The more the merrier: a meta-analysis of efficacy of multi-behavior interventions to reduce substance use

Objective: Death and morbidity associated with substance use have risen continuously over last few decades, increasing the need for rigorous examination of promising programs. Interventions attempting to change multiple behaviors are a new approach designed to address interconnected problems such as the misuse of both alcohol and drugs. The purpose of this meta-analysis was to examine the efficacy of multi-behavior interventions in the substance use domain. Moreover, our synthesis estimated the optimal number of recommendations for intervention efficacy and explored the influence of factors associated with the types of samples or methods used in the synthesized studies. Methods: A research synthesis of multi-target interventions addressing substance-use was conducted to measure change in both behavioral and clinical outcomes between the pretest and follow-up. Results: Fifty-two reports (k = 110, n = 19,991) were included in our analysis. Change across all groups was d = 0.30 (CI = [0.23, 0.30]) for overall outcomes, d = 0.31 (CI = [0.24, 0.38]) for behavioral outcomes, and d = 0.22 (CI = [0.09, 0.35]) for clinical outcomes. Multi-behavior interventions were especially efficacious when targeting at-risk samples, targeting ethnic minority groups, and were culturally appropriate. Furthermore, findings indicated that the number of targeted behaviors was linearly related to intervention efficacy, with interventions that recommended four or more behaviors being the most efficacious. Conclusions: In the midst of the current substance use epidemic, innovative multi-behavior programs appear to hold promise and should be implemented more widely to establish effectiveness in other settings

A New Type of Crumb Rubber Asphalt Mixture: A Dry Process Design and Performance Evaluation

To obtain a crumb rubber asphalt mixture with excellent performance, this study combined trans-polyoctenamer rubber (TOR), crumb rubber, and other additives to establish a new type of crumb rubber (CRT). The objective of this study was to design and evaluate the road performance of the new type of crumb rubber asphalt mixture (CRTAM) with a skeleton dense texture through a dry process. First, the skeleton intrusion compact volume method was used to optimize the grading of coarse and fine aggregates, and the design of the CRTAM gradation was carried out through the same and unequal volume replacement grading method. Then, three types of road performance were analyzed: high-temperature stability, low-temperature crack resistance, and water stability. The results showed that 2% and 2.5% CRT met a low-temperature index with equal volume substitution, and the six gradations obtained by unequal volume replacement with 2% CRT complied with the requirements of a skeleton dense texture. When the substitution ratio was 1.5 and 0.5, the high-temperature performance was better. In addition, when the substitution ratio was 0.5, the flexural strain energy density was the highest and the low-temperature performance was the best. Including considerations of economic benefits, it is recommended that the CRT content be 2% and the substitution ratio be 0.5

Synchronized Dual-arm Rearrangement via Cooperative mTSP

Synchronized dual-arm rearrangement is widely studied as a common scenario in industrial applications. It often faces scalability challenges due to the computational complexity of robotic arm rearrangement and the high-dimensional nature of dual-arm planning. To address these challenges, we formulated the problem as cooperative mTSP, a variant of mTSP where agents share cooperative costs, and utilized reinforcement learning for its solution. Our approach involved representing rearrangement tasks using a task state graph that captured spatial relationships and a cooperative cost matrix that provided details about action costs. Taking these representations as observations, we designed an attention-based network to effectively combine them and provide rational task scheduling. Furthermore, a cost predictor is also introduced to directly evaluate actions during both training and planning, significantly expediting the planning process. Our experimental results demonstrate that our approach outperforms existing methods in terms of both performance and planning efficiency

PO-034 Effect of Voluntary Exercise on Cartilage Morphology of Knee Osteoarthritis in Obese Mice Induced by High-fat Diet

Objective To examine the effect of voluntary wheel-running exercise on cartilage morphology of knee osteoarthritis(KOA) in obese mice induced by high-fat diet,and explore the protective role of 4 weeks voluntary wheel-running exercise on KOA,finally providing effective experimental evidence for clinical treatment of knee osteoarthritis. Methods C57BL/6J mice were randomly assigned to the C-Sed group,C-Ex group,HF-Sed group and HF-Ex group.The control groups were fed a control diet(13.5% kcal from fat),and the high-fat groups were fed a high-fat diet(60% kcal from fat).After feeding 8 weeks different diets,the exercise groups were starting running.In order to examine the effect of voluntary wheel-running exercise on cartilage morphology of KOA,the joint of knee were harvested to be fixed,decalcified and embedded in paraffin,and the four-micrometer-thick sections were stained with both HE and toluidine blue . Results After feeding twelve weeks different diets,the body mass of the high-fat diet group mice has a significant increase,which demonstrates that high-fat diet could successfully induce the mice obese.From the results of HE and toluidine blue,in comparison to the C-Sed group,the surface of the knee articular cartilage in the HF-Sed group was not intact and smooth,and the thickness of articular cartilage has a significant decrease（p<0.001）;contrary to the HF-Sed group,the surface of the knee articular cartilage in HF-Ex group was slightly smooth,and there was significant increase in cartilage thickness. Conclusions Four weeks voluntary wheel-running exercise can increase cartilage thickness ,decrease the Mankin’s score and delay the degeneration of knee cartilage in obese mice.To conclude,the short-term wheel-running exercise protects against obesity-induced KOA

Rhodium(III)-Catalyzed C–H Alkenylation/Directing Group Migration for the Regio- and Stereoselective Synthesis of Tetrasubstituted Alkenes

An efficient Rh(III)-catalyzed C-H alkenylation/directing group migration cascade between indoles and alkynes for the assembly of tetrasubstituted alkenes is reported. The carbamoyl directing group migrates to the carbon of the alkene moiety of the products through rare Rh-catalyzed C-N bond cleavage after the C-H alkenylation step and thus acts as an internal amidation reagent. This protocol shows broad substrate scope, excellent regio/stereoselectivity, and good to excellent yields

OR-024 Changes of mitochondrial autophagy - related genes and autophagosome after skeletal muscle blunt trauma

Objective Objective: To study the changes of mitochondrial autophagy-related genes and autophagosome after skeletal muscle blunt trauma, to reveal the changes of mitochondrial adaptive repair process after skeletal muscle blunt trauma, and to elucidate the mechanism of blunt trauma repair process. Methods Methods: Sixty - four male Wistar rats were randomly divided into control group and blunt trauma group三 (divided into 12h group, 2d group, 5d group, 7d group, 10d group, 15d group and 30d group) according to the time of extraction. The expression of HIF-1α, AMPKα2, BNIP3 and NIX protein in skeletal muscle hypoxia and autophagy-related factors were measured by Western-Blot. QRT-PCR was performed to analyze the expression levels of HIF-1α, AMPKα2, BNIP3 and NIX. The ultrastructure and autophagic formation at different time points were observed by transmission electron microscopy (TEM). Results Results: The expression of HIF-1α and AMPKα2 protein reached the peak at 12h and 2d, and the expression of HIF-1α was significantly higher than that of the control group (P <0.05). The expression of AMPKα2 was significantly higher at 5 days after injury (P <0.05), and reached the normal level at 10 days. BNIP3 began to decline after 5 days, but still higher than normal at 10 days after treatment. NIX expression peak appeared at 12h and 2d after injury, with high-express to 7d. The expression of HIF-1α and AMPKα2 mRNA was significantly higher than that of the control group (P <0.01), but decreased until 5d (P <0.05), then decreased to normal level. The mRNA expression of BNIP3 and NIX was basically the same as their protein performance. A number of autophagosomes were observed at 12 h after injury, and the number of autophagosomes increased gradually at 2-7 d. After 10 days, the number of autophagosomes decreased compared with that of 12 h-7 d after blunt. And after 15 days, the number of autophagosites decreased gradually. Conclusions Conclusion: The changes of early stage metabolic regulator AMPKα2 and hypoxia-sensitive factor HIF-1αafter skeletal muscle blunt trauma indicated that  an energy crisis occurred in the skeletal muscle after injury, and the hypoxic environment was formed. The mitochondrial autophagy, the expression of BNIP3 and NIX showed that mitochondrial autophagy was activated and hypoxia induced mitochondrial autophagy at early skeletal muscle contusion peroid. Hypoxia-induced mitochondrial autophagy could remove the damaged mitochondria, maintain mitochondrial quality and provide raw materials for new mitochondria generation, facilitate the rapid recovery of damaged skeletal muscle, which may be a compensatory mechanism of the body response to injury

The Transcription Factor IRF4 Determines the Anti-tumor Immunity of CD8+ T cells

Understanding the factors that regulate T cell infiltration and functional states in solid tumors is crucial for advancing cancer immunotherapies. Here, we discovered that the expression of interferon regulatory factor 4 (IRF4) was a critical T cell intrinsic requirement for effective anti-tumor immunity. Mice with T-cell-specific ablation of IRF4 showed significantly reduced T cell tumor infiltration and function, resulting in accelerated growth of subcutaneous syngeneic tumors and allowing the growth of allogeneic tumors. Additionally, engineered overexpression of IRF4 in anti-tumor CD8+ T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into effector T cell states. As a result, IRF4-engineered anti-tumor T cells exhibited significantly improved anti-tumor efficacy, and inhibited tumor growth either alone or in combination with PD-L1 blockade. These findings identify IRF4 as a crucial cell-intrinsic driver of T cell infiltration and function in tumors, emphasizing the potential of IRF4-engineering as an immunotherapeutic approach

PSMD10/gankyrin induces autophagy to promote tumor progression through cytoplasmic interaction with ATG7 and nuclear transactivation of ATG7 expression.

Although autophagy is most critical for survival of cancer cells, especially in fast-growing tumors, the mechanism remains to be fully characterized. Herein we report that PSMD10/gankyrin promotes autophagy in hepatocellular carcinoma (HCC) in response to starvation or stress through 2 complementary routes. PSMD10 was physically associated with ATG7 in the cytoplasm, and this association was enhanced by initial nutrient deprivation. Subsequently, PSMD10 translocated into the nucleus and bound cooperatively with nuclear HSF1 (heat shock transcription factor 1) onto the ATG7 promoter, upregulated ATG7 expression in the advanced stage of starvation. Intriguingly, the type of PSMD10-mediated autophagy was independent of the proteasome system, although PSMD10 has been believed to be an indispensable chaperone for assembly of the 26S proteasome. A significant correlation between PSMD10 expression and ATG7 levels was detected in human HCC biopsies, and the combination of these 2 parameters is a powerful predictor of poor prognosis. The median survival of sorafenib-treated HCC patients with high expression of PSMD10 was much shorter than those with low expression of PSMD10. Furthermore, PSMD10 augmented autophagic flux to resist sorafenib or conventional chemotherapy, and inhibition of autophagy suppressed PSMD10-mediated resistance. We conclude that these results present a novel mechanism involving modulation of ATG7 by PSMD10 in sustaining autophagy, promoting HCC cell survival against starvation or chemotherapy. Targeting of PSMD10 might therefore be an attractive strategy in HCC treatment by suppressing autophagy and inducing HCC cell sensitivity to drugs