Bioaccessibility and health risk assessment of hydrophobic organic pollutants in soils from four typical industrial contaminated sites in China.

There have been reports of potential health risks for people from hydrophobic organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), and organophosphate flame retardants (OPFRs). When a contaminated site is used for residential housing or public utility and recreation areas, the soil-bound organic pollutants might pose a threat to human health. In this study, we investigated the contamination profiles and potential risks to human health of 15 PAHs, 6 PCHs, and 12 OPFRs in soils from four contaminated sites in China. We used an in vitro method to determine the oral bioaccessibility of soil pollutants. Total PAHs were found at concentrations ranging from 26.4 ng/g to 987 ng/g. PCHs (0.27‒14.3 ng/g) and OPFRs (6.30‒310 ng/g) were detected, but at low levels compared to earlier reports. The levels of PAHs, PCHs, and OPFRs released from contaminated soils into simulated gastrointestinal fluids ranged from 1.74% to 91.0%, 2.51% to 39.6%, and 1.37% to 96.9%, respectively. Based on both spiked and unspiked samples, we found that the oral bioaccessibility of pollutants was correlated with their logKow and molecular weight, and the total organic carbon content and pH of soils. PAHs in 13 out of 38 contaminated soil samples posed potential high risks to children. When considering oral bioaccessibility, nine soils still posed potential risks, while the risks in the remaining soils became negligible. The contribution of this paper is that it corrects the health risk of soil-bound organic pollutants by detecting bioaccessibility in actual soils from different contaminated sites.

Clinical evaluation of closed tray impression and intraoral scanning techniques in single posterior tissue-level implant-supported crowns: A self-controlled case study.

STATEMENT OF PROBLEM: Different techniques have been used to record the locations of dental implants, yet research examining the clinical outcomes of posterior implant-supported prostheses generated by different techniques, particularly concerning their fit, is lacking. PURPOSE: The purpose of this self-controlled study was to evaluate the clinical outcomes of closed tray impression making and intraoral scanning for single posterior implant-supported restorations. MATERIAL AND METHODS: Eighty-two participants with a single missing posterior tooth were included. The restorations were delivered a minimum of 3 months after tissue-level implant placement. Each participant was provided with 2 screw-retained monolithic zirconia crowns, produced using 3-dimensional (3D) gel deposition from both closed tray impression making (control group) and intraoral scanning using an iTero scanner (experimental group). The recording operating time, the patient comfort assessed using a visual analog scale (VAS), and the fit of the crowns were recorded during clinical evaluation. The paired t test and Mann-Whitney U test were conducted to statistically analyze the differences between the 2 techniques (α=.05). RESULTS: Seventy-six participants completed the study with a dropout rate of 7.3%. The mean ±standard deviation recording operating time of the control and experimental groups was 683 ±164 and 777 ±407 s, respectively (P<.05). The mean ±standard deviation VAS score of the control and experimental groups was 2.6 ±1.6 and 1.3 ±1.0, respectively (P<.05). The crowns in both groups showed excellent marginal fit (P>.05), but the occlusal contacts of crowns in the experimental group were significantly better (P<.05), while the interproximal contacts were significantly worse (P<.05) compared with those in the control group. In the control group, 1 crown was rated as Delta for occlusal contact and deemed clinically unacceptable. CONCLUSIONS: In single posterior tissue-level implant-supported restorations, the clinical outcomes of most of the screw-retained monolithic zirconia crowns generated from closed tray impression making and intraoral scanning with the iTero system and fabricated by 3D gel deposition were acceptable. Compared with the closed tray impression technique, intraoral scanning resulted in better patient comfort and occlusal contacts but worse interproximal contacts. Efficiency was lower with intraoral scanning.

Association between Pre-operative Body Mass Index and Surgical Infection in Perihilar Cholangiocarcinoma Patients Treated with Curative Resection: A Multi-center Study.

Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.

[Progress in Surgical Treatment of Upper Urinary Tract Stones in Children].

The incidence of urinary calculi in children has been increasing annually,and most of the cases are upper urinary tract stones.At present,surgery is the main way to treat upper urinary tract stones in children.With the gradual development of minimally invasive techniques in surgery,percutaneous nephrolithotomy,retrograde intrarenal surgery,and extracorporeal shock wave lithotripsy have become the main methods for treating upper urinary tract stones in children.We reviewed the current progress in surgical treatment of upper urinary tract stones in children and provided prospects for future treatment options.

Establishment of human corneal epithelial organoids for ex vivo modelling dry eye disease.

Dry eye disease (DED) is a growing public health concern affecting millions of people worldwide and causing ocular discomfort and visual disturbance. Developing its therapeutic drugs based on animal models suffer from interspecies differences and poor prediction of human trials. Here, we established long-term 3D human corneal epithelial organoids, which recapitulated the cell lineages and gene expression signature of the human corneal epithelium. Organoids can be regulated to differentiate ex vivo, but the addition of FGF10 inhibits this process. In the hyperosmolar-induced DED organoid model, the release of inflammatory factors increased, resulting in damage to the stemness of stem cells and a decrease in functional mucin 1 protein. Furthermore, we found that the organoids could mimic clinical drug treatment responses, suggesting that corneal epithelial organoids are promising candidates for establishing a drug testing platform ex vivo. In summary, we established a functional, long-term 3D human epithelial organoid that may serve as an ex vivo model for studying the functional regulation and disease modelling.

Evaluating Virtual Contrast-enhanced MRI (VCE-MRI) in Nasopharyngeal Carcinoma Radiotherapy: A Retrospective Analysis for Primary Gross Tumor Delineation.

PURPOSE: To investigate the potential of virtual contrast-enhanced MRI (VCE-MRI) for gross-tumor-volume (GTV) delineation of nasopharyngeal carcinoma (NPC) using multi-institutional data. METHODS AND MATERIALS: This study retrospectively retrieved T1-weighted (T1w), T2-weighted (T2w) MRI, gadolinium-based contrast-enhanced MRI (CE-MRI) and planning CT of 348 biopsy-proven NPC patients from three oncology centers. A multimodality-guided synergistic neural network (MMgSN-Net) was trained using 288 patients to leverage complementary features in T1w and T2w MRI for VCE-MRI synthesis, which was independently evaluated using 60 patients. Three board-certified radiation oncologists and two medical physicists participated in clinical evaluations in three aspects: image quality assessment of the synthetic VCE-MRI, VCE-MRI in assisting target volume delineation, and effectiveness of VCE-MRI-based contours in treatment planning. The image quality assessment includes distinguishability between VCE-MRI and CE-MRI, clarity of tumor-to-normal tissue interface and veracity of contrast enhancement in tumor invasion risk areas. Primary tumor delineation and treatment planning were manually performed by radiation oncologists and medical physicists, respectively. RESULTS: The mean accuracy to distinguish VCE-MRI from CE-MRI was 31.67%; no significant difference was observed in the clarity of tumor-to-normal tissue interface between VCE-MRI and CE-MRI; for the veracity of contrast enhancement in tumor invasion risk areas, an accuracy of 85.8% was obtained. The image quality assessment results suggest that the image quality of VCE-MRI is highly similar to real CE-MRI. The mean dosimetric difference of planning target volumes were less than 1Gy. CONCLUSIONS: The VCE-MRI is highly promising to replace the use of gadolinium-based CE-MRI in tumor delineation of NPC patients.

Metal-organic framework based self-powered devices for human body energy harvesting.

The shift from traditional bulky electronics to smart wearable devices represents a crucial trend in technological advancement. In recent years, the focus has intensified on harnessing thermal and mechanical energy from human activities to power small wearable electronics. This vision has attracted considerable attention from researchers, with an emphasis on the development of suitable materials that can efficiently convert human body energy into usable electrical form. Metal-organic frameworks (MOFs), with their unique tunable structures, large surface areas, and high porosity, emerge as a promising material category for human body energy harvesting due to their ability to be precisely engineered at the molecular level, which allows for the optimization of their properties to suit specific energy harvesting needs. This article explores the progressive development of MOF materials, highlighting their potential in the realm of self-power devices for wearable applications. It first introduces the typical energy harvesting routes that are particularly suitable for harvesting human body energy, including thermoelectric, triboelectric, and piezoelectric techniques. Then, it delves into various research advances that have demonstrated the efficacy of MOFs in capturing and converting body-generated energy into electrical energy, emphasizing on the conceptual design, device fabrication, and applications in medical health monitoring, human-computer interaction, and motion monitoring. Furthermore, it discusses potential future directions for research in MOF-based self-powered devices and outlines perspectives that could drive breakthroughs in the efficiency and practicality of these devices.

Enhancing Effect of Fullerene Guest and Counterion on the Structural Stability and Electrical Conductivity of Octahedral Metallo-Supramolecular Cages.

Metallo-supramolecular cages have garnered tremendous attention for their diverse yet molecular-level precision structures. However, physical properties of these supramolecular ensembles, which are of potential significance in molecular electronics, remain largely unexplored. We herein constructed a series of octahedral metallo-cages and cage-fullerene complexes with notably enhanced structural stability. As such, we could systematically evaluate the electrical conductivity of these ensembles at both single-molecule level and aggregated bulk state (as well-defined films). Our findings reveal that counteranions and fullerene guests play a pivotal role in determining the electrical conductivity of aggregated state, while such effects are less significant for single-molecule conductance. Both counteranions and fullerenes effectively tune the electronic structures and packing density of metallo-supramolecular assemblies, and facilitate efficient charge transfer between the cage hosts and fullerenes, resulting in a notable one order of magnitude increase in electrical conductivity of the aggregated state.

Skeletal muscle: molecular structure, myogenesis, biological functions, and diseases.

Skeletal muscle is an important motor organ with multinucleated myofibers as its smallest cellular units. Myofibers are formed after undergoing cell differentiation, cell-cell fusion, myonuclei migration, and myofibril crosslinking among other processes and undergo morphological and functional changes or lesions after being stimulated by internal or external factors. The above processes are collectively referred to as myogenesis. After myofibers mature, the function and behavior of skeletal muscle are closely related to the voluntary movement of the body. In this review, we systematically and comprehensively discuss the physiological and pathological processes associated with skeletal muscles from five perspectives: molecule basis, myogenesis, biological function, adaptive changes, and myopathy. In the molecular structure and myogenesis sections, we gave a brief overview, focusing on skeletal muscle-specific fusogens and nuclei-related behaviors including cell-cell fusion and myonuclei localization. Subsequently, we discussed the three biological functions of skeletal muscle (muscle contraction, thermogenesis, and myokines secretion) and its response to stimulation (atrophy, hypertrophy, and regeneration), and finally settled on myopathy. In general, the integration of these contents provides a holistic perspective, which helps to further elucidate the structure, characteristics, and functions of skeletal muscle.

Naoxintong capsule for treating cardiovascular and cerebrovascular diseases: from bench to bedside.

Naoxintong Capsule (NXT), a renowned traditional Chinese medicine (TCM) formulation, has been broadly applied in China for more than 30 years. Over decades, accumulating evidences have proven satisfactory efficacy and safety of NXT in treating cardiovascular and cerebrovascular diseases (CCVD). Studies have been conducted unceasingly, while this growing latest knowledge of NXT has not yet been interpreted properly and summarized comprehensively. Hence, we systematically review the advancements in NXT research, from its chemical constituents, quality control, pharmacokinetics, to its profound pharmacological activities as well as its clinical applications in CCVD. Moreover, we further propose specific challenges for its future perspectives: 1) to precisely clarify bioactivities of single compound in complicated mixtures; 2) to evaluate the pharmacokinetic behaviors of NXT feature components in clinical studies, especially drug-drug interactions in CCVD patients; 3) to explore and validate its multi-target mechanisms by integrating multi-omics technologies; 4) to re-evaluate the safety and efficacy of NXT by carrying out large-scale, multicenter randomized controlled trials. In brief, this review aims to straighten out a paradigm for TCM modernization, which help to contribute NXT as a piece of Chinese Wisdom into the advanced intervention strategy for CCVD therapy.

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Adaptor protein CEMIP reduces the chemosensitivity of small cell lung cancer via activation of an SRC-YAP oncogenic module.

Small cell lung cancer (SCLC) is a recalcitrant malignancy with dismal prognosis due to rapid relapse after an initial treatment response. More effective treatments for SCLC are desperately needed. Our previous studies showed that cell migration-inducing hyaluronan binding protein (CEMIP) functionally promotes SCLC cell proliferation and metastasis. In this study, we investigated whether and how CEMIP regulates the chemosensitivity of SCLC. Through the GDSC database, we found that CEMIP expression levels were positively correlated with the IC50 values of several commonly used chemotherapeutic drugs in SCLC cells (cisplatin, gemcitabine, 5-fluorouracil and cyclophosphamide). We demonstrated that overexpression or knockdown of CEMIP in SCLC cells resulted in a notable increase or reduction in the IC50 value of cisplatin or etoposide, respectively. We further revealed that CEMIP functions as an adaptor protein in SCLC cells to interact with SRC and YAP through the 1-177 aa domain and 820-1361 aa domain, respectively, allowing the autophosphorylation of Y416 and activation of SRC, thus facilitating the interaction between YAP and activated SRC, and resulting in increased phosphorylation of Y357, protein stability, nuclear accumulation and transcriptional activation of YAP. Overexpressing SRC or YAP counteracted the CEMIP knockdown-mediated increase in the sensitivity of SCLC cells to cisplatin and etoposide. The combination of the SRC inhibitor dasatinib or the YAP inhibitor verteporfin and cisplatin/etoposide (EP regimen) displayed excellent synergistic antitumor effects on SCLC both in vitro and in vivo. This study demonstrated that targeted therapy against the CEMIP/SRC/YAP complex is a potential strategy for SCLC and provides a rationale for the development of future clinical trials with translational prospects.

Hemodynamic activity is not parsimoniously tuned to index-of-difficulty in movement with dual requirements on speed-accuracy.

Background: Reaching movements are crucial for daily living and rehabilitation, for which Fitts' Law describes a speed-accuracy trade-off that movement time increases with task difficulty. This study aims to investigate whether cortical activation in motor-related areas is directly linked to task difficulty as defined by Fitts' Law. Understanding this relationship provides a physiological basis for parameter selection in therapeutic exercises. Methods: Sixteen healthy subjects performed 2D reaching movements using a rehabilitation robot, with their cortical responses detected using functional near-infrared spectroscopy (fNIRS). Task difficulty was manipulated by varying target size and distance, resulting in 3 levels of index-of-difficulty (ID). Kinematic signals were recorded alongside cortical activity to assess the relationship among movement time, task difficulty, and cortical activation. Results: Our results showed that movement time increased with ID by 0.2974s/bit across all subjects (conditional r2 = 0.6434, p < 0.0001), and all subjects showed individual trends conforming Fitts' Law (all p < 0.001). Neither activation in BA4 nor in BA6 showed a significant correlation with ID (p > 0.05), while both the target size and distance, as well as the interaction between them, showed a significant relationship with BA4 or BA6 activation (all p < 0.05). Conclusion: This study found that although kinematic measures supported Fitts' Law, cortical activity in motor-related areas during reaching movements did not correlate directly with task difficulty as defined by Fitts' Law. Additional factors such as muscle activation may call for different cortical control even when difficulty was identical.

The Mechanism of Jinkui Wenjing Tang in the Treatment of Anovulatory Dysfunctional Uterine Bleeding was Explored Through Network Pharmacology and Molecular Docking Technology.

Objectives: Jinkui Wenjing Tang (JKWJT), a Traditional Chinese Medicine prescription for gynecological menstrual adjustment, is also used to treat continuous uterine bleeding and abdominal pain. However, the mechanism of action, potential targets, and active ingredients of JKWJT in the treatment of anovulatory dysfunctional uterine bleeding (ADUB) remain unknown. Therefore, it is imperative to explore the molecular mechanism of JKWJT. Methods: The chemical composition and target of JKWJT were obtained by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the SwissTargetPrediction website. ADUB-related targets were collected through the GeneCards database. The protein-protein interaction network was constructed from the target protein. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. The binding of the compounds in JKWJT and the potential therapeutic target molecules was verified by molecular docking. Finally, immunohistochemistry, Western Blotting, and qPCR were used for target expression validation within ADUB patient tissues. Results: The putative targets of JKWJT for the treatment of ADUB mainly involve ESR1, VEGFA, TNF, AR, OXTR, and PCNA. Functional enrichment analysis showed that the therapeutic effect of JKWJT on ADUB was correlated to response to estradiol, gland development, regulation of hormone levels as well as endocrine resistance, estrogen signaling pathway, HIF-1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, prolactin signaling pathway. Molecular docking showed that the target OXTR was expected to have a good binding affinity with 4 corresponding compounds (Girinimbin, icosa-11, 14, 17-trienoic acid methyl ester, Kanzonol F, and Obacunone). After treatment with JKWJT, OXTR relative protein expression and mRNA levels were significantly reduced in ADUB patients. Conclusion: In this study, the basic pharmacological effects, and mechanisms of JKWJT in the treatment of ADUB were elucidated, thus providing a clinical basis for the treatment of ADUB by JKWJT.

[Research progress in targeting DNA G-quadruplexes using natural products].

DNA G-quadruplex(G4) is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres. G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets. Natural products have long been important sources of anticancer drug development. In recent years, significant progress has been made in the discovery of natural drugs targeting DNA G4s, with many DNA G4s have been confirmed as promising targets of natural products, including MYC-G4, KRAS-G4, PDGFR-ß-G4, BCL-2-G4, VEGF-G4, and telomeric G4. This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms. It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s. This review will serve as a valuable reference for the research on natural products, particularly in the development of novel antitumor medications.

Minisci-Type Dehydrogenative Coupling of C(sp3)-H and N-Heteroaromatics Enabled by Photoelectrochemical Hydrogen Atom Transfer.

Minisci-type dehydrogenative coupling of C(sp3)-H and N-heteroaromatics was performed with N-hydroxysuccinimide as a hydrogen atom transfer catalyst in a photoelectrochemical cell composed of a mesoporous BiVO4 photoanode and a Pt electrode. In the absence of metal catalysts and chemical oxidants, a range of N-heteroarenes (e.g., quinolines, isoquinolines, and quinoxaline) can undergo coupling with various C(sp3)-H partners to form the corresponding products in excellent yields.

On-Surface Synthesis of Five-Membered Copper Metallacycles Using Terminal Alkynes.

We present our studies on the adsorption, deprotonation, and reactions of 4,4″-diethynyl-1,1':4',1″-terphenyl on Cu(111) under ultrahigh-vacuum conditions using scanning tunneling microscopy combined with density functional theory calculations. Sequential annealing treatments induce deprotonation of pristine molecules followed by chemical reactions, resulting in branched nanostructures. Within the nanostructures, a previously unreported, double-spot linkage is observed. Our density functional theory calculations unravel that this linkage corresponds to a five-membered copper metallacycle.

Electron beam lithography of GeTe through polymorphic phase transformation.

We report two previously undiscovered phases of GeTe including the sphalerite (c-) phase and the hexagonal (h-) phase with interlayer van der Waals gaps. A polymorphic phase transformation from rhombohedral α-GeTe to c- and h-GeTe at near room temperature is first realized via electron beam irradiation. Their underlying thermodynamics and kinetics are illustrated using the in situ heating experiments and molecular dynamics simulations. Density-functional theory calculations indicate that c-GeTe exhibits typical metallic behavior and h-GeTe is a narrow-gap semiconductor with a strong spin-orbital coupling effect. Our findings shed light on a strategy for designing GeTe-based quantum devices compromising nanopillars and heterostructures via an atomic-scale electron beam lithography technique.