The significance of CD4+ and CD8+ T lymphocyte infiltration in esophageal squamous cell carcinoma.

PURPOSE: To investigate the relationship between the abundance of CD4+ and CD8+ T cells in the tumor microenvironment and the prognosis of patients with esophageal squamous cell carcinoma, and to analyze their correlation and explore its clinical value. MATERIALS AND METHODS: In total, we enrolled 120 cases of esophageal squamous cell carcinoma diagnosed. The abundance of CD4+ and CD8+ T lymphocytes in the tissue specimens of esophageal cancer was examined by immunohistochemistry. We measured the correlation between the abundance of CD4+ and CD8+ T lymphocytes and the clinical and pathological characteristics and prognosis of esophageal squamous cell carcinoma. RESULTS: The tissue abundance of CD4+ T lymphocytes was closely related to tumor prognosis (P < 0.05). Similarly, there was a statistically significant relationship between the tissue abundance of CD8+ T lymphocytes and patients' prognosis (P < 0.05), indicating that a high abundance of CD8+ T lymphocytes predicts better prognosis in esophageal squamous cell carcinoma. Surprisingly, we found that a higher CD4+/CD8+ ratio predicted a better prognosis of esophageal squamous cell carcinoma. CONCLUSIONS: The tissue abundance of CD4+ and CD8+ T lymphocytes can serve as an important indicator for predicting the long-term survival of patients with esophageal squamous cell carcinoma. A high CD4+/CD8+ ratio may improve patients' prognosis through several pathways. The association of this ratio with clinical and pathological characteristics may explain the poor efficacy of immunotherapy in patients with esophageal cancer. These findings may help us find new targets for immunotherapy by exploring the immune microenvironment of esophageal squamous cell carcinoma.

Construction and catalysis role of a kinetic promoter based on lithium-insertion technology and proton exchange strategy for lithium-sulfur batteries.

The high theoretical energy density and specific capacity of lithium-sulfur (Li-S) batteries have garnered considerable attention in the prospective market. However, ongoing research on Li-S batteries appears to have encountered a bottleneck, with unresolved key technical challenges such as the significant shuttle effect and sluggish reaction kinetics. This investigation explores the catalytic efficacy of three catalysts for Li-S batteries and elucidates the correlation between their structure and catalytic impacts. The results suggest that the combined utilization of lithium-insertion technology and a proton exchange approach for δ-MnO2 can optimize its electronic structure, resulting in an optimal catalyst (H/Li inserted δ-MnO2, denoted as HLM) for the sulfur reduction reaction. The replacement of Mn sites in δ-MnO2 with Li atoms can enhance the structural stability of the catalyst, while the introduction of H atoms between transition metal layers contributes to the satisfactory catalytic performance of HLM. Theoretical calculations demonstrate that the bond length of Li2S4 adsorbed by the HLM molecule is elongated, thereby facilitating the dissociation process of Li2S4 and enhancing the reaction kinetics in Li-S batteries. Consequently, the Li-S battery utilizing HLM as a catalyst achieves a high areal specific capacity of 4.2 mAh cm-2 with a sulfur loading of 4.1 mg cm-2 and a low electrolyte/sulfur (E/S) ratio of 8 µL mg-1. This study introduces a methodology for designing effective catalysts that could significantly advance practical developments in Li-S battery technology.

Correction for: Cornel iridoid glycoside exerts a neuroprotective effect on neuroinflammation in rats with brain injury by inhibiting NF-kB and STAT3.

[This corrects the article DOI: 10.1007/s13205-019-1697-5.].

Bone-Targeted Supramolecular Nanoagonist Assembled by Accurate Ratiometric Herbal-Derived Therapeutics for Osteoporosis Reversal.

Developing novel strategies for defeating osteoporosis has become a world-wide challenge with the aging of the population. In this work, novel supramolecular nanoagonists (NAs), constructed from alkaloids and phenolic acids, emerge as a carrier-free nanotherapy for efficacious osteoporosis treatment. These precision nanoagonists are formed through the self-assembly of berberine (BER) and chlorogenic acid (CGA), utilizing noncovalent electrostatic, π-π, and hydrophobic interactions. This assembly results in a 100% drug loading capacity and stable nanostructure. Furthermore, the resulting weights and proportions of CGA and BER within the NAs are meticulously controlled with strong consistency when the CGA/BER assembly feed ratio is altered from 1:1 to 1:4. As anticipated, our NAs themselves could passively target osteoporotic bone tissues following prolonged blood circulation, modulate Wnt signaling, regulate osteogenic differentiation, and ameliorate bone loss in ovariectomy-induced osteoporotic mice. We hope this work will open a new strategy to design efficient herbal-derived Wnt NAs for dealing with intractable osteoporosis.

FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Improving Natural Microcrystalline Graphite Performances by a Dual Modification Strategy toward Practical Application of Lithium Ion Batteries.

Microcrystalline graphite (MG), as a kind of natural graphite (NG), holds great potential for use as an anode material for lithium-ion batteries (LIBs) due to low raw material cost, good electrolyte compatibility, and relatively long cycle life. Nevertheless, the relatively low reversible capacity and poor initial Coulombic efficiency (ICE) of the MG anode largely limit its practical application in LIBs. In order to improve the lithium storage capacity of MG, three kinds of oxidant intercalators are applied to treat the original MG, and the as-obtained MG is further modified by a thin carbon layer. The results indicate that using H2SO4-C2H2O4 as oxidant intercalators and subsequent carbon coating layer modification are the optimum techniques, and they can increase the interlayer distance, introduce defects to decrease the volume expansion, and generate channels for fast Li+ diffusion. Meanwhile, the carbon coating layer can reduce the specific surface area of graphite and greatly improve the ICE and cycling performance. Especially, the OEMGC-2 anodes prepared by the dual modification strategies represent a high reversible capacity of 349.4 mA h g-1 at 0.2C with a satisfactory ICE of 90.2%, indicating that the MG can also be considered as a high performance and low-cost anode material of LIBs.

Protective effect of electroacupuncture at ST36 against damage of intestinal mucosa, oxidative stress and apoptosis induced by 5-FU chemotherapy in mice with colon cancer. / 电针"足三里"å‡è½»å¤§è‚ ç™Œå°é¼ åŒ–ç–—åŽè‚ é»è†œæŸä¼¤åŠå ¶å¯¹æ°§åŒ–åº”æ¿€å’Œç»†èƒžå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on intestinal mucosal damage, intestinal mucosal oxidative stress injury and apoptosis induced by 5-fluorouraeil (5-FU) chemotherapy in colorectal cancer-bearing mice. METHODS: Thirty male BALB/c mice were randomly divided into normal control, colorectal cancer (CT26), 5-FU, non-acupoint and ST36 groups, with 6 mice in each group. Except for those of the normal control group, mice of the remaining 4 groups received subcutaneous implantation of colorectal CT26 cell suspension (0.1 mL) in the right armpit for establishing colorectal cancer model. Rats of the 5-FU group, non-acupoint group and ST36 group were given with 5 mg/mL 5-FU solution once every 3 days for a total of 21 days. For mice of the non-acupoint group and ST36 group, EA (2 Hz, 1-2 mA) was applied to bilateral ST36 or non-acupoints (the bilateral sunken spots about 3 mm to the midpoint between the tail root and the anus) for 5 min after each intraperitoneal infusion of 5-FU, once every 3 days, for a total of 21 days. After the intervention, the diarrhea index was assessed. The length of colon (from the endpoint of cecum to the anal orifice) was measured. Histopathological changes of colonic mucosa were observed by H.E. staining, and the length of colonic villi was measured. The content of malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of colonic tissue were detected by thibabituric acid, xanthine oxidase and colorimetric method, respectively. The rate of cell apoptosis in the colonic tissue was measured by TUNEL assay. The positive expressions of Bax and Bcl-2 in colonic tissue were determined by immunohistochemistry. RESULTS: The CT26 model group didn't show any significant changes in the diarrhea index, colon length, colon villus length, MDA content, SOD and GSH-Px activities, colonic cell apoptosis rate, and Bax and Bcl-2 expression levels when compared with the normal group. Compared with the CT26 group, the 5-FU group had a remarkable increase in the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level (P<0.01, P<0.05), and a marked decrease in the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level (P<0.01), suggesting the side effects of administration of 5-FU. Compared with the 5-FU group, the diarrhea index, MDA content, colonic cell apoptosis rate and Bax expression level were markedly decreased (P<0.05, P<0.01) and those of the colon length, colon villus length, SOD and GSH-Px activities and Bcl-2 expression level were obviously increased (P<0.01) in the ST36 group. Compared with the 5-FU group, the non-acupoint group also had an increase in the colon villus length, SOD and GSH-Px activities (P<0.01, P<0.05) and a decrease in the cell apoptosis rate (P<0.01). CONCLUSIONS: EA at ST36 has a positive effect in reducing intestinal mucosal damage induced by 5-FU chemotherapy in cancer-bearing mice, which may be related to its function in relieving oxidative stress injury and inhibiting apoptosis of colonic tissue.

Picroside III Ameliorates Colitis in Mice: A Study Based on Colon Transcriptome and Fecal 16S Amplicon Profiling.

Picroside III (Pic), an iridoid glycoside derived from Picrorhiza scrophulariiflora, exhibits therapeutic potential in mending damage to the intestinal mucosa. This study aimed to explore Pic's regulatory impact on intestinal inflammation and the gut microbiota in mice with dextran sulfate sodium (DSS)-induced colitis. The findings revealed that pretreatment with Pic mitigated the DSS-induced escalation of the disease activity index (DAI), alleviated intestinal damage, and attenuated intestinal inflammation in mice. RNA-seq analysis, complemented by experimental validation, elucidated that Pic significantly hindered Akt phosphorylation in the colon tissues of colitis-afflicted mice. Furthermore, 16S rRNA sequencing demonstrated that Pic pretreatment effectively rectified microbial dysbiosis in colitis mice by elevating the abundance of Lactobacillus murinus and Lactobacillus gasseri. These observations suggest that Pic's efficacy in colitis treatment stems from its inhibition of intestinal inflammation via the suppression of the PI3K-Akt pathway and modulation of gut microbiota. This study contributes novel scientific insights into the potential application of Pic in the management of inflammatory bowel disease (IBD).

Activation of P2Y1R impedes intestinal mucosa repair during colitis.

Delayed intestinal mucosal healing is one of the pathogenic bases for the recurrence of inflammatory bowel disease (IBD), but how the IBD inflammatory environment impedes intestinal mucosa repair remains unclear. Adenosine diphosphate (ADP) is an endogenous ligand of P2Y1R that is highly produced at sites of inflammation. We herein identify a novel role of ADP to directly facilitate inflammation-induced epithelial permeability, delay wound healing, and disrupt tight junction integrity, and we found that P2Y1R, a receptor preferentially activated by ADP, was significantly upregulated in the colonic mucosa of ulcerative colitis (UC) patients and in colonic epithelial cells of colitis mice. Inhibition of P2Y1R significantly increased the epithelial permeability, decreased the wound healing capacity, and impaired the tight junction integrity in TNF-α-challenged Caco-2 cells. In parallel, the same effects in promoting intestinal mucosa repair were observed in DSS-induced colitis in P2Y1R-/- mice. Mechanistic investigation revealed that P2Y1R inhibition facilitated epithelial AMP-activated protein kinase (AMPK) phosphorylation and gut microbiota homeostasis reconstruction. Taken together, these findings highlight that P2Y1R activation plays an important role in impeding intestinal mucosa repair during colitis, and that P2Y1R is an attractive target for the therapy of IBD.

Association between napping and cognitive impairment: A systematic review and meta-analysis.

STUDY OBJECTIVES: Increasing evidence suggests that napping is associated with cognitive impairment and dementia, but the conclusions are inconsistent. Moreover, the extent of the risk is uncertain. We therefore conducted a systematic review and meta-analysis to quantify the connection between napping and cognitive impairment. METHODS: We performed a systematic search of PubMed, EMBASE, Web of Science, and Cochrane Library for studies that were published up to June 2023, and assessed associations between napping and cognitive impairment. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as the effect sizes for all studies. Heterogeneity and potential publication biases were assessed. RESULTS: A total of 4535 papers were retrieved, with 20 reports assessing the relationships between napping and cognitive impairment. Pooled analysis indicated that napping was associated with dementia (OR = 1.14; 95% CI: 1.07-1.21). Importantly, we found that those napping longer than 30, 45, and 60 min/day were 35%, 41%, and 40%, respectively, more likely to have an increased risk of cognitive impairment (30 min: OR = 1.35; 95% CI: 1.24-1.48; 45 min: OR = 1.41; 95% CI: 1.27-1.58; 60 min: OR = 1.40; 95% CI: 1.26-1.56). North America and Europe showed that associations existed between napping and cognitive impairment (North America: OR = 1.15; 95% CI: 1.04-1.27; Europe: OR = 1.13; 95% CI: 1.08-1.18). CONCLUSIONS: This meta-analysis indicated associations between long napping durations and cognitive impairment or dementia, suggesting that longer napping might be a potential risk factor of adverse cognitive outcomes.

Preparation of superhydrophobic sponge and its application in oil-water separation and treatment of polymer-containing wastewater.

At present, the application prospect of superhydrophobic materials in oil-water separation, an-tibacterial and other aspects have attracted more and more attention. However, preparing a simple and low-cost superhydrophobic material remains a challenge. Using acetone as solvent, candle soot, silver/silica nanoparticles and polydimethylsiloxane were uniformly mixed to form a mixed solution, and the superhydrophobic sponge was successfully prepared by spraying method. The results show that the superhydrophobic sponge has high water contact Angle (162°) and excellent oil-water separation efficiency, which can realize effective treatment of polymerized wastewater. In addition, the superhydrophobic sponge showed better antibacterial properties on the surface of Escherichia coli and Staphylococcus aureus. In this work, a simple way to prepare superhydro-phobic oil-water separation material is proposed. The preparation process is green, the material is easy to obtain, and it is expected to be widely used in practical production.

DL-3-n-butylphthalide improves the endothelium-dependent vasodilation in high-fat diet-fed ApoE-/- mice via suppressing inflammation, endothelial necroptosis and apoptosis.

Impaired endothelium-dependent vasodilation in atherosclerosis is a high-risk factor for myocardial infarction and ischemic stroke, and inflammation, necroptosis and apoptosis contribute to endothelial dysfunction in atherosclerosis. Although DL-3-n-butylphthalide (NBP) has been widely used in treating ischemic stroke, its effect on endothelium-dependent vasodilation remains unknown. This study aims to explore whether NBP is able to improve endothelium-dependent vasodilation in atherosclerosis and the underlying mechanisms. Male ApoE-/- mice were fed with a high-fat diet (HFD) for 9-16 weeks to establish a model of atherosclerosis. NBP were given to the mice after eating HFD for 6 weeks and atorvastatin served as a positive control. The endothelium-dependent vasodilation, the blood flow velocity, the atherosclerotic lesion area, the serum levels of lipids, inflammatory cytokines and necroptosis-relevant proteins (RIPK1, RIPK3 and MLKL), and the endothelial necroptosis and apoptosis within the aorta were measured. Human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low-density lipoprotein (ox-LDL) for 48 h to mimic endothelial injury in atherosclerosis, lactate dehydrogenase release, the ratio of necroptosis and apoptosis and the expression of necroptosis-relevant proteins were examined. Similar to atorvastatin, NBP improves endothelium-dependent vasodilation, decreases aortic flow velocity and reduces atherosclerotic lesion area in HFD-fed ApoE-/- mice, concomitant with a reduction in serum lipids, inflammatory cytokines and necroptosis-relevant proteins, and endothelial necroptosis and apoptosis. Consistently, NBP inhibited necroptosis and apoptosis in ox-LDL-treated HUVECs. Based on these observations, we conclude that NBP exerts beneficial effects on improving the endothelium-dependent vasodilation in atherosclerosis via suppressing inflammation, endothelial necroptosis and apoptosis.

Toxoplasma gondii gra5 deletion mutant protects hosts against Toxoplasma gondii infection and breast tumors.

Toxoplasma gondii is the causative agent of toxoplasmosis, a zoonotic disease that poses a threat to human health and a considerable loss to livestock farming. At present, clinical therapeutic drugs mainly target T. gondii tachyzoites and fail to eradicate bradyzoites. Developing a safe and effective vaccine against toxoplasmosis is urgent and important. Breast cancer has become a major public health problem and the therapeutic method needs to be further explored. Many similarities exist between the immune responses caused by T. gondii infection and the immunotherapy for cancers. T. gondii dense granule organelles secrete immunogenic dense granule proteins (GRAs). GRA5 is localized to the parasitophorous vacuole membrane in the tachyzoite stage and the cyst wall in the bradyzoite stage. We found that T. gondii ME49 gra5 knockout strain (ME49Δgra5) was avirulent and failed to form cysts but stimulated antibodies, inflammatory cytokines, and leukocytes infiltration in mice. We next investigated the protective efficacy of ME49Δgra5 vaccination against T. gondii infection and tumor development. All the immunized mice survived the challenge infection of either wild-type RH, ME49, VEG tachyzoites, or ME49 cysts. Moreover, ME49Δgra5 tachyzoite inoculation in situ attenuated the growth of murine breast tumor (4T1) in mice and prevented 4T1's lung metastasis. ME49Δgra5 inoculation upregulated the levels of Th1 cytokines and tumor-infiltrating T cells in the tumor microenvironment and triggered anti-tumor responses by increasing the number of natural killer, B, and T cells, macrophages, and dendritic cells in the spleen. Collectively, these results suggested that ME49Δgra5 was a potent live attenuated vaccine against T. gondii infection and breast cancer.

Density Functional Theory Computation and Machine Learning Studies of Interaction between Au3 Clusters and 20 Natural Amino Acid Molecules.

The optimal adsorption sites and the binding energies of neutral Au3 clusters with 20 natural amino acids under the gas phase and water solvation were systematically investigated based on density functional theory (DFT) calculations. The calculation results showed that in the gas phase Au3 tends to bind with N atoms of amino groups in amino acids, except methionine, which tends to bind with Au3 through S atoms. Under water solvation, Au3 clusters tended to bind to N atoms of amino groups and N atoms of side chain amino groups in amino acids. However, methionine and cysteine bind more strongly to the gold atom through the S atom. Based on the binding energy data of Au3 clusters and 20 natural amino acids under water solvation calculated by DFT, a machine learning model (gradient boosted decision tree) was proposed to predict the optimal binding Gibbs free energy (ΔG) of the interaction between Au3 clusters and amino acids. The main factors affecting the strength of the interaction between Au3 and amino acids were uncovered by the feature importance analysis.

Combined use of a 980­nm diode laser and preoperative intravesical instillation of pirarubicin for the prevention of short­term recurrence of non­muscle invasive bladder cancer: A pilot study.

At present, transurethral resection of bladder tumors (TURBT) is the main surgical method for treating non-muscle invasive bladder cancer (NMIBC), but its postoperative recurrence needs to be prevented. The aim of the present study was to investigate the efficacy of a 980-nm diode laser combined with preoperative intravesical instillation of pirarubicin (THP) for the prevention of NMIBC recurrence. The data of 120 patients with NMIBC who underwent transurethral resection between May 2021 and July 2022 were retrospectively collected, and these patients were followed up. The patients were divided into four groups based on the surgical method used and preoperative intravesical instillation of THP as follows: i) 980-nm diode laser with THP (LaT); ii) 980-nm diode laser alone (La); iii) TURBT with THP (TUT); and iv) TURBT alone (TU). Clinicopathological variables, postoperative complications and short-term outcomes among the aforementioned groups were analyzed. The blood loss volume and the incidence of perforation and delayed bleeding were significantly lower in the LaT and La groups compared with those in the TUT and TU groups. The days of bladder irrigation, catheter extubation and postoperative hospitalization were significantly shorter in the LaT and La groups compared with the TUT and TU groups. The detection rate of suspicious lesions was significantly higher in the THP irrigation groups (LaT and TUT) compared with that in the saline irrigation groups (La and TU). Tumor diameter and number, 980-nm laser and THP irrigation were shown to be independent risk factors in the Cox regression analysis. In addition, the recurrence-free survival (RFS) rate of the LaT group was significantly higher than that of the other three groups. In conclusion, a 980-nm diode laser can effectively reduce intraoperative blood loss and the incidence of perforation, and accelerate postoperative recovery. Preoperative intravesical instillation of THP is conducive to identifying suspicious lesions. The combination of a 980-nm laser with preoperative THP intravesical instillation can significantly prolong RFS time.

Saffron Petal, an Edible Byproduct of Saffron, Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting Macrophage Activation and Regulating Gut Microbiota.

Saffron petal (SP) is an agricultural byproduct in the process of the crude drug saffron, accounting for 90% of the dry weight of saffron flowers. To promote the utilization of SP in the food and pharmaceutical industries, its anti-inflammatory activities were evaluated on LPS-activated RAW 264.7 cells and DSS-challenged colitic mice. The results indicated that the SP extract had a notable effect in alleviating the clinical manifestations of colitis, such as reduction in body weight, improvement in disease activity index, mitigation of colon shortening, and alleviation of colon tissue damage. Moreover, SP extract significantly suppressed macrophage infiltration and activation, evidenced by a decrease in colonic F4/80 macrophages and suppression of the transcription and secretion of colonic tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in DSS-challenged colitic mice. In vitro, SP extract also significantly suppressed nitric oxide production, COX-2 and iNOS expressions, and TNF-α and IL-1ß transcription of activated RAW 264.7 cells. Network pharmacology-guided research identified that SP extract significantly downregulated Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro. In parallel, SP extract also effectively corrected microbial dysbiosis by increasing the abundance of Bacteroides acidifaciens, Bacteroides vulgatus, Lactobacillus murinus, and Lactobacillus gasseri. These findings indicate that the effectiveness of SP extract in treating colitis is demonstrated by its ability to reduce macrophage activation, inhibit the PI3K/Akt and MAPK pathways, and regulate gut microbiota, suggesting that SP extract holds great potential as a therapeutic option for colitis.

Picroside III, an Active Ingredient of Picrorhiza scrophulariiflora, Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity.

This study aims to explore the protective effects of Picroside III, an active ingredient of Picrorhiza scrophulariiflora, on the intestinal epithelial barrier in tumor necrosis factor-α (TNF-α) induced Caco-2 cells and dextran sulfate sodium (DSS) induced colitis in mice. Results show that Picroside III significantly alleviated clinical signs of colitis including body weight loss, disease activity index increase, colon shortening, and colon tissue damage. It also increased claudin-3, ZO-1 and occludin expressions and decreased claudin-2 expression in the colon tissues of mice with colitis. In vitro, Picroside III also significantly promoted wound healing, decreased the permeability of cell monolayer, upregulated the expressions of claudin-3, ZO-1 and occludin and downregulated the expression of claudin-2 in TNF-α treated Caco-2 cells. Mechanism studies show that Picroside III significantly promoted AMP-activated protein kinase (AMPK) phosphorylation in vitro and in vivo, and blockade with AMPK could significantly attenuate the upregulation of Picroside III in ZO-1 and occludin expressions and the downregulation of claudin-2 expression in TNF-α treated Caco-2 cells. In conclusion, this study demonstrates that Picroside III attenuated DSS-induced colitis by promoting colonic mucosal wound healing and epithelial barrier function recovery via the activation of AMPK.

Towards toxic and narcotic medication detection with rotated object detectors.

Background: Recent years have witnessed the advancement of deep learning vision technologies and applications in the medical industry. Intelligent devices for specific medication management could alleviate workload of medical staff by providing assistance services to identify drug specifications and locations. Methods: In this work, object detectors based on the you only look once (YOLO) algorithm are tailored for toxic and narcotic medication detection tasks in which there are always numerous of arbitrarily oriented small bottles. Specifically, we propose a flexible annotation process that defines a rotated bounding box with a degree ranging from 0° to 90° without worry about the long-short edges. Moreover, a mask-mapping-based non-maximum suppression method has been leveraged to accelerate the post-processing speed and achieve a feasible and efficient medication detector that identifies arbitrarily oriented bounding boxes. Results: Extensive experiments have demonstrated that rotated YOLO detectors are highly suitable for identifying densely arranged drugs. Six thousand synthetic data and 523 hospital collected images have been taken for training of the network. The mean average precision of the proposed network reaches 0.811 with an inference time of less than 300 ms. Conclusions: This study provides an accurate and fast drug detection solution for the management of special medications. The proposed rotated YOLO detector outperforms its YOLO counterpart in terms of precision.

Exploration of the Atomic Pathway of Seed-Mediated Growth from Icosahedral [Au25(SR)18]- to Bi-Icosahedral Au38(SR)24 and Au44(SR)26 Clusters Based on the 2e- Hopping Mechanism.

Size growth is ubiquitous in the gold nanocluster synthesis. However, the atomic-level mechanism of seed-mediated growth of gold clusters remains mysterious. In this study, the seed-mediated growth pathway from the icosahedral [Au25(SR)18]- cluster to the bi-icosahedral Au38(SR)24 and Au44(SR)26 clusters is studied based on the two-electron (2e-) hopping mechanism. First, atomic structures of three key intermediate clusters, [Au29(SR)20]-, [Au33(SR)22]-, and Au41(SR)25, are predicted based on the 2e--unit decomposition strategy. The theoretically simulated UV-Vis spectra based on the predicted structure model of [Au29(SR)20]- and [Au33(SR)22]- matched well with the experimental curves reported previously. Based on the predicted intermediate cluster structures, the size growth pathway from the eight-electron (8e-) [Au25(SR)18]- cluster to 14-electron (14e-) Au38(SR)24 and 18-electron (18e-) Au44(SR)26 clusters is determined. In the step of formation of bi-icosahedral Au38(SR)24 from icosahedral [Au25(SR)18]-, two Au4 units are first formed. The third 2e- hopping step results in formation of an icosahedron unit. The present studies offered new insights into the formation and size conversion mechanism of ligand-protected gold nanoclusters containing icosahedral cores.

Vulvar intraepithelial neoplasia, grade III, treated with photodynamic therapy: A case report.

Vulvar intraepithelial neoplasia (VIN) is a precancerous lesion on the vulvar epidermis that does not invade or metastasize to surrounding stroma; it manifests as atypical intraepithelial hyperplasia on the vulva. Most patients with VIN are diagnosed early, and treatment with standardized therapy often leads to complete regression of symptoms. The treatment of VIN is still a challenge for clinicians because, in most cases, surgery is destructive and risky. However, photodynamic therapy (PDT) was recommended as a new treatment for VIN. Herein, we report the case of a patient with a large-area high-grade VIN lesion complicated by human papillomavirus infection. The patient could not undergo surgical treatment. However, treatment with PDT was performed in our outpatient department. There was slight pain during the treatment after multi-point injection of micro-lidocaine (0.05 mL/dot) was given. No recurrence was noted after 13 months of follow-up. More importantly, scarring and other major side effects were not detected. Therefore, PDT can be a useful alternative treatment for patients with VIN with large lesions or multifocal high-grade VIN.