Miracle-dz/UniFAR-FTUs huggingface dataset:
Review of the bulk and surface chemistry of iron in atmospherically relevant systems containing humic-like substances

As the fourth most abundant element by mass in the Earth's crust, iron is ubiquitous and its chemistry is rich and interdisciplinary in nature. This review synthesizes the current state of knowledge of iron chemistry in multicomponent atmospheric aerosols. This knowledge is also applicable to other atmospherically relevant systems that include iron-containing anthropogenic nanodust, ocean surfaces and buildings. Because of the abundance of humic-like substances in these systems, this review focuses on the chemistry of these substances with iron compounds. Findings from field measurements and laboratory studies are summarized to highlight the major themes in the chemical reactivity of iron, which varies depending on the solubility, the redox conditions, the absence and presence of UV-visible light and reactive oxygen species, the pH and the temperature. This review also highlights the key differences between the bulk and surface chemistry of iron-containing materials, which varies considerably because of the structure of the interfacial water and the solvent cage effect. Additional laboratory, field and modelling studies are needed to better understand the contributions of transition metal chemistry to the formation of secondary organic aerosols and also the chemistry, uptake and release of trace gas phase species. This information will improve the predictive power of models that incorporate aerosol chemistry and physics.
Anti‐tumour effects of a dual cancer‐specific oncolytic adenovirus on Breast Cancer Stem cells

Apoptin can specifically kill cancer cells but has no toxicity to normal cells. Human telomerase reverse transcriptase (hTERT) can act as a tumour‐specific promoter by triggering the expression of certain genes in tumour cells. This study aims to investigate the inhibitory effects and to explore the inhibitory pathway of a dual cancer‐specific recombinant adenovirus (Ad‐apoptin‐hTERTp‐E1a, Ad‐VT) on breast cancer stem cells. Breast cancer cell spheres were obtained from MCF‐7 cells through serum‐free suspension culture. The cell spheres were detected by flow cytometry for CD44+ CD24− cell subsets. The stemness of MCF‐7‐CSC cells was confirmed by in vivo tumorigenesis experiments. The inhibitory effect of the recombinant adenoviruses on MCF‐7‐CSC cells was evaluated by CCK‐8 assay. In addition, the stemness of adenovirus‐infected MCF‐7‐CSC cells was analysed by testing the presence of CD44+ CD24− cell subsets. The ability of the recombinant adenovirus to induce MCF‐7‐CSC cell apoptosis was detected by staining JC‐1, TMRM and Annexin V. Our results showed that a significantly higher proportion of the CD44+ CD24− cell subsets was present in MCF‐7‐CSC cells with a significantly increased expression of stem cell marker proteins. The MCF‐7‐CSC cells, whlist exhibited a strong tumorigenic ability with a certain degree of stemness in mice, were shown to be strongly inhibited by recombinant adenovirus Ad‐VT through cell apoptosis. In addition, Ad‐VT was shown to exert a killing effect on BCSCs. These results provide a new theoretical basis for the future treatment of breast cancer.
The Response of Arbuscular Mycorrhizal Fungal Communities to the Soil Environment of Underground Mining Subsidence Area in Northwest China

Fully mechanized mining technology applied over a very large working face is typically utilized for coal exploitation in Northwest China and triggered two types of land subsidence above the goaf edge and center. However, the effects of mining subsidence on arbuscular mycorrhizal fungal (AMF) communities are still unknown. Here, we investigated the soil physicochemical properties and the response of AMF communities to the soil environment at the margin and center of the subsidence area of the same working face. Our results showed the soil water content, nutrient content and enzyme activity were significantly decreased with land desertification at the margin of the subsidence area but were less affected at the subsidence center. Utilizing high-throughput sequence analysis, six Glomeromycotan genera were detected. The relative abundance of Glomus and Ambispora at the margin of the subsidence area decreased, while Paraglomus and Diversispora increased. The total OTU richness was significantly correlated with moisture. Redundancy analysis showed the main environmental factors driving the changes in AMF community structure were available nitrogen, available potassium and available phosphorus. All these results indicated land cracks need to be repaired in time at subsidence edge to prevent the decline of soil fertility.
Impact of clinical pharmacy in oncology and hematology centers: A systematic review

Background Oncology and hematology is a complex and specific area that requires monitoring by a multidisciplinary team capable of personalizing the treatment of each patient. Clinical pharmacy services have the potential to contribute significantly to the effective and economical care of cancer patients. Objective To evaluate, synthesize and critically present the available evidence on the impact of the Clinical Pharmacy in the treatment of patients with hematological cancer. Method A review was carried out on the bases PubMed/MEDLINE, LILACS and Google Scholar. The included studies were: studies that evaluated the effects of pharmaceutical interventions in clinical in oncology and hematology services and having as a population patient with hematological cancer. Results 17 studies were selected among 745 identified. 4.771 patients were included, with an average follow-up time of 15.3 months. Patients affected by some type of hematological cancer, undergoing chemotherapy treatment, showed better adherence and continuity when accompanied by a clinical pharmacist, added to this professional in carrying out interventions, provides control of symptoms such as cancer pain, nausea and constipation and, thus, contributes to decrease the length of hospital stay. Conclusion The implementation of a Clinical Pharmacy service in oncology and hematology centers contributes significantly to the effectiveness of pharmacotherapeutic treatment, treatment costs reduction, safety increase in the use of medications and the patient’s quality of life.
Expression of Telomeric Repeat–Containing RNA Decreases in Sarcopenia and Increases after Exercise and Nutrition Intervention

Sarcopenia is defined as aging-related loss of muscle mass and function. Telomere length in chromosomes shortens with age and is modulated by telomeric repeat-containing RNA (TERRA). This study aimed to explore the impact of aging and sarcopenia on telomere length and TERRA expression, and changes following strengthening exercise and nutrition intervention (supplement of branched-chain amino acids, calcium and vitamin D3) for 12 weeks in the sarcopenic population. Older adults (≥65 years old) were divided into non-sarcopenic controls (n = 36) and sarcopenic individuals (n = 36) after measurement of grip strength and body composition. The relative telomere length of leukocytes in all research participants was evaluated using the T/S ratio (telomere/single copy gene), and relative TERRA expression of leukocytes was determined by reverse-transcription qPCR (RT-qPCR). Generalized estimating equation (GEE) was used to analyze the influence of sarcopenia and intervention on the outcomes. There was no significant difference in telomere length between control subjects and participants with sarcopenia. TERRA expression was lower in sarcopenic participants compared to that in non-sarcopenic controls (5.18 ± 2.98 vs. 2.51 ± 1.89; p < 0.001). In the sarcopenic group, intervention significantly increased TERRA expression, but not telomere length. The GEE analysis demonstrated that TERRA expression was negatively associated with sarcopenia (β coefficient = −2.705, p < 0.001) but positively associated with intervention (β coefficient = 1.599, p = 0.023). Sarcopenia is associated with a decrease in TERRA expression in leukocytes. Rebound TERRA expression (returning to the level similar to the non-sarcopenic controls) was observed in the sarcopenic group after exercise and nutrition intervention. Future studies are warranted to examine the potential of TERRA as a biomarker for sarcopenia and its subsequent responses to intervention.
Flow Cytometric Methods for the Detection of Intracellular Signaling Proteins and Transcription Factors Reveal Heterogeneity in Differentiating Human B Cell Subsets

The flow cytometric detection of intracellular (IC) signaling proteins and transcription factors (TFs) will help to elucidate the regulation of B cell survival, proliferation and differentiation. However, the simultaneous detection of signaling proteins or TFs with membrane markers (MMs) can be challenging, as the required fixation and permeabilization procedures can affect the functionality of conjugated antibodies. Here, a phosphoflow method is presented for the detection of activated NF-κB p65 and phosphorylated STAT1, STAT3, STAT5 and STAT6, together with the B cell differentiation MMs CD19, CD27 and CD38. Additionally, a TF-flow method is presented that allows the detection of the B cell TFs PAX5, c-MYC, BCL6 and AID and antibody-secreting cell (ASC) TFs BLIMP1 and XBP-1s, together with MMs. Applying these methods on in vitro-induced human B cell differentiation cultures showed significantly different steady-state levels, and responses to stimulation, of phosphorylated signaling proteins in CD27-expressing B cell and ASC populations. The TF-flow protocol and Uniform Manifold Approximation and Projection (UMAP) analysis revealed heterogeneity in TF expression within stimulated CD27- or CD38-expressing B cell subsets. The methods presented here allow for the sensitive analysis of STAT, NF-κB p65 signaling and TFs, together with B cell differentiation MMs, at single-cell resolution. This will aid the further investigation of B cell responses in both health and disease.
Prognostic Value and Immunohistochemical Analysis of Mismatch Repair Deficiency in Patients with Stage II and III Colorectal Carcinoma—A Single-Center Study

Background and objectives: Deficient mismatch repair (MMR) status is associated with good prognosis but poor therapeutic response to adjuvant chemotherapy in patients with colorectal cancer. However, there are some opposed arguments considering therapeutic outcomes in patients with evidenced MMR deficiency in colorectal cancer. The aim of the study was the investigation of prognostic value and immunohistochemical analysis of the MMR-deficiency tumors. Materials and Methods: The study enrolled 104 patients with resected stage II and III colorectal cancer samples from the period 2018–2019. Results: The tumors with deficient MMR status were significantly associated with age up to 50 years and right-sided localization (p < 0.001). During the follow-up period of 22.43 ± 6.66 months, 21 patients (20.2%) died, whereas 14 patients (13.5%) had relapses. The loss of mutL homologue 1/postmeiotic segregation increased 2 (MLH1/PMS2) expression, compared to proficient MMR tumors, was associated with shorter disease-free survival in patients with lymphovascular invasion (p < 0.05), perineural invasion (p < 0.01), stage III (p < 0.05) and high-grade tumor (p < 0.05). Conclusions: This retrospective pilot study of a single-center cohort of patients with stage II and III colorectal cancer highlights the clinical importance of using immunohistochemistry (IHC) analysis as a guide for diagnostic algorithm in a country with limited resources, but with a high prevalence of colorectal carcinoma in the young patients. MMR-deficiency tumors compared with proficient MMR colorectal cancer was not shown to be a significant predictor of disease-free and overall survival.
Desynchronized Functional Activities Between Brain White and Gray Matter in Major Depression Disorder

Alterations in gray matter (GM) have been recognized as playing an important role in the neurobiological mechanism underlying major depressive disorder (MDD) and antidepressant responses. However, little is known about white matter (WM) connectivity in MDD, leaving an incomplete understanding of the pathophysiology of the disorder.
Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease

Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme’s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.
Finite-Time Command-Filtered Composite Adaptive Neural Control of Uncertain Nonlinear Systems

This article presents a new command-filtered composite adaptive neural control scheme for uncertain nonlinear systems. Compared with existing works, this approach focuses on achieving finite-time convergent composite adaptive control for the higher-order nonlinear system with unknown nonlinearities, parameter uncertainties, and external disturbances. First, radial basis function neural networks (NNs) are utilized to approximate the unknown functions of the considered uncertain nonlinear system. By constructing the prediction errors from the serial–parallel nonsmooth estimation models, the prediction errors and the tracking errors are fused to update the weights of the NNs. Afterward, the composite adaptive neural backstepping control scheme is proposed via nonsmooth command filter and adaptive disturbance estimation techniques. The proposed control scheme ensures that high-precision tracking performances and NN approximation performances can be achieved simultaneously. Meanwhile, it can avoid the singularity problem in the finite-time backstepping framework. Moreover, it is proved that all signals in the closed-loop control system can be convergent in finite time. Finally, simulation results are given to illustrate the effectiveness of the proposed control scheme.
Non-Contact Heart Rate Detection When Face Information Is Missing during Online Learning

Research shows that physiological signals can provide objective data support for the analysis of human emotions. At present, non-contact heart rate data have been employed in the research of medicine, intelligent transportation, smart education, etc. However, it is hard to detect heart rate data using non-contact traditional methods during head rotation, especially when face information is missing in scenarios such as online teaching/learning. Traditional remote photoplethysmography (rPPG) methods require a static, full frontal face within a fixed distance for heart rate detection. These strict requirements make it impractical to measure heart rate data in real-world scenarios, as a lot of videos only partially record the subjects’ face information, such as profile, too small distance, and wearing a mask. The current algorithm aims to solve the problem of head deflections between 30 degrees and 45 degrees by employing a symmetry substitution method, which can replace the undetected region of interest (ROI) with the detectable one. When face information is partially missing, our algorithm uses face–eye location to determine ROI. The results show that the method in this paper can solve certain practical problems related to heart rate detection, with a root mean square error (RMSE) under 7.64 bpm.
Association of Subjective Hearing Loss and Apolipoprotein E ε4 Allele on Alzheimer's Disease Neurodegeneration

Objective: Hearing loss (HL) and apolipoprotein E ε4 (ApoE4) allele are both dementia risk factors. No research has investigated the association of these variables regarding dementia, specifically Alzheimer's disease. Our goal was to evaluate HL and ApoE4 allele positivity toward degree of Alzheimer's neurodegeneration. Study Design: Retrospective. Setting: Academic. Patients: Alzheimer's neuropathology obtained from brain tissue databank. Documented demographics, subjective hearing status, cognition, and ApoE4. Subjects divided into four groups based on hearing status and ApoE4 positivity. Main Outcome Measures: Differences in cognition (clinical dementia rating, mini mental state examination (MMSE), geriatric depression score) and Alzheimer's neuropathology staging (Braak, CERAD) between groups. Results: Two-hundred and fifty-nine subjects. No significant difference between groups, with regard to hearing status or ApoE4 positivity, in premorbid cognition, including scores for clinical dementia rating and MMSE (p = 0.2332). HL subjects had less severe neuropathology, as compared with normal hearing subjects. For example, high grade Braak stage was present in 27.1 and 51.0% of HL and normal hearing subjects, respectively (p = 0.0263). This finding was in context of equivocal clinical cognition between groups. ApoE4+ individuals had more severe neurodegeneration; for example, 65.7 and 33.5% with high grade Braak stage for ApoE4+ and ApoE4– subjects, respectively (p < 0.0001). Conclusion: Subjective HL subjects had less severe neuropathology with no difference in cognition, suggesting an additive effect of HL to cognitive burden of Alzheimer's neuropathology. HL appeared to increase cognitive burden, but wasn’t manifested by greater neurodegeneration. This is clinically relevant in that treating HL could slow Alzheimer's disease progression.
Developing an advanced gut on chip model enabling the study of epithelial cell/fibroblast interactions

Organoids are widely used as a model system to study gut pathophysiology; however, they fail to fully reproduce the complex, multi-component structure of the intestinal wall. We present here a new gut on chip model that allows the co-culture of primary epithelial and stromal cells. The device has the topography and dimensions of the mouse gut and is based on a 3D collagen I scaffold. The scaffold is coated with a thin layer of laminin to mimic the basement membrane. To maintain the scaffold structure while preserving its cytocompatibility, the collagen scaffold was rigidified by threose-based post-polymerization treatment. This treatment being cytocompatible enabled the incorporation of primary intestinal fibroblasts inside the scaffold, reproducing the gut stromal compartment. We observed that mouse organoids, when deposited into crypts, opened up and epithelialized the scaffold, generating a polarized epithelial monolayer. Proper segregation of dividing and differentiated cells along the crypt–villus axis was achieved under these conditions. Finally, we show that the application of fluid shear stress allows the long-term culture of this intestinal epithelium. Our device represents a new biomimetic tool that captures key features of the gut complexity and could be used to study gut pathophysiology.
Defect spectroscopy of sidewall interfaces in gate-all-around silicon nanosheet FET

Through time-dependent defect spectroscopy and low-frequency noise measurements, we investigate and characterize the differences of carrier trapping processes occurred by different interfaces (top/sidewall) of the gate-all-around silicon nanosheet field-effect transistor (GAA SiNS FET). In a GAA SiNS FET fabricated by the top-down process, the traps at the sidewall interface significantly affect the device performance as the width decreases. Compare to expectations, as the width of the device decreases, the subthreshold swing (SS) increases from 120 to 230 mV/dec, resulting in less gate controllability. In narrow-width devices, the effect of traps located at the sidewall interface is significantly dominant, and the 1/f 2 noise, also known as generation–recombination (G–R) noise, is clearly appeared with an increased time constant (τ i ). In addition, the probability density distributions for the normalized current fluctuations (ΔI D) show only one Gaussian in wide-width devices, whereas they are separated into four Gaussians with increased in narrow-width devices. Therefore, fitting is performed through the carrier number fluctuation-correlated with mobility fluctuations model that separately considered the effects of sidewall. In narrow-width GAA SiNS FETs, consequently, the extracted interface trap densities (N T ) distribution becomes more dominant, and the scattering parameter ( αSC ) distribution increases by more than double.
First-in-Human Phase I Study of MP0250, a First-in-Class DARPin Drug Candidate Targeting VEGF and HGF, in Patients With Advanced Solid Tumors

PURPOSE A first-in-human study was performed with MP0250, a DARPin drug candidate. MP0250 specifically inhibits both vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) with the aim of disrupting the tumor microenvironment. PATIENTS AND METHODS A multicenter, open-label, repeated-dose, phase I study was conducted to assess the safety, tolerability, and pharmacokinetics of MP0250 in 45 patients with advanced solid tumors. In the dose-escalation part, 24 patients received MP0250 as a 3-hour infusion once every 2 weeks at five different dose levels (0.5-12 mg/kg). Once the maximum tolerated dose (MTD) was established, 21 patients were treated with a 1-hour infusion (n = 13, 8 mg/kg, once every 2 weeks and n = 8, 12 mg/kg, once every 3 weeks) of MP0250 in the dose confirmation cohorts. RESULTS In the dose-escalation cohort, patients treated with 12 mg/kg MP0250 once every 2 weeks experienced dose-limiting toxicities. Therefore, MTD was 8 mg/kg once every 2 weeks or 12 mg/kg once every 3 weeks. The most common adverse events (AEs) were hypertension (69%), proteinuria (51%), and diarrhea and nausea (both 36%); hypoalbuminemia was reported in 24% of patients. Most AEs were consistent with inhibition of the VEGF and HGF pathways. Exposure was dose-proportional and sustained throughout the dosing period for all patients (up to 15 months). The half-life was about 2 weeks. Signs of single-agent antitumor activity were observed: 1 unconfirmed partial response with a time to progression of 23 weeks and 24 patients with stable disease, with the longest duration of 72 weeks and a median duration of 18 weeks. CONCLUSION MP0250 is a first-in-class DARPin drug candidate with suitable tolerability and appropriate pharmacokinetic properties for further development in combination with other anticancer therapies.