An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer.

Metformin has utility in cancer prevention and treatment, though the mechanisms for these effects remain elusive. Through genetic screening in C. elegans, we uncover two metformin response elements: the nuclear pore complex (NPC) and acyl-CoA dehydrogenase family member-10 (ACAD10). We demonstrate that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the GDP-bound state necessary to stimulate mTORC1. Biguanide-induced inactivation of mTORC1 subsequently inhibits growth through transcriptional induction of ACAD10. This ancient metformin response pathway is conserved from worms to humans. Both restricted nuclear pore transit and upregulation of ACAD10 are required for biguanides to reduce viability in melanoma and pancreatic cancer cells, and to extend C. elegans lifespan. This pathway provides a unified mechanism by which metformin kills cancer cells and extends lifespan, and illuminates potential cancer targets. PAPERCLIP.

Anomalous thermal transport under high pressure in boron arsenide.

High pressure represents extreme environments and provides opportunities for materials discovery1-8. Thermal transport under high hydrostatic pressure has been investigated for more than 100 years and all measurements of crystals so far have indicated a monotonically increasing lattice thermal conductivity. Here we report in situ thermal transport measurements in the newly discovered semiconductor crystal boron arsenide, and observe an anomalous pressure dependence of the thermal conductivity. We use ultrafast optics, Raman spectroscopy and inelastic X-ray scattering measurements to examine the phonon bandstructure evolution of the optical and acoustic branches, as well as thermal conductivity under varied temperatures and pressures up to 32 gigapascals. Using atomistic theory, we attribute the anomalous high-pressure behaviour to competitive heat conduction channels from interactive high-order anharmonicity physics inherent to the unique phonon bandstructure. Our study verifies ab initio theory calculations and we show that the phonon dynamics-resulting from competing three-phonon and four-phonon scattering processes-are beyond those expected from classical models and seen in common materials. This work uses high-pressure spectroscopy combined with atomistic theory as a powerful approach to probe complex phonon physics and provide fundamental insights for understanding microscopic energy transport in materials of extreme properties.

The CsAP2-09-CsWRKY25-CsRBOH2 cascade confers resistance against citrus bacterial canker by regulating ROS homeostasis.

Citrus bacterial canker (CBC) is a serious bacterial disease caused by Xanthomonas citri subsp. citri (Xcc) that adversely impacts the global citrus industry. In a previous study, we demonstrated that overexpression of an Xcc-inducible apetala 2/ethylene response factor encoded by Citrus sinensis, CsAP2-09, enhances CBC resistance. The mechanism responsible for this effect, however, is not known. In the present study, we showed that CsAP2-09 targeted the promoter of the Xcc-inducible WRKY transcription factor coding gene CsWRKY25 directly, activating its transcription. CsWRKY25 was found to localize to the nucleus and to activate transcriptional activity. Plants overexpressing CsWRKY25 were more resistant to CBC and showed higher expression of the respiratory burst oxidase homolog (RBOH) CsRBOH2, in addition to exhibiting increased RBOH activity. Transient overexpression assays in citrus confirmed that CsWRKY25 and CsRBOH2 participated in the generation of reactive oxygen species (ROS) bursts, which were able to restore the ROS degradation caused by CsAP2-09 knockdown. Moreover, CsWRKY25 was found to bind directly to W-box elements within the CsRBOH2 promoter. Notably, CsRBOH2 knockdown had been reported previously to reduce the CBC resistance, while demonstrated in this study, CsRBOH2 transient overexpression can enhance the CBC resistance. Overall, our results outline a pathway through which CsAP2-09-CsWRKY25 transcriptionally reprograms CsRBOH2-mediated ROS homeostasis in a manner conducive to CBC resistance. These data offer new insight into the mechanisms and regulatory pathways through which CsAP2-09 regulates CBC resistance, highlighting its potential utility as a target for the breeding of CBC-resistant citrus varieties.

Spatial proteomic landscape of primary and relapsed hepatocellular carcinoma reveals immune escape characteristics in early relapse.

BACKGROUND AIMS: Surgical resection serves as the principal curative strategy for hepatocellular carcinoma (HCC), yet the incidence of postoperative recurrence remains alarmingly high. However, the spatial molecular structural alterations contributing to postoperative recurrence in HCC are still poorly understood. APPROACH RESULTS: We employed imaging mass cytometry to profile the in-situ expression of 33 proteins within 358,729 single cells of 92 clinically annotated surgical specimens from 46 patients who were treated with surgical resections for primary and relapsed tumors. We revealed the recurrence progression of HCC was governed by the dynamic spatial distribution and functional interplay of diverse cell types across adjacent normal, tumor margin, and intratumor regions. Our exhaustive analyses revealed an aggressive, immunosuppression-related spatial ecosystem in relapsed HCC. Additionally, we illustrated the prominent implications of the TME of tumor margins in association with relapse HCC. Moreover, we identified a novel subpopulation of dendritic cells (PDL1+CD103+ DCs) enriched in the peritumoral area that correlated with early postoperative recurrence, which was further validated in an external cohort. Through the analysis of scRNA-seq data, we found the interaction of PDL1+CD103+ DCs with regulatory T cells and exhausted T cells enhanced immunosuppression and immune escape via multiple ligand-receptor pathways. CONCLUSIONS: We comprehensively depicted the spatial landscape of single-cell dynamics and multicellular architecture within primary and relapsed HCC. Our findings highlight spatial organization is a prominent determinant of HCC recurrence and provide a valuable insight into the immune evasion mechanisms driving recurrence.

Photochemically Controlled Release of the Glucose Transporter 1 Inhibitor for Glucose Deprivation Responses and Cancer Suppression Research.

Cancer cells need a greater supply of glucose mainly due to their aerobic glycolysis, known as the Warburg effect. Glucose transport by glucose transporter 1 (GLUT1) is the rate-limiting step for glucose uptake, making it a potential cancer therapeutic target. However, GLUT1 is widely expressed and performs crucial functions in a variety of cells, and its indiscriminate inhibition will cause serious side effects. In this study, we designed and synthesized a photocaged GLUT1 inhibitor WZB117-PPG to suppress the growth of cancer cells in a spatiotemporally controllable manner. WZB117-PPG exhibited remarkable photolysis efficiency and substantial cytotoxicity toward cancer cells under visible light illumination with minimal side effects, ensuring its safety as a potential cancer therapy. Furthermore, our quantitative proteomics data delineated a comprehensive portrait of responses in cancer cells under glucose deprivation, underlining the mechanism of cell death via necrosis rather than apoptosis. We reason that our study provides a potentially reliable cancer treatment strategy and can be used as a spatiotemporally controllable trigger for studying nutrient deprivation-related stress responses.

A natural non-synonymous single nucleotide polymorphism in GmbHLH113 negates its inhibitory effect on root hair elongation in soybean.

Root hair length (RHL) is an important character that affects nutrient acquisition in plants. The regulatory network in soybean controlling RHL is yet to be fully understood. In this study, we identified a quantitative trait locus (QTL) regulating RHL. One candidate causal gene in this QTL (GmbHLH113), preferentially expressed in root hairs, was annotated as encoding a basic helix-loop-helix transcription factor. In wild soybeans, the allelic type of GmbHLH113 with a glycine in the 13th residue, which was associated with a reduction in RHL, was shown to localize in the nucleus and activate gene transcription. Another allelic type with a single nucleotide polymorphism that resulted in a glutamate in the 13th residue is fixed in cultivated soybeans, and it lost the ability to localize to the nucleus or negatively regulate RHL. The ectopic expression of GmbHLH113 from W05 in Arabidopsis root hairs resulted in shorter RHL and reduced phosphorus (P) accumulation in shoots. Hence, a loss-of-function allele in cultivated soybeans might have been selected during domestication due to its association with a longer RHL and improved nutrient acquisition.

Developing an SNP dataset for efficiently evaluating soybean germplasm resources using the genome sequencing data of 3,661 soybean accessions.

BACKGROUND: Single nucleotide polymorphism (SNP) markers play significant roles in accelerating breeding and basic crop research. Several soybean SNP panels have been developed. However, there is still a lack of SNP panels for differentiating between wild and cultivated populations, as well as for detecting polymorphisms within both wild and cultivated populations. RESULTS: This study utilized publicly available resequencing data from over 3,000 soybean accessions to identify differentiating and highly conserved SNP and insertion/deletion (InDel) markers between wild and cultivated soybean populations. Additionally, a naturally occurring mutant gene library was constructed by analyzing large-effect SNPs and InDels in the population. CONCLUSION: The markers obtained in this study are associated with numerous genes governing agronomic traits, thus facilitating the evaluation of soybean germplasms and the efficient differentiation between wild and cultivated soybeans. The natural mutant gene library permits the quick identification of individuals with natural mutations in functional genes, providing convenience for accelerating soybean breeding using reverse genetics.

Cobalt-Catalyzed Acceptorless Dehydrogenation of Primary Amines to Nitriles.

The direct double dehydrogenation from primary amines to nitriles without an oxidant or hydrogen acceptor is both intriguing and challenging. In this paper, we describe a non-noble metal catalyst capable of realizing such a transformation with high efficiency. A cobalt-centered N,N-bidentate complex was designed and employed as a metal-ligand cooperative dehydrogenation catalyst. Detailed kinetic studies, control experiments, and DFT calculations revealed the crucial hydride transfer, proton transfer, and hydrogen evolution processes. Finally, a tandem outer-sphere/inner-sphere mechanism was proposed for the dehydrogenation of amines to nitriles through an imine intermediate.

Site-Recognition-Induced Structural and Photoluminescent Evolution of the Gold-Pincer Nanocluster.

The induced structural transformation provides an efficient way to precisely modulate the fine structures and the corresponding performance of gold nanoclusters, thus constituting one of the important research topics in cluster chemistry. However, the driving forces and mechanisms of these processes are still ambiguous in many cases, limiting further applications. In this work, based on the unique coordination mode of the pincer ligand-stabilized gold nanocluster Au8(PNP)4, we revealed the site-recognition mechanism for induced transformations of gold nanoclusters. The "open nitrogen sites" on the surface of the nanocluster interact with different inducers including organic compounds and metals and trigger the conversion of Au8(PNP)4 to Au13 and Au9Ag4 nanoclusters, respectively. Control experiments verified the site-recognition mechanism, and the femtosecond and nanosecond transient absorption spectroscopy revealed the electronic and photoluminescent evolution accompanied by the structural transformation.

Semaglutide alters gut microbiota and improves NAFLD in db/db mice.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease associated with type 2 diabetes mellitus (T2D). NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and even cancer, all of which have a very poor prognosis. Semaglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist, has been recognized as a specific drug for the treatment of diabetes. In this study, we used a gene mutation mouse model (db/db mice) to investigate the potential liver-improving effects of semaglutide. The results showed that semaglutide improved lipid levels and glucose metabolism in db/db mice. HE staining and oil red staining showed alleviation of liver damage and reduction of hepatic lipid deposition after injection of semaglutide. In addition, semaglutide also improved the integrity of gut barrier and altered gut microbiota, especially Alloprevotella, Alistpes, Ligilactobacillus and Lactobacillus. In summary, our findings validate that semaglutide induces modifications in the composition of the gut microbiota and ameliorates NAFLD, positioning it as a promising therapeutic candidate for addressing hepatic steatosis and associated inflammation.

Overexpression of the WRKY transcription factor gene NtWRKY65 enhances salt tolerance in tobacco (Nicotiana tabacum).

BACKGROUND: Salt stress severely inhibits plant growth, and the WRKY family transcription factors play important roles in salt stress resistance. In this study, we aimed to characterize the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance. RESULTS: This study characterized the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance using four NtWRKY65 overexpression lines. NtWRKY65 is localized to the nucleus, has transactivation activity, and is upregulated by NaCl treatment. Salinity treatment resulted in the overexpressing transgenic tobacco lines generating significantly longer roots, with larger leaf area, higher fresh weight, and greater chlorophyll content than those of wild type (WT) plants. Moreover, the overexpressing lines showed elevated antioxidant enzyme activity, reduced malondialdehyde content, and leaf electrolyte leakage. In addition, the Na+ content significantly decreased, and the K+/Na+ ratio was increased in the NtWRKY65 overexpression lines compared to those in the WT. These results suggest that NtWRKY65 overexpression enhances salinity tolerance in transgenic plants. RNA-Seq analysis of the NtWRKY65 overexpressing and WT plants revealed that NtWRKY65 might regulate the expression of genes involved in the salt stress response, including cell wall component metabolism, osmotic stress response, cellular oxidant detoxification, protein phosphorylation, and the auxin signaling pathway. These results were consistent with the morphological and physiological data. These findings indicate that NtWRKY65 overexpression confers enhanced salinity tolerance. CONCLUSIONS: Our results indicated that NtWRKY65 is a critical regulator of salinity tolerance in tobacco plants.

Building Block Metal Nanocluster-Based Growth in 1D Direction.

Metal nanoclusters with precisely modulated structures at the nanoscale give us the opportunity to synthesize and investigate 1D nanomaterials at the atomic level. Herein, it realizes selective 1D growth of building block nanocluster "Au13 Cd2 " into three structurally different nanoclusters: "hand-in-hand" (Au13 Cd2 )2 O, "head-to-head" Au25 , and "shoulder-to-shoulder" Au33 . Detailed studies further reveals the growth mechanism and the growth-related tunable properties. This work provides new hints for the predictable structural transformation of nanoclusters and atomically precise construction of 1D nanomaterials.

The wall-associated receptor-like kinase CsWAKL01, positively regulated by the transcription factor CsWRKY53, confers resistance to citrus bacterial canker via regulation of phytohormone signaling.

Citrus bacterial canker (CBC) is a disease that poses a major threat to global citrus production and is caused by infection with Xanthomonas citri subsp. citri (Xcc). Wall-associated receptor-like kinase (WAKL) proteins play an important role in shaping plant resistance to various bacterial and fungal pathogens. In a prior report, CsWAKL01 was identified as a candidate Xcc-inducible gene found to be upregulated in CBC-resistant citrus plants. However, the functional role of CsWAKL01 and the mechanisms whereby it may influence resistance to CBC have yet to be clarified. Here, CsWAKL01 was found to localize to the plasma membrane, and the overexpression of the corresponding gene in transgenic sweet oranges resulted in the pronounced enhancement of CBC resistance, whereas its knockdown had the opposite effect. Mechanistically, the ability of CsWAKL01 was linked to its ability to reprogram jasmonic acid, salicylic acid, and abscisic acid signaling activity. CsWRKY53 was further identified as a transcription factor capable of directly binding the CsWAKL01 promoter and inducing its transcriptional upregulation. CsWRKY53 silencing conferred greater CBC susceptibility to infected plants. Overall, these data support a model wherein CsWRKY53 functions as a positive regulator of CsWAKL01 to enhance resistance to CBC via the reprogramming of phytohormone signaling. Together these results offer new insight into the mechanisms whereby WAKLs shape phytopathogen resistance while underscoring the potential value of targeting the CsWRKY53-CsWAKL01 axis when seeking to breed CBC-resistant citrus plant varieties.

A study on whether deep learning models based on CT images for bone density classification and prediction can be used for opportunistic osteoporosis screening.

This study utilized deep learning to classify osteoporosis and predict bone density using opportunistic CT scans and independently tested the models on data from different hospitals and equipment. Results showed high accuracy and strong correlation with QCT results, showing promise for expanding osteoporosis screening and reducing unnecessary radiation and costs. PURPOSE: To explore the feasibility of using deep learning to establish a model for osteoporosis classification and bone density value prediction based on opportunistic CT scans and to verify its generalization and diagnostic ability using an independent test set. METHODS: A total of 1219 cases of opportunistic CT scans were included in this study, with QCT results as the reference standard. The training set: test set: independent test set ratio was 703: 176: 340, and the independent test set data of 340 cases were from 3 different hospitals and 4 different CT scanners. The VB-Net structure automatic segmentation model was used to segment the trabecular bone, and DenseNet was used to establish a three-classification model and bone density value prediction regression model. The performance parameters of the models were calculated and evaluated. RESULTS: The ROC curves showed that the mean AUCs of the three-category classification model for categorizing cases into "normal," "osteopenia," and "osteoporosis" for the training set, test set, and independent test set were 0.999, 0.970, and 0.933, respectively. The F1 score, accuracy, precision, recall, precision, and specificity of the test set were 0.903, 0.909, 0.899, 0.908, and 0.956, respectively, and those of the independent test set were 0.798, 0.815, 0.792, 0.81, and 0.899, respectively. The MAEs of the bone density prediction regression model in the training set, test set, and independent test set were 3.15, 6.303, and 10.257, respectively, and the RMSEs were 4.127, 8.561, and 13.507, respectively. The R-squared values were 0.991, 0.962, and 0.878, respectively. The Pearson correlation coefficients were 0.996, 0.981, and 0.94, respectively, and the p values were all < 0.001. The predicted values and bone density values were highly positively correlated, and there was a significant linear relationship. CONCLUSION: Using deep learning neural networks to process opportunistic CT scan images of the body can accurately predict bone density values and perform bone density three-classification diagnosis, which can reduce the radiation risk, economic consumption, and time consumption brought by specialized bone density measurement, expand the scope of osteoporosis screening, and have broad application prospects.

Real-World Effectiveness of Omalizumab in Chronic Urticaria: A Clinical Observational Study.

INTRODUCTION: The purpose of this study was to assess the clinical effectiveness and safety profile of omalizumab as a therapeutic intervention for chronic urticaria (CU). METHODS: From March 1, 2023, to September 30, 2023, data on a cohort comprising 96 patients with CU, who underwent treatment with omalizumab at our medical institution's allergy clinic, were systematically compiled. Subsequent to the administration of omalizumab, the therapeutic efficacy was assessed utilizing the 7-day urticaria activity score and the urticaria control test. RESULTS: Based on the statistical analysis, the mean duration of therapeutic intervention was 2.4 ± 1.3 months, with a corresponding mean cumulative dosage of 765 ± 450 mg. Of the subset of 42 patients with CU who were subjected to a follow-up period exceeding 3 months, it was observed that the treatment led to complete symptom remission, and no instances of recurrence were documented. Notably, there were statistically significant differences in the treatment duration and the cumulative dosage between patients who experienced co-morbid conditions and those who did not (p < 0.01, 95% CI: 0.280-1.326; p < 0.01, 95% CI: 0.597-2.997). Furthermore, there were significant differences in the treatment duration and cumulative dosage between patients in the combined allergic rhinitis group and those in the non-combined allergic rhinitis group (p < 0.01, 95% CI: 0.204-1.305; p = 0.01, 95% CI: 0.326-2.860). CONCLUSION: Omalizumab demonstrates efficacy in the management of CU among Chinese patients by exerting effective symptom control and facilitating the regression of skin lesions. The assessment of its therapeutic efficacy typically requires a 12-week treatment period. Moreover, the co-occurrence of CU with other allergic disorders serves as a pertinent consideration for the adjustment of omalizumab dosing regimens.

Inhibitory modulation of action potentials in crayfish motor axons by fluoxetine.

The goal of this report is to explore how K2P channels modulate axonal excitability by using the crayfish ventral superficial flexor preparation. This preparation allows for simultaneous recording of motor nerve extracellular action potentials (eAP) and intracellular excitatory junctional potential (EJP) from a muscle fiber. Previous pharmacological studies have demonstrated the presence of K2P-like channels in crayfish. Fluoxetine (50 µM) was used to block K2P channels in this study. The blocker caused a gradual decline, and eventually complete block, of motor axon action potentials. At an intermediate stage of the block, when the peak-to-peak amplitude of eAP decreased to ∼60%-80% of the control value, the amplitude of the initial positive component of eAP declined at a faster rate than that of the negative peak representing sodium influx. Furthermore, the second positive peak following this sodium influx, which corresponds to the after-hyperpolarizing phase of intracellularly recorded action potentials (iAP), became larger during the intermediate stage of eAP block. Finally, EJP recorded simultaneously with eAP showed no change in amplitude, but did show a significant increase in synaptic delay. These changes in eAP shape and EJP delay are interpreted as the consequence of depolarized resting membrane potential after K2P channel block. In addition to providing insights to possible functions of K2P channels in unmyelinated axons, results presented here also serve as an example of how changes in eAP shape contain information that can be used to infer alterations in intracellular events. This type of eAP-iAP cross-inference is valuable for gaining mechanistic insights here and may also be applicable to other model systems.

Unusual immunosuppressive pyridine-containing bisnor- (c23), tetranor- (c21) and pentanor- (c20) sesterterpenoids from Tibetan Leucosceptrum canum.

An unusual pyridine-containing sesterterpenoid, leucosceptrodine (1), and five new nor-leucosceptrane sesterterpenoids, including bisnor- (C23, 2), tetranor- (C21, 3) and pentanor- (C20, 4-6) skeletons, were isolated from the leaves of Tibetan Leucosceptrum canum. Their structures including their absolute configurations were determined by extensive spectroscopic analyses and quantum chemical calculations. A single crystal of one epimer (5) was crystallized from a pair of inseparable epimers, and its structure including its absolute configuration was determined by X-ray crystallographic analysis. The immunosuppressive activities of compounds 1-4 with different potencies were evaluated by inhibiting the secretion of cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

Near-Infrared Absorbing Para-Azaquinodimethane Conjugated Polymers Synthesized via the Transition-Metal-Free Route toward Efficient Photothermal Conversion.

Conjugated polymers with strong absorption in the second near-infrared (NIR-II) window have multiple applications. However, the development of new type of NIR-II conjugated polymers via facile and green methods remains challenging. Herein, this work reports a mild and convenient transition-metal-free method to synthesize near-infrared absorbing quinoidal conjugated polymers containing para-azaquinodimethane (AQM) moieties. The AQM quinoidal conjugated polymers with unique molecular structures and tunable optoelectronic properties can be synthesized by combining the Knoevenagel polycondensation of aromatic dialdehyde monomers with commercially available 1,4-diacetyl-2,5-piperazinedione and the following alkylation reaction. The resultant polymer PQ-DPP shows remarkable NIR-II absorption with a narrow band gap of about 1.08 eV. PQ-DPP nanoparticles exhibit high photothermal conversion efficiency of up to 48% under 1064 nm laser irradiation (1 W cm-2) endowing this polymer with potential in bio-related applications.

IP3R1-mediated MAMs formation contributes to mechanical trauma-induced hepatic injury and the protective effect of melatonin.

INTRODUCTION: There is a high morbidity and mortality rate in mechanical trauma (MT)-induced hepatic injury. Currently, the molecular mechanisms underlying liver MT are largely unclear. Exploring the underlying mechanisms and developing safe and effective medicines to alleviate MT-induced hepatic injury is an urgent requirement. The aim of this study was to reveal the role of mitochondria-associated ER membranes (MAMs) in post-traumatic liver injury, and ascertain whether melatonin protects against MT-induced hepatic injury by regulating MAMs. METHODS: Hepatic mechanical injury was established in Sprague-Dawley rats and primary hepatocytes. A variety of experimental methods were employed to assess the effects of melatonin on hepatic injury, apoptosis, MAMs formation, mitochondrial function and signaling pathways. RESULTS: Significant increase of IP3R1 expression and MAMs formation were observed in MT-induced hepatic injury. Melatonin treatment at the dose of 30 mg/kg inhibited IP3R1-mediated MAMs and attenuated MT-induced liver injury in vivo. In vitro, primary hepatocytes cultured in 20% trauma serum (TS) for 12 h showed upregulated IP3R1 expression, increased MAMs formation and cell injury, which were suppressed by melatonin (100 µmol/L) treatment. Consequently, melatonin suppressed mitochondrial calcium overload, increased mitochondrial membrane potential and improved mitochondrial function under traumatic condition. Melatonin's inhibitory effects on MAMs formation and mitochondrial calcium overload were blunted when IP3R1 was overexpressed. Mechanistically, melatonin bound to its receptor (MR) and increased the expression of phosphorylated ERK1/2, which interacted with FoxO1 and inhibited the activation of FoxO1 that bound to the IP3R1 promoter to inhibit MAMs formation. CONCLUSION: Melatonin prevents the formation of MAMs via the MR-ERK1/2-FoxO1-IP3R1 pathway, thereby alleviating the development of MT-induced liver injury. Melatonin-modulated MAMs may be a promising therapeutic therapy for traumatic hepatic injury.

First-round accreditation and pass rates on licensing examination at different medical schools in China: Closing the performance gap.

BACKGROUND: Although the accreditation approach is widely used to ensure the quality of medical education in many countries, there is scant empirical evidence on whether and how it improves actual medical school performance. We focused on conditions in China, which introduced an accreditation system during the 2010s. Specifically, we examined the relationship between first-round accreditation and actual performance based on the results of medical licensing examinations. Referring to organisation theory, we hypothesised that the impacts of accreditation would depend on existing performance gaps. METHOD: In 2022, we analysed panel data from 105 Chinese medical schools during accreditation (2012 to 2021) and pass rates on medical licensing examinations (2011 to 2019), as matched into 834 school-year records in a window of years before and after accreditation. We employed fixed-effects regression models with a comparison group to exclude factors that may have confounded the impacts of accreditation time. We also demonstrated the heterogeneous effects of accreditation by tier and performance gap of medical schools. RESULTS: The conservative estimates showed a substantial cumulative improvement (over 15 percentage points) in pass rates during the years before accreditation, with no clear trend indicating performance drops in the years after accreditation. Lower-tiered medical schools gained greater benefits from accreditation. Medical schools with a larger prior performance gap achieved a greater percentage point increase in pass rates with the passage of time in pre-accreditation years. CONCLUSIONS: This is the first empirical study to investigate whether accreditation has bridged performance gaps among medical schools. The results support the value of accreditation in China, a country that recently established the system, and might work as a substitute for missing information on early accreditation history in countries with long-established accreditation systems. We encourage more studies in countries that have recently introduced accreditation systems.