Governance effects of pollution reduction and carbon mitigation of carbon emission trading policy in China.

China's carbon emission trading policy plays a crucial role in achieving both its "3060" dual carbon objectives and the United Nations Sustainable Development Goal 13 (SDG 13) on climate action. The policy's effectiveness in reducing pollution and mitigating carbon emissions holds significant importance. This paper investigated whether China's carbon emission trading policy affects pollution reduction (PM2.5 and SO2) and carbon mitigation (CO2) in pilot regions, using panel data from 30 provinces and municipalities in China from 2005 to 2019 and employing a multi-period difference-in-differences (DID) model. Furthermore, it analyzed the heterogeneity of carbon market mechanisms and regional variations. Finally, it examined the governance pathways for pollution reduction and carbon mitigation from a holistic perspective. The results indicate that: (1) China's carbon emission trading policy has reduced CO2 emissions by 18% and SO2 emissions by 36% in pilot areas, with an immediate impact on the "carbon mitigation" effect, while the "pollution reduction" effect exhibits a time lag. (2) Higher carbon trading prices lead to stronger "carbon mitigation" effect, and larger carbon market scales are associated with greater "pollution reduction" effects on PM2.5. Governance effects on pollution reduction and carbon mitigation vary among pilot regions: Carbon markets of Beijing, Chongqing, Shanghai, and Tianjin show significant governance effects in both "pollution reduction" and "carbon mitigation", whereas Guangdong's carbon market exhibits only a "pollution reduction" effect, and Hubei's carbon market demonstrates only a "carbon mitigation" effect. (3) Currently, China's carbon emission trading policy achieves pollution reduction and carbon mitigation through "process management" and "end-of-pipe treatment". This study could provide empirical insights and policy implications for pollution reduction and carbon mitigation, as well as for the development of China's carbon emission trading market.

Covalent targeted radioligands potentiate radionuclide therapy.

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.

Traditional herbal medicine: Therapeutic potential in acute gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute gouty arthritis (AGA) is characterized by a rapid inflammatory reaction caused by the build-up of monosodium urate (MSU) crystals in the tissues surrounding the joints. This condition often associated with hyperuricemia (HUA), is distinguished by its symptoms of intense pain, active inflammation, and swelling of the joints. Traditional approaches in AGA management often fall short of desired outcomes in clinical settings. However, recent ethnopharmacological investigations have been focusing on the potential of Traditional Herbal Medicine (THM) in various forms, exploring their therapeutic impact and targets in AGA treatment. AIM OF THE REVIEW: This review briefly summarizes the current potential pharmacological mechanisms of THMs - including active ingredients, extracts, and prescriptions -in the treatment of AGA, and discusses the relevant potential mechanisms and molecular targets in depth. The objective of this study is to offer extensive information and a reference point for the exploration of targeted AGA treatment using THMs. MATERIALS AND METHODS: This review obtained scientific publications focused on in vitro and in vivo studies of anti-AGA THMs conducted between 2013 and 2023. The literature was collected from various journals and electronic databases, including PubMed, Elsevier, ScienceDirect, Web of Science, and Google Scholar. The retrieval and analysis of relevant articles were guided by keywords such as "acute gouty arthritis and Chinese herbal medicine," "acute gouty arthritis herbal prescription," "acute gouty arthritis and immune cells," "acute gouty arthritis and inflammation," "acute gouty arthritis and NOD-like receptor thermoprotein domain associated protein 3 (NLRP3)," "acute gouty arthritis and miRNA," and "acute gouty arthritis and oxidative stress." RESULTS: We found that AGA has a large number of therapeutic targets, highlighting the effectiveness the potential of THMs in AGA treatment through in vitro and in vivo studies. THMs and their active ingredients can mitigate AGA symptoms through a variety of therapeutic targets, such as influencing macrophage polarization, neutrophils, T cells, natural killer (NK) cells, and addressing factors like inflammation, NLRP3 inflammasome, signaling pathways, oxidative stress, and miRNA multi-target interactions. The anti-AGA properties of THMs, including their active components and prescriptions, were systematically summarized and categorized based on their respective therapeutic targets. CONCLUSION: phenolic, flavonoid, terpenoid and alkaloid compounds in THMs are considered the key ingredients to improve AGA. THMs and their active ingredients achieve enhanced efficacy through interactions with multiple targets, of which NLRP3 is a main therapeutic target. Nonetheless, given the intricate composition of traditional Chinese medicine (TCM), additional research is required to unravel the underlying mechanisms and molecular targets through which THMs alleviate AGA.

Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study.

BACKGROUND: In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule's efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice. METHODS: This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators. RESULTS: Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group. CONCLUSIONS: Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA. TRIAL REGISTRATION: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.

Hydroxamic acid hybrids: Histone deacetylase inhibitors with anticancer therapeutic potency.

Histone deacetylases (HDACs), a class of enzymes responsible for the removal of acetyl functional groups from the lysine residues in the amino-terminal tails of core histones, play a critical role in the modulation of chromatin architecture and the regulation of gene expression. Dysregulation of HDAC expression has been closely associated with the development of various cancers. Histone deacetylase inhibitors (HDACis) could regulate diverse cellular pathways, cause cell cycle arrest, and promote programmed cell death, making them promising avenues for cancer therapy with potent efficacy and favorable toxicity profiles. Hybrid molecules incorporating two or more pharmacophores in one single molecule, have the potential to simultaneously inhibit two distinct cancer targets, potentially overcome drug resistance and minimize drug-drug interactions. Notably, hydroxamic acid hybrids, exemplified by fimepinostat and tinostamustine as potential HDACis, could exert the anticancer effects through induction of apoptosis, differentiation, and growth arrest in cancer cells, representing useful scaffolds for the discovery of novel HDACis. The purpose of this review is to summarize the current scenario of hydroxamic acid hybrids as HDACis with anticancer therapeutic potential developed since 2020 to facilitate further rational exploitation of more effective candidates.

Current scenario of quinolone hybrids with potential antibacterial activity against ESKAPE pathogens.

The ESKAPE (Escherichia coli/E. coli, Staphylococcus aureus/S. aureus, Klebsiella pneumonia/K. pneumoniae, Acinetobacter Baumannii/A. baumannii, Pseudomonas aeroginosa/P. aeroginosa and Enterobacter spp.) pathogens, which could escape or evade common therapies through diverse antimicrobial resistance mechanisms and biofilm formation, are deemed as highly virulent bacteria responsible for life-threatening diseases, calling for novel chemotherapeutics. Quinolones including 2-quinolones and 4-quinolones have occupied a propitious place in drug design and development due to their excellent pharmacological profiles. Quinolones especially fluoroquinolones could inhibit the synthesis of nucleic acid of ESKAPE pathogens, leading to the rupture of bacterial chromosome. However, the resistance of ESKAPE pathogens to quinolones develops rapidly and spreads widely. Accordingly, it has become increasingly urgent to enhance the potency of quinolones against both drug-susceptible and drug-resistant ESKAPE pathogens. Quinolone hybrids can bind with different drug targets simultaneously and have been considered as useful prototypes to circumvent drug resistance. The purpose of this review is to summarize the current scenario (2018-present) of quinolone hybrids with potential antibacterial activity against ESKAPE pathogens, together with the structure-activity relationships and mechanisms of action to facilitate further rational design of more effective candidates.

Effect of integrated Traditional Chinese and Western Medicine on gout.

OBJECTIVE: To evaluate the curative effect of integrated Traditional Chinese and Western Medicine on gout, and to investigate the therapy timing and exact treatment options of integrated medicine. METHODS: Totally 860 patients were enrolled, including 460 patients with intermittent gout, 200 patients with active Traditional Chinese Medicine (TCM) syndrome (TCM syndrome score ≥ 6) and 200 patients with stable TCM syndrome (score < 6). They were randomly divided into intervention and control groups. The control group was treated according to Western Medicine guidelines. The intervention group was treated with integrated Traditional Chinese and Western Medicine. The efficacy of TCM syndrome, joint pain score, joint swelling score, ESR, C-reactive protein, serum uric acid, liver and kidney function, and the duration of remission of TCM syndrome were compared between the two groups before and after treatments. RESULTS: For the patients with stable TCM syndrome, there was no significant difference in the effective rate and inefficiency between the intervention group and the control group. For the active type, the effective rate of the intervention group is better than the control group significantly. For the stable type, there was no significant difference between the intervention group and the control group in improving the scores of joint pain and swelling, reducing the level of ESR, C-reactive protein, serum uric acid and improving liver and kidney function. For the active type, the differences between the two groups were significant. The stable stage of gout in the intervention group was longer than the control group. CONCLUSION: For the gout patients with stable TCM syndrome in the acute stage of gout, we can use TCM treatment or Western Medicine alternatively; for the patients with active TCM syndrome, the scheme of combination of Traditional Chinese and Western Medicine can be applied, with the better curative effect than any medicine alone.

Early detection of pancreatic cancer: Where are we now and where are we going?

Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various "omics" studies including genomics, epigenomics, non-coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva). Although many biomarkers for early detection of PC have been discovered through various methods, larger scale and rigorous validation is required before their application in the clinic. In addition, more effective and specific biomarkers of PC are urgently needed.