The potential of Lycium barbarum miR166a in kidney cancer treatment.

Predator species of animal can absorb plant microRNA that can regulate target gene expression and physiological function across species. The herb Lycium barbarum, a traditional Chinese medicine, has a wide range of antitumor effects. However, there are no reports on the effects of microRNA derived from it on the cross-border regulation of renal cell carcinoma (RCC). We performed in vitro and in vivo experiments to explore the role and mechanism of the L. barbarum-derived microRNA miR166a (Lb-miR166a) in cross-border regulation of RCC. Our mRNA sequencing analysis showed that Lb-miR166a regulates the expression of various genes in tumor cells, including 1232 upregulated genes and 581 downregulated genes, which were enriched to 1094 Gene Ontology entries and 43 Kyoto Encyclopedia of Genes and Genomes pathways. In vitro cell experiments confirmed that Lb-miR166a can inhibit the proliferation of RCC cells, promote the apoptosis of tumor cells, and inhibit the invasion and metastasis of tumor cells by regulating the expression of related genes. Furthermore, our in vivo tumor-bearing experiment showed that subcutaneous tumor formation volume decreased in Lb-miR166a mice, along with the number of liver metastases. This study elucidates the role and mechanism of Lb-miR166a in RCC treatment (Fig. 1). Our results further mechanistically confirm the antitumor properties of L. barbarum. Our study may contribute to the clinical development of a targeted drug for RCC treatment.

A Multitask Network for People Counting, Motion Recognition, and Localization Using Through-Wall Radar.

Due to the outstanding penetrating detection performance of low-frequency electromagnetic waves, through-wall radar (TWR) has gained widespread applications in various fields, including public safety, counterterrorism operations, and disaster rescue. TWR is required to accomplish various tasks, such as people detection, people counting, and positioning in practical applications. However, most current research primarily focuses on one or two tasks. In this paper, we propose a multitask network that can simultaneously realize people counting, action recognition, and localization. We take the range-time-Doppler (RTD) spectra obtained from one-dimensional (1D) radar signals as datasets and convert the information related to the number, motion, and location of people into confidence matrices as labels. The convolutional layers and novel attention modules automatically extract deep features from the data and output the number, motion category, and localization results of people. We define the total loss function as the sum of individual task loss functions. Through the loss function, we transform the positioning problem into a multilabel classification problem, where a certain position in the distance confidence matrix represents a certain label. On the test set consisting of 10,032 samples from through-wall scenarios with a 24 cm thick brick wall, the accuracy of people counting can reach 96.94%, and the accuracy of motion recognition is 96.03%, with an average distance error of 0.12 m.

New Medium Bandgap Donor D-A1 -D-A2 Type Copolymers Based on Anthra[1,2-b: 4,3-b":6,7-c"'] Trithiophene-8,12-dione Groups for High-Efficient Non-Fullerene Polymer Solar Cells.

A new acceptor unit anthra[1,2-b: 4,3-b': 6,7-c'']trithiophene-8,12-dione (А3Т) (A2) is synthesized and used to design D-A1 -D-A2 medium bandgap donor copolymers with same thiophene (D) and A2 units but different A1, i.e., fluorinated benzothiadiazole (F-BTz) and benzothiadiazole (BTz) denoted as P130 and P131, respectively. Their detailed optical and electrochemical properties are examined. The copolymers show good solubility in common organic solvents, broad absorption in the visible spectral region from 300 to 700 nm, and deeper HOMO levels of -5.45 and -5.34 eV for P130 and P131, respectively. Finally, an optimized polymer solar cell (PSC) based on P131 as the donor and narrow bandgap non-fullerene small molecule acceptor Y6 demonstrated a power conversion efficiency (PCE) of >11.13%. To further improve the efficiency of the non-fullerene PSC, the P130 is optimized by introducing a fluorine atom into the BTz unit, F-BTz acceptor unit, and PCE PSC based on P130: Y6 active layer increased to >15.28%, which is higher than that for the non-fluorinated analog P131:Y6. The increase in the PCE for former PSC is attributed to the more crystalline nature and compact π-π stacking distance, leading to more balanced charge transport and reduced charge recombination. These remarkable results demonstrate that A3T-based copolymer P130 with F-BTz as the second acceptor is a promising donor material for high-performance PSCs.

Novel Pyrrolo [3,4-b] Dithieno [3, 2-f:2″,3″-h] Quinoxaline-8,10 (9H)-Dione Based Wide Bandgap Conjugated Copolymers for Bulk Heterojunction Polymer Solar Cells.

Two D-A copolymers consisting of fused ring pyrrolo-dithieno-quinoxaline acceptors are synthesized with different donor units, i.e., benzodithiophene (BDT) with alkylthienyl (P134) and 2-ethylhexyloxy (P117) side chains. These copolymers are used as donors and a narrow bandgap acceptor Y6 to fabricate bulk heterojunction polymer solar cell devices. Owing to the strong electron-deficient fused ring pyrrolo-bithieno-quinoxaline and weak alkyl thienyl side chains in BDT, the polymer solar cells (PSCs) based on P134:Y6 attain the power conversion efficiency (PCE) of 15.42%, which is higher than the P117:Y6 counterpart (12.14%). The superior value of PCE for P134:Y6 can be associated with more well-adjusted charge transport, weak charge recombination, proficient exciton generation, and dissociation into free charge carriers and their subsequent charge collection owing to the dense π-π stacking distance and more considerable crystal coherence length for the P134:Y6 thin films. This investigation confirms the great potential of a strong acceptor-weak donor tactic for developing efficient D-A copolymers consists of quinoxaline acceptor for PSCs.

Thermally Activated Delayed Fluorescence in CuI Complexes Originating from Restricted Molecular Vibrations.

The mechanism of thermally activated delayed fluorescence (TADF) in molecules in aggregated or condensed solid states has been rarely studied and is not well understood. Nevertheless, many applications of TADF emitters are strongly affected by their luminescence properties in the aggregated state. In this study, two new isomeric tetradentate CuI complexes which simultaneously show aggregation induced emission (AIE) and TADF characteristics are reported for the first time. We provide direct evidence that effectively restricting the vibrations of individual molecules is a key requisite for TADF in these two CuI complexes through in-depth photophysical measurements combined with kinetic methods, single crystal analysis and theoretical calculations. These findings should stimulate new molecular engineering endeavours in the design of AIE-TADF active materials with highly emissive aggregated states.

Polymer Acceptor Based on B←N Units with Enhanced Electron Mobility for Efficient All-Polymer Solar Cells.

We demonstrate that polymer electron acceptors with excellent all-polymer solar-cell (all-PSC) device performance can be developed from polymer electron donors by using B←N units. By alleviating the steric hindrance effect of the bulky pendant moieties on the conjugated polymers that contain B←N units, the π-π stacking distance of polymer backbones is decreased and the electron mobility is consequently enhanced by nearly two orders of magnitude. As a result, the power conversion efficiency of all-PSCs with the polymer acting as the electron acceptor is greatly improved from 0.12 % to 5.04 %. This PCE value is comparable to that of the best all-PSCs with state-of-the-art polymer acceptors.

An Electron-Deficient Building Block Based on the B←N Unit: An Electron Acceptor for All-Polymer Solar Cells.

A double B←N bridged bipyridyl (BNBP) is a novel electron-deficient building block for polymer electron acceptors in all-polymer solar cells. The B←N bridging units endow BNBP with fixed planar configuration and low-lying LUMO/HOMO energy levels. As a result, the polymer based on BNBP units (P-BNBP-T) exhibits high electron mobility, low-lying LUMO/HOMO energy levels, and strong absorbance in the visible region, which is desirable for polymer electron acceptors. Preliminary all-polymer solar cell (all-PSC) devices with P-BNBP-T as the electron acceptor and PTB7 as the electron donor exhibit a power conversion efficiency (PCE) of 3.38%, which is among the highest values of all-PSCs with PTB7 as the electron donor.

Developing conjugated polymers with high electron affinity by replacing a C-C unit with a B←N unit.

The key parameters of conjugated polymers are lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels. Few approaches can simultaneously lower LUMO and HOMO energy levels of conjugated polymers to a large extent (>0.5 eV). Disclosed herein is a novel strategy to decrease both LUMO and HOMO energy levels of conjugated polymers by about 0.6 eV through replacement of a C-C unit by a B←N unit. The replacement makes the resulting polymer transform from an electron donor into an electron acceptor, and is proven by fluorescence quenching experiments and the photovoltaic response. This work not only provides an effective approach to tune the LUMO/HOMO energy levels of conjugated polymers, but also uses organic boron chemistry as a new toolbox to develop conjugated polymers with high electron affinity for polymer optoelectronic devices.

Design, synthesis, and optoelectronic properties of dendrimeric Pt(II) complexes and their ability to inhibit intermolecular interaction.

Dendrimeric Pt(II) complexes [(C(∧)N)Pt(dpm)] and [Pt(C(∧)N)2] (Hdpm = dipivaloylmethane, HC(∧)N = 1,2-diphenylbenzoimidazole and its derivatives containing the carbazole dendrons) have been synthesized and characterized systematically. All of the complexes display green emission in the range of 495-535 nm that originated from the 360-440 nm absorption bands, which are assigned to dπ(Pt)→π*(L) metal-to-ligand charge transfer (MLCT) mixed with intraligand π(L)→π*(L) transition. Solution photoluminescence quantum yield (φp 0.26-0.31) of the heteroleptic complexes [(C(∧)N)Pt(dpm)] obviously increases when compared with that of complex [(C(∧)N)Pt(acac)]. Organic light-emitting diode devices based on these Pt(II) complexes with a multilayer configuration were fabricated and gave desirable electroluminescent (EL) performances, such as non- or less red-shifted EL spectra, in comparison with the photoluminescence spectra and slow efficiency roll-off with increasing brightness or current density. Complex [(t-BuCzCzPBI)Pt(dpm)] (where t-BuCzCzPBI = 1-(4-(3,6-di-(3,6-di-t-butyl-carbazol-9-yl))carbazol-9-yl)phenyl-2-phenylbenzoimidazole) showed the best performance, with a maximum current efficiency of 29.31 cd/A and a maximum external quantum efficiency (EQE) of 9.04% among the fabricated devices. Likewise, for homoleptic [Pt(t-BuCzCzPBI)2] dendrimer, the powder φp (0.14) and maximum EQE (0.74%) improve by 7 and 7.4 times, respectively, as high as they do for nondendrimeric [Pt(1,2-diphenylbenzoimidazole)2] (0.02, 0.10%), although its efficiency is still lower than that of the heteroleptic counterpart due to the severely distorted square-planar geometry of the emitting core. These results reveal that large steric hindrance from ancillary ligand (dpm) or the homoleptic conformation can effectively inhibit intermolecular interaction for these dendrimeric Pt(II) complexes.

A right convergence area of the prefrontal lobe is involved in the improvement of semantic fluency in patients with post-stroke aphasia.

OBJECTIVES: This study aimed to longitudinally observe the improvement mechanism of semantic fluency in subacute post-stroke aphasia (PSA) patients using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twelve PSA patients, about one month after onset, were enrolled in this study and received speech-language therapy (SLT) for one month. Auditory comprehension and semantic fluency were evaluated using the Western Aphasia Battery (WAB) and the Animal Fluency Test. Before and after treatment, rs-fMRI data were collected, and the dice similarity coefficient was used to measure the spatial similarity between each patient's lesion and a reference lesion. The left posterior inferior temporal gyrus (pITG) was used as a seed to calculate the normalized functional connectivity in whole-brain voxel analysis using DPABI software for statistical analysis. RESULTS: The dice similarity coefficient between each patient's lesion and the reference lesion showed moderate to high intensity (0.57 ± 0.14) in the Montreal Neurological Institute space. After treatment, we found a significant increase in functional connectivity between the left pITG and the right prefrontal lobe convergence area (peak t = 8.219, Gaussian random field multiple comparison correction, voxel p < 0.001, cluster p < 0.05). The increase in functional connectivity was negatively correlated with the improvement in auditory comprehension (r =-0.707, p = 0.033) and positively correlated with the improvement in semantic fluency (r = 0.79, p = 0.02). CONCLUSION: The improvement of semantic fluency in subacute PSA patients may require the participation of the right convergence area of the prefrontal lobe.

Light Emission and Conductance Fluctuations in Electrically Driven and Plasmonically Enhanced Molecular Junctions.

Electrically connected and plasmonically enhanced molecular junctions combine the optical functionalities of high field confinement and enhancement (cavity function), and of high radiative efficiency (antenna function) with the electrical functionalities of molecular transport. Such combined optical and electrical probes have proven useful for the fundamental understanding of metal-molecule contacts and contribute to the development of nanoscale optoelectronic devices including ultrafast electronics and nanosensors. Here, we employ a self-assembled metal-molecule-metal junction with a nanoparticle bridge to investigate correlated fluctuations in conductance and tunneling-induced light emission at room temperature. Despite the presence of hundreds of molecules in the junction, the electrical conductance and light emission are both highly sensitive to atomic-scale fluctuations-a phenomenology reminiscent of picocavities observed in Raman scattering and of luminescence blinking from photoexcited plasmonic junctions. Discrete steps in conductance associated with fluctuating emission intensities through the multiple plasmonic modes of the junction are consistent with a finite number of randomly localized, point-like sources dominating the optoelectronic response. Contrasting with these microscopic fluctuations, the overall plasmonic and electronic functionalities of our devices feature long-term survival at room temperature and under an electrical bias of a few volts, allowing for measurements over several months.

Risk stratification in gastric cancer lung metastasis: Utilizing an overall survival nomogram and comparing it with previous staging.

BACKGROUND: Gastric cancer (GC) is prevalent and aggressive, especially when patients have distant lung metastases, which often places patients into advanced stages. By identifying prognostic variables for lung metastasis in GC patients, it may be possible to construct a good prediction model for both overall survival (OS) and the cumulative incidence prediction (CIP) plot of the tumour. AIM: To investigate the predictors of GC with lung metastasis (GCLM) to produce nomograms for OS and generate CIP by using cancer-specific survival (CSS) data. METHODS: Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance, epidemiology, and end results program database. The major observational endpoint was OS; hence, patients were separated into training and validation groups. Correlation analysis determined various connections. Univariate and multivariate Cox analyses validated the independent predictive factors. Nomogram distinction and calibration were performed with the time-dependent area under the curve (AUC) and calibration curves. To evaluate the accuracy and clinical usefulness of the nomograms, decision curve analysis (DCA) was performed. The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer (AJCC) staging system by utilizing Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). Finally, the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared. RESULTS: For the purpose of creating the OS nomogram, a CIP plot based on CSS was generated. Cox multivariate regression analysis identified eleven significant prognostic factors (P < 0.05) related to liver metastasis, bone metastasis, primary site, surgery, regional surgery, treatment sequence, chemotherapy, radiotherapy, positive lymph node count, N staging, and time from diagnosis to treatment. It was clear from the DCA (net benefit > 0), time-dependent ROC curve (training/validation set AUC > 0.7), and calibration curve (reliability slope closer to 45 degrees) results that the OS nomogram demonstrated a high level of predictive efficiency. The OS prediction model (New Model AUC = 0.83) also performed much better than the old Cox-AJCC model (AUC difference between the new model and the old model greater than 0) in terms of risk stratification (P < 0.0001) and verification using the IDI and NRI. CONCLUSION: The OS nomogram for GCLM successfully predicts 1- and 3-year OS. Moreover, this approach can help to appropriately classify patients into high-risk and low-risk groups, thereby guiding treatment.

Fine tuning of the PCDTBT-OR:PC71BM blend nanoscale phase separation via selective solvent annealing toward high-performance polymer photovoltaics.

Solution-processable polymer solar cells show great promise for providing a cost-effective route to create lightweight and flexible solar energy conversion devices. The photoactive layer comprising the conjugated polymer donor and fullerene derivative acceptor must be optimized to form bicontinuous nanoscale phase separation in order for efficient exciton dissociation and charge collection due to the short exciton diffusion length of organic semiconductors. The donor polymer poly[9-(heptadecan-9-yl)-9H-carbazole- 2,7-diyl-alt-(5,6-bis(hexyloxy)-4,7-di(thiophen-2- yl)benzo[c][1,2,5]thiadiazole)-5,5-diyl] (PCDTBT-OR) has a deeper highest occupied molecular orbital level compared to its counterpart PCDTBT, and shows promise in increasing the open-circuit voltage and power conversion efficiency (PCE) of polymer solar cells. The phase separation evolution of the PCDTBT-OR:PC71BM blend with various weight ratios under tetrahydrofuran (THF) vapor annealing and its influence on the photovoltaic performance is investigated in detail. It is found that THF vapor annealing can promote the acceptor PC71BM aggregation from the donor PCDTBT-OR matrix to form nanoscale donor/acceptor phase separation for efficient exciton dissociation and charge collection depending on the donor/acceptor weight ratio and the annealing time. The THF vapor-annealed PCDTBT-OR:PC71BM solar cells exhibit remarkable enhancement, with a PCE of 7.01% compared to 3.25% of the as-cast solar cells with the same active layer thickness. This work provides a general methodology to construct nano-interpenetrating networks for homogeneous polymer/fullerene blends and is potentially applicable to the roll-to-roll manufacturing of polymer solar cells.

Glutathione S-transferase P1 gene polymorphism and bladder cancer susceptibility: an updated analysis.

Studies investigating the association between glutathione S-transferase P1 (GSTP1) gene polymorphism and bladder cancer (BC) risk have reported conflicting results. In order to clarify the effect of GSTP1 polymorphism on the BC susceptibility, we conducted an updated system review of published epidemiology studies to provide more precise evidence. We performed a systematic search of PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI). 20 studies with 4,428 BC cases and 5,457 controls were identified. The combined analyses based on all studies showed that there was a significant difference in the genotype distribution in GSTP1(A313G) polymorphism between BC cases and controls not only in Asians (GG vs. AA + AG, OR = 1.59, 95 % CI = 1.01-2.51) but also in Caucasians (GG vs. AA + AG, OR = 1.51, 95 % CI = 1.11-2.06). Upon stratification for smoking status, we observed no statistically significant difference in genotype distribution of GSTP1 in ever-smokers. Combination of the high-risk genotypes (GSTM1 null + GSTT1 null + GSTP1 313 A/G or G/G) demonstrated further increase in the BC risk (OR = 6.64, 95 %CI = 3.63-12.16). This meta-analysis suggests that GSTP1 313 G/G polymorphism is a strong predisposing risk factor for BC.

The diagnostic or prognostic values of FADD in cancers based on pan­cancer analysis.

Previous studies have determined that aberrant expression of the fas-associated death domain (FADD) contributes to the development of cancer. However, no pan-cancer analysis has been reported to explore the relationship between FADD and various cancers. Multiple databases were screened to identify cancer datasets for the present study and to validate the expression of FADD in various tumors. The association of FADD alteration with cancer prognosis, clinical features and tumor immunity was also evaluated. Reverse transcription-quantitative PCR (RT-qPCR) was utilized to confirm the expression of FADD in breast, colon, liver and gastric cancer cells. Analysis of Gene Expression Omnibus database and The Cancer Genome Atlas database indicated that FADD was highly expressed in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma, cholangiocarcinoma, colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD) and prostate adenocarcinoma, whereas RT-qPCR results revealed that FADD was highly expressed in breast cancer and colon cancer. Further analyses demonstrated that FADD expression was significantly altered in ESCA, head and neck squamous cell carcinoma (HNSC), lung squamous cell carcinoma and BRCA. FADD expression was observed to be a risk factor of the overall survival in patients with HNSC, LIHC and LUAD as demonstrated by Kaplan-Meier and Cox regression analyses. The results of the present study demonstrated that FADD is highly expressed in numerous malignancies and can be utilized as a biomarker for the diagnosis of BRCA, COAD, LIHC and stomach adenocarcinoma. Moreover, FADD expression is a predictive risk factor for the development of HNSC, LIHC and LUAD and can potentially be used as a prognostic marker for these cancers.

The role of miR-199a-3p in inhibiting the proliferation of spermatogonial stem cells under heat stress.

MicroRNAs (miRNAs) play a crucial role in regulating various physiological processes, including cell differentiation, proliferation, and apoptosis. However, their specific functions in response to heat stress are not fully understood. This study aimed to investigate the regulatory effects of miR-199a-3p on the proliferation of heat stress-treated spermatogonial stem cells (SSCs). SSCs were isolated from mouse testes and cultured in vitro to identify marker molecules. Lentiviruses carrying miR-199a-3p-over, miR-199a-3p-inhibit, and ID4-over constructs were generated for stable transfection. Luciferase assay was employed to confirm the targeting relationship between miR-199a-3p and ID4. An in vitro SSCs heat stress model was established, and the miR-199a-3p-inhibit and ID4-over groups were included. Cellular proliferation was assessed using CCK-8, EdU, and cell cycle analysis methods after heat stress. Expression levels of miR-199a-3p and ID4 were evaluated by western blotting and qRT-PCR. The results demonstrated that miR-199a-3p-over inhibited SSCs proliferation, while ID4-over promoted an increase in SSCs number. Luciferase assay confirmed the regulatory effect of miR-199a-3p on ID4 expression. Moreover, after heat stress treatment, miR-199a-3p-inhibit and ID4-over enhanced SSCs proliferation compared to the control group. These findings suggest that miR-199a-3p modulates SSCs proliferation by targeting ID4, especially under heat stress conditions.

Element variation in a clam shell and its implications for cold seep irregular eruptions: Calyptogena sp. in the Haima cold seep.

Cold seep is characterized by methane-rich fluids released from subsurface reservoirs, and it sustains the chemosynthetic ecosystems on the seafloor. Previous studies suggest that the activity of cold seep could affect the seawater chemistry and ambient temperature. However, the short-term seep activity was hardly reconstructed due to the focus of studies on carbonate or sediment. Vent macrofauna provide such an opportunity by recording in shells the immediate environment in which they grow. The carbonate skeleton of organisms could theoretically preserve environmental variation. Therefore, high-resolution archives are urgently required to understand the influence of cold seep activity on biogeochemistry. In this study, SEM, EDS mapping, EBSD mapping, and LA-ICP-MS analyses were conducted on a clam (Calyptogena sp.) shell collected alive in 2018 from the Haima cold seep in South China Sea. The CaCO3, Na, Mg, Sr, and Ba contents and the Sr/Ca, Ba/Ca, and Na/Ca ratios in the hinge plate were measured on LA-ICP-MS by spot analysis and line scanning. The element contents in the hinge are as follows: Mg (38.5-109 µg/g), Na (3117-5246 µg/g), Sr (970-5371 µg/g), and Ba (2.9-11.5 µg/g). The results show that Sr, Re, and Ba content vary synchronously along the direction of growth, but Na has an opposite trend. The element analyses indicate that the eruption of the Haima cold seep was irregular, causing temperature, redox state, and pH changes in the cold seep ecosystem. These findings show that the irregular cold seep activities exert vital influences on the biogeochemistry of the cold seep ecosystem, which shed a light on cold seep biomonitoring.

Lactobacillus rhamnosus GG and butyrate supplementation in rats with bone cancer reduces mechanical allodynia and increases expression of µ-opioid receptor in the spinal cord.

Introduction: Chronic cancer pain is one of the most unbearable symptoms for the patients with advanced cancer. The treatment of cancer pain continues to possess a major challenge. Here, we report that adjusting gut microbiota via probiotics can reduce bone cancer pain (BCP) in rats. Methods: The model of BCP was produced by tumor cell implantation (TCI) to the tibia in rats. Continuous feeding of Lactobacillus rhamnosus GG (LGG) was used to modulate the gut microbiota. Mechanical allodynia, bone destruction, fecal microbiota, and neurochemical changes in the primary dorsal root ganglion (DRG) and the spinal dorsal horn (DH) were assessed. Results: LGG supplementation (109 CFU/rat/day) delayed the production of BCP for 3-4 days and significantly alleviated mechanical allodynia within the first 2 weeks after TCI. TCI-induced proinflammatory cytokines TNF-α and IL-ß in the DH, and TCI-induced bone destruction in the tibia were both significantly reduced following LGG supplementation examined on day 8 after TCI. Meanwhile, we found that LGG supplementation, in addition to inhibiting TCI-induced pain, resulted in a significantly increased expression of the µ-opioid receptor (MOR) in the DH, but not in the DRG. LGG supplementation significantly potentiated the analgesic effect of morphine. Furthermore, LGG supplementation led to an increase in butyrate levels in the feces and serum and a decrease in histone deacetylase 2 (HDAC2) expression in the DH. Feeding TCI-rats with sodium butyrate solution alone, at a dose of 100 mg/kg, resulted in decreased pain, as well as decreased HDAC2 expression and increased MOR expression in the DH. The increased expression of MOR and decreased HDAC2 were also observed in neuro-2a cells when we treated the cells with serum from TCI rats with supplementation of LGG or sodium butyrate. Discussion: This study provides evidence that reshaping the gut microbiota with probiotics LGG can delay the onset of cancer pain. The butyrate-HDAC2-MOR pathway may be the underlying mechanism for the analgesic effect of LGG. These findings shed light on an effective, safe, and non-invasive approach for cancer pain control and support the clinical implication of probiotics supplementation for patients with BCP.

Nrf2/HO-1 blocks TXNIP/NLRP3 interaction via elimination of ROS in oxygen-glucose deprivation-induced neuronal necroptosis.

Acute ischemic stroke (AIS) is known to trigger a cascade of inflammatory events that induces secondary tissue damages. As a type of regulated inflammatory cell death, necroptosis is associated with AIS, whilst its regulation during neuroinflammation is not well understood. In particular, the actual function of NOD-like-receptor family pyrin domain-containing-3(NLRP3) inflammasome in cortical neuronal necroptosis still not clear. Herein, we explored the function of nuclear factor erythroid-2 related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) in oxygen-glucose deprivation (OGD) induced neuronal necroptosis and its underlying mechanism. To establish an in vitro model of neuronal necrosis, we used OGD/caspase-8 inhibitors (Q-VD-OPh, QVD) to treat rat primary cortical neurons (PCNs) after reoxygenation, wherein we found that the model cause an elevated ROS levels by mediating TXNIP/NLRP3 interactions, which in turn activated the NLRP3 inflammasome. Also, we observed that regulation of nuclear factor erythroid-2 related factor-2 (Nrf2) promoted heme oxygenase-1 (HO-1) expression and decreased TXNIP (a protein that relate oxidative stress to activation of inflammasome) and ROS levels, which negatively regulated the expression of OGD-induced activation of NLRP3 inflammasomes. In addition, HO-1 weakened NLRP3 inflammation body activation, which suggests that Nrf2-regulated HO-1 could block the interaction between TXNIP and NLRP3 in OGD/R-treated cortical neurons by inhibiting ROS production. Our study has discovered the importance of Nrf2/HO-1 signaling cascade for inhibiting inflammasome of NLRP3, which negatively regulated necrosis. Therefore, NLRP3 is considered a potential target for a novel neuroprotective approach, which can expand the therapeutic windows of stroke drugs.

Platinum(II)-bis(aryleneethynylene) complexes for solution-processible molecular bulk heterojunction solar cells.

Four new solution-processible small-molecular platinum(II)-bis(aryleneethynylene) complexes consisting of benzothiadiazole as the electron acceptor and triphenylamine and/or thiophene as the electron donor were conveniently synthesized and characterized by physicochemical and computational methods, and utilized as the electron-donor materials in the fabrication of solution-processed bulk heterojunction (BHJ) solar cells. The effect of different electron-donor groups in these small molecules on the optoelectronic and photovoltaic properties was also examined. The optical and time-dependent density functional theory studies showed that the incorporation of stronger electron-donor groups significantly enhanced the solar-absorption abilities of the complexes. These molecular complexes can serve as good electron donors for fabricating BHJ devices by blending them with the [6,6]-phenyl-C(71)-butyric acid methyl ester (PC(70)BM) as the electron acceptor. The best power conversion efficiency of 2.37% was achieved with the open-circuit voltage of 0.83 V, short-circuit current density of 7.10 mA cm(-2) and fill factor of 0.40 under illumination of an AM 1.5 solar-cell simulator. The spin-coated thin films showed p-channel field-effect charge transport with hole mobilities of up to 2.4×10(-4) cm(2) V(-1) s(-1) for these molecules. The present work illuminates the potential of well-defined organometallic complexes in developing light-harvesting small molecules for efficient power generation in organic photovoltaics implementation.