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Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in‐depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT‐PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA‐induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti‐lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine‐mediated anti‐tumor therapy. [ABSTRACT FROM AUTHOR]

In our previous study, target drug delivery and treatment of malignant tumors have been achieved by using platelets as carriers loading nano-chemotherapeutic agents (ND-DOX). However, drug release from ND-DOX-loaded platelets is dependent on negative platelet activation by tumor cells, whose activation is not significant enough for the resulting drug release to take an effective anti-tumor effect. Exploring strategies to proactively manipulate the controlled release of drug-laden platelets is imperative. The present study innovatively revealed that photodynamic action can activate platelets in a spatiotemporally controlled manner. Consequently, based on the previous study, platelets were used to load iron oxide-polyglycerol-doxorubicin-chlorin e6 composites (IO-PG-DOX-Ce6), wherein the laser-triggered drug release ability and anti-tumor capability were demonstrated. The findings suggested that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability. Importantly and interestingly, drug-loaded platelets were significantly activated by laser irradiation, characterized by intracellular ROS accumulation and up-regulation of CD62p. Additionally, scanning electron microscopy (SEM) and hydrated particle size results also showed a significant aggregation response of laser irradiated-drug-loaded platelets. Further transmission electron microscopy (TEM) measurements indicated that the activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells. Finally, the co-culture model of drug-loaded platelets and tumor cells proved that laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. Overall, the present study discovers a drug-loaded platelets delivery using photodynamic effect, enabling laser-controlled intelligent drug delivery and anti-tumor therapy, which provides a novel and feasible approach for clinical application of cytopharmaceuticals. What is the context? 1. Platelets were applied to load IO-PG-DOX-Ce6, wherein the laser-triggered drug release and anti-tumor effect were investigated in vitro. 2. The findings indicated that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability, which may attribute to the activation of autophagy in platelets. 3. IO-PG-DOX-Ce6-loaded platelets could be significantly activated by laser irradiation (690 nm). 4. Activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells 5. The co-culture model of drug-loaded platelets and tumor cells proved that the laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. What is new? 1. Platelets could be utilized as the vehicle to load photosensitizer-loaded-nano-drug. 2. Photodynamic action can activate platelets in a spatiotemporally controlled manner, which could be a tool to regulate the activation of platelets. 3. The laser-triggered activation of drug-loaded platelets allows for target release of cargo. 4. The limitation of the current research is that only in vitro experiments were carried out to demonstrate our conclusions. What is impact? The present work provides a novel and feasible approach for the clinical application of cytopharmaceuticals. [ABSTRACT FROM AUTHOR]

The tumor-associated macrophage (TAM) serves as an immunosuppressive agent in the malignant tumor microenvironment, facilitating the development and metastasis of lung cancer. The photodynamic effect destabilizes cellular homeostasis owing to the generation of reactive oxygen species (ROS), resulting in the enhanced pro-inflammatory function of immunocytes. In our previous study, the Ce6-mediated photodynamic effect was found to have kept the viability of macrophages and to remodel them into the M1 phenotype. However, the mechanism remains unrevealed. The present study now explores the mechanism of photodynamic therapy (PDT)-mediated reprogramming of macrophages. As expected, Ce6-mediated PDT was capable of generating reactive oxygen species, which was continuously degraded, causing "low intensity" damage to DNA and thereby triggering subsequent DNA damage response in macrophages. The autophagy was thus observed in Ce6-treated macrophages and was shown to protect cells from being photodynamically apoptotic. More importantly, Ce6 PDT could activate the stimulator of interferon genes (STING) molecule, a sensor of DNA damage, which could activate the downstream nuclear factor kappa-B (NF-κB) upon activation, mediating the polarization of macrophages towards the M1 phenotype thereupon. In addition, inhibition of ROS induced by PDT attenuated the DNA damage, STING activation, and M1-phenotype reprogramming. Furthermore, the silence of the STING weakened Ce6 treatment-mediated M1 remodeling of macrophages as well. Altogether, these findings indicate the Ce6-induced photodynamic effect polarizes macrophages into an M1 phenotype through oxidative DNA damage and subsequent activation of the STING. This work reveals the crucial mechanism by which photodynamic therapy regulates the macrophage phenotype and also provides a novel intervenable signaling target for remodeling macrophages into the M1 phenotype. [ABSTRACT FROM AUTHOR]

Background: Giant condyloma acuminatum (GCA), also called Buschke–Löwenstein tumor, presents as a verrucous infiltrating lesion and is caused by sexual transmission of human papilloma virus. The optimal treatment is controversial and there are no standard guidelines because of its rarity and frequent recurrence. It has a relatively high local recurrence rate. Objective: We here report eight patients (six men and two women) with GCA whose lesions were successfully treated topically with traditional Chinese medicine (TCM) preparations, paiteling. Methods and Materials: We administered topical TCM preparations to eight patients diagnosed with GCA who had refused surgery. The treatment process included three stages, their durations depending on the speed of resolution of the lesions and the results of visual inspection with acetic acid. Results: No significant complications occurred in any patient. The functional and esthetic outcomes were satisfactory. No recurrences were detected during follow-up. Conclusion: Topical treatment with TCM preparations may be a good alternative to surgery or other traditional methods for the treatment of GCA. This treatment has the advantages of being non-invasive, painless, and having a low risk of recurrence, and may be a useful adjunct to mainstream medical treatments. [ABSTRACT FROM AUTHOR]

Objective. Rapid on-site evaluation (ROSE) is an effective and efficient auxiliary examination, but its value for CT-guided percutaneous fine-needle aspiration (FNA) in the diagnosis of pulmonary occupying lesions is unclear. This study is aimed at evaluating the clinical utility of ROSE for CT-guided percutaneous FNA. Methods. We reviewed 234 patients from September 2018 to April 2019. The result using ROSE was compared with the final pathological diagnosis of CT-guided percutaneous FNA, and we also compared the complications between the ROSE group and the NO-ROSE group. The final pathological diagnosis results served as the gold standard. We also analyzed the diagnostic rate of FNA and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of malignancy. The correlation between diverse pathological types of lung cancer was also taken into consideration. Results. In total, 132 patients underwent CT-guided percutaneous FNA with ROSE (ROSE group), and 102 did not (NO-ROSE group). The diagnostic rate, sensitivity, specificity, PPV, and NPV of the ROSE group were 91.6%, 89.1%, 94.1%, 93.4%, and 90.1%, respectively. The complication rates of the ROSE group and the NO-ROSE group were 8.33% and 16.67%, respectively. This difference was not statistically significant (P > 0.05). In subsets of adenocarcinoma (AC) and small cell lung cancer (SCLC) patients, the ROSE result was highly consistent with the final pathological result. Conclusion. CT-guided percutaneous FNA combined with ROSE has a high diagnostic rate, sensitivity, and specificity for pulmonary occupying lesions and an acceptable rate of complications. This method is worthy of wide use given its high efficiency and safety. [ABSTRACT FROM AUTHOR]

Aim: To explore changes in anxiety and work stress among new nurses in the first year of a 2‐year residency programme. Background: Few studies have examined the anxiety and work stress of new nurses in a residency programme. Methods: This longitudinal study examined levels of anxiety and work stress among newly employed nurses over 1 year at 1 week and 1, 2, 3, 6, 9 and 12 months. Participants were purposively sampled from a medical centre in Taiwan. The Beck Anxiety Inventory and the Nurse Stress Checklist were used to measure anxiety and stress, respectively. Results: The nurses (N = 200) generally perceived mild levels of anxiety and moderate work stress. However, anxiety and stress peaked at the first and second months. Levels stabilized by the sixth month. General ward nurses perceived higher stress levels than did those in emergency or operating rooms. Conclusions: Stress and work anxiety for new nurses peaked at 1–2 months of employment. Implications for Nursing Management: Nurse managers, preceptors and educators must work together with newly employed nurses in individualized learning and support, doing so to improve the transition experience and reduce levels of work stress and anxiety. [ABSTRACT FROM AUTHOR]

Acquired perforating dermatosis (APD) is an uncommon skin disease characterized by umbilicated hyperkeratotic lesions, and involves the transepidermal elimination of dermal components, including collagen and elastic fibers. The disease can affect patients with systemic disorders, especially those with chronic renal failure or diabetes mellitus. The current paper described four cases of patients with APD and investigated the clinical characteristics and prognosis of APD, as well as its possible link with systemic disorders. In each of the four cases, the patient had systemic disorders before the onset of APD, three had concomitant renal and thyroid disorders and one had hepatocirrhosis secondary to chronic hepatitis C. The results of the present study showed that APD occurred after the transient worsening of the original systemic disease. Furthermore, it was revealed that dermatosis symptoms were alleviated upon remission of the original systemic disorder, without specific dermatological treatment. Dermatosis symptoms improved in all four patients, indicating that the management of the associated systematic diseases was essential for the successful clinical outcomes of APD. [ABSTRACT FROM AUTHOR]

We discovered that the function of cytochrome C can be modulated by DNA nanoribbons. Meanwhile, the interplay between the DNA nanoribbons and the native cytochrome C and the possible mechanisms are also discussed. [ABSTRACT FROM AUTHOR]

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Background: Pneumatic injections of non-cross-linked hyaluronic acid are effective in skin rejuvenation, however, the associated biophysical parameters and appearance have not been evaluated. Objectives: To determine the changes in skin biophysical parameters after facial pneumatic injections of non-cross-linked hyaluronic acid. Patients and methods: Twenty-eight healthy female volunteers received pneumatic injections of non-cross-linked hyaluronic acid into the face for consecutive 5 weeks. Skin biophysical parameter assessment and clinical evaluation were performed using the CK Multi-Probe Adapter and Visia system. Five of the volunteers also underwent retroauricular skin biopsy before and after the last treatment. The skin tissues were all stained with Masson-trichrome, Verhoeff-van Gieson stain, and hematoxylin-eosin to evaluate the changes in collagen, elastic fibers, and the epidermis, before and after the last treatment. Results: Transepidermal water loss was significantly lower in week 4 (18.46 ± 4.70 g/h/m2) than at the baseline (22.03 ± 7.15 g/h/m2, p < 0.05). Skin texture was better in week 4 (599.29 ± 354.32) than at the baseline (668.43 ± 342.55, p < 0.05). Skin pores also improved significantly at week 4 (934.07 ± 458.78) compared to the baseline (1024.57 ± 415.31, p < 0.05). Skin wrinkles were improved at the 3-month follow-up (29.29 ± 11.11) compared to the baseline (35.83 ± 16.05, p < 0.05). Conclusion: Pneumatic injections of non-cross-linked hyaluronic acid improved skin TEWL, texture, pores, and wrinkles. [ABSTRACT FROM AUTHOR]

A series of CeO2 nanocrystals with different sizes have been synthesized with DNA as the template by a hydrothermal synthesis method. The peroxidase-like activity of the CeO2 nanocrystals was found to be strongly enhanced by DNA doping. [ABSTRACT FROM AUTHOR]

Hyperkeratosis of the nipple and areola is an uncommon dermatosis without well-defined etiology, which occurs mostly in young women and may only be a cosmetic problem. In 1938, Levy-Frankel classified this disease into three variants; type I involves hyperkeratosis with an epidermal nevus, and has rarely been reported. We report a case of a 23-year-old woman with long-term bilateral pigmentation and thickening of the nipples and areolae, accompanied with dark brown, flat lesions with a linear distribution on her left forearm. The verrucous plaques were asymptomatic and could be scratched off by the patient herself. Consequently, she did not seek medical care for more than ten years. The prevalence of this condition is likely underestimated because many affected individuals are not sufficiently motivated to seek medical attention. [ABSTRACT FROM AUTHOR]

Forest harvesting adjustment is a decision-making, large and complex system. In this paper, we analysis the shortcomings of the traditional harvest adjustment problems, and establish the model of multi-target harvest adjustment. As intelligent optimization, chaotic genetic algorithm has the parallel mechanism and the inherent global optimization characteristics which are suitable for multi-objective planning the settlement of the issue, specially in complex occasions where there are many objective functions and optimize variables. In order to solve the problem of forest harvesting adjustment, this paper introduces a genetic algorithm to the Forest Farm of Qiujia Liancheng Longyan for forest harvesting adjustment firstly. And the experimental result shows that the method is feasible and effective, and it can provide satisfactory solution for policy makers. [ABSTRACT FROM AUTHOR]

The genetic variation of isozymes [esterase (EST), superoxide dismutase (SOD), malate dehydrogenase (MDH), malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PD)] extracted from two different adult tissues (adductor muscle and gill) of Pteria penguin R. and offspring from two stocks of Pinctada martensii D. were analysed by vertical polyacrylamide gel electrophoresis. The result showed an obvious and stable variation in the isozyme phenotypes in two different pearl oyster species. The SOD and EST isozymes from gill and MDH, ME and G6PDH from adductor muscle were species-specific. The electrophoretograms of these isozymes could be used as markers to differentiate the two pearl oysters. Between inbreeding and hybridized stocks of P. martensii, the electrophoresis patterns of isozymes were alike, but the similarities of electrophoretograms in the inbreeding progenies were higher than in the hybridized ones. The characteristic electrophoretograms of isozymes could be applied as molecular markers in the breeding of pearl oysters. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of an ankle-foot orthosis (AFO) on balance performance in patients with hemiparesis of short and long duration. Design: Within-subject random order of intervention, cross-sectional study design. Settings: Medical centres and district hospitals. Subjects: Forty-two subjects with hemiparesis of short duration (< six months) and 61 subjects of long duration (> 12 months). Measurements: The balance and gait ability of subjects were evaluated both with an AFO and without. The static and dynamic balance activities were evaluated by the Balance Master System, whereas the functional balance was assessed with the Berg Balance Scale. The speed and cadence were also measured during a 10-metre walk. Paired t-test was used to determine the effect of the AFO. Results: In subjects with hemiparesis of short duration, we found that subjects wearing an AFO showed significant improvements in (1) weight-bearing distribution during quiet standing (p = 0.042, 95% confidence interval (CI) 0.521, 7.325), (2) body sway during standing on foam surface with eyes open (p = 0.020, 95% CI 0.020, 0.680) and eyes closed (p = 0.041, 95% CI 0.023, 0.921), (3) movement velocity during limit of stability test (LOS) – toward the affected side (p = 0.037, 95% Cl - 0.978, -0.042) and nonaffected side (p = 0.008, 95% CI -2.223, -0.377), (4) maximal excursion toward the affected side (p = 0.042, 95% CI -19.546, -0.071), and (5) speed (p = 0.028, 95% CI -0.204, -0.017) and cadence (p = 0.021, 95% CI -22.983, -1.864). Such effects were not observed in subjects with hemiparesis of long duration. Conclusions: For the subjects with hemiparesis of short duration, the AFO improves the symmetry in quiet and dynamic standing balances. It also increases speed and cadence. However, its effectiveness is minimal for patients of long duration. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence showed that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Programmed Death Ligand 1 (PD-L1) is expressed in many cancer cell types, while its binding partner Programmed Death 1 (PD1) is expressed in activated T cells and antigen-presenting cells. Whereas, its dysregulation in the microenvironment is poorly understood. In the present study, we confirmed that evodiamine downregulates MUC1-C, resulting in modulating PD-L1 expression in non-small cell lung cancer (NSCLC). Methods: Cell viability was measured by MTT assays. Apoptosis, cell cycle and surface PD-L1 expression on NSCLC cells were analyzed by flow cytometry. The expression of MUC1-C and PD-L1 mRNA was measured by real time RT-PCR methods. Protein expression was examined in evodiamine-treated NSCLC cells using immunoblotting or immunofluorescence assays. The effects of evodiamine treatment on NSCLC sensitivity towards T cells were investigated using human peripheral blood mononuclear cells and Jurkat, apoptosis and IL-2 secretion assays. Female H1975 xenograft nude mice were used to assess the effect of evodiamine on tumorigenesis in vivo. Lewis lung carcinoma model was used to investigate the therapeutic effects of combination evodiamine and anti-PD-1 treatment. Results: We showed that evodiamine significantly inhibited growth, induced apoptosis and cell cycle arrest at G2 phase of NSCLC cells. Evodiamine suppressed IFN-γ-induced PD-L1 expression in H1975 and H1650. MUC1-C mRNA and protein expression were decreased by evodiamine in NSCLC cells as well. Evodiamine could downregulate the PD-L1 expression and diminish the apoptosis of T cells. It inhibited MUC1-C expression and potentiated CD8+ T cell effector function. Meanwhile, evodiamine showed good anti-tumor activity in H1975 tumor xenograft, which reduced tumor size. Evodiamine exhibited anti-tumor activity by elevation of CD8+ T cells in vivo in Lewis lung carcinoma model. Combination evodiamine and anti-PD-1 mAb treatment enhanced tumor growth control and survival of mice. Conclusions: Evodiamine can suppress NSCLC by elevating of CD8+ T cells and downregulating of the MUC1-C/PD-L1 axis. Our findings uncover a novel mechanism of action of evodiamine and indicate that evodiamine represents a potential targeted agent suitable to be combined with immunotherapeutic approaches to treat NSCLC cancer patients. MUC1-C overexpression is common in female, non-smoker, patients with advanced-stage adenocarcinoma. [ABSTRACT FROM AUTHOR]

We report on the fluorinated form of Cpd 5 as a cell growth inhibitor. This compound is 3-fold more potent than the parent Cpd 5 and is predicted, using the semi-empirical AM1 method to be only an arylator of cysteine-containing proteins, without generating reactive oxygen species. [Copyright &y& Elsevier]