How Does Systemic Design Facilitate the Sustainability Transition of Rural Communities? A Comparative Case Study between China and Italy

Rural sustainability has emerged as a 'wicked problem' for practitioners within and outside design. Many efforts that adopted a systematic approach since the 1980s paved the road for addressing such a systemic problem. Moreover, stakeholders from the systemic design field have made significant strides by developing a systemic approach to rural systems since 2012 and implementing numerous localised design practices globally. Despite these efforts, the essence of systemic design for sustainable rural development remains relatively unclear because of its infancy. Therefore, this study tries to answer the question of "how does systemic design facilitate the sustainability transition of rural communities" by conducting field visits to two typical systemic design projects: Future Village Lab in rural China (Tieniu Village) and Systemic Design Lab in Italy (Ostana). Thereafter, drawing on insights from organisational management studies, this study pioneers a novel theoretical framework called 'Situation-Cognition-Action' to compare and analyse these two cases. The results highlight the role of systemic design in contributing to rural sustainability by enhancing the understanding of complex situations, fostering cognitive capacity, and creating a solution ecosystem for collaborative action. Finally, it elucidates how systemic design addresses three crucial trade-offs and effectively promotes rural sustainability in various rural contexts

A Novel Intralymphatic Nanocarrier-Delivery System for Cisplatin Therapy in Breast Cancer with Improved Tumor Efficacy and Lower Systemic Toxicity In Vivo

Background A lymphatically delivered nanoconjugate of cisplatin was evaluated in an orthotopic mouse model of locoregionally metastatic breast cancer (LABC) to determine if it can overcome some of the limitations of standard cisplatin therapy such as high systemic toxicity. Methods Human breast cancer cells (107 MDA-MB-468LN) were injected into the mammary fat pad of female nu/nu mice. Once tumor volume reached 50 mm3; intravenous cisplatin or subcutaneous hyaluronan-cisplatin [HA-cisplatin] nanoconjugate was given 1/week × 3 at 3.3 mg/kg (platinum basis). Results Nanoconjugates co-localized with the tumors after subcutaneous peritumoral injection and demonstrated improved efficacy to intravenous cisplatin. After one month, renal tubular hemorrhage and edema were more prevalent in the intravenous formulation compared to subcutaneous HA-cisplatin nanoconjugates. Conclusions This nanocarrier delivery platform focuses drug in the areas where tumor burden is greatest, potentially reducing systemic toxicity, and has future applicability as a neoadjuvant or adjuvant therapy for LABC

Drug delivery to the lymphatic system: importance in future cancer diagnosis and therapies

This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Delivery on 2009-08, available online: http://www.tandfonline.com/10.1517/17425240903085128.Cancer is the second leading cause of death in the US. Currently, protocols for cancer treatment include surgery to remove diseased and suspect tissues, focused radiation, systemic chemotherapy, immunotherapy and their combinations. With conventional chemotherapy, it is almost impossible to deliver anticancer drugs specifically to the tumor cells without damaging healthy organs or tissues. Over the past several decades, efforts have been made to improve drug delivery technologies that target anticancer drugs specifically to tumor cells. It has been known for over four decades that the lymphatics are the first site of metastasis for most solid cancers; however, few efforts have been made to localize chemotherapies to lymphatic tissues. Trials of several systemic targeted drug delivery systems based on nanoparticles containing chemotherapeutic agents (e.g., liposomal doxorubicin) have shown similar antitumor activity but better patient tolerance compared with conventional formulations. Animal studies have demonstrated that nanoparticles made of natural or synthetic polymers and liposomal carriers have higher accumulation in the lymph nodes and surrounding lymphatics compared to conventional intravenous therapies. This combination has the potential to both reduce nonspecific organ toxicities and increase the chemotherapeutic dose to the most likely sites of locoregional cancer metastasis

Pharmacokinetics and Disposition of a Localized Lymphatic Polymeric Hyaluronan Conjugate of Cisplatin in Rodents

Cisplatin (CDDP) is an effective anticancer agent for many solid tumors but has significant systemic toxicity limiting its use in many patients. We have designed a loco-regional delivery system to increase platinum levels in the lymphatics, where early metastasis is most likely to occur, while reducing systemic toxicities. CDDP was conjugated to a biocompatible polymer hyaluronan (HA), with a conjugation degree of approximately 20% (w/w). Conjugates were delivered via subcutaneous injection into the mammary fat pad of rats. Intravenous hyaluronan–cisplatin (HA–Pt) exhibited an increased plasma area under the curve (AUC) 2.7-fold compared to conventional CDDP but with a reduced peak plasma level (Cmax), and HA–Pt increased the ipsilateral lymph node AUC by 3.8-fold compared to CDDP. Urine creatinine was unchanged over 30 days following dosing of HA–Pt. This study demonstrates that intralymphatic drug delivery with polymer-conjugated platinum may provide greater tissue and systemic plasma concentrations of platinum than intravenous CDDP. In addition, localized particle delivery augmented distribution in the loco-regional tissue basin where tumor burden predominates, while renal toxicity compared to standard intravenous CDDP was significantly reduced

Continuous variable entanglement enhancement and manipulation by a sub-threshold type-II optical parametric amplifier

We experimentally demonstrate that the quantum entanglement between amplitude and phase quadratures of optical modes produced from a non-degenerate optical parametric amplifier (NOPA) can be enhanced and manipulated phase-sensitively by means of another NOPA. When both NOPAs operate at de-amplification, the entanglement degree is increased at the cavity resonance of the second NOPA. When the first NOPA operates at de-amplification and the second one at amplification, the spectral features of the correlation variances are significantly changed. The experimental results are in good agreement with the theoretical expectation

Effects of nanomaterial physicochemical properties on in vivo toxicity

It is well recognized that physical and chemical properties of materials can alter dramatically at nanoscopic scale, and the growing use of nanotechnologies requires careful assessment of unexpected toxicities and biological interactions. However, most in vivo toxicity concerns focus primarily on pulmonary, oral, and dermal exposure to ultrafine particles. As nanomaterials expand as therapeutics and as diagnostic tools, parenteral administration of engineered nanomaterials should also be recognized as a critical aspect for toxicity consideration. Due to the complex nature of nanomaterials, conflicting studies have led to different views of their safety. Here, the physicochemical properties of four representative nanomaterials (dendrimers, carbon nanotubes, quantum dots, and gold nanoparticles) as it relates to their toxicity after systemic exposure is discussed

Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells.

Radiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative analysis of RT-treated recurrent tumors versus primary counterparts in GBM patients, RT-treated orthotopic GBM tumors xenografts versus untreated tumors and radioresistant GBM cells versus wild type cells. The results reveal that activation of STAT3, a well-defined redox-sensitive transcriptional factor, is causally linked with GBM adaptive radioresistance. Database analysis also agrees with the worse prognosis in GBM patients due to the STAT3 expression-associated low RT responsiveness. However, although the radioresistant GBM cells can be resensitized by inhibition of STAT3, a fraction of radioresistant cells can still survive the RT combined with STAT3 inhibition or CRISPR/Cas9-mediated STAT3 knockout. A complementally enhanced activation of ERK1/2 by STAT3 inhibition is identified responsible for the survival of the remaining resistant tumor cells. Dual inhibition of ERK1/2 and STAT3 remarkably eliminates resistant GBM cells and inhibits tumor regrowth. These findings demonstrate a previously unknown feature ofSTAT3-mediated ERK1/2 regulation and an effective combination of two targets in resensitizing GBM to RT

Pulmonary delivery of cisplatin-hyaluronan conjugates via endotracheal instillation for the treatment of lung cancer

Cisplatin (CDDP) intravenous treatments suffer several dose-limiting toxicity issues. Hyaluronan (HA), a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system. An alteration in input rate and administration route through pulmonary delivery of hyaluronan-cisplatin conjugate (HA-Pt) may increase local lung CDDP concentrations and decrease systemic toxicity. Sprague-Dawley rats were split into four groups: i.v. CDDP (3.5 mg/kg), i.v. HA-Pt conjugate (3.5 mg/kg equivalent CDDP), lung instillation CDDP and lung instillation HA-Pt conjugate. Total platinum level in the lungs of the HA-Pt lung instillation group was 5.7-fold and 1.2-fold higher than the CDDP intravenous group at 24 h and 96 h, respectively. A 1.1-fold increase of Pt accumulation in lung draining nodes for the HA-Pt lung instillation group was achieved at 24 h relative to the CDDP i.v. group. In the brain and kidneys, the CDDP i.v. group had higher tissue/plasma ratios compared to the HA-Pt lung instillation group. Augmented tissue distribution from CDDP i.v. could translate into enhanced tissue toxicity compared to the altered input rate and distribution of the intrapulmonary nanoformulation. In conclusion, a local pulmonary CDDP delivery system was developed with increased platinum concentration in the lungs and draining nodes compared to i.v. therapy