A review of the clinical efficacy of FDA-approved antibody‒drug conjugates in human cancers.

While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.

Does international trade reduce global carbon inequality? Evidence from a producer-consumer shared responsibility.

Addressing global carbon inequality constitutes an important task for both international negotiations on climate-change mitigation and the achievement of sustainable development goals. Soaring international trade might become a vigorous modifier for reducing global carbon inequality through production reallocation and economic boosts in different countries. However, this effect remains largely unexplored, not only because of little awareness of the windfall benefits from international trade but also because of debates on quantifying global carbon inequality from both production- and consumption-based perspectives. To avoid incomplete implications from a single perspective, this study first adapted a producer-consumer shared responsibility to evaluate global carbon inequality using the technology-adjusted consumption-based accounting method for 189 countries from 2006 to 2016. A dynamic panel data model was developed to examine the different channels through which international trade affects global carbon inequality in developed and developing countries. The results demonstrate that even with increasing carbon emissions, less global carbon inequality was witnessed from 2006 to 2016. International trade plays an important role in reducing global carbon inequality, mostly by stimulating the economy and increasing household income in developing countries. However, production reallocation via international trade fails in reducing the emission responsibilities of developed countries, rendering this futile in alleviating global carbon inequality. Carbon leakage that transfers carbon-intensive production across borders can lead to this unintended result, and more stringent cross-border regulations such as the carbon border adjustment mechanism can be effective. This study not only highlights the pivotal role of international trade in reducing global carbon inequality but also the future direction of international cooperation on climate change mitigation in a globalized world.

Optimizing skin disease diagnosis: harnessing online community data with contrastive learning and clustering techniques.

Skin diseases pose significant challenges in China. Internet health forums offer a platform for millions of users to discuss skin diseases and share images for early intervention, leaving large amount of valuable dermatology images. However, data quality and annotation challenges limit the potential of these resources for developing diagnostic models. In this study, we proposed a deep-learning model that utilized unannotated dermatology images from diverse online sources. We adopted a contrastive learning approach to learn general representations from unlabeled images and fine-tuned the model on coarsely annotated images from Internet forums. Our model classified 22 common skin diseases. To improve annotation quality, we used a clustering method with a small set of standardized validation images. We tested the model on images collected by 33 experienced dermatologists from 15 tertiary hospitals and achieved a 45.05% top-1 accuracy, outperforming the published baseline model by 3%. Accuracy increased with additional validation images, reaching 49.64% with 50 images per category. Our model also demonstrated transferability to new tasks, such as detecting monkeypox, with a 61.76% top-1 accuracy using only 50 additional images in the training process. We also tested our model on benchmark datasets to show the generalization ability. Our findings highlight the potential of unannotated images from online forums for future dermatology applications and demonstrate the effectiveness of our model for early diagnosis and potential outbreak mitigation.

Deep skin diseases diagnostic system with Dual-channel Image and Extracted Text.

Background: Due to the lower reliability of laboratory tests, skin diseases are more suitable for diagnosis with AI models. There are limited AI dermatology diagnostic models combining images and text; few of these are for Asian populations, and few cover the most common types of diseases. Methods: Leveraging a dataset sourced from Asia comprising over 200,000 images and 220,000 medical records, we explored a deep learning-based system for Dual-channel images and extracted text for the diagnosis of skin diseases model DIET-AI to diagnose 31 skin diseases, which covers the majority of common skin diseases. From 1 September to 1 December 2021, we prospectively collected images from 6,043 cases and medical records from 15 hospitals in seven provinces in China. Then the performance of DIET-AI was compared with that of six doctors of different seniorities in the clinical dataset. Results: The average performance of DIET-AI in 31 diseases was not less than that of all the doctors of different seniorities. By comparing the area under the curve, sensitivity, and specificity, we demonstrate that the DIET-AI model is effective in clinical scenarios. In addition, medical records affect the performance of DIET-AI and physicians to varying degrees. Conclusion: This is the largest dermatological dataset for the Chinese demographic. For the first time, we built a Dual-channel image classification model on a non-cancer dermatitis dataset with both images and medical records and achieved comparable diagnostic performance to senior doctors about common skin diseases. It provides references for exploring the feasibility and performance evaluation of DIET-AI in clinical use afterward.

Mechanisms of the Ammonium Sulfate Roasting of Spent Lithium-Ion Batteries.

Ammonium sulfate ((NH4)2SO4) assisted roasting has been proven to be an effective way to convert spent lithium-ion battery cathodes to water-soluble salts. Herein, thermogravimetric (TG) experiments are performed to analyze the mechanism of the sulfation conversion process. First, the reaction activation energies of the sulfate-assisted roasting are 88.87 and 95.27 kJ mol-1, which are calculated by Kissinger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO) methods, respectively. Then, nucleation and growth are determined and verified as the sulfation reaction model by the Satava-Sesták method. Finally, sub-reactions of the sulfation process are investigated and reaction controlling mechanisms are determined by the contribution of sub-reaction. Based on the thermogravimetric analysis, the phase boundary reaction is found to dominate in the initial step of the roasting process (α < 0.6) while the nucleation reaction controlls the following step (α > 0.6), agreeing well with changing trend of activation energy. Overall, thermogravimetric analysis is a general way to study the mechanism of the various roasting processes.

How Do Extracellular Vesicles Play a Key Role in the Maintenance of Bone Homeostasis and Regeneration? A Comprehensive Review of Literature.

The maintenance of bone homeostasis includes both bone resorption by osteoclasts and bone formation by osteoblasts. These two processes are in dynamic balance to maintain a constant amount of bone for accomplishing its critical functions in daily life. Multiple cell type communications are involved in these two complex and continuous processes. In recent decades, an increasing number of studies have shown that osteogenic and osteoclastic extracellular vesicles play crucial roles in regulating bone homeostasis through paracrine, autosecretory and endocrine signaling. Elucidating the functional roles of extracellular vesicles in the maintenance of bone homeostasis may contribute to the design of new strategies for bone regeneration. Hence, we review the recent understandings of the classification, production process, extraction methods, structure, contents, functions and applications of extracellular vesicles in bone homeostasis. We highlight the contents of various bone-derived extracellular vesicles and their interactions with different cells in the bone microenvironment during bone homeostasis. We also summarize the recent advances in EV-loaded biomaterial scaffolds for bone regeneration and repair.

Allocating China's 2025 CO2 emission burden shares to 340 prefecture cities: methods and findings.

Peak emission is an important policy/scheme for all the countries to respond greenhouse gas mitigation. The key is how to distribute the emission burden shares to its sub-regions. This study aims to develop a prefecture city leveled CO2 emission allocation model by integrating multi-indicators method and benchmark method so that China's 2025 (end year of 14th Five-Year Plan, FYP) CO2 emission burdens can be allocated to its prefecture cities and provinces. Results show that China's total CO2 emission will reach 12 billion tons in 2025. The majority of such emission will occur in the east China due to its more developed economy and dense population. Cities with high emissions are usually allocated more emission quotas, such as Shanghai, Tianjin, Chongqing, Tangshan, Yulin, Suzhou, and Ningbo. The top five provinces with higher CO2 emission quotas are traditionally high-emission and energy-intensive provinces, including Shandong, Jiangsu, Inner Mongolia, Henan, and Hebei. The national CO2 emission intensity will decrease by 69.35% in 2025 compared to the 2005 level. The CO2 emission intensity reduction rates among the 340 Chinese cities is found to be fluctuating significantly from 16 to 74% during the 14th FYP. Finally, policy recommendations are raised for mitigating city level CO2 emissions by considering the local realities.

Mechanistic Investigation of H2 O2 -dependent Chemiluminescence from Tetrabromo-1,4-Benzoquinone.

As a H2 O2 -dependent bioluminescent substrate, tetrabromo-1,4-benzoquinone (TBBQ) was first isolated from acorn worm. The mechanism of chemiluminescence (CL) corresponding to the bioluminescence (BL) of acorn worm is largely unknown, let alone the mechanism of BL. In this article, we firstly studied the chemical and physical processes, and mechanism of H2 O2 -dependent CL from TBBQ by theoretical and experimental methods. The research results indicate: the CL process is initiated by a nucleophilic substitution reaction, which leads to the formation of an anionic dioxetane through five consecutive reactions; the anionic dioxetane decomposes to the first singlet excited state (S1 ) via a conical interaction of the potential energy surfaces (PESs) between the ground (S0 ) and S1 state; the anionic S1 -state changes to its neutral form by a proton transfer from the solvent and this neutral product is assigned as the actual luminophore. Moreover, the experimental detection of CL, . OH and the identifications of 2,3-dibromo maleic acid and 2-bromo malonic acid as the major final products provide direct evidence of the theoretically suggested mechanism. Finally, this study proves that the activity of the H2 O2 -dependent CL from TBBQ is significantly lower than the one from tetrachloro-1,4-benzoquinone (TCBQ), which is caused by the weaker electron withdrawing effect and the stronger heavy atomic effect of bromine.

Clinical Application of Cytokines in Cancer Immunotherapy.

Cytokines are key components of the immune system and play pivotal roles in anticancer immune response. Cytokines as either therapeutic agents or targets hold clinical promise for cancer precise treatment. Here, we provide an overview of the various roles of cytokines in the cancer immunity cycle, with a particular focus on the clinical researches of cytokine-based drugs in cancer therapy. We review 27 cytokines in 2630 cancer clinical trials registered with ClinicalTrials.gov that had completed recruitment up to January 2021 while summarizing important cases for each cytokine. We also discuss recent progress in methods for improving the delivery efficiency, stability, biocompatibility, and availability of cytokines in therapeutic applications.

Mechanistic Study on Chemiluminescence of Chloranilic Acid by Co(II)-Mediated Fenton-like System.

Reacting with H2O2, tetrachloro-1,4-benzoquinone (TCBQ) produces chemiluminescence (CL), but chloranilic acid (CA), the dihydroxylation product of TCBQ, does not. However, an unprecedented strong CL generates from CA/H2O2 in the presence of Co(II). Why? We performed quantum chemical calculations on the entire reaction process of CA/H2O2 and CA/H2O2/Co(II) systems. The computational results indicate: for CA/H2O2 system, the reason leading to non-CL as: there is no free •OH produced by CA/H2O2, which prevents the subsequent reaction from taking place; for CA/H2O2/Co(II) system, the chemical process resulting in the CL as: First, a neutral dioxetane is formed via six sequential reactions. Then, the neutral dioxetane decomposes to generate a neutral excited-state (S1) product via a gradually reversible charge transfer initiated luminescence mechanism. A conical intersection of the ground and the S1-state potential energy surfaces facilitates the production of the S1-state product. Ultimately, the neutral S1-state product emits light as a practical light emitter. The key component for forming dioxetane and the following CL is the intrinsically generated •OH, which is roaming around at the region of C2 atoms of the CA moiety, instead of being free. The quantum chemical calculations supported the experimental observation and conclusion by providing the mechanistic explanation in detail.

Theoretical Study on Chemiluminescence of H2O2-dependent Tetrachloro-1,4-benzoquinone.

Compared with O2-dependent chemiluminescence (CL) and bioluminescence (BL), H2O2-dependent ones are far from being completely understood. A two-step mechanism for H2O2-dependent CL production from tetrachloro-1,4-benzoquinone (TCBQ) was proposed based on experimental evidence of detecting the formation of several intermediates and products. This mechanism is not yet supported by theoretical evidence, and its details remain unknown. In the present paper, we performed multireference and (time-dependent) density functional theory calculations on the complete reaction process of TCBQ with H2O2 to produce CL. The calculations reproduced the experimentally observed two-step CL. Although the reactants are different, the first and second CLs follow very similar reaction processes and mechanisms. First, an anionic dioxetane is formed via five sequential reactions. The intrinsically produced •OH is crucial for forming dioxetane. Subsequently, the anionic dioxetane decomposes to produce an anionic excited-state (S1) product. A conical interaction of the ground and the S1-state potential energy surfaces is responsible for producing the S1-state product. Finally, the S1-state anionic product changes to its neutral form, and the latter emits light as an actual light emitter. This mechanism could be extended to luminescent systems of all H2O2-dependent tetrahalogenated quinoids, including acorn worms, because TCBQ/H2O2 is a typical representative of these luminescent systems.

The distribution and drivers of PM2.5 in a rapidly urbanizing region: The Belt and Road Initiative in focus.

The accelerating urbanization has led to serious air pollution dominated by PM2.5, posing a critical challenge for the environmental sustainability of the Belt and Road Initiative (BRI). However, a focus on the distribution and drivers of PM2.5 concentrations in BRI is lacking. To fill in the gap, this study explores the spatio-temporal distribution of PM2.5 concentrations in 74 nations partnering the BRI and identifies the socioeconomic and natural drivers behind the variation through the joint use of spatial autocorrelation and regression analyses. We find that the PM2.5 concentrations of BRI show significant spatial autocorrelation and spatial heterogeneity on the national scale. The most heavily polluted regions are observed mainly in China, Southeast Asia, South Asia, West Asia and North Africa, particularly in the Arabian Gulf region. Energy intensity and per capita electricity consumption act as the major drivers of the PM2.5 concentrations, whereas the expanding forest area contributes to the decrease in PM2.5 concentrations notably. Our findings highlight the need for speeding up new-type urbanization as part of the green BRI practice, calling for international cooperation and coordinated action aimed at enhancing synergies of air-quality and climate policies that at present are mostly launched and implemented in isolation. From a broader point of view, in struggling towards BRI's cleaner air, more attention should be paid to creating policy synergies between the green BRI, the Paris Agreement, and the United Nations 2030 Agenda for Sustainable Development.

Recovery and regeneration of LiCoO2-based spent lithium-ion batteries by a carbothermic reduction vacuum pyrolysis approach: Controlling the recovery of CoO or Co.

An environmentally benign vacuum pyrolysis (VP) approach is employed to recover Li and Co from spent LiCoO2-based lithium-ion batteries (LIBs). First, the electroactive materials were separated from the current collector by the VP method from 623 to 823 K with an attempt to choose an appropriate temperature. Then, the as-received cathode materials were mixed with different amounts of graphite from the anode to selectively convert LiCoO2 to Co or CoO and Li2CO3 by carbothermic reduction under vacuum and at 873 to 1273 K. After carbothermic reduction, the pyrolyzed powder was leached in water to separate Li2CO3 from Co/CoO. By alternating the C/LiCoO2 mass ratio and the pyrolysis temperature, a recovery rate reaches over 93% for Li and 99% for Co. Finally, the recovered CoO and Li2CO3 were used to regenerated LiCoO2 that delivered a specific capacity of 145 mAh g-1 at 1C and retaining 93% of the initial capacity after 100 cycles. Overall, a multi-vacuum-pyrolysis approach offers a closed-loop route for the management of spent LIBs without using any hazardous chemicals.