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We theoretically investigate the properties of the N-TTQD-S system: thermoelectric coefficients strongly depend on the ratio of superconducting gap to interdot coupling, as well as asymmetry and interference effects.

Ir3 is reported to photodegrade CAIX under hypoxia, which improve the cancer immune microenvironment, and induce immunogenic pyroptosis through lipid peroxidation under hypoxia.

Epithelioid sarcoma is a rare but aggressive soft tissue sarcoma that presents a significant diagnostic and management challenge to clinicians. We report a 31-year-old female who presented with a non-healing ulcer of three years’ duration on her left thumb after a burn. Examination revealed an ulcerative tumour invading the bone with areas of haemorrhage. Microscopic examination showed an epithelioid neoplasm with central necrosis. The neoplastic cells formed dyscohesive sheets, slit-like channels, and pseudovascular spaces. Erythrocytes were frequently observed in these areas. The neoplastic malignant cells were diffusely positive for cytokeratin AE1/AE3, EMA, vimentin, Fli-1; while focally positive for CD34 and CD31. The morphology and immunophenotype overlap with a vascular neoplasm. Additional immunohistochemical stain revealed loss of SMARCB1/INI1 expression supporting the diagnosis of epithelioid sarcoma of distal type, angiomatoid variant. We present a distinctive case of angiomatoid epithelioid sarcoma that developed in a burn ulcer and highlight pathological characteristics that distinguish it from epithelioid vascular neoplasms.

Objective: To evaluate the efficacy of Tian dan shu gan rehabilitation exercise in improving the short-term survival quality of patients after percutaneous coronary intervention (PCI) and explore whether patients’ symptoms, physical function, cognitive function, and psychosocial function are improved after this exercise. Methods: Patients with acute myocardial infarction who underwent PCI in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine from August to November 2020 were selected. A total of 110 patients were selected by the convenience sampling method. Patients in the control group were given routine nursing measures after PCI for coronary heart disease, and patients in the experimental group received Tian dan shu gan rehabilitation exercise in addition to routine nursing. Results: After 3 wk, the quality of life in the experimental group was improved compared with that in the control group, and the differences in symptom scores, physical functions, cognitive functions, and psychosocial functions were statistically significant (P < 0.01). After 3 wk of Tian dan shu gan rehabilitation exercise, patients with body mass index (BMI) between 27 and 29.9 had the highest score of body function, which was statistically significantly better compared with that of other groups (P < 0.001). Patients who had remained bachelors for a long period of time had the highest score of symptoms, which was statistically significant compared with the other groups (P < 0.001). The nursing satisfaction of the experimental group was 96.3%. Conclusions: Tian dan shu gan rehabilitation exercise was effective in improving the short-term quality of life of patients with acute myocardial infarction after PCI, and the nursing satisfaction rate was high, use of which should be further extended to more clinical patients.

Chemoproteomics has emerged as a key technology to expand the functional space in complex proteomes for probing fundamental biology and for discovering new small-molecule-based therapies. Here we report a modification-centric computational tool termed pChem to provide a streamlined pipeline for unbiased performance assessment of chemoproteomic probes. The pipeline starts with an experimental setting for isotopically coding probe-derived modifications that can be automatically recognized by pChem, with masses accurately calculated and sites precisely localized. pChem exports on-demand reports by scoring the profiling efficiency, modification homogeneity and proteome-wide residue selectivity of a tested probe. The performance and robustness of pChem were benchmarked by applying it to eighteen bioorthogonal probes. These analyses reveal that the formation of unexpected probe-derived modifications can be driven by endogenous reactive metabolites (for example, bioactive aldehydes and glutathione). pChem is a powerful and user-friendly tool that aims to facilitate the development of probes for the ever-growing field of chemoproteomics.

Chloride is the most abundant anion in living systems. Most natural or synthetic chloride anionophores function via hydrogen-bonding interactions. However, dynamic metal-anion coordination can also...

IntroductionThis study aimed to investigate the genetic factors promoting widespread Q6 dissemination of tet(X4) between Escherichia coli and to characterize the genetic contexts of tet(X4).MethodsWe isolated E. coli from feces, water, soil and flies collected across a large-scale chicken farm in China in 2020. Antimicrobial susceptibility testing and PFGE typing were used to identify tigecycline resistance and assess clonal relationships among isolates. Plasmids present and genome sequences were analyzed by conjugation, S1 pulsed-field gel electrophoresis (PFGE), plasmid stability testing and whole-genome sequencing.ResultsA total of 204 tigecycline-resistant E. coli were isolated from 662 samples. Of these, we identified 165 tet(X4)-carrying E. coli and these strains exhibited a high degree of multidrug resistance. Based on the geographical location distribution of the sampled areas, number of samples in each area and isolation rate of tigecycline-resistant strains and tet(X4)-carrying isolates, 72 tet(X4)-positive isolates were selected for further investigation. Tigecycline resistance was shown to be mobile in 72 isolates and three types of tet(X4)-carrying plasmids were identified, they were IncHI1 (n = 67), IncX1 (n = 3) and pO111-like/IncFIA(HI1) (n = 2). The pO111-like/IncFIA(HI1) is a novel plasmid capable of transferring tet(X4). The transfer efficiency of IncHI1 plasmids was extremely high in most cases and IncHI1 plasmids were stable when transferred into common recipient strains. The genetic structures flanked by IS1, IS26 and ISCR2 containing tet(X4) were complex and varied in different plasmids.DiscussionThe widespread dissemination of tigecycline-resistant E. coli is a major threat to public health. This data suggests careful use of tetracycline on farms is important to limit spread of resistance to tigecycline. Multiple mobile elements carrying tet(X4) are in circulation with IncHI1 plasmids the dominant vector in this setting.

The high-order harmonic generation from H[Formula: see text] has been theoretically investigated by numerically solving the two-dimensional time-dependent Schrödinger equation. A sharp minimum can be seen in the harmonic spectrum for larger internuclear distance. Moreover, the electron transition process between the ground state and the first excited state competes with the ionization process at larger internuclear distance, which is the main reason of the spectral minimum. By superposing the static electric field and adjusting the orientation angle [Formula: see text], it is further proved that the electron transition frequency between two lowest electronic states can be decoded by the minimum.

Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H

This work uses a combination of simulations performed via numerical models and field observations studied the attenuation of deep-hole blasting stress waves and the evolution mechanism of cracks in a jointed rock mass. First, we conclude that the larger the joint angle is, the larger is the transmission coefficient and smaller is the fractal dimension. Second, the time difference between the peak stress difference and the maximum principal stress on both sides of the blasting hole in the horizontal direction of the rock mass with joints is relatively large, but there is no significant difference in the vertical direction. Finally, an unjointed-rock-mass model and multiple parallel joint model are established to explore the attenuation of stress waves and damage effect of multiple joint rock mass, it is concluded that the larger the angle, the smaller is the particle peak velocity and amplitude attenuation, and as the number of stress waves passing through the joints increases, the amplitude gradually decreases and the high-frequency amplitude decreases more significantly than the low-frequency amplitude. The research conclusions of this paper further reveal the damage mechanism induced by a blasting stress wave on jointed rock masses and the law of stress wave propagation and attenuation.

BackgroundThis study aimed to investigate whether visceral adipose tissue index (VATI) is a significant risk factor for the early recurrence (ER) of HBV-related hepatocellular carcinoma (HCC) (≤5 cm) after hepatectomy.MethodsThe recruited cohort patients who were positive for hepatitis B virus, presented with surgically confirmed HCC (≤5 cm) from Army Medical University (internal training cohort: n = 192) and Chongqing Medical University (external validation group: n = 46). We measured VATI, subcutaneous adipose tissue index (SATI) via computed tomography (CT). ER was defined as recurrence within 2 years after hepatectomy. The impact of parameters on outcome after hepatectomy for HCC was analyzed.ResultsUnivariate analysis showed that alpha-fetoprotein levels (p = 0.044), body mass index (BMI) (p p p p 2/m2) and low risk (2/m2) groups. The prognosis of low risk group was significantly higher than that of high risk group (p ConclusionVATI was an independent risk factor for the ER, and higher VATI was closely related to poor outcomes after hepatectomy for HBV-related HCC (≤5 cm).

Additional file 1. Additional information regarding the ESI-MS, biodistribution data, and HPLC analysis of the precursors is available through the supplementary information file.

To determine whether glutamine consumption is associated with embryo quality and aneuploidy, a retrospective study was conducted in an in vitro fertilization center. Spent embryo culture media from patients undergoing assisted reproduction treatment and preimplantation genetic testing (PGT) were obtained on day 3 of in vitro culture. Embryo quality was assessed for cell number and fragmentation rate. PGT for aneuploidy was performed using whole genome amplification and DNA sequencing. Glutamine levels in spent embryo culture media were analyzed by gas chromatography–mass spectrometry. The results demonstrated that glutamine was a primary contributor to the classification of the good-quality and poor-quality embryos based on the orthogonal partial least-squares discriminant analysis model. Glutamine consumption in the poor-quality embryos was significantly higher than that in the good-quality embryos (P P

A binding-enhanced ruthenium-based photosensitizer is reported for photodegradation of carbonic anhydrase IX.

This study aimed to identify the neurophysiologic bases of auditory attention deficits in children with attention-deficit/hyperactivity disorder (ADHD), focusing on the electroencephalography component of auditory spatial selective attention [the N2 anterior contralateral component (N2ac)]. EEG data were collected from 7- to 11-year-old children with ADHD (n = 54) and age-, sex-, and IQ-matched typically developing (TD) children (n = 61), while they performed an auditory spatial selective task. For behavior, the children with ADHD showed a shorter reaction time (RT) but a higher RT coefficient of variability (RTCV) than TD children. For ERPs, the TD group showed a significant “adult-like” N2ac component; however, the N2ac component was absent in children with ADHD. More importantly, the smaller N2ac component could predict longer RT in both groups, as well as higher severity of inattentive symptoms in children with ADHD. Our results indicated that 7- to 11-year-old TD children have developed an “adult-like” ability to balance auditory target selection and distractor suppression; the absence of N2ac in children with ADHD provided novel evidence supporting their dysfunctional auditory spatial selective attention.

DNA damage repair is considered to be an important mechanism of cisplatin resistance, and the roles of iron homeostasis in action mechanisms of cisplatin have not been studied yet. Herein, a Pt(IV) prodrug (

Slip and instability of coal-rock parting-coal structure (CRCS) subjected to excavation disturbance can easily induce coal-rock dynamic phenomena in deep coal mines. In this paper, the failure characteristics and influencing factors of CRCS slip and instability were investigated by theoretical analysis, numerical simulations, and field observations. The following main results are addressed: (1) the slip and instability of CRCS induced by excavation are due to stress release, and the damage of the rock parting is partitioned into three parts: shear failure zone, slipping zone, and splitting failure zone from inside to outside with slip; (2) the slip and instability process of CRCS is accompanied by initiation, expansion, and intersection of shear and tensile cracks. The development of the cracks is dominated by shear behaviour, while the tensile crack is the main factor affecting fracture and instability of CRCS; and (3) slip and instability of CRCS are characterized by stick-slip first and then stable slip, accompanied with high P-wave velocity and rockburst danger coefficient based on microseismic tomography.

A mitochondria targeting dual-action platinumIV prodrug exhibits high anticancer activity in triple negative breast cancer cells. The complex intervenes in several cellular processes including DNA damage, perturbation of mitochondrial bioenergetics and induction of necrosis to kill cancer cells.

IntroductionBlepharospasm is uncommon in Parkinson's disease, especially in the peak-dose dyskinesia period.Case presentationWe herein present the case of a patient with PD who developed blepharospasm in the peak-dose dyskinesia period. The symptom was improved by taking amantadine.ConclusionThe current report expands the phenomenology of peak-dose dykinesia in PD to include dystonic blepharospasm. This complication of levodopa therapy may respond to amantadine despite the dystonic appearance of movements.

Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene-containing Ir(III) photosensitizer (IrFc1) that can bind with transferrin and be transported into triple-negative breast cancer (TNBC) cells via a transferrin receptor-mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self-amplifying process. Upon irradiation, IrFc1 induces the generation of lipid oxidation to cause ferroptosis in TNBC cells, which promotes immunogenic cell death (ICD) under both normoxia and hypoxia. In vivo, IrFc1 treatment elicits a CD8

Activation of the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two Pt

IntroductionThe frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currently unknown. This study aimed to determine the frequency of CDAbs in Chinese children with T1D and describe the relationship between CDAbs and circRNAs.Materials and methodsEighty patients diagnosed with T1D were screened for CDAbs and CD-predisposing genes, and circRNAs in peripheral blood mononuclear cells (PBMCs) were collected from 47 patients. The Gene Expression Omnibus (GEO) database was searched for candidate circRNAs in related studies on T1D PBMCs. Data on clinical characteristics (i.e., blood glucose control, residual islet function, and daily insulin dosage) and immunophenotypes (i.e., islet autoantibodies and immune cell subsets) were collected.ResultsIn total, 35.0% of patients were positive for CDAbs. CD-predisposing genes accounted for 52.5% of the genes, and no significant difference in frequency was found between the CDAb-positive (CDAb+) and CDAb-negative (CDAb–) groups. In addition, among the differentially expressed circRNAs from the GEO database, five highly conserved circRNAs homologous to humans and mice were screened, and only the expression of hsa_circ_0004564 in the CDAb+ group significantly decreased (CDAb+ vs. CDAb–:1.72 ± 1.92 vs. 11.12 ± 8.59, p = 6.0 × 10–6), while the expression of hsa_circ_0004564 was upregulated in the general T1D population. Moreover, its parental gene RAPH1 was significantly upregulated (CDAb+ vs. CDAb–:1.26 ± 0.99 vs. 0.61 ± 0.46, p = 0.011). Importantly, the positive correlation between hsa_circ_0004564 and CD3+ cells was validated in children with T1D after adjustments for CDAbs (p = 0.029), while there were no correlations between hsa_circ_0004564 and clinical characteristics or other immune cell subsets (i.e., CD4+ T cells, CD8+ T cells, and natural killer cells).ConclusionThis study highlights the importance of screening for CD in Chinese children with T1D, considering the high prevalence of CDAb positivity and CD-predisposing genes. The profile of candidate circRNAs in children with T1D with CDAbs was different from that in previous reports on general T1D patients from the GEO database. Moreover, hsa_circ_0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and CD.

BackgroundStimulator of interferon genes (STING) is an innate immune sensor of cytoplasmic double-stranded DNA originating from microorganisms and host cells. The activation of cytosolic DNA-STING pathway in tumor microenvironments is usually linked to more robust adaptive immune responses to tumors, however the intracellular function of STING in regulatory T cells is largely unknown. In the present study, we aimed to explore the contribution of intracellular STING activation to regulatory T cell induction (iTreg) in cervical cancer (CC) microenvironments.MethodsBlood samples and tumor specimens were obtained from patients with CC. The intratumoral STING, CCL22, CD8 and forkhead box P3 (FOXP3) expression levels were measured by immunohistochemistry. T cell-specific STING conditional knockout mice (CD4-Cre/STINGflox/flox, TKO) were generated, and syngeneic TC-1 tumor model were investigated. The differentiation and molecular regulatory pathway of human and murine iTreg under different treatments were investigated by ex vivo assays, immunoblotting and quantitative PCR. Tumor-associated exosomes (T-EXO) were isolated from CC cell lines and exosomal contents were identified by ELISA and Western blot analysis. The impact of T-EXO on T cell differentiation was tested in in vitro cell culture.ResultsIncreased STING, CCL22 level, FOXP3+ cells but decreased CD8+ cells in tumor tissues predicted poor survival. Tumor-bearing CD4-Cre-STINGflox/flox (TKO) mice displayed slower tumor growth tendencies as well as fewer FOXP3+ cells but higher CD8+ cell proportion in tumor tissues than wild-type (WT) mice. Activating of STING signaling cooperated with T cell receptor, interleukin-2 receptor and transforming growth factor-beta (TGF-β) signals to promote CD4+CD25highFOXP3+ iTreg differentiation from both human and murine CD4+-naïve T cells from WT and IFNAR−/− mice but not TKO or IRF3−/− mice in vitro. Ectopic STING, TBK1 or IRF3 expression promoted iTreg differentiation from human CD4+-naïve T cells. T cell-intrinsic STING activation induced FOXP3 transcription through TBK1-IRF3-mediated SMAD3 and STAT5 phosphorylation independent of interferon-β. In CC, tumor-derived exosomes activated STING signaling in tumor-infiltrated T cells by exosomal TGF-β, cyclic GMP-AMP synthase and 2’-3’-cGAMP, leading to iTreg expansion.ConclusionsThese findings highlight a novel mechanism for iTreg expansion mediated by tumor-derived exosome-activated T cell-intrinsic STING signal, and provide a rationale for developing immunotherapeutic strategies targeting STING signal in CC.

Erectile dysfunction (ED) is closely associated with smooth muscle dysfunction, but its underlying mechanisms remains incompletely understood. We here reported that the reduced expression of myosin phosphatase target subunit 1 (MYPT1), the main regulatory unit of myosin light chain phosphatase, was critical for the development of vasculogenic ED. Male MYPT1 knockout mice had reduced fertility and the penises displayed impaired erections as evidenced by reduced intracavernous pressure (ICP). The penile smooth muscles of the knockout mice displayed enhanced response to G-Protein Couple Receptor agonism and depolarization contractility and resistant relaxation. We further identified a natural compound lotusine that increased the MYPT1 expression by inhibiting SIAH1/2 E3 ligases-mediated protein degradation. This compound sufficiently restored the ICP and improved histological characters of the penile artery of Mypt1 haploinsufficiency mice. In diabetic ED mice (db/db), the decreased expression of MYPT1 was measured, and ICP was improved by lotusine treatment. We conclude that the reduction of MYPT1 is the major pathogenic factor of vasculogenic ED. The restoration of MYPT1 by lotusine improved the function of injured penile smooth muscles, and could be a novel strategy for ED therapy.

Many studies have reported minor complications and disturbance of the gut microbiota after colonoscopy. Compared with air, carbon dioxide (COThirty-eight healthy subjects were assessed and twenty were randomized to receive either COBaseline characteristics were similar in both groups. The recovery of minor complications after colonoscopy was faster in the COCO

Ferroptosis regulates cell death through reactive oxygen species (ROS)-associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with no clear evidence. Herein, we report the first example of an LD/nucleus dual-targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor-acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual-targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis-related diseases.

Accurate predictions of the coal temperature in coal spontaneous combustion (CSC) are important for ensuring coal mine safety. Gas coal (the Zhaolou coal mine in Shandong Province, China) was used in this paper. A large CSC experimental device was adopted to obtain its characteristic temperatures from the macroscopic characteristics of gas production. A simulated annealing-support vector machine (SA-SVM) prediction model was proposed to reflect the complex nonlinear mapping between characteristic gases and the coal temperature. The risk degree of CSC was estimated in the time domain, and the model was verified by using in situ data from an actual working face. Furthermore, back-propagation neural network (BPNN) and single SVM methods were adopted for comparison. The results showed that the BPNN could not adapt to the small-sample problem due to overfitting and the output of a single SVM was unstable due to its strong dependence on the setting of hyperparameters. Through the SA global optimization process, the optimal combination of hyperparameters was obtained. Therefore, SA-SVM had higher prediction accuracy, robustness, and error tolerance rate and better environmental adaptability. These findings have certain practical significances for eliminating the hidden danger of CSC in the gob and providing timely warnings about potential danger.

Carbonic anhydrase IX (CAIX) is overexpressed in many cancer types. Herein, a CAIX targeting and binding-enhanced ruthenium-based photodegrader, Ru-dppz-CAi, is constructed by conjugating the photosensitizer with the inhibiting group

Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor–mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gα t proteins, suggesting an interaction between Tas2R and AChR signaling cascades in the relaxation process. Biochemically, the Gα t released by Tas2R activation complexes with AChR and blocks the Gα q cycling of AChR signal transduction. More importantly, a bitter substance, kudinoside A, not only attenuates airway constriction but also significantly inhibits pulmonary inflammation and tissue remodeling in COPD rats, indicating its modulation of additional Gα q -associated pathological processes. Thus, our results suggest that Tas2R activation may be an ideal strategy for halting multiple pathological processes of COPD.

Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor-mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gα

The alternations in the hypoxic and immune microenvironment are closely related to the therapeutic effect and prognosis of oral squamous cell carcinoma (OSCC). Herein, a new nanocomposite, TiOsub2/sub@Ru@siRNA is constructed from a ruthenium-based photosensitizer (Ru) modified-TiOsub2/subnanoparticles (NPs) loaded with siRNA of hypoxia-inducible factor-1α (HIF-1α). Under visible light irradiation, TiOsub2/sub@Ru@siRNA can elicit both Type I and Type II photodynamic effects, which causes lysosomal damage, HIF-1α gene silencing, and OSCC cell elimination efficiently. As a consequence of hypoxia relief and pyroptosis induction, TiOsub2/sub@Ru@siRNA reshapes the immune microenvironment by downregulation of key immunosuppressive factors, upregulation of immune cytokines, and activation of CD4sup+/supand CD8sup+/supT lymphocytes. Furthermore, patient-derived xenograft (PDX) and rat oral experimental carcinogenesis models prove that TiOsub2/sub@Ru@siRNA-mediated photodynamic therapy significantly inhibits the tumor growth and progression, and markedly enhances cancer immunity. In all, this study presents an effective hypoxia-adaptive photo-immunotherapeutic nanosystem with great potential for OSCC prevention and treatment.

Metal complexes have shown great potential in cancer immunotherapy. This review briefly introduces the basic concepts and strategies of cancer immunotherapy and summarizes the recent discoveries on the immune effects of traditional platinum-based anticancer compounds. In addition, we also outline the latest research progresses on metal complexes for cancer immunotherapy focusing on platinum, ruthenium, iridium, rhenium and copper complexes. Finally, the research perspectives and unsolved problems on the applications of metallo-anticancer agents in cancer immunotherapy are purposed.