Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor

Background Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. Results The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. Conclusions This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment. Graphical Abstract

Recent decrease in summer precipitation over the Iberian Peninsula closely links to reduction of local moisture recycling

The inherently dry summer climate of the Iberian Peninsula (IP) is undergoing drought exacerbated by more intense warming and reduced precipitation. Although many studies have studied changes in summer climate factors, it is still unclear how the changes in moisture contribution from the source lead to the decrease in summer precipitation. This study investigates the differences in the IP precipitationshed between 1980–1997 and 1998–2019 using the Water Accounting Model-2layers with ERA5 data, and assesses the role of local recycling and external moisture in reducing summer precipitation. Our findings indicate that the moisture contributions from the local IP, and from the west and the east of the precipitationshed contributed 1.7, 3.6 and 1.1 mm mon−1 less precipitation after 1997 than before 1997, accounting for 26 %, 57 % and 17 % of the main source supply reduction, respectively. The significant downward trend of the IP local recycling closely links to the disappearance of the wet years after 1997 as well as the decrease of local contribution in the dry years. Moreover, the feedback between the weakened local moisture recycling and the drier land surface can exacerbate the local moisture scarcity and summer drought.

Mitochondria-Targeted Nanoplatforms For Enhanced Photodynamic Therapy Against Hypoxia Tumor

Background: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers.Results: The as-synthesized nanoplatforms penetrated deeply into the interior regions of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment.Conclusions: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.

Crohn’s disease triggering ileoileal intussusception in an adult

Intussusception is defined as the telescoping of a segment of the gastrointestinal tract (intussusceptum) into an immediately adjacent distal bowel (intussuscipiens), causing venous congestion, edema, and blood supply reduction. Adult intussusception is a rare entity which can be with or without lead-point. Cases without lead-point frequently occurs in children or adults with celiac disease and Crohn’s disease and with lead point is caused by an underlying neoplasm, benign or malignant frequently presenting with bowel obstruction and acute abdomen. A 41-years-old male presented to our outpatient clinic with a history of recurrent abdominal pain. The clinical presentation and CT scan findings led to the diagnosis of ileoileal intussusception. Subsequently he underwent laparotomy which revealed an ileal intussusception, which was investigated and was found to be of Crohn’s etiology.

Impact of orthognathic surgery on the prevalence of dehiscence in Class II and Class III surgical-orthodontic patients:

ABSTRACT Objectives The objectives were to evaluate and compare the presence of bone dehiscence before and after orthognathic surgery. Materials and Methods In this retrospective study, 90 cone-beam computed tomography (CBCT) scans from 45 patients were evaluated. Class II (n = 23) and Class III (n = 22) orthodontic patients who were being prepared for orthognathic surgery were measured. CBCT scans were obtained about 30 days prior to (T0) and 6 months after (T1) double jaw orthognathic surgery. The distance between the cemento-enamel junction (CEJ) and the alveolar bone crest was assessed at the buccal and lingual surfaces of all teeth, on both sides and arches, except for the second premolars and the second and third molars. A total of 1332 sites were measured for Class II (644) and Class III (688) patients. The software used was OsiriX (version 3.3 32-bit). Data were compared with Wilcoxon and McNemar tests at the 5% level. Results Bone dehiscence before surgery was present in 26% and 15% of the Class II and III groups, respectively. The presence of dehiscence increased to 31% in the Class II and 20% in the Class III patients after surgery (P < .05). Conclusions The prevalence of dehiscence increased slightly in Class II and Class III surgical-orthodontic patients after orthognathic surgery. Temporary vascular supply reduction and oral hygiene difficulties may explain these results; however, more studies are needed.

Competencies diversification in COVID-19 pandemic conditions (case of congress-exhibition service market)

The article considers the contemporary state of congress-exhibition service market as critical. Organizing the major events which have non-negligible impact on economical, innovative, technological, investment processes has been limited due to the new coronavirus infection (COVID-19). Decision-making process of putting limitation on activities organization has been derived from external environment adverse events aligned with current sanitary-epidemiological situation. There has been analyzed the potential loss due to cancelling or rescheduling congress-exhibition events in 2020. Demand and supply reduction necessitate searching alternative development directions and core business diversification. In the capacity one of potential and perspective directions There was stated a social activity vector of Roscongress foundation as a non-financial development institution and organization of Saint-Petersburg International Economic Forum, and Expoforum International, Ltd. as operator of holding forum venue. Saint-Petersburg International Economic Forum has endowed with not only economic impact but also influence on forming-up communications intended to favor realization of the social programs during offline traditional holding event. There have been analyzed the quantitative indicators dynamics of St.-Petersburg International Economic Forum and qualitative indicators in the context of thematic zones of social orientation, which gives the ground to state the wide institutional influence on social economic processes in tourism destination and in other fields. Cooperation programs diversification with local communities has been allowing positive image creation as one of elements of destination strategic promotion on the world congress and tourist map.

Impact of COVID-19 Pandemic on Labour Supply, Wages and Gross Value Added in India

This article estimates the first-order supply shock through labour supply reduction associated with the containment measures taken by the Government of India to control COVID-19 spread. We provide the estimates for Lockdown 1.0 and Lockdown 2.0, from 25 March to 3 May 2020, when india had the highest stringency measures in the world. To get an extensive impact of the COVID-19 pandemic on the labour market, we carry out an in-depth analysis of labour supply shocks by employment status, industry level and occupation. The workers impacted are those who work in a non-essential industry and are not able to work from home. To identify jobs that cannot be done from home, we use a novel approach and construct an occupation-based Remote Labour Index (RLI) for India. Using the PLFS (2017–2018) we find that 116.18 million (25% of the total employed) and 78.93 million (17% of total employed) workers were affected during Lockdown 1.0 and Lockdown 2.0, respectively. The expected monthly wage and income loss to workers is estimated to be Rs. 864.5 billion (2017–2018 prices). Further, the reduction of Gross Value Added (2012–2012 prices) is estimated at 14% compared to a no-COVID scenario. JEL Classification Codes: E01, J21, J22, J24, J33, J38

The price elasticity of demand for illicit drugs: A systematic review

Three pillars—harm reduction, demand reduction and supply reduction—underpin the harm minimisation framework of Australia’s drug policy. Much of the activity undertaken by law enforcement is aimed at reducing the availability of illicit drugs and thereby increasing price and reducing demand. This article presents a contemporary, systematic review of research exploring the price elasticity of demand for illicit drugs. Overall, the results indicate that the demand for illicit drugs is, on average, weakly price inelastic—a 10 percent increase in the price of illicit drugs results in a decrease in demand of approximately nine percent. The degree of elasticity varies by drug type, with the greatest elasticity indicated, albeit on a small number of studies, for amphetamine-type substances. The international differences seen point to a need for more Australian research, ideally with robust experimental methodologies and across a range of drug types.