Protraction of Mandibular Second Molar for Substitution of Adjacent Missing First Molar With a Mini-Implant-Anchored Albert Loop Appliance.

Protraction of mandibular posterior teeth into edentulous regions is challenging in clinical practice. This case demonstrated a minor tooth movement of a mandibular second molar to substitute its adjacent missing first molar in a 15-year-old female. An efficient bodily movement of the mandibular second molar was achieved through a mini-implant-anchored protraction loop appliance. With this carefully designed biomechanical system, over 10-mm molar protraction was accomplished within 14 months without mesial or lingual tipping. The adjacent third molar erupted spontaneously during the protraction process and drafted mesially. Through brackets and segmented archwire after the protraction, the second and third molars were successfully protracted and good buccal interdigitation was achieved. The combination of the Albert protraction loop and mini-implant allows for more efficient protraction of the mandibular molars, avoiding mesial tipping and lingual rotation of the molars.

COVID-19 acts like a stress test, uncovering the vulnerable part of the human body: a retrospective study of 1640 cases in China.

BACKGROUND: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits multi-organ damage with diverse complications, the correlation between age, gender, medical history and clinical manifestations of novel coronavirus disease 2019 (COVID-19) patients was investigated. METHODS: 1640 patients who were infected with SARS-CoV-2 and hospitalized at the First Affiliated Hospital of Ningbo University from 22 December 2022 to 1 March 2023 were categorized and analysed. Normal distribution test and variance homogeneity test were performed. Based on the test results, one-way analysis of variance, Pearson's chi-squared test and logistic regression analysis were conducted in the study. RESULTS: According to the ANOVA, there was a significant difference in the age distribution (P = .001) between different clinical presentations, while gender did not (P = .06). And regression analysis showed that age, hypertension, atherosclerosis and cancer were significant hazard factors for the development of predominant clinical manifestations in patients hospitalized with novel COVID-19. Additionally, infection with SARS-CoV-2 has the potential to exacerbate the burden on specific diseased or related organs. CONCLUSION: The elderly who are infected with SARS-CoV-2 ought to be treated with emphasis not only on antiviral therapy but also on individualized treatment that takes their medical history and comorbidities into account.

Phenolic constituents from the branches of Viburnum chinshanense as potential α-amylase and α-glucosidase inhibitory agents.

This paper reports the isolation of two undescribed phenolic glycosides (1 and 2), together with seven known compounds (3-9) from the branches of Viburnum chinshanense. The structures of undescribed compounds were elucidated by comprehensive spectroscopic methods (1D NMR, 2D NMR, and HRESIMS). The sugar units of compounds 1 and 2 were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of the monosaccharides. Furthermore, the α­amylase and α-glucosidase inhibitory activities of all isolates were evaluated and compounds 1, 5, and 8 displayed potential α­amylase and α-glucosidase inhibitory activities. The molecular docking analyses of compounds 1 and 8 with the potent inhibition towards the target enzymes were also performed.

Neuropeptides affecting social behavior in mammals: oxytocin.

Oxytocin (OXT), a neuropeptide consisting of only nine amino acids, is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OXT is best known for its role in lactation and parturition, recent research has shown that it also has a significant impact on social behaviors in mammals. However, a comprehensive review of this topic is still lacking. In this paper, we systematically reviewed the effects of OXT on social behavior in mammals. These effects of OXT from the perspective of five key behavioral dimensions were summarized: parental behavior, anxiety, aggression, attachment, and empathy. To date, researchers have agreed that OXT plays a positive regulatory role in a wide range of social behaviors, but there have been controversially reported results. In this review, we have provided a detailed panorama of the role of OXT in social behavior and, for the first time, delved into the underlying regulatory mechanisms, which may help better understand the multifaceted role of OXT. Levels of OXT in previous human studies were also summarized to provide insights for diagnosis of mental disorders.

N-Alkylation through the Borrowing Hydrogen Pathway Catalyzed by the Metal-Organic Framework-Supported Iridium-Monophosphine Complex.

Further development in the area of medicinal chemistry requires facile and atom-economical C-N bond formation from readily accessible precursors using recyclable and reusable catalysts with low process toxicity. In this work, direct N-alkylation of amines with alcohols is performed with a series of Ir-phosphine-functionalized metal-organic framework (MOF) heterogeneous catalysts. The grafted monophosphine-Ir complexes were studied comprehensively to illustrate the ligand-dependent reactivity. The afforded MOF catalysts exhibited high reactivity and selectivity toward N-alkylamine product formation, especially UiO-66-PPh2-Ir, which showed 90% conversion after recycling with no catalyst residue remaining in the product after the reaction. Furthermore, analyses of the active catalyst, mechanistic studies, control experiments, and H2 adsorption tests are consistent with the conclusion that immobilization of the iridium complex on the MOF support enables the formation of the iridium-monophosphine complex and enhances its stability during the reaction. To illustrate the potential of the catalyst for application in medicinal chemistry, two pharmaceutical precursors were synthesized with up to 99% conversion and selectivity.

[Ozone Sensitivity Analysis in Urban Beijing Based on Random Forest].

The basis and key step to developing ozone (O3) prevention and control measures is determining the non-linear relationship between O3 and its precursors. Based on online observations of O3, volatile organic compounds (VOCs), nitrogen oxides (NOx), and meteorological elements from April to September 2020 at an urban site in Beijing, we analyzed the pollution characteristics of O3 and its precursors, explored key factors affecting O3 using the random forest (RF) model combined with SHAP values, and explored the O3-VOCs-NOx sensitivity through a multi-scenarios analysis. The results of correlation analysis showed that the hourly concentration of O3 was significantly positively correlated with temperature (T) and negatively correlated with TVOCs and NOx. However, in terms of the daily values, O3 was significantly positively correlated with T, TVOCs, and NOx. The simulated O3 values by the RF model agreed with the measured values. The SHAP values of each characteristic variable were further calculated. The results suggested that T and NOx showed the two highest effects on O3, with positive and negative values, respectively. Based on the average NOx and VOCs on O3 pollution days during the observation period (the base scenario), multi-scenarios with different NOx and VOCs were set up. The RF model was used to calculate O3 under different scenarios and obtain the O3 isopleth (EKMA curve). The results showed that the O3-VOCs-NOx sensitivity in urban areas of Beijing was in the VOCs-limited regime, which was consistent with the results obtained from the observation-based box model(OBM). This indicated that the RF model could be used as a complementary method for O3-VOCs-NOx sensitivity analysis.

Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling.

BACKGROUND: Senescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson's disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced premature senescence model, and a mouse model of PD were used to investigate the effect of metformin on astrocyte senescence in vivo and in vitro. Immunofluorescence staining and flow cytometric analyses were performed to evaluate the mitochondrial function. We stereotactically injected AAV carrying GFAP-promoter-cGAS-shRNA to mouse substantia nigra pars compacta regions to specifically reduce astrocytic cGAS expression to clarify the potential molecular mechanism by which metformin inhibited the astrocyte senescence in PD. RESULTS: We showed that metformin inhibited the astrocyte senescence in vitro and in PD mice. Mechanistically, metformin normalized mitochondrial function to reduce mitochondrial DNA release through mitofusin 2 (Mfn2), leading to inactivation of cGAS-STING, which delayed astrocyte senescence and prevented neurodegeneration. Mfn2 overexpression in astrocytes reversed the inhibitory role of metformin in cGAS-STING activation and astrocyte senescence. More importantly, metformin ameliorated dopamine neuron injury and behavioral deficits in mice by reducing the accumulation of senescent astrocytes via inhibition of astrocytic cGAS activation. Deletion of astrocytic cGAS abolished the suppressive effects of metformin on astrocyte senescence and neurodegeneration. CONCLUSIONS: This work reveals that metformin delays astrocyte senescence via inhibiting astrocytic Mfn2-cGAS activation and suggest that metformin is a promising therapeutic agent for age-associated neurodegenerative diseases.

Rapid determination of glyphosate and glufosinate in human blood by probe electrospray ionization tandem mass spectrometry.

In forensic science, glyphosate (GLYP) and glufosinate (GLUF), a class of non-selective broad-spectrum herbicides, have been frequently encountered in many fatal poisoning and suicide cases due to their widespread availability. Therefore, it is essential to develop an effective method for detecting these compounds. Some conventional methods, such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), have been reported to detect these compounds. However, these methods are not ideal for their time-consuming and non-sensitive feature. Herein, probe electrospray ionization (PESI) tandem mass spectrometry (MS/MS), a fast and sensitive technique, was applied for the determination of GLYP and GLUF in human blood, which can obtain analytical results within 0.5 min without derivatization and chromatographic separation. After protein precipitation of blood samples, the supernatant was mixed with isopropanol and ultra-pure water (1:1 v/v). Then, 8 µL of the mixture was introduced into the plastic sample plate for PESI-MS/MS analysis. The limits of detection (LODs) of the method were 0.50 µg/mL and 0.25 µg/mL for two analytes, and the limits of quantitation (LOQs) were both 1.00 µg/mL, which are higher than the concentration of reported poisoning and fatal cases. In the linear range of 1-500 µg/mL, the regression coefficients (r2) for GLYP and GLUF were over 0.99. The matrix effects ranged from 94.8 % to 119.5 %, and the biases were below 4.3 %. The recoveries ranged between 84.8 % and 107.4 %, and the biases were below 7.6 %. Meanwhile, the method was effectively utilized to detect and quantify the blood, urine, and other samples. Consequently, the results suggest that PESI-MS/MS is a straightforward, fast, and sensitive method for detecting GLUF and GLYP in forensics. In the future, PESI-MS/MS will become an indispensable technique for polar substances in grassroots units of public security where rapid detection is essential.

MACTFusion: Lightweight Cross Transformer for Adaptive Multimodal Medical Image Fusion.

Multimodal medical image fusion aims to integrate complementary information from different modalities of medical images. Deep learning methods, especially recent vision Transformers, have effectively improved image fusion performance. However, there are limitations for Transformers in image fusion, such as lacks of local feature extraction and cross-modal feature interaction, resulting in insufficient multimodal feature extraction and integration. In addition, the computational cost of Transformers is higher. To address these challenges, in this work, we develop an adaptive cross-modal fusion strategy for unsupervised multimodal medical image fusion. Specifically, we propose a novel lightweight cross Transformer based on cross multi-axis attention mechanism. It includes cross-window attention and cross-grid attention to mine and integrate both local and global interactions of multimodal features. The cross Transformer is further guided by a spatial adaptation fusion module, which allows the model to focus on the most relevant information. Moreover, we design a special feature extraction module that combines multiple gradient residual dense convolutional and Transformer layers to obtain local features from coarse to fine and capture global features. The proposed strategy significantly boosts the fusion performance while minimizing computational costs. Extensive experiments, including clinical brain tumor image fusion, have shown that our model can achieve clearer texture details and better visual quality than other state-of-the-art fusion methods.

A complementary method with PFBBr-derivatization based on a GC-EI-MS platform for the simultaneous quantitation of short-, medium- and long-chain fatty acids in murine plasma and feces samples.

Fatty acids (FAs) are essential molecules in all organisms and are involved in various physiological and pathophysiological processes. Pentafluorobenzyl bromide (PFBBr) is commonly used for FA derivatization for gas chromatography-mass spectrometry (GC-MS) quantification by chemical ionization (CI). While CI is the conventional ionization mode for PFBBr derivatization, the electron ionization (EI) source has also demonstrated efficacy in achieving satisfactory analytical performance for the analysis of PFB esters. In this study, we present a novel approach utilizing PFBBr-derivatization on a GC-EI-MS platform to quantitatively analyze a comprehensive range of 44 fatty acids (FAs) spanning from C2 to C24. The method's sensitivity, precision, accuracy, linearity, recovery, and matrix effect were rigorously validated against predetermined acceptance criteria. In comparison to the conventional CI ionization mode, the utilization of PFBBr-derivatization in GC-EI-MS exhibits a wider range of applications and achieves comparable sensitivity levels to the conventional CI platform. By using this method, we successfully quantified 44 FAs in plasma and feces samples from the mice with deoxynivalenol (DON)-induced kidney injury. Among these, the levels of most FA species were increased in the DON-exposure group compared with the control group. The orthogonal partial least squares discriminant analysis (OPLS-DA) of all the tested FAs showed a visual separation of the two groups, indicating DON exposure resulted in a disturbance of the FA profile in mice. These results indicate that the established method by integration of GC-MS with PFBBr derivatization is an efficient approach to quantify the comprehensive FA profile, which includes short-, medium- and long-chain FAs. In addition, our study provides new insights into the mechanism underlying DON exposure-induced kidney injury.

An effective strategy for assembling the sex-limited chromosome.

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.

Fish Arginase constrains Excessive Production of Nitric Oxide and Limits Mitochondrial Damage during Aeromonas hydrophila infection.

Bacteria-enhanced inducible nitric oxide synthase (iNOS) overproduces nitric oxide (NO) leading to mitochondrial and cellular damage. In mammals, arginase (ARG), the enzyme consuming the same substrate L-arginine with iNOS, was believed to inhibit iNOS activity by competing the substrate. But in fish, this conception has been widely challenged. In this study, the gene expression using real-time quantitative PCR (RT-qPCR) technology showed that when stimulated by Aeromonas hydrophila (A. hydrophila), grass carp (gc) iNOS was up-regulated in head kidney monocytes/macrophages (M0/MФ), and its changes were not detected in the whole tissue of liver or spleen, showing a high degree of cell-specific expression pattern. At the same time, gcARG2 had a high basal expression in tissues and was up-regulated by A. hydrophila stimulation. Next, phthalaldehyde-primaquine reaction was first used in the determination of intracellular urea in fish cells. It was found that the induced gcARG2 led to an increase in the intracellular urea content. Moreover, urea and NO production in M0/MФ were increased in a substrate dose-dependent manner from 30 and 100 µM of L-arginine and reached the highest yield at 300 and 3000 µM of L-arginine, respectively. Furthermore, head kidney M0/MФ was cultured in RPMI1640 medium containing physiological concentration (500 µM) of L-arginine to evaluate the effect of ARG. Under A. hydrophila stimulation, treatment with the arginase inhibitor S-(2-boronoethyl)-l-cysteine (BEC) showed that inhibition of arginase could further enhance the NO production stimulated by A. hydrophila. This in turn led to a cumulation in peroxynitrite (ONOO-) content and an injure of the mitochondrial membrane potential. Our study showed for the first time that fish ARG in head kidney M0/MФ can limit excessive production of NO and harmful products by iNOS to maintain mitochondrial and cellular homeostasis.

Achyranthes bidentata Blume (Amaranthaceae): a review of its botany, traditional uses, phytochemistry, pharmacology, and toxicology.

OBJECTIVES: Achyranthes bidentata Blume (A. bidentata) is a plant of Amaranthaceae family, and its root is the main medicinal part, named "Huai-Niu-Xi." It is used to expel blood stasis through menstruation, tonify liver and kidney, strengthen muscles and bones, and induce diuresis. This review aimed to provide a systematic summary of botany, traditional uses, phytochemistry, pharmacology, and toxicology of A. bidentata. METHODS: The present review covers the literature survey. The data have been collected from various journals, books, and some of the electronic search via Internet-based information such as Web of Science, PubMed, Google Scholar, Google patents, CNKI, SpringerLink, online electronic journals, and ScienceDirect. KEY FINDINGS: So far, more than 270 metabolites have been isolated from A. bidentata, including terpenoids, steroids, alkaloids, flavonoids, and so on. Among them, terpenoids and steroids are the main metabolites. The extract and metabolites exert multiple pharmacological activities such as alleviating osteoarthritis effect, antiosteoporosis activity, neuroprotective effect, antidiabetic activity-associated complications, immunoregulatory activity, and so on. SUMMARY: Some traditional uses of A. bidentata need further in-depth studies to confirm. Similarly, the separation and screening of active compounds, as well as the corresponding molecular mechanisms of action of compounds, are also needed to be studied.

Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.

OBJECTIVE: Non-small-cell lung cancer (NSCLC) is a deadly form of cancer that exhibits extensive intercellular communication which contributed to chemoradiotherapy resistance. Recent evidence suggests that arrange of key proteins are involved in lung cancer progression, including gap junction proteins (GJPs). METHODS AND RESULTS: In this study, we examined the expression patterns of GJPs in NSCLC, uncovering that both gap junction protein, beta 2 (GJB2) and gap junction protein, beta 2 (GJB3) are increased in LUAD and LUSC. We observed a correlation between the upregulation of GJB2, GJB3 in clinical samples and a worse prognosis in patients with NSCLC. By examining the mechanics, we additionally discovered that nuclear factor erythroid-2-related factor 1 (NFE2L1) had the capability to enhance the expression of connexin26 and connexin 31 in the NSCLC cell line A549. In addition, the use of metformin was discovered to cause significant downregulation of gap junction protein, betas (GJBs) by limiting the presence of NFE2L1 in the cytoplasm. CONCLUSION: This emphasizes the potential of targeting GJBs as a viable treatment approach for NSCLC patients receiving metformin.

Activation of ASIC3/ERK pathway by paeoniflorin improves intestinal fluid metabolism and visceral sensitivity in slow transit constipated rats.

Slow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside compound extracted from the dried root of Paeonia lactiflora, has been found to alleviate STC, but the mechanisms of its effect remain unclear. The present study aimed to investigate the effects and mechanisms of PF on intestinal fluid metabolism and visceral sensitization in rats with compound diphenoxylate-induced STC. Based on the evaluation of the laxative effect, the abdominal withdrawal reflex test, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were used to detect the visceral sensitivity, fluid metabolism-related proteins, and acid-sensitive ion channel 3/extracellular signal-regulated kinase (ASIC3/ERK) pathway-related molecules. PF treatment not only attenuated compound diphenoxylate-induced constipation symptoms and colonic pathological damage in rats but also ameliorated colonic fluid metabolic disorders and visceral sensitization abnormalities, as manifested by increased colonic goblet cell counts and mucin2 protein expression, decreased aquaporin3 protein expression, improved abdominal withdrawal reflex scores, reduced visceral pain threshold, upregulated serum 5-hydroxytryptamine, and downregulated vasoactive intestinal peptide levels. Furthermore, PF activated the colonic ASIC3/ERK pathway in STC rats, and ASIC3 inhibition partially counteracted PF's modulatory effects on intestinal fluid and visceral sensation. In conclusion, PF alleviated impaired intestinal fluid metabolism and abnormal visceral sensitization in STC rats and thus relieved their symptoms through activation of the ASIC3/ERK pathway.

Deciphering chemoresistance in osteosarcoma: Unveiling regulatory mechanisms and function through the lens of noncoding RNA.

Osteosarcoma (OS) is a primary malignant bone tumor and is prevalent in children, adolescents, and elderly individuals. It has the characteristics of high invasion and metastasis. Neoadjuvant chemotherapy combined with surgical resection is the most commonly used treatment for OS. However, the efficacy of OS is considerably diminished by chemotherapy resistance. In recent years, noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, are hot topics in the field of chemotherapy resistance research. Several studies have demonstrated that ncRNAs are substantially associated with chemoresistance in OS. Thus, the present study overviews the abnormally expressed ncRNAs in OS and the molecular mechanisms involved in chemoresistance, with an emphasis on their function in promoting or inhibiting chemoresistance. ncRNAs are expected to become potential therapeutic targets for overcoming drug resistance and predictive biomarkers in OS, which are of great significance for enhancing the therapeutic effect and improving the prognosis.

Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.