity. The pooled results showed that TXLC appears to have some efficacy in improving cardiac function and relieving angina symptoms, but there is limited evidence that it improves cardiovascular event rates, hemorheology, lipids, or hs-CRP. In the assessment of drug safety, TXLC was associated with different degrees of adverse drug reactions. Conclusion: Based on the evidence, TXLC may be effective as an adjuvant treatment for angina pectoris of CHD. However, the quality of the evidence is low, and the drug's safety must be carefully interpreted. In future studies, high-quality randomized controlled trials are needed to confirm the effectiveness and safety of TXLC. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022365372).

2'-Hydroxycinnamaldehyde Alleviates Intestinal Inflammation by Attenuating Intestinal Mucosal Barrier Damage Via Directly Inhibiting STAT3.

BACKGROUND: The currently available clinical therapeutic drugs for ulcerative colitis (UC) are considered inadequate owing to certain limitations. There have been reports on the anti-inflammatory effects of 2'-hydroxycinnamaldehyde (HCA). However, whether HCA can improve UC is still unclear. Here, we aimed to investigate the pharmacological effects of HCA on UC and its underlying molecular mechanisms. METHODS: The pharmacological effects of HCA were comprehensively investigated in 2 experimental setups: mice with dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-treated fetal human colon (FHC) cells. Furthermore, the interaction between HCA and signal transducer and activator of transcription 3 (STAT3) was investigated using molecular docking. The FHC cells with STAT3 knockdown or overexpression and mice with intestinal epithelium-specific STAT3 deletion (STAT3ΔIEC) were used to evaluate whether STAT3 mediated the pharmacological effects of HCA. RESULTS: 2'-Hydroxycinnamaldehyde attenuated dysregulated expression of inflammatory cytokines in a dose-dependent manner while increasing the expression of tight junction proteins, reducing the apoptosis of intestinal epithelial cells, and effectively alleviating inflammation both in vivo and in vitro. 2'-Hydroxycinnamaldehyde bound directly to STAT3 and inhibited its activation. The modulation of STAT3 activation levels due to STAT3 knockdown or overexpression influenced the mitigating effects of HCA on colitis. Further analysis indicated that the remission effect of HCA was not observed in STAT3ΔIEC mice, indicating that STAT3 mediated the anti-inflammatory effects of HCA. CONCLUSIONS: We present a novel finding that HCA reduces colitis severity by attenuating intestinal mucosal barrier damage via STAT3. This discovery holds promise as a potential new strategy to alleviate UC.

The current clinical therapeutic drugs for ulcerative colitis (UC) remain inadequate owing to certain adverse events. Administration of 2ʹ-hydroxycinnamaldehyde (HCA) significantly reduces colitis severity via direct inhibition of STAT3 to attenuate intestinal mucosal barrier damage. Hence, HCA may be a potential new strategy in UC.

Benchmarking of Coatings for Cathode Active Materials in Solid-State Batteries Using Surface Analysis and Reference Electrodes.

Fast and reliable evaluation of degradation and performance of cathode active materials (CAMs) for solid-state batteries (SSBs) is crucial to help better understand these systems and enable the synthesis of well-performing CAMs. However, there is a lack of well-thought-out procedures to reliably evaluate CAMs in SSBs. Current approaches often rely on X-ray photoelectron spectroscopy (XPS) for the evaluation of degradation. Unfortunately, XPS sensitivity is not very high, and minor but relevant degradation products may not be detected and distinguished. Furthermore, degradation caused by the current collector (CC) itself is usually not distinguished from CAM-induced degradation. This study uses a modified CC, which allows us to separate electrochemical degradation caused by the CC from degradation at the CAM itself. Using this CC, we present an approach using time-of-flight secondary ions mass spectrometry (ToF-SIMS) that offers high sensitivity and reliability. Principal component analysis (PCA) is applied to differentiate secondary ions as well as identify those mass fragments that correlate with degradation products. This approach also enables distinguishing between different pathways of degradation. To evaluate the kinetic performance of the samples, three-electrode rate tests are performed. Electrochemical characterization evaluates the kinetic performance of the samples under investigation. The samples are finally rated with a score that allows a reliable comparison between the different materials and offers a complete picture of the materials' characteristics in terms of electrochemical performance and degradation.

Graded-Band-Gap Zinc-Tin Oxide Thin-Film Transistors with a Vertically Stacked Structure for Wavelength-Selective Photodetection.

Filter-free wavelength-selective photodetectors have garnered significant attention due to the growing demand for smart sensors, artificial intelligence, the Internet of Everything, and so forth. However, the challenges associated with large-scale preparation and compatibility with complementary metal-oxide-semiconductor (CMOS) technology limit their wide-ranging applications. In this work, we address the challenges by constructing vertically stacked graded-band-gap zinc-tin oxide (ZTO) thin-film transistors (TFTs) specifically designed for wavelength-selective photodetection. The ZTO thin films with various band gaps are fabricated via atomic layer deposition (ALD) by varying the ALD cycle ratios of zinc oxide (ZnO) and SnO2. The ZTO film with a small Sn ratio exhibits a decreased band gap, and the resultant TFT shows a degraded performance, which can be attributed to the Sn4+ dopant introducing a series of deep-state energy levels in the ZnO band gap. As the ratio of Sn increases further, the band gap of the ZTO also increases, and the mobility of the ZTO TFT increases up to 30 cm2/V s, with a positive shift of the threshold voltage. The photodetectors employing ZTO thin films with distinct band gaps show different spectral responsivities. Then, vertically stacked ZTO (S-ZTO) thin films, with gradient band gaps increasing from the bottom to the top, have been successfully deposited using consecutive ALD technology. The S-ZTO TFT shows decent performance with a mobility of 18.4 cm2/V s, a threshold voltage of 0.5 V, an on-off current ratio higher than 107, and excellent stability under ambient conditions. The resultant S-ZTO TFT also exhibits obviously distinct photoresponses to light at different wavelength ranges. Furthermore, a device array of S-ZTO TFTs demonstrates color imaging by precisely reconstructing patterned illuminations with different wavelengths. Therefore, this work provides CMOS-compatible and structure-compact wavelength-selective photodetectors for advanced and integrable optoelectronic applications.

Dietary long-chain fatty acids promote colitis by regulating palmitoylation of STAT3 through CD36-mediated endocytosis.

The Western diet, characterized by its high content of long-chain fatty acids (LCFAs), is widely recognized as a significant triggering factor for inflammatory bowel disease (IBD). While the link between a high-fat diet and colitis has been observed, the specific effects and mechanisms remain incompletely understood. Our study provides evidence that the diet rich in LCFAs can disrupt the integrity of the intestinal barrier and exacerbate experimental colitis in mice. Mechanistically, LCFAs upregulate the signal transducer and activator of transcription-3 (STAT3) pathway in the inflammatory model, and STAT3 knockout effectively counters the pro-inflammatory effects of LCFAs on colitis. Specifically, palmitic acid (PA), a representative LCFA, enters intestinal epithelial cells via the cluster of differentiation 36 (CD36) pathway and participates in the palmitoylation cycle of STAT3. Inhibiting this cycle using pharmacological inhibitors like 2-Bromopalmitate (2-BP) and ML349, as well as DHHC7 knockdown, has the ability to alleviate inflammation induced by PA. These findings highlight the significant role of dietary LCFAs, especially PA, in the development and progression of IBD. Diet adjustments and targeted modulation offer potential therapeutic strategies for managing this condition. Model of LCFAs involvement in the palmitoylation cycle of STAT3 upon internalization into cells. Following cellular uptake through CD36, LCFAs are converted to palmitoyl-CoA. In the presence of DHHC7, palmitoyl-CoA binds to STAT3 at the C108 site, forming palmitoylated STAT3. Palmitoylation further promotes phosphorylation at the Y705 site of STAT3. Subsequently, palmitoylated STAT3 undergoes depalmitoylation by APT2 and translocates to the nucleus to exert its biological functions.

2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation.

BACKGROUND & AIMS: 2'-Fucosyllactose (2'-FL), the primary constituent of human milk oligosaccharides, has been identified as a potential regulator of inflammation in inflammatory bowel disease. Despite this recognition, the specific mechanisms through which 2'-FL alleviates ulcerative colitis (UC) remain ambiguous. This study seeks to investigate the potential anti-inflammatory properties of 2'-FL concerning intestinal inflammation and uncover the associated mechanisms. METHODS: C57BL/6J mice were orally administered a daily dose of 500 mg/kg 2'-FL for 11 consecutive days, followed by the induction of colitis using 3 % (wt/vol) dextran sulfate sodium (DSS) for the final 6 days. Subsequently, a comprehensive range of techniques, including an Acyl-biotin exchange assay, fluorescein-isothiocyanate-labeled dextran assay, histopathology, ELISA, quantitative real-time PCR, Western blot, immunofluorescence staining, immunohistochemistry staining, Alcian blue-periodic acid schiff staining, TdT-mediated dUTP nick end labeling, transmission electron microscopy, iTRAQ quantitative proteomics, bioinformatics analysis, and the generation of signal transducer and activator of transcription 3 (STAT3) knockout mice, were employed to explore the relevant molecular mechanisms. RESULTS: Administration of 2'-FL significantly ameliorated DSS-induced colitis in mice and enhanced the integrity of the intestinal mucosal barrier. 2'-FL downregulated the phosphorylation of STAT3 and inhibited STAT3-related signaling pathways in colon tissues, which, in turn, reduced inflammatory responses. Interestingly, knockdown of STAT3 attenuated the protective effects of 2'-FL, highlighting that 2'-FL-mediated inflammatory attenuation is dependent on STAT3 expression. Additionally, 2'-FL could influence STAT3 activation by modulating the palmitoylation and depalmitoylation of STAT3. CONCLUSIONS: 2'-FL promotes the recovery of the intestinal mucosal barrier and suppresses inflammation in ulcerative colitis by inhibiting the palmitoylation and phosphorylation of STAT3.

Maintaining Excellent Mechanical Properties via Additive Manufacturing of Low-N 25Cr-Type Duplex Stainless Steel.

Duplex stainless steel (DSS) exhibits good mechanical properties and corrosion resistance, and has attracted more and more attention within the fields of both science and technology. However, the increasing levels of N and of Cr, Mo, etc., as alloying elements in DSS increase production difficulty. In particular, the N element increases the risk of Cr2N precipitation, which can seriously deteriorate the thermal plasticity of DSS, while increasing its strength. For this reason, a low-N-content 25Cr-type DSS was designed in order to adapt additive manufacturing processes. With regard to the nano-inclusions of oxide precipitation and effective grain refinement, and considering the benefits of selective laser melting fabrication, a low-N 25Cr-type duplex stainless steel with a 0.09 wt.% N content achieved high mechanical properties, with a yield strength of 712 MPa and an elongation of 27.5%, while the V-notch impact toughness was 160 J/cm2. The microstructure evolution and the reasons behind the improvement in mechanical properties will be discussed in detail.

H19 Promoter DNA Methylation is Lower Among Early Abortion Patients Undergoing IVF Embryo Transfer.

BACKGROUND: H19 is the first long noncoding RNA (lncRNA) found to be associated with gene imprinting. It is highly expressed in the embryonic stage and may have important regulatory effects on human embryonic development. We investigated the differences between the levels of H19 promoter DNA methylation in the chorionic villi of patients who experienced spontaneous abortion (SA) following in vitro fertilization embryo transfer (IVF-ET) and those of patients with a normal early pregnancy (NEP). We also analyzed the associated DNA methyltransferase (DNMT) activity. METHODS: Chorionic villus tissue from patients with SA and NEP were collected. The DNA methylation levels of two CpG islands in the promoter region of the H19 gene in the two groups were detected by bisulfite sequencing, and the mRNA expression of DNMTs was analyzed by real-time polymerase chain reaction. RESULTS: The sample size of each group was 32, and there were no significant differences in baseline data, including age, parity, and body mass index, between the two groups. Among the 7 CpG islands measured, the methylation rates of 3 CpG islands (CpG 1, 6, and 7) were significantly lower in the SA group than in the NEP group (P < 0.01). The methylation levels of the other 4 CpG islands were not significantly different between the two groups. There were no differences in the expression of DNMT1 between the two groups (P > 0.05), but DNMT3a and DNMT3b RNA levels were significantly lower in SA group than in the NEP group (P < 0.01). CONCLUSIONS: The lower H19 promoter DNA methylation levels found in the chorionic villi of patients with SA patients following IVF-ET may be explained by decreased expression of DNMT3a and DNMT3b.

Fungal endophyte promotes plant growth and disease resistance of Arachis hypogaea L. by reshaping the core root microbiome under monocropping conditions.

Fungal endophytes play critical roles in helping plants adapt to adverse environmental conditions. The root endophyte Phomopsis liquidambaris can promote the growth and disease control of peanut plants grown under monocropping systems; however, how such beneficial traits are produced is largely unknown. Since the plant endophytic microbiome is directly linked to plant growth and health, and the composition of which has been found to be potentially influenced by microbial inoculants, this study aims to clarify the roles of root endophytic bacterial communities in P. liquidambaris-mediated plant fitness enhancement under monocropping conditions. Here, we found that P. liquidambaris inoculation induced significant changes in the root bacterial community: enriching some beneficial bacteria such as Bradyrhizobium sp. and Streptomyces sp. in the roots, and improving the core microbial-based interaction network. Next, we assembled and simplified a synthetic community (SynII) based on P. liquidambaris-derived key taxa, including Bacillus sp. HB1, Bacillus sp. HB9, Burkholderia sp. MB7, Pseudomonas sp. MB2, Streptomyces sp. MB6, and Bradyrhizobium sp. MB15. Furthermore, the application of the simplified synthetic community suppressed root rot caused by Fusarium oxysporum, promoted plant growth, and increased peanut yields under continuous monocropping conditions. The resistance of synII to F. oxysporum is related to the increased activity of defense enzymes. In addition, synII application significantly increased shoot and root biomass, and yield by 35.56%, 81.19%, and 34.31%, respectively. Collectively, our results suggest that the reshaping of root core microbiota plays an important role in the probiotic-mediated adaptability of plants under adverse environments.

Vinylene-Linked Emissive Covalent Organic Frameworks for White-Light-Emitting Diodes.

Covalent organic frameworks (COFs) have gained considerable attention due to their highly conjugated π-skeletons, rendering them promising candidates for the design of light-emitting materials. In this study, we present two vinylene-linked COFs, namely, VL-COF-1 and VL-COF-2, which were synthesized through the Knoevenagel condensation of 2,4,6-trimethyl-1,3,5-triazine with terephthalaldehyde or 4,4'-biphenyldicarboxaldehyde. Both VL-COF-1 and VL-COF-2 exhibited excellent chemical and thermal stability. The presence of vinylene linkages between the constituent building blocks in these COFs resulted in broad excitation and emission properties. Remarkably, the designed VL-COFs demonstrated bright emission, fast fluorescence decay, and high stability, making them highly attractive for optoelectronic applications. To assess the potential of these VL-COFs in practical devices, we fabricated white-light-emitting diodes (WLEDs) coated with VL-COF-1 and VL-COF-2. Notably, the WLEDs coated with VL-COF-1 achieved high-quality white light emission, closely approximating standard white light. The promising performance of VL-COF-coated WLEDs suggests the feasibility of utilizing COF materials for stable and efficient lighting applications.

A HER2-targeting antibody-MMAE conjugate RC48 sensitizes immunotherapy in HER2-positive colon cancer by triggering the cGAS-STING pathway.

Human epidermal growth factor receptor 2 (HER2) is a protein that is overexpressed in some types of cancer, including breast and urothelial cancer. Here we found that HER2 was present in a portion of colon cancer patients, raising the possibility of using anti-HER2 therapy. RC48, a novel antibody-drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-HER2 antibody tethered via a linker, showed a comparable therapeutic effect in both HER2 low expressed (IHC2+/FISH- or IHC+) and high expressed urothelial cancer patients. In vitro studies using colon cancer cell lines showed that RC48 effectively impeded the proliferation of HER2-positive cells, indicating its potential as a treatment for HER2-positive colon cancer. Mechanism study showed that RC48 not only induces cell cycle arrest but also disrupts HER2-mediated restain of cGAS-STING signaling, potentially activating an immune response against the cancer cells. The administration of RC48 significantly reduced the growth of HER2-positive colon cancer and made HER2-positive colon cancer cells more susceptible to immunotherapy. The results of our study will contribute to determining the feasibility of RC48 as a therapeutic option for HER2-positive colon cancer.

Exosomal-miR-129-2-3p derived from Fusobacterium nucleatum-infected intestinal epithelial cells promotes experimental colitis through regulating TIMELESS-mediated cellular senescence pathway.

Fusobacterium nucleatum (Fn) infection is known to exacerbate ulcerative colitis (UC). However, the link between Fn-infected intestinal epithelial cell (IEC)-derived exosomes (Fn-Exo) and UC progression has not been investigated. Differentially expressed miRNAs in Fn-Exo and non-infected IECs-derived exosomes (Con-Exo) were identified by miRNA sequencing. Then, the biological role and mechanism of Fn-Exo in UC development were determined in vitro and in vivo. We found that exosomes delivered miR-129-2-3p from Fn-infected IECs into non-infected IECs, exacerbating epithelial barrier dysfunction and experimental colitis. Mechanically, Fn-Exo induces DNA damage via the miR-129-2-3p/TIMELESS axis and subsequently activates the ATM/ATR/p53 pathway, ultimately promoting cellular senescence and colonic inflammation. In conclusion, Exo-miR-129-2-3p/TIMELESS/ATM/ATR/p53 pathway aggravates cellular senescence, barrier damage, and experimental colitis. The current study revealed a previously unknown regulatory pathway in the progression of Fn-infectious UC. Furthermore, Exosomal-miR-129-2-3p in serum and TIMELESS may function as novel potential diagnostic biomarkers for UC and Fn-high-UC.

Vaccination against coronavirus disease 2019 in patients with pulmonary hypertension: a national prospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH. METHODS: In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients. RESULTS: In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). CONCLUSIONS: COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Improving Flavonoid Accumulation of Bioreactor-Cultured Adventitious Roots in Oplopanax elatus Using Yeast Extract.

Oplopanax elatus is an endangered medicinal plant, and adventitious root (AR) culture is an effective way to obtain its raw materials. Yeast extract (YE) is a lower-price elicitor and can efficiently promote metabolite synthesis. In this study, the bioreactor-cultured O. elatus ARs were treated with YE in a suspension culture system to investigate the elicitation effect of YE on flavonoid accumulation, serving for further industrial production. Among YE concentrations (25-250 mg/L), 100 mg/L YE was the most suitable for increasing the flavonoid accumulation. The ARs with various ages (35-, 40-, and 45-day-old) responded differently to YE stimulation, where the highest flavonoid accumulation was found when 35-day-old ARs were treated with 100 mg/L YE. After YE treatment, the flavonoid content increased, peaked at 4 days, and then decreased. By comparison, the flavonoid content and antioxidant activities in the YE group were obviously higher than those in the control. Subsequently, the flavonoids of ARs were extracted by flash extraction, where the optimized extraction process was: 63% ethanol, 69 s of extraction time, and a 57 mL/g liquid-material ratio. The findings provide a reference for the further industrial production of flavonoid-enriched O. elatus ARs, and the cultured ARs have potential application for the future production of products.

High Performance On-Chip Energy Storage Capacitors with Plasma-Enhanced Atomic Layer-Deposited Hf0.5Zr0.5O2/Al-Doped Hf0.25Zr0.75O2 Nanofilms as Dielectrics.

Concurrently achieving high energy storage density (ESD) and efficiency has always been a big challenge for electrostatic energy storage capacitors. In this study, we successfully fabricate high-performance energy storage capacitors by using antiferroelectric (AFE) Al-doped Hf0.25Zr0.75O2 (HfZrO:Al) dielectrics together with an ultrathin (1 nm) Hf0.5Zr0.5O2 underlying layer. By optimizing the Al concentration in the AFE layer with the help of accurate controllability of the atomic layer deposition technique, an ultrahigh ESD of 81.4 J cm-3 and a perfect energy storage efficiency (ESE) of 82.9% are simultaneously achieved for the first time in the case of the Al/(Hf + Zr) ratio of 1/16. Meanwhile, both the ESD and ESE exhibit excellent electric field cycling endurance within 109 cycles under 5~5.5 MV cm-1, and robust thermal stability up to 200 °C. Thus, the fabricated capacitor is very promising for on-chip energy storage applications due to favorable integratability with the standard complementary metal-oxide-semiconductor (CMOS) process.

Integrative multi-omics deciphers the spatial characteristics of host-gut microbiota interactions in Crohn's disease.

Dysregulated host-microbial interactions play critical roles in initiation and perpetuation of gut inflammation in Crohn's disease (CD). However, the spatial distribution and interaction network across the intestine and its accessory tissues are still elusive. Here, we profile the host proteins and tissue microbes in 540 samples from the intestinal mucosa, submucosa-muscularis-serosa, mesenteric adipose tissues, mesentery, and mesenteric lymph nodes of 30 CD patients and spatially decipher the host-microbial interactions. We observe aberrant antimicrobial immunity and metabolic processes across multi-tissues during CD and determine bacterial transmission along with altered microbial communities and ecological patterns. Moreover, we identify several candidate interaction pairs between host proteins and microbes associated with perpetuation of gut inflammation and bacterial transmigration across multi-tissues in CD. Signature alterations in host proteins (e.g., SAA2 and GOLM1) and microbes (e.g., Alistipes and Streptococcus) are further imprinted in serum and fecal samples as potential diagnostic biomarkers, thus providing a rationale for precision diagnosis.

IRF7 and IFIT2 in mediating different hemorrhage outcomes for non-small cell lung cancer after bevacizumab treatment.

Background: Lung cancer has some of the highest morbidity and mortality worldwide among cancers, with non-small cell lung cancer (NSCLC) accounting for 85% of lung cancer diagnoses. Severe pulmonary hemorrhage (PH) is a serious potential adverse event in the treatment of lung cancer with bevacizumab. Significant clinical differences have been observed between patients with lung adenocarcinoma (LUAD) and those with lung squamous cell carcinoma (LUSC) after bevacizumab treatment; however, the underlying causes is unclear and requires further study. Methods: First, tumor tissues from LUAD and LUSC patients were stained with antibodies targeting CD31 and CD34 to assess the difference in microvessel density (MVD). Tube formation assays were performed using HMEC-1 cells cocultured with lung cancer cells. Single-cell sequencing data obtained from lung cancer tissues were then downloaded and analyzed to identify differentially expressed genes related to angiogenesis in LUAD and LUSC tumors. Real-time polymerase chain reaction, immunofluorescence analysis, small interfering RNA analysis, and enzyme-linked immunosorbent assay were performed to clarify the underlying causes. Results: The MVD of LUAD tissues was higher than that of LUSC tissues. Additionally, endothelial cells cocultured with LUAD cells had a higher MVD than did those cocultured with LUSC cells. Although bevacizumab mainly targets vascular endothelial growth factor (VEGF), the expression of VEGF in LUSC and LUAD cells was not significantly different (P>0.05). Further experiments showed that interferon regulatory factor 7 (IRF7) and interferoninduced protein with tetratricopeptide repeats 2 (IFIT2) were differentially expressed between LUSC and LUAD tumors. Higher IRF7 levels and lower IFIT2 levels in LUAD tumors were associated with higher MVD in LUAD tissues, which may be responsible for the different hemorrhage outcomes after bevacizumab treatment. Conclusions: Our data indicated that IRF7 and IFIT2 may account for the differential hemorrhage outcomes in patients with NSCLC after bevacizumab treatment, revealing a new mechanism underlying bevacizumab-induced pulmonary hemoptysis.