Stress triggers irritable bowel syndrome with diarrhea through a spermidine-mediated decline in type I interferon.

Irritable bowel syndrome with diarrhea (IBS-D) is a common and chronic gastrointestinal disorder that is characterized by abdominal discomfort and occasional diarrhea. The pathogenesis of IBS-D is thought to be related to a combination of factors, including psychological stress, abnormal muscle contractions, and inflammation and disorder of the gut microbiome. However, there is still a lack of comprehensive analysis of the logical regulatory correlation among these factors. In this study, we found that stress induced hyperproduction of xanthine and altered the abundance and metabolic characteristics of Lactobacillus murinus in the gut. Lactobacillus murinus-derived spermidine suppressed the basal expression of type I interferon (IFN)-α in plasmacytoid dendritic cells by inhibiting the K63-linked polyubiquitination of TRAF3. The reduction in IFN-α unrestricted the contractile function of colonic smooth muscle cells, resulting in an increase in bowel movement. Our findings provided a theoretical basis for the pathological mechanism of, and new drug targets for, stress-exposed IBS-D.

Photodynamic therapy with intratumoral injection of photosensitizers combined with immunotherapy brings hope to patients with refractory cutaneous malignant ulcers.

Cutaneous squamous cell carcinoma (CSCC) is common among the elderly, typically treated with surgery. However, for surgery-ineligible patients or those with non-healing wounds progressing to malignant ulcers, non-surgical local treatments are viable. This case details an 80-year-old with recurrent back CSCC and intractable malignant ulcers post-radiotherapy and chemotherapy. Treatment involved Hematoporphyrin Derivative (HpD) Photodynamic Therapy (PDT) with low-dose cindilimab immunotherapy (intravenous and intralesional). Two cycles achieved lesion remission, altering peripheral immune cell counts. HpD-PDT combined with immunotherapy is promising for treating CSCC, particularly with malignant ulcers.

Realizing Excellent Infrared Nonlinear Optical Performance in Eu-Based Chalcogenides via Rational Cross Substitution Strategy.

In recent years, rare-earth-based chalcogenides have gained attention promising materials in the field of infrared nonlinear optical (IR-NLO) applications owing to their exceptional physicochemical properties. However, they frequently encounter challenges such as adverse two-photon absorption and low laser-induced damage thresholds (LIDTs) caused by narrow optical band gaps (Eg), which limit their practical utility. In this study, we started with the centrosymmetric (CS) parent compound EuGa2S4 to develop two new noncentrosymmetric (NCS) Eu-based chalcogenides, namely, EuZnSiS4 and EuCdSiS4, employing a rational cross-substitution strategy. Despite having identical stoichiometry, both compounds crystallize in distinct NCS orthorhombic space groups [Fdd2 (no. 43) vs Ama2 (no. 40)], as confirmed by single-crystal structure analysis. Their crystal structures feature highly distorted tetrahedral motifs interconnected via corner-sharing, forming unique two-dimensional layers that host Eu2+ cations. Furthermore, both compounds exhibit robust phase-matching second-harmonic generation (SHG) intensities of 1.5 × AgGaS2 for EuZnSiS4 and 2.8 × AgGaS2 for EuCdSiS4 under 2050 nm excitation. They also demonstrate high LIDTs (approximately 14-17 × AgGaS2), wide Eg (>2.5 eV), and transparency windows extending up to 18.2 µm. Particularly noteworthy, EuCdSiS4 stands out as a pioneering example in the Eu-based IR-NLO system for successfully combining a broad Eg (>2.56 eV, equivalent to that of AgGaS2) with a significant SHG effect (>1.0 × AgGaS2) simultaneously. Structural analyses and theoretical insights underscore that the reasonable combination of asymmetric functional units plays a pivotal role in driving the CS-to-NCS structural transformation and enhancing the NLO and linear optical properties of these Eu-based chalcogenides. This study presents a promising chemical pathway for advancing rare-earth-based functional materials and suggests exciting opportunities for their future applications in IR-NLO technologies.

Bifunctional Oxygen-Defect Bismuth Catalyst toward Concerted Production of H2O2 with over 150% Cell Faradaic Efficiency in Continuously Flowing Paired-Electrosynthesis System.

The electrosynthesis of hydrogen peroxide (H2O2) from O2 or H2O via the two-electron (2e-) oxygen reduction (2e- ORR) or water oxidation (2e- WOR) reaction provides a green and sustainable alternative to the traditional anthraquinone process. Herein, a paired-electrosynthesis tactic is reported for concerted H2O2 production at a high rate by coupling the 2e- ORR and 2e- WOR, in which the bifunctional oxygen-vacancy-enriched Bi2O3 nanorods (Ov-Bi2O3-EO), obtained through electrochemically oxidative reconstruction of Bi-based metal-organic framework (Bi-MOF) nanorod precursor, are used as both efficient anodic and cathodic electrocatalysts, achieving concurrent H2O2 production at both electrodes with high Faradaic efficiencies. Specifically, the coupled 2e- ORR//2e- WOR electrolysis system based on such distinctive oxygen-defect Bi catalyst displays excellent performance for the paired-electrosynthesis of H2O2, delivering a remarkable cell Faradaic efficiency of 154.8% and an ultrahigh H2O2 production rate of 4.3 mmol h-1 cm-2. Experiments combined with theoretical analysis reveal the crucial role of oxygen vacancies in optimizing the adsorption of intermediates associated with the selective two-electron reaction pathways, thereby improving the activity and selectivity of the 2e- reaction processes at both electrodes. This work establishes a new paradigm for developing advanced electrocatalysts and designing novel paired-electrolysis systems for scalable and sustainable H2O2 electrosynthesis.

Screening Strategy Identifies an Overlooked Deep-Ultraviolet Transparent Nonlinear Optical Crystal.

In the deep-ultraviolet (DUV) region, nonlinear optical (NLO) crystals must meet stringent requirements, including a large optical band gap and sufficient second harmonic generation (SHG) response. Typically, these criteria are fulfilled by borates, carbonates and nitrates containing π-conjugated groups. In contrast, sulfates and phosphates, with polarizabilities significantly smaller than those of π-conjugated groups, struggle to achieve similar performance. Here, we present the discovery of Mg2PO4Cl, a magnesium-based phosphate, identified from over 10,000 phosphates based on a polar-axial-symmetry screening strategy, which exhibits the highest SHG response (5.2 × KH2PO4 (KDP)) with phase-matching ability among non-π-conjugated DUV transparent NLO crystals. This compound belongs to the Pna21 space group, with [PO4] units consistently aligned along the 21 screw axis and glide planes throughout its crystal structure. Theoretical calculations attribute its remarkable SHG effect to the orderly arrangement of heteroanionic [MgO5Cl] and [MgO4Cl2] polyhedra alongside isolated [PO4] tetrahedra, supported by Berry phase analysis. Furthermore, a crystallographic structure analysis of phosphates and sulfates with significant SHG effects validates the effectiveness of our screening strategy. These findings offer valuable insights into the origins of NLO effects in non-π-conjugated compounds from both a material design and structural chemistry perspective, inspiring future efforts to revitalize DUV phosphates.

Broadband and fabrication-tolerant 3-dB couplers with topological valley edge modes.

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

Young infants with symptomatic tetralogy of Fallot: Shunt or primary repair?

Objectives: The optimal treatment strategy for symptomatic young infants with tetralogy of Fallot (TOF) is unclear. We sought to compare the outcomes of staged repair (SR) (shunt palliation followed by second-stage complete repair) versus primary repair (PR) at 2 institutions that have exclusively adopted each strategy. Methods: We performed propensity score-matched comparison of 143 infants under 4 months of age who underwent shunt palliation at one institution between 1993 and 2021 with 122 infants who underwent PR between 2004 and 2018 at another institution. The primary outcome was mortality. Secondary outcomes were postoperative complications, durations of perioperative support and hospital stays, and reinterventions. Median follow-up was 8.3 years (interquartile range, 8.1-13.4 years). Results: After the initial procedure, hospital mortality (shunt, 2.8% vs PR, 2.5%; P = .86) and 10-year survival (shunt, 95%; 95% confidence interval [CI], 90%-98% vs PR, 90%; 95% CI, 81%-95%; P = .65) were similar. The SR group had a greater risk of early reinterventions but similar rates of late reinterventions. Propensity score matching yielded 57 well-balanced pairs. In the matched cohort, the SR group had similar freedom from reintervention (55%; 95% CI, 39%-68% vs 59%; 95% CI, 43%-71%; P = .85) and greater survival (98%; 95% CI, 88%-99.8% vs 85%; 95% CI, 69%-93%; P = .02) at 10 years, as the result of more noncardiac-related mortalities in the PR group. Conclusions: In symptomatic young infants with TOF operated at 2 institutions with exclusive treatment protocols, the SR strategy was associated with similar cardiac-related mortality and reinterventions as the PR strategy at medium-term follow-up.

Zinc finger protein 180 induces an apoptotic phenotype by activating METTL14 transcriptional activity in colorectal cancer.

Zinc finger protein 180 (ZNF180) is a multifunctional protein that interacts with nucleic acids and regulates various cellular processes; however, the function of ZNF180 in colorectal cancer (CRC) remains unclear. The present study investigated the role and function of ZNF180 in CRC, and aimed to reveal the underlying molecular mechanism. The results revealed that ZNF180 was downregulated in CRC tissues and was associated with a good prognosis in patients with CRC. Additionally, the expression of ZNF180 was downregulated by methylation in CRC. In vivo and in vitro experiments revealed that ZNF180 overexpression was functionally associated with the inhibition of cell proliferation and the induction of apoptosis. Mechanistically, chromatin immunoprecipitation­PCR and luciferase assays demonstrated that ZNF180 markedly regulated the transcriptional activity of methyltransferase 14, N6­adenosine­methyltransferase non­catalytic subunit (METTL14) by directly binding to and activating its promoter region. Simultaneous overexpression of ZNF180 and knockdown of METTL14 indicated that the reduction of METTL14 could suppress the effects of ZNF180 on the induction of apoptosis. Clinically, the present study observed a significant positive correlation between ZNF180 and METTL14 expression levels, and low expression of ZNF180 and METTL14 predicted a poor prognosis in CRC. Overall, these findings revealed a novel mechanism by which the ZNF180/METTL14 axis may modulate apoptosis and cell proliferation in CRC. This evidence suggests that this axis may serve as a prognostic biomarker and therapeutic target in patients with CRC.

Electromagnetic Cellularized Patch with Wirelessly Electrical Stimulation for Promoting Neuronal Differentiation and Spinal Cord Injury Repair.

Although stem cell therapy holds promise for the treatment of spinal cord injury (SCI), its practical applications are limited by the low degree of neural differentiation. Electrical stimulation is one of the most effective ways to promote the differentiation of stem cells into neurons, but conventional wired electrical stimulation may cause secondary injuries, inflammation, pain, and infection. Here, based on the high conductivity of graphite and the electromagnetic induction effect, graphite nanosheets with neural stem cells (NSCs) are proposed as an electromagnetic cellularized patch to generate in situ wirelessly pulsed electric signals under a rotating magnetic field for regulating neuronal differentiation of NSCs to treat SCI. The strength and frequency of the induced voltage can be controlled by adjusting the rotation speed of the magnetic field. The generated pulsed electrical signals promote the differentiation of NSCs into functional mature neurons and increase the proportion of neurons from 12.5% to 33.7%. When implanted in the subarachnoid region of the injured spinal cord, the electromagnetic cellularized patch improves the behavioral performance of the hind limbs and the repair of spinal cord tissue in SCI mice. This work opens a new avenue for remote treatment of SCI and other nervous system diseases.

Reason and control strategy for denitrification and anammox sludge flotation in nitrogen removal process: Mechanisms, strategies and perspectives.

Anaerobic biological treatment technology, especially denitrification and anaerobic ammonia oxidation (anammox) technology as mainstream process, played dominant role in the field of biological wastewater treatment. However, the above process was prone to sludge floating during high load operation and thereby affecting the efficient and stable operation of the system. Excessive production of extracellular polymeric substance (EPS) was considered to be the main reason for anaerobic granular sludge flotation, but the summaries in this area were not comprehensive enough. In this review, the potential mechanisms of denitrification and anammox sludge floatation were discussed from the perspective of granular sludge structural characteristics, nutrient transfer, and microbial flora change respectively, and the corresponding control strategies were also summarized. Finally, this paper indicated that future research on sludge flotation should focus on reducing the negative effects of EPS in sludge particles.

Self-supported bimetallic array superstructures for high-performance coupling electrosynthesis of formate and adipate.

The coupling electrosynthesis involving CO2 upgrade conversion is of great significance for the sustainable development of the environment and energy but is challenging. Herein, we exquisitely constructed the self-supported bimetallic array superstructures from the Cu(OH)2 array architecture precursor, which can enable high-performance coupling electrosynthesis of formate and adipate at the anode and the cathode, respectively. Concretely, the faradaic efficiencies (FEs) of CO2-to-formate and cyclohexanone-to-adipate conversion simultaneously exceed 90% at both electrodes with excellent stabilities. Such high-performance coupling electrosynthesis is highly correlated with the porous nanosheet array superstructure of CuBi alloy as the cathode and the nanosheet-on-nanowire array superstructure of CuNi hydroxide as the anode. Moreover, compared to the conventional electrolysis process, the cell voltage is substantially reduced while maintaining the electrocatalytic performance for coupling electrosynthesis in the two-electrode electrolyzer with the maximal FEformate and FEadipate up to 94.2% and 93.1%, respectively. The experimental results further demonstrate that the bimetal composition modulates the local electronic structures, promoting the reactions toward the target products. Prospectively, our work proposes an instructive strategy for constructing adaptive self-supported superstructures to achieve efficient coupling electrosynthesis.

Central Metal-Triggered Structural Transformation of a 2D Layered MOF: Mechanistic Studies and Applications.

The structural transformation of metal-organic frameworks (MOFs) has attracted increasing interests, which has not only produced various new structures but also served as a fantastic platform for MOF-based kinetic analysis. Multiple reaction conditions have been documented to cause structural transformation; nevertheless, central metal-induced topological alteration of MOFs is rare. Herein, we reported a structural transformation of a 2D layered Cd-MOF driven by Cd(II) ions. After being submerged in the aqueous solution of cadmium nitrate, the twofold interpenetrated 2D network of [Cd(hsb-2)(bdc)·5H2O]n [HSB-W10; bdc: 1,4-benzenedicarboxylate; hsb-2:1,2-bis(4'-pyridylmethylamino)-ethane] was converted into a novel noninterpenetrated 2D network [Cd1.5(hsb-2)(bdc)1.5(H2O)2·H2O]n (HSB-W16). This partial dissolution-recrystallization process was investigated by integrating controlled experiments, 1H NMR spectra, and photographic tracking analysis. Furthermore, a novel strategy combining in situ multicomponent dye encapsulation and central metal-triggered structural transformation was developed for the fabrication of MOF materials with white-light emission. By adopting this strategy, different dye guest molecules were concurrently introduced into the HSB-W16 host matrix, leading to a range of white-light-emitting MOF composites. This work will enable detailed studies of solid-state transformations and demonstrate a promising application prospect for structural transformation.

Construction of ceRNA regulatory networks for active pulmonary tuberculosis.

Delayed diagnosis in patients with pulmonary tuberculosis (PTB) often leads to serious public health problems. High throughput sequencing was used to determine the expression levels of lncRNAs, mRNAs, and miRNAs in the lesions and adjacent health lung tissues of patients with PTB. Their differential expression profiles between the two groups were compared, and 146 DElncRs, 447 DEmRs, and 29 DEmiRs were obtained between lesions and adjacent health tissues in patients with PTB. Enrichment analysis for mRNAs showed that they were mainly involved in Th1, Th2, and Th17 cell differentiation. The lncRNAs, mRNAs with target relationship with miRNAs were predicted respectively, and correlation analysis was performed. The ceRNA regulatory network was obtained by comparing with the differentially expressed transcripts (DElncRs, DEmRs, DEmiRs), then 2 lncRNAs mediated ceRNA networks were established. The expression of genes within the network was verified by quantitative real-time PCR (qRT-PCR). Flow cytometric analysis revealed that the proportion of Th1 cells and Th17 cells was lower in PTB than in controls, while the proportion of Th2 cells increased. Our results provide rich transcriptome data for a deeper investigation of PTB. The ceRNA regulatory network we obtained may be instructive for the diagnosis and treatment of PTB.

Exercise Capacity and Reoperation Late After Transatrial Fallot Repair.

BACKGROUND: The exercise capacity long after repair of tetralogy of Fallot, when performed exclusively with a transatrial repair, is unclear. It is also unknown whether echocardiography and cardiopulmonary exercise testing can predict the risk of reoperation in this patient group. METHOD: We retrospectively reviewed the clinical records of 59 patients who underwent cardiopulmonary exercise testing after transatrial Fallot repair at a single centre. Patients underwent cardiopulmonary exercise testing at a mean age of 16.6±4.4 years, and at 15.3±4.1 years after Fallot repair. RESULTS: At testing, the volume of oxygen consumption at maximal exercise (VO2 max) was 71%±13% and the oxygen pulse was 80%±17% of predicted values. Seventeen (17) patients (29%) had a VO2 max superior to 80% of the predicted value. Thirty-two (32) patients (56%) had severe pulmonary regurgitation, three (5%) had moderate pulmonary regurgitation, and 12 (21%) had mild pulmonary regurgitation. After a mean of 7.8±3.9 years following cardiopulmonary exercise testing (23±5.3 years after the repair), 21 (40%) patients underwent reoperation. Right ventricular dilation and systolic function on echocardiography were both significantly associated with subsequent reoperation rates. Patients who had severe right ventricular dilation were eight times more likely to undergo subsequent reoperation (hazard ratio 8.67; 1.82-41.3; p=0.007). No cardiopulmonary exercise testing variable independently predicted reoperation. CONCLUSIONS: The exercise capacity at adolescence following transatrial repair of tetralogy of Fallot is maintained at around 70% of predicted values. Only the patients with normal right ventricular size and normal right ventricular function seemed to be protected from reoperation over the subsequent decade. We found no exercise variables which predicted reoperation.

Breast cancer clinical outcomes and tumor immune microenvironment: cross-dialogue of multiple epigenetic modification profiles.

The discovery of RNA methylation alterations associated with cancer holds promise for their utilization as potential biomarkers in cancer diagnosis, prognosis, and prediction. RNA methylation has been found to impact the immunological microenvironment of tumors, but the specific role of methylation-related genes (MRGs), particularly in breast cancer (BC), the most common cancer among women globally, within the tumor microenvironment remains unknown. In this study, we obtained data from TCGA and GEO databases to investigate the expression patterns of MRGs in both genomic and transcriptional domains in BC. By analyzing the data, we identified two distinct genetic groupings that were correlated with clinicopathological characteristics, prognosis, degree of TME cell infiltration, and other abnormalities in MRGs among patients. Subsequently, an MRG model was developed to predict overall survival (OS) and its accuracy was evaluated in BC patients. Additionally, a highly precise nomogram was created to enhance the practical usability of the MRG model. In low-risk groups, we observed lower TBM values and higher TIDE scores. We further explored how MRGs influence a patient's prognosis, clinically significant characteristics, response to therapy, and the TME. These risk signatures have the potential to improve treatment strategies for BC patients and could be applied in future clinical settings. Moreover, they may also be utilized to determine prognosis and biological features in these patients.

Integrated single-cell and bulk RNA-sequencing data reveal molecular subtypes based on lactylation-related genes and prognosis and therapeutic response in glioma.

Objectives: Glioma, the most common and aggressive form of brain cancer, possesses a complex biology, which makes elucidating its underlying mechanisms and developing effective treatment strategies challenging. Lactylation is a recently discovered post-translational modification and has emerged as a novel research target to understand its role in various biological processes and diseases. Herein, we explored the role of lactylation in gliomas. Methods: Single-cell RNA-sequencing (scRNA-seq) data were downloaded from the Tumour Immune Single-Cell Hub database. The R package 'Seurat' was used for processing the scRNA-seq data. Lactylation-related genes were identified from published literature and the Molecular Signatures Database. An unsupervised clustering method was used to identify glioma subtypes based on identified lactylation-related genes. Differences among the various clusters were examined, including clinical features, differentially expressed genes (DEGs), enriched pathways and immune cell infiltrates. A lactylation score was generated to predict the overall survival (OS) of patients with glioma using DEGs between the two clusters. Results: The lactylation-related genes were obtained from the scRNA-seq data, identifying two molecular subtypes, and a prognostic signature was established to stratify patients with glioma into high- and low-score groups. Analysis of the tumour immune microenvironment revealed that patients in the high-score group exhibited increased immune cell infiltration, chemokine expression and immune checkpoint expression but exhibited worse OS and better response to immunotherapy. Conclusions: Altogether, we established a novel signature based on lactylation-related clusters for robust survival prediction and immunotherapeutic response in gliomas.

Experimental Direct Quantum Fidelity Learning via a Data-Driven Approach.

Fidelity estimation is an important technique for evaluating prepared quantum states in noisy quantum devices. A recent theoretical work proposed a frugal approach called neural quantum fidelity estimation (NQFE) [X. Zhang et al., Phys. Rev. Lett. 127, 130503 (2021).PRLTAO0031-900710.1103/PhysRevLett.127.130503]. While this requires a much smaller number of measurement operators than full quantum state tomography, it uses a weight-based floating measurement strategy that predetermines the top global Pauli operators that contribute the most to the fidelity and uses discrete fidelity intervals as predictions. In this Letter, we develop a measurement-fixed NQFE based on a transformer model which requires less measurement cost and can output continuous estimates of fidelity. Here we further experimentally apply the NQFE in a realistic situation using a nuclear spin quantum processor. We prepare the ground states of local Hamiltonians and arbitrary states and investigate how to estimate their fidelity with reference states, and we compare the fidelity estimation strategy with our and the original NQFE to conventional tomography. It is shown that NQFE can estimate the fidelity with comparable accuracy to the tomography approach. In the future, NQFE will become an important tool for benchmarking quantum states ahead of the advent of well-trusted fault-tolerant quantum computers.

A longitudinal electrophysiological and behavior dataset for PD rat in response to deep brain stimulation.

Here we presented an electrophysiological dataset collected from layer V of the primary motor cortex (M1) and the corresponding behavior dataset from normal and hemi-parkinson rats over 5 consecutive weeks. The electrophysiological dataset was constituted by the raw wideband signal, neuronal spikes, and local field potential (LFP) signal. The open-field test was done and recorded to evaluate the behavior variation of rats among the entire experimental cycle. We conducted technical validation of this dataset through sorting the spike data to form action potential waveforms and analyzing the spectral power of LFP data, then based on these findings a closed-loop DBS protocol was developed by the oscillation activity response of M1 LFP signal. Additionally, this protocol was applied to the hemi-parkinson rat for five consecutive days while simultaneously recording the electrophysiological data. This dataset is currently the only publicly available dataset that includes longitudinal closed-loop DBS recordings, which can be utilized to investigate variations of neuronal activity within the M1 following long-term closed-loop DBS, and explore additional reliable biomarkers.