Combination of radiotherapy and PD-L1 blockade induces abscopal responses in EGFR-mutated lung cancer through activating CD8 T cells.

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8T cells has not been investigated intensively.

Who benefit from adjuvant chemotherapy in stage I lung adenocarcinoma? A multi-dimensional model for candidate selection.

Background: Despite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. [1] While it is still disputable whether adjuvant chemotherapy is necessary for stage I patients. [2] IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis.

Low-frequency Stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy.

Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus. It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy, but still lacks effective treatments. Here, we aimed to test the effects of low-frequency stimulation (LFS) at the subiculum for secondary epileptogenesis in a mouse model.

Efficient Delivery of Gemcitabine by Estrogen Receptor-Targeted PEGylated Liposome and Its Anti-Lung Cancer Activity In Vivo and In Vitro.

Lung cancer is one of the main causes of cancer-related deaths. At present, the main treatment method for lung cancer is chemotherapy. Gemcitabine (GEM) is widely applied in lung cancer treatment, but its lack of targeting ability and serious side effects limit its application.

A novel estrogen-targeted PEGylated liposome co-delivery oxaliplatin and paclitaxel for the treatment of ovarian cancer.

Ovarian cancer is the second cause of death among gynecological malignancies. In this study, we designed a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin and paclitaxel (ES-SSL-OXA/PTX) which could target estrogen receptor (ER) highly expressed on the surface of SKOV-3 cells to enhance therapeutic efficacy and reduce the side effects for SKOV-3 tumor therapy. ES-SSL-OXA/PTX was prepared by thin film hydration method and exhibited a uniform spherical morphology.

3D-CEUS tracking of injectable chemo-sonodynamic therapy-enabled mop-up of residual renal cell carcinoma after thermal ablation.

Thermal ablation (TA), as a minimally invasive therapeutic technique, has been extensively used to the treatment of solid tumors, such as renal cell carcinoma (RCC), which, unfortunately, still fails to overcome the high risk of local recurrence and distant metastasis since the incomplete ablation cannot be ignored due to various factors such as the indistinguishable tumor margins and limited ablation zone. Herein, we report the injectable thermosensitive hydrogel by confining curcumin (Cur)-loaded hollow mesoporous organosilica nanoparticles (Cur@HMON@gel) which can locate in tumor site more than half a month and mop up the residual RCC under ultrasound (US) irradiation after transforming from colloidal sol status to elastic gel matrix at physiological temperature. Based on the US-triggered accelerated diffusion of the model chemotherapy drug with multi-pharmacologic functions, the sustained and controlled release of Cur has been demonstrated .

vcfpop: Performing population genetics analyses for autopolyploids and aneuploids based on next-generation sequencing data sets.

Polyploids are cells or organisms with a genome consisting of more than two sets of homologous chromosomes. Polyploid plants have important traits that facilitate speciation and are thus often model systems for evolutionary, molecular ecology and agricultural studies. However, due to their unusual mode of inheritance and double-reduction, diploid models of population genetic analysis cannot properly be applied to autopolyploids.

Estrone-Conjugated PEGylated Liposome Co-Loaded Paclitaxel and Carboplatin Improve Anti-Tumor Efficacy in Ovarian Cancer and Reduce Acute Toxicity of Chemo-Drugs.

Purpose: Ovarian cancer is the most lethal gynecologic malignancy. The combination of paclitaxel (PTX) and carboplatin (CBP) is the first-line remedy for clinical ovarian cancer. However, due to the limitations of adverse reaction and lacking of targeting ability, the chemotherapy of ovarian cancer is still poorly effective.

A random forest algorithm predicting model combining intraoperative frozen section analysis and clinical features guides surgical strategy for peripheral solitary pulmonary nodules.

Background: Intraoperative frozen section (FS) analysis has been used to guide the extent of resection in patients with solitary pulmonary nodules (SPNs), but its accuracy varies greatly among different hospitals. Artificial intelligence (AI) and multidimensional data technology are developing rapidly these years, meanwhile, surgeons need better methods to guide the surgical strategy of SPNs. We established predicting models combining FS results with multidimensional perioperative clinical features using logistic regression analysis and the random forest (RF) algorithm to get more accurate extent of SPN resection.

Estrone-targeted PEGylated Liposomal Nanoparticles for Cisplatin (DDP) Delivery in Cervical Cancer.

Cisplatin (DDP), a first-line chemo-drug for cervical cancer therapy, has limited the clinical use due to its high-dose administration and strong side effects. In this study, estrone-targeted PEGylated Liposomal DDP (ES-SSL-DDP) was prepared by thin-film hydration method and characterized. ES-SSL-DDP presented a spherical structure, with a particle size of about 97.

Effects of cadmium exposure on thyroid gland and endochondral ossification in Rana zhenhaiensis.

Discovery of elevated concentrations of cadmium in the natural environment has increased awareness because of their potential threats. Amphibians are negatively affected due to their moderate sensitivity to cadmium. Here, we conduct acute and subchronic toxicity tests to examine whether, and to what extent, cadmium exposure disturbs metamorphosis, growth, and kinetic ability of Rana zhenhaiensis.

Sequential Ultrasound-Triggered and Hypoxia-Sensitive Nanoprodrug for Cascade Amplification of Sonochemotherapy.

Hypoxia, the typical and conspicuous characteristic of most solid tumors, worsens the tumor invasiveness and metastasis. Here, we engineered a sequential ultrasound (US)/hypoxia-sensitive sonochemotherapeutic nanoprodrug by initially synthesizing the hypoxia-activated azo bond-containing camptothecin (CPT) prodrug (CPT-Azo) and then immobilizing it into the mesopores of sonosensitizer-integrated metal organic frameworks (MOF NPs). Upon entering the hypoxic tumor microenvironment (TME), the structure of CPT-Azo immobilized MOFs (denoted as MCA) was ruptured and the loaded nontoxic CPT-Azo prodrug was released from the MOF NPs.

Manipulation of cadmium and diethylhexyl phthalate on Rana chensinensis tadpoles affects the intestinal microbiota and fatty acid metabolism.

Gastrointestinal tract and intestine microbiota can both have deep effects on the lipid metabolism and immune function of amphibians. Additionally, the composition and structure of the microbial community are influenced by environmental pollutions. It is noteworthy that environmental compounds such as Cd and DEHP are pervasive in the aquatic environment and do not exist in isolation, and single exposure experiments cannot well explain the effects of unpredictable interactions between co-existing compounds on amphibians.

In vitro and in vivo Evaluation of a Novel Estrogen-Targeted PEGylated Oxaliplatin Liposome for Gastric Cancer.

Background: Chemotherapy is still the main first-line treatment for advanced metastatic gastric cancer, but it has the limitations of serious side effects and drug resistance. Conventional liposome has been substantially used as drug carriers, but they lack targeting character with lower drug bioavailability in tumor tissues. Based on the above problems, a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin (ES-SSL-OXA) was prepared to further improve the metabolic behavior, the safety profile, and the anti-tumor efficacy of oxaliplatin.

Secondary Epileptogenesis: Common to See, but Possible to Treat?

Secondary epileptogenesis is a common phenomenon in epilepsy, characterized by epileptiform discharges from the regions outside the primary focus. It is one of the major reasons for pharmacoresistance and surgical failure. Compared with primary epileptogenesis, the mechanism of secondary epileptogenesis is usually more complex and diverse.

Engineering Oxygen-Irrelevant Radical Nanogenerator for Hypoxia-Independent Magnetothermodynamic Tumor Nanotherapy.

Tumor hypoxia substantially lowers the treatment efficacy of oxygen-relevant therapeutic modalities because the production of reactive oxygen species in oxygen-relevant anticancer modalities is highly dependent on oxygen level in tumor tissues. Here a distinctive magnetothermodynamic anticancer strategy is developed that takes the advantage of oxygen-irrelevant free radicals produced from magnetothermal decomposable initiators for inducing cancer-cell apoptosis in vitro and tumor suppression in vivo. Free-radical nanogenerator is constructed through in situ engineering of a mesoporous silica coating on the surface of superparamagnetic Mn and Co-doped nanoparticles (MnFe O @CoFe O , denoted as Mag) toward multifunctionality, where mesoporous structure provides reservoirs for efficient loading of initiators and the Mag core serves as in situ heat source under alternating magnetic field (AMF) actuation.

Prognostic Value of Inflammatory Biomarkers in Patients With Stage I Lung Adenocarcinoma Treated With Surgical Dissection.

Objective: Inflammation plays a crucial role in tumorigenesis and progression. Our purpose was to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII), and develop a nomogram to predict the cancer-specific survival (CSS) and disease-free survival (DFS) of stage I lung adenocarcinoma patients.

Methods: 1431 patients undergoing surgical resection with pathologically confirmed stage I lung adenocarcinoma were reviewed.

Altered temperature affect body condition and endochondral ossification in Bufo gargarizans tadpoles.

Bufo gargarizans is one kind of economic animals with higher medicinal value in China. In this study, B. gargarizans (Bufo gargarizans) tadpoles were reared at three different water temperature (15, 22 and 29 °C) from Gosner stages 28-46.

Oxygen-Independent Photocleavage of Radical Nanogenerator for Near-IR-Gated and H O-Mediated Free-Radical Nanotherapy.

The oxygen-dependent nature and limited penetration capacity of visible light render the low efficiency of photodynamic therapy in hypoxic and deep-seated tumors. Therefore, the development of oxygen-free photoactivated chemotherapy (PACT) to generate cytotoxic reactive oxygen species by near-IR (NIR) light-cleavable photocages is in high demand. Here, an oxygen-irrelevant PACT strategy based on NIR light-triggered hydroxyl radicals (•OH) generation is developed for free-radical nanotherapy.

Subicular Caspase-1 Contributes to Pharmacoresistance in Temporal Lobe Epilepsy.

Objective: Unidentified mechanisms largely restrict the viability of effective therapies in pharmacoresistant epilepsy. Our previous study revealed that hyperactivity of the subiculum is crucial for the genesis of pharmacoresistance in temporal lobe epilepsy (TLE), but the underlying molecular mechanism is not clear.

Methods: Here, we examined the role of subicular caspase-1, a key neural pro-inflammatory enzyme, in pharmacoresistant TLE.

Influence of octylphenol on gene expression of gonadotropins and their receptors, testicular structure and mating behavior of male Rana chensinensis.

In the present study, responses of the Chinese brown frog (Rana chensinensis) to exposure to different doses and duration of Octyphenol (OP) which degraded from alkylphenol ethoxylates (APEs) were characterized during the adult periods. The effects of OP on growth, development and reproduction and the expression of genes in gonad were investigated. The expression levels of fshβ, lhβ, fshr and lhr had significant differences as the exposure time increased.

Long-term music adjuvant therapy enhances the efficacy of sub-dose antiepileptic drugs in temporal lobe epilepsy.

Aims: Noninvasive music adjuvant therapy shows great potential in improving seizure control when combined with routine antiepileptic drugs. However, the diversity of previous music protocols has resulted in disparate outcomes. The optimized protocol and features for music adjuvant therapy are still not fully understood which limits its feasibility.

Effects of temperature on growth, development and the leptin signaling pathway of Bufo gargarizans.

Climate change is one of the most important causes of the decline in amphibians. Changes in temperature have an important effect on the growth and development and energy metabolism of amphibians. The aim of this study is to unravel the effects of temperature on the leptin signaling pathway of Bufo gargarizans and its molecular mechanisms.