Synthesis of Metal-Nitrogen-Carbon Electrocatalysts with Atomically Regulated Nitrogen-Doped Polycyclic Aromatic Hydrocarbons.

Tuning the active site structure of metal-nitrogen-carbon electrocatalysts has recently attracted increasing interest. Herein, we report a bottom-up synthesis strategy in which atomically regulated N-doped polycyclic aromatic hydrocarbons (N-PAHs) of NxC42-x (x = 1, 2, 3, 4) were used as ligands to allow tuning of the active site's structures of M-Nx and establish correlations between the structures and electrocatalytic properties. Based on the synthesis process, detailed characterization, and DFT calculation results, active structures of Nx-Fe1-Nx in Fe1-Nx/RGO catalysts were constructed. The results demonstrated that the extra uncoordinated N atoms around the Fe1-N4 moieties disrupted the π-conjugated NxC42-x ligands, which led to more localized electronic state in the Fe1-N4 moieties and superior catalytic performance. Especially, the Fe1-N4/RGO exhibited optimized performance for ORR with E1/2 increasing by 80 mV and Jk at 0.85 V improved 18 times (compared with Fe1-N1/RGO). This synthesis strategy utilizing N-PAHs holds significant promise for enhancing the controllability of metal-nitrogen-carbon electrocatalyst preparation.

Tumor Cell Membrane-Encapsulated MLA Solid Lipid Nanoparticles for Targeted Diagnosis and Radiosensitization Therapy of Cutaneous Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) is a common nonmelanoma skin cancer. Radiotherapy plays an integral role in treating SCC due to its characteristics, such as diminished intercellular adhesion, heightened cell migration and invasion capabilities, and immune evasion. These problems lead to inaccurate tumor boundary positioning and radiotherapy tolerance in SCC treatment. Thus, accurate localization and enhanced radiotherapy sensitivity are imperative for effective SCC treatment. To address the existing limitations in SCC therapy, we developed monoglyceride solid lipid nanoparticles (MG SLNs) and enveloped them with the A431 cell membrane (A431 CM) to create A431@MG. The characterization results showed that A431@MG was spherical. Furthermore, A431@MG had specific targeting for A431 cells. In A431 tumor-bearing mice, A431@MG demonstrated prolonged accumulation within tumors, ensuring precise boundary localization of SCC. We further advanced the approach by preparing MG SLNs encapsulating 5-aminolevulinic acid methyl ester (MLA) and desferrioxamine (DFO) with an A431 CM coating to yield A431@MG-MLA/DFO. Several studies have revealed that DFO effectively reduced iron content, impeding protoporphyrin IX (PpIX) biotransformation and promoting PpIX accumulation. Simultaneously, MLA was metabolized into PpIX upon cellular entry. During radiotherapy, the heightened PpIX levels enhanced reactive oxygen species (ROS) generation, inducing DNA and mitochondrial damage and leading to cell apoptosis. In A431 tumor-bearing mice, the A431@MG-MLA/DFO group exhibited notable radiotherapy sensitization, displaying superior tumor growth inhibition. Combining A431@MG-MLA/DFO with radiotherapy significantly improved anticancer efficacy, highlighting its potential to serve as an integrated diagnostic and therapeutic strategy for SCC.

Neglected immunoregulation: M2 polarization of macrophages triggered by low-dose irradiation plays an important role in bone regeneration.

Current studies have found that low-dose irradiation (IR) can promote bone regeneration. However, mechanism studies of IR-triggered bone regeneration mainly focus on the effects of osteoblasts, neglecting the role of the surrounding immune microenvironment. Here in this study, in vitro proliferation experiments showed that low-dose IR ≤2 Gy could promote the proliferation of bone marrow mesenchymal stem cells (BMSCs), and qRT-PCR assay showed that low-dose IR ≤2 Gy could exert the M2 polarization of Raw264.7 cells, while IR >2 Gy inhibited BMSC proliferation and triggered M1 polarization in Raw264.7 cells. The ALP and mineralized nodules staining showed that low-dose IR ≤2 Gy not only promoted osteoblast mineralization through IR-triggered osteoblast proliferation but also through M2 polarization of Raw264.7 cells, while high-dose IR >2 Gy had the opposite effect. The co-incubation of BMSC with low-dose IR irradiated Raw264.7 cell supernatants increased the mRNA expression of BMP-2 and Osx. The rat cranial defects model revealed that low-dose IR ≤2 Gy gradually promoted bone regeneration, while high-dose IR >2 Gy inhibited bone regeneration. Detection of macrophage polarity in peripheral blood samples showed that low-dose IR ≤2 Gy increased the expression of CD206 and CD163, but decreased the expression of CD86 and CD80 in macrophages, which indicated M2 polarization of macrophages in vivo, while high-dose IR had the opposite effect. Our finding innovatively revealed that low-dose IR ≤2 Gy promotes bone regeneration not only by directly promoting the proliferation of osteoblasts but also by triggering M2 polarization of macrophages, which provided a new perspective for immune mechanism study in the treatment of bone defects with low-dose IR.

Risk factors for neck pain in college students: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 epidemic, the prevalence of neck pain among college students has increased due to the shift from offline to online learning and increasing academic and employment pressures. Therefore, this systematic review aimed to identify the personal, occupational, and psychological factors associated with the development of neck pain to promote the development of preventive strategies and early intervention treatment. METHODS: Seven electronic databases were searched from inception to December 2022 for cross-sectional studies, cohort studies, case----control studies, and randomized controlled trials (RCTs) on neck pain. The quality of the selected studies were assessed by American Agency for Healthcare Research and Quality (AHRQ) or the Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the effects of the included risk factors on neck pain. RESULTS: Thirty studies were included, including 18,395 participants. And a total of 33 potentially associated risk factors were identified. Ultimately, 11 risk factors were included in the meta-analysis after assessing, and all results were statistically significant (P < 0.05). The factors supported by strong evidence mainly include the improper use of the pillow (OR = 2.20, 95% CI: 1.39 to 3.48), lack of exercise (OR = 1.88, 95% CI: 1.53 to 2.30), improper sitting posture (OR = 1.97, 95% CI: 1.39 to 2.78), history of neck and shoulder trauma (OR = 2.32, 95% CI: 1.79 to 3.01), senior grade (OR = 2.86, 95% CI: 2.07 to 3.95), staying up late (OR = 1.80, 95% CI: 1.35 to 2.41), long-time electronic product usage daily (OR = 1.53, 95% CI: 1.33 to 1.76), long-time to bow head (OR = 2.04, 95% CI: 1.58 to 2.64), and emotional problems (OR = 2.09; 95% CI: 1.66  to 2.63). Risk factors supported by moderate evidence were high stress (OR = 1.61, 95% CI: 1.02 to 2.52) and female gender (OR = 1.69, 95% CI: 1.52 to 1.87). CONCLUSION: This study obtained 11 main risk factors affecting college students neck pain, including improper use of the pillow, lack of exercise, improper sitting posture, history of neck and shoulder trauma, senior grade, staying up late, long-term electronic product usage daily, long time to bow head, high stress, emotional problems and female gender.

Chinese medicinal herbs for reducing endocrine therapy-induced side effects in patients with hormone receptor-positive breast cancer: a systematic review and meta-analysis.

CONTEXT: Chinese medicinal herbs (CMH) have been considered a potentially efficacious approach for patients with breast cancer that experience adverse effects from endocrine treatment. OBJECTIVE: To investigate the impact of CMH on endocrine therapy-induced side effects in patients with hormone receptor-positive (HR+) breast cancer. METHODS: Ten databases (e.g., PubMed, Web of Science, Cochrane Library, China National Knowledge Information Database and other databases) were searched up to 20 May 2022. The search terms included Chinese herb, breast cancer, endocrine therapy, clinical trial and their mesh terms. The study selection and data extraction were performed by two independent reviewers. The risk of bias was evaluated using the Cochrane risk of bias method. RESULTS: A total of 31 studies with 2288 patients were included. There were significant improvements in bone mineral density (BMD) [lumbar BMD (MD 0.08, 95% CI 0.07 to 0.09, p < 0.00001) and femoral neck BMD (MD 0.08, 95% CI 0.07 to 0.10, p < 0.00001)] and bone gal protein (BGP) (MD 0.24, 95% CI 0.17 to 0.31, p < 0.00001), with a significant reduction in triglycerides (MD -0.53, 95% CI -1.00 to -0.07, p < 0.05) and no effect on estradiol levels (MD 0.90, 95% CI -0.31 to 2.12, p = 0.15). CONCLUSIONS: CMH combined with complementary therapy can moderately reduce endocrine therapy-induced side effects, including bone loss and dyslipidemia in patients with HR + breast cancer, revealing the potential role of CMH in treating (HR+) breast cancer. More high-quality RCTs are warranted to further validate the effectiveness and safety of CMH.

Mettl3 downregulation in germinal vesicle oocytes inhibits mRNA decay and the first polar body extrusion during maturation†.

In oocytes, mRNA decay is essential for maturation and subsequent events, such as maternal-zygotic transition, zygotic genomic activation, and embryo development. Reversible N6-methyladenosine RNA methylation directly regulates transcription, pre-mRNA splicing, mRNA export, mRNA stability, and translation. Here, we identified that downregulation of N6-methyladenosine modification by microinjecting a methyltransferase-like 3 (Mettl3)-specific small interfering RNA into mouse germinal vesicle oocytes led to defects in meiotic spindles and the first polar body extrusion during maturation in vitro. By further quantitative real-time polymerase chain reaction and Poly(A)-tail assay analysis, we found that N6-methyladenosine methylation mainly acts by reducing deadenylation of mRNAs mediated by the carbon catabolite repression 4-negative on TATA less system, thereby causing mRNA accumulation in oocytes. Meanwhile, transcriptome analysis of germinal vesicle oocytes revealed the downregulation of transcripts of several genes encoding ribosomal subunits proteins in the Mettl3 small interfering RNA-treated group, suggesting that N6-methyladenosine modification might affect translation. Together, our results indicate that RNA methylation accelerates mRNA decay, confirming the critical role of RNA clearance in oocyte maturation.

Dual-Channel Theranostic System for Quantitative Self-Indication and Low-Temperature Synergistic Therapy of Cancer.

A conventional theranostic system usually employs a single fluorescence channel to show the pharmacokinetic events, which usually fails to quantitatively reveal the true cumulative drug release and with low accuracy. Herein, indocyanine green (ICG) and chlorins e6 (Ce6) are selected not only as conventional photothermal/photodynamic agents, but also to offer two independent fluorescence channels to cross validate the authenticity of pharmacokinetic events and to quantitatively reveal cumulative drug release in tumor tissues in a "turn on" manner. Employing the Ca2+ of amorphous calcium carbonate as a reversible linker, the photosensitivity and fluorescence of Ce6 are physically quenched by ICG during circulation to reduce the side effect of photodynamic therapy (PDT) while being readily restored in tumor tissue to reveal the quantitative drug release. Most importantly, the combination of photothermal therapy (PTT) and PDT allows low-temperature synergistic therapy of cancer through the controlled expression of heat shock protein in cells and mild hyperthermia enhanced reactive oxygen species diffusion/penetration among cells. This work not only develops a facile approach to fabricate a dual-channel theranostic system to precisely indicate the accumulation and quantitative drug release in tumor tissue, but also presents a unique low-temperature synergistic strategy to destroy tumor in an effective and minimally invasive manner.

Constructing Co-N-C Catalyst via a Double Crosslinking Hydrogel Strategy for Enhanced Oxygen Reduction Catalysis in Fuel Cells.

Exploiting platinum-group-metal (PGM)-free electrocatalysts with remarkable activity and stability toward oxygen reduction reaction (ORR) is of significant importance to the large-scale commercialization of proton exchange membrane fuel cells (PEMFCs). Here, a high-performance and anti-Fenton reaction cobalt-nitrogen-carbon (Co-N-C) catalyst is reported via employing double crosslinking (DC) hydrogel strategy, which consists of the chemical crosslinking between acrylic acid (AA) and acrylamide (AM) copolymerization and metal coordinated crosslinking between Co2+ and P(AA-AM) copolymer. The resultant DC hydrogel can benefit the Co2+ dispersion via chelated Co-N/O bonds and relieve metal agglomeration during the subsequent pyrolysis, resulting in the atomically dispersed Co-Nx/C active sites. By optimizing the ratio of AA/AM, the optimal P(AA-AM)(5-1)-Co-N catalyst exhibits a high content of nitrogen doping (12.36 at%) and specific surface area (1397 m2 g-1 ), significantly larger than that of the PAA-Co-N catalyst (10.59 at%/746 m2 g-1 ) derived from single crosslinking (SC) hydrogel. The electrochemical measurements reveal that P(AA-AM)(5-1)-Co-N possesses enhanced ORR activity (half-wave potential (E1/2 ) ≈0.820 V versus the reversible hydrogen electrode (RHE)) and stability (≈4 mV shift in E1/2 after 5000 potential cycles in 0.5 m H2 SO4 at 60 ºC) relative to PAA-Co-N, which is higher than most Co-N-C catalysts reported so far.

Modulation of Aggregation-Caused Quenching to Aggregation-Induced Emission: Finding a Biocompatible Polymeric Theranostics Platform for Cancer Therapy.

Dual intramolecular FRET polymers are synthesized via Suzuki coupling and their luminescence characteristics from aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) is modulated conveniently by adjusting the charged ratios. The finally obtained AIE polymer is further employed to construct doxorubicin loaded nanoparticles as a promising theranostics platform for cancer therapy.

Silencing of long noncoding RNA SRRM2-AS exerts suppressive effects on angiogenesis in nasopharyngeal carcinoma via activating MYLK-mediated cGMP-PKG signaling pathway.

Long noncoding RNAs (lncRNAs) play a crucial role in several malignances, involving nasopharyngeal carcinoma (NPC), a heterogeneous disease. This study investigated mechanism of serine/arginine repetitive matrix protein 2-alternative splicing (SRRM2-AS) in NPC cell proliferation, differentiation, and angiogenesis. Initially, differentially expressed lncRNAs were screened out via microarray analysis. Vascular endothelial growth factor (VEGF) protein positive rate and microvessel density (MVD) were determined in NPC and adjacent tissues. NPC CNE-2 cells were treated with a series of vector and small interfering RNA to explore the effect of SRRM2-AS in NPC. The target relationship between myosin light chain kinase (MYLK) and SRRM2-AS was verified. Levels of SRRM2-AS, MYLK, cGMP, PKG, VEGF, PCNA, Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase 3 were determined after transfection. Finally, the effect of SRRM2-AS on cell proliferation, colony formation, angiogenesis, cell cycle, and apoptosis in NPC was evaluated. SRRM2-AS was highly expressed and MYLK was poorly expressed in NPC tissues. VEGF protein positive rate and MVD were elevated in NPC tissues. MYLK was confirmed to be a target gene of SRRM2-AS. Silencing of SRRM2-AS elevated levels of MYLK, cGMP, PKG, Bax, and Caspase 3, but decreased levels of VEGF, PCNA, Ki-67, and Bcl-2. Especially, silencing of SRRM2-AS suppressed cell proliferation, colony formation and angiogenesis, blocked cell cycle, and enhanced cell apoptosis in NPC. Our results suggested that silencing of SRRM2-AS protected against angiogenesis of NPC cells by upregulating MYLK and activating the cGMP-PKG signaling pathway, which provides a new target for NPC treatment.

Evidence for Ferroelectricity of All-Inorganic Perovskite CsPbBr3 Quantum Dots.

The combination of ferroelectric-optical properties in halide perovskites has attracted tremendous interess because of its potential for optoelectronic and energy applications. However, very few reports focus on the ferroelectricity of all-inorganic halide perovskites quantum dots. Herein, we report a excellent ferroelectricity in CsPbBr3 quantum dots (QDs) with a saturation polarization of 0.25 µC/cm2. Differential scanning calorimetry, X-ray diffraction, and transmission electronic microscopy revealed that the mechanism of ferroelectric-paraelectric switching of CsPbBr3 QDs can be attributed to the phase transition from cubic phase (Pm3̅m) to the orthorhombic phase (Pna21). In the orthorhombic CsPbBr3, the distortion of octahedral [PbBr6]4- structural units and the off-center Cs+ generated the slightly separated centers of positive charge and negative charge, resulting in the ferroelectric properties. The variable-temperature emission spectrum from 328 to 78 K exhibits green luminescence and a gradual red shift due to the phase transition. This finding opens up an avenue to explore the ferroelectric-optical properties of inorganolead halide perovskites for high-performance multifunctional materials.

Global Urban Carbon Networks: Linking Inventory to Modeling.

Cities utilize and manipulate an immense amount of global carbon flows through their economic and technical activities. Here, we establish the carbon networks of eight global cities by tracking the carbon exchanges between various natural and economic components. The metabolic properties of these carbon networks are compared by combining flow-based and interpretative network metrics. We further assess the relations of these carbon metabolic properties of cities with their socioeconomic attributes that are deemed important in urban development and planning. We find that, although there is a large difference in city-level carbon balance and flow pattern, a similarity in intercomponent relationships and metabolic characteristicsdoes exist. Cities with lower per capita carbon emissions tend to have healthier metabolic systems with more cooperative resource allocation among various industries, which indicates that there may be synergy between urban decarbonization and carbon-containing resource system optimization. A combination of indicators from flow balance and network models is a promising scheme for linking sector-based carbon inventories to system-based simulations of carbon management efforts. With this done, we may be able to reduce the knowledge gap with respect to how various carbon flows in cities can be concertedly managed considering both the restraint from their climate mitigation goals as well as the impact on urban social and economic development.

Comparative Life-Cycle Assessment of Aquifer Thermal Energy Storage Integrated with in Situ Bioremediation of Chlorinated Volatile Organic Compounds.

Due to the increasing need for sustainable energy and environmental quality in urban areas, the combination of aquifer thermal energy storage (ATES) and in situ bioremediation (ISB) has drawn much attention as it can deliver an integrated contribution to fulfill both demands. Yet, little is known about the overall environmental impacts of ATES-ISB. Hence, we applied a life-cycle assessment (LCA) to evaluate the environmental performance of ATES-ISB, which is also compared with the conventional heating and cooling system plus ISB alone (CHC + ISB). Energy supply via electricity is revealed as the primary cause of the environmental impacts, contributing 61.26% impacts of ATES-ISB and 72.91% impacts of CHC + ISB. Specifically, electricity is responsible for over 95% of water use, global warming potential, acidification potential, and respiratory inorganics, whereas the production of the biological medium for bioremediation causes more than 85% of the eco- and human toxicity impacts in both cases. The overall environmental impact of ATES-ISB is two times smaller than that of CHC + ISB. Sensitivity analysis confirms the importance of electricity consumption and electron donor production to the environmental impacts in both energy supply and bioremediation. Thus, future studies and practical applications seeking possible optimization of the environmental performances of ATES-ISB are recommended to focus more on these two essential elements, e.g., electricity and electron donor, and their related parameters. With the comprehensive LCA, insight is obtained for better characterizing the crucial factors as well as the relevant direction for future optimization research of the ATES-ISB system.

Urban-rural carbon footprint disparity across China from essential household expenditure: Survey-based analysis, 2010-2014.

Household activities have become an increasingly important driver of carbon emission in China during economic transition. In quest of a more coordinated and efficient mitigation strategy, it is crucial to track the dynamics of carbon footprint discrepancy between urban and rural households across various regions. In this study, combing household-level expenditure survey with multi-regional input-output model, we quantify the urban-rural carbon footprint disparity originated from six essential expenditure categories, they are food, clothing, housing, utility, transport, and post and telecommunication. We assess the roles these essential consumptions play in contributing to carbon footprint disparity across different provincial regions in China during 2010-2014. The results show that the overall per capita household carbon footprint in China increased by 202% during this period, but the annual growth rate actually decreased from 27.5% to 11.4%. Despite urban-rural disparity expanded by 155% over 2010-2014, the annual changing rate slowed down (from 14.9% to 8.2%). Although the per capita carbon footprints in some less-developed regions such as northwest, northeast and central provinces are relatively small, they tend to have a bigger difference between urban and rural households than other more-developed provinces. The expenditure on utility and food plays a major part in urban-rural carbon footprint disparity for most regions, and their share has been increasing over time. Though historically, income inequality tends to be lower with increase in household income and footprint, this lifting effect becomes more uncertain when regions are moving towards a more developed stage.

Changing Urban Carbon Metabolism over Time: Historical Trajectory and Future Pathway.

Cities are expected to play a major role in carbon emissions mitigation. A key step in decoupling urban economy from carbon emissions is to understand the full impact of socioeconomic development on urban metabolism over time. Herein, we establish a system-based framework for modeling the variation of urban carbon metabolism through time by integrating a metabolic flow inventory, input-output model, and network analysis. Using Beijing as a case study, we track the historical trajectory of carbon flows embodied in urban final consumption over 1985-2012. We find that while the tendency of increase in direct carbon emission continues within this time frame, consumption-based carbon footprint might have peaked around 2010. Significant transitions in emission intensity and roles sectors play in transferring carbon over the period are important signs of decoupling urban development from carbonization. Our further analysis of driving factors reveals a strong competition between efficiency gains and consumption level rise, showing a cumulative contribution of -584% and 494% to total carbon footprint, respectively. Projection into a future pathway suggests there is still a great potential for carbon mitigation for the city, but a strong mitigation plan is required to achieve such decarbonization before 2030. By bridging temporal metabolic model and socioeconomic planning, this framework fills one of the main gaps between monitoring of urban metabolism and design of a low-carbon economy.

Tracking Inter-Regional Carbon Flows: A Hybrid Network Model.

The mitigation of anthropogenic carbon emissions has moved beyond the local scale because they diffuse across boundaries, and the consumption that triggers emissions has become regional and global. A precondition of effective mitigation is to explicitly assess inter-regional transfer of emissions. This study presents a hybrid network model to track inter-regional carbon flows by combining network analysis and input-output analysis. The direct, embodied, and controlled emissions associated with regions are quantified for assessing various types of carbon flow. The network-oriented metrics called "controlled emissions" is proposed to cover the amount of carbon emissions that can be mitigated within a region by adjusting its consumption. The case study of the Jing-Jin-Ji Area suggests that CO2 emissions embodied in products are only partially controlled by a region from a network perspective. Controlled carbon accounted for about 70% of the total embodied carbon flows, while household consumption only controlled about 25% of Beijing's emissions, much lower than its proportion of total embodied carbon. In addition to quantifying emissions, the model can pinpoint the dominant processes and sectors of emissions transfer across regions. This technique is promising for searching efficient pathways of coordinated emissions control across various regions connected by trade.

The effects of resistance exercise in patients with knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To analyze the effectiveness of resistance exercise in the treatment of knee osteoarthritis on pain, stiffness, and physical function. DESIGN: Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, the Web of Science, and Chinese Biomedical Literature Database were searched from the date of inception to August 2015. METHODS: Trials comparing effects of resistance exercise intervention with either non-intervention or psycho-educational intervention were selected by two reviewers independently. The risk of bias was assessed and studies with similar outcomes were pooled using a fixed or random effects model. RESULTS: Data from 17 randomized clinical trials including 1705 patients were integrated. The main source of methodological bias in the selected studies was lack of double blinding. The meta-analysis results suggested that resistance exercise training relieved pain (standard mean difference [SMD]: -0.43; 95% confidence interval [CI]: -0.57 to -0.29; P < 0.001), alleviated stiffness (SMD: -0.31; 95%: CI -0.56 to -0.05; P = 0.02), and improved physical function (SMD -0.53; 95% CI: -0.70 to -0.37; P < 0.001). CONCLUSION: Resistance exercise is beneficial in terms of reducing pain, alleviating stiffness, and improving physical function in patients with knee osteoarthritis.

Nonzero-Sum Relationships in Mitigating Urban Carbon Emissions: A Dynamic Network Simulation.

The "stove-pipe" way of thinking has been mostly used in mitigating carbon emissions and managing socioeconomics because of its convenience of implementation. However, systems-oriented approaches become imperative in pursuit of an efficient regulation of carbon emissions from systems as complicated as urban systems. The aim of this paper is to establish a dynamic network approach that is capable of assessing the effectiveness of carbon emissions mitigation in a more holistic way. A carbon metabolic network is constructed by modeling the carbon flows between economic sectors and environment. With the network shocked by interventions to the sectoral carbon flows, indirect emissions from the city are accounted for under certain carbon mitigation strategies. The nonzero-sum relationships between sectors and environmental components are identified based on utility analysis, which synthesize the nature of direct and indirect network interactions. The results of the case study of Beijing suggest that the stove-pipe mitigation strategies targeted the economic sectors might be not as efficient as they were expected. A direct cutting in material or energy import to the sectors may result in a rebound in indirect emissions and thus fails to achieve the carbon mitigation goal of the city as a whole. A promising way of foreseeing the dynamic mechanism of emissions is to analyze the nonzero-sum relationships between important urban components. Thinking cities as systems of interactions, the network approach is potentially a strong tool for appraising and filtering mitigation strategies of carbon emissions.

Advances in Composite Biofilm Biomimetic Nanodrug Delivery Systems for Cancer Treatment.

Single biofilm biomimetic nanodrug delivery systems based on single cell membranes, such as erythrocytes and cancer cells, have immune evasion ability, good biocompatibility, prolonged blood circulation, and high tumor targeting. Because of the different characteristics and functions of each single cell membrane, more researchers are using various hybrid cell membranes according to their specific needs. This review focuses on several different types of biomimetic nanodrug-delivery systems based on composite biofilms and looks forward to the challenges and possible development directions of biomimetic nanodrug-delivery systems based on composite biofilms to provide reference and ideas for future research.

Frequency-dependent selection of neoantigens fosters tumor immune escape and predicts immunotherapy response.

Cancer is an evolutionary process shaped by selective pressure from the microenvironments. However, recent studies reveal that certain tumors undergo neutral evolution where there is no detectable fitness difference amongst the cells following malignant transformation. Here, through computational modeling, we demonstrate that negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is highly similar to neutral evolution. Crucially, NFDS promotes high antigenic heterogeneity and early immune evasion in hypermutable tumors, leading to poor responses to immune checkpoint blockade (ICB) therapy. Our model also reveals that NFDS is characterized by a negative association between average clonality and total burden of neoantigens. Indeed, this unique feature of NFDS is common in the whole-exome sequencing (WES) datasets (357 tumor samples from 275 patients) from four melanoma cohorts with ICB therapy and a non-small cell lung cancer (NSCLC) WES dataset (327 tumor samples from 100 patients). Altogether, our study provides quantitative evidence supporting the theory of NFDS in cancer, explaining the high prevalence of neutral-looking tumors. These findings also highlight the critical role of frequency-dependent selection in devising more efficient and predictive immunotherapies.