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Acid-base dissociable antibiotic-metal complexes are known to be emerging contaminants in the aquatic environments. However, little information is available on the photochemical properties and toxicity of these complex forms. This study investigated the spectral properties of three fluoroquinolones (FQs) with and without metal ions Fe(III), Cu(II), and Al(III) in solutions under different pH conditions, as well as evaluated the changes in toxicity due to the complex with these metal ions using luminescent bacteria (vibrio fischeri). FQs showed a higher tendency to coordinate metal ions under alkaline conditions compared to neutral and acidic conditions, and the formation of complexes weakened the ultraviolet-absorbing ability of FQs. At pH = 7.0, Cu(II) quenched the fluorescence intensity of FQs. Moreover, their Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy were explored, revealing that the coordination sites of Cu(II) in three FQs were situated in a bidentate manner through the oxygen atom of the deprotonated carboxyl group and cyclic carbonyl oxygen atom. This conclusion was further verified by the theory of molecular surface electrostatic potential. In addition, except for complexes of ciprofloxacin-metals, enhanced toxicity of FQs upon coordination with Fe(III) was observed, while reduced toxicity was found for coordination with Cu(II) and Al(III). These results are important for accurately evaluating the photochemical behavior and risk of these antibiotics in aquatic environments contaminated with metal ions.

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Noninvasive pharmacological strategies like nicotinamide mononucleotide (NMN) supplementation can effectively address age-related ovarian infertility by maintaining or enhancing oocyte quality and quantity. This study revealed that ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes. Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed. Additionally, a significant increase in the number of ovarian follicles in aging individuals was noted. Scanning electron microscopy data indicated that NMN significantly alters the density and morphology of lipid droplets and mitochondria in granulosa cells, suggesting potential targets and mechanisms. Transcriptomic analysis and validation experiments collectively suggested that the beneficial effects of NMN on aging ovaries are mediated through enhanced mitochondrial function, improved energy metabolism, and reduced inflammation levels. Our results suggest that NMN supplementation could improve the health status of aging ovaries and enhance ovarian reserve, offering new insights into addressing fertility challenges in older women through assisted reproductive technology.

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In recent years, the application of 3D printing technology in the energetic materials field has proved its ability to innovate traditional charging methods and fabricate complex structures to improve combustion/detonation performance. The melt extrusion technology is the most promising way to fabricate complex structures and multiple components of melt-cast explosives. In this study, a paraffine-based composite was used to substitute melt-cast explosives, and a Design of Experiments approach based on central composite design was adopted to investigate the influence of layer thickness, percent infill, extrusion temperature, and printing velocity on the roughness of printed samples. The results showed that layer thickness and printing velocity could significantly influence the roughness of printed specimens, and no obvious voids or cracks inside the specimens can be detected in computed tomography. In addition, a composite-shaped grain was successfully fabricated via the EAM-D-1 printer, which proved the feasibility of 3D printing melt-cast explosives with complex structures. This work will greatly help to achieve 3D printing melt-cast explosives with complex structures and higher accuracy.

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This study aims to evaluate the feasibility of large language model (LLM) in answering pathology questions based on pathology reports (PRs) of colorectal cancer (CRC). Four common questions (CQs) and corresponding answers about pathology were retrieved from public webpages. These questions were input as prompts for Chat Generative Pretrained Transformer (ChatGPT) (gpt-3.5-turbo). The quality indicators (understanding, scientificity, satisfaction) of all answers were evaluated by gastroenterologists. Standard PRs from 5 CRC patients who received radical surgeries in Shanghai Changzheng Hospital were selected. Six report questions (RQs) and corresponding answers were generated by a gastroenterologist and a pathologist. We developed an interactive PRs interpretation system which allows users to upload standard PRs as JPG images. Then the ChatGPT's responses to the RQs were generated. The quality indicators of all answers were evaluated by gastroenterologists and out-patients. As for CQs, gastroenterologists rated AI answers similarly to non-AI answers in understanding, scientificity, and satisfaction. As for RQ1-3, gastroenterologists and patients rated the AI mean scores higher than non-AI scores among the quality indicators. However, as for RQ4-6, gastroenterologists rated the AI mean scores lower than non-AI scores in understanding and satisfaction. In RQ4, gastroenterologists rated the AI scores lower than non-AI scores in scientificity (P = 0.011); patients rated the AI scores lower than non-AI scores in understanding (P = 0.004) and satisfaction (P = 0.011). In conclusion, LLM could generate credible answers to common pathology questions and conceptual questions on the PRs. It holds great potential in improving doctor-patient communication.

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With continuous advancements in interventional radiology, considerable progress has been made in transarterial therapies for hepatocellular carcinoma (HCC) in recent years, and an increasing number of research papers on transarterial therapies for HCC have been published. In this editorial, we comment on the article by Ma et al published in the recent issue of the World Journal of Gastro intestinal Oncology: "Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC". We focus specifically on the current research status and future directions of transarterial therapies. In the future, more studies are needed to determine the optimal transarterial local treatment for HCC. With the emergence of checkpoint immunotherapy modalities, it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

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Infants with biallelic IL7R loss-of-function variants have severe combined immune deficiency (SCID) characterized by the absence of autologous T lymphocytes, but normal counts of circulating B and NK cells (T-B+NK+ SCID). We report 6 adults (aged 22 to 59 years) from 4 kindreds and 3 ancestries (Colombian, Israeli Arab, Japanese) carrying homozygous IL7 loss-of-function variants resulting in combined immunodeficiency (CID). Deep immunophenotyping revealed relatively normal counts and/or proportions of myeloid, B, NK, and innate lymphoid cells. By contrast, the patients had profound T cell lymphopenia, with low proportions of innate-like adaptive mucosal-associated invariant T and invariant NK T cells. They also had low blood counts of T cell receptor (TCR) excision circles, recent thymic emigrant T cells and naive CD4+ T cells, and low overall TCR repertoire diversity, collectively indicating impaired thymic output. The proportions of effector memory CD4+ and CD8+ T cells were high, indicating IL-7-independent homeostatic T cell proliferation in the periphery. Intriguingly, the proportions of other T cell subsets, including TCRγδ+ T cells and some TCRαß+ T cell subsets (including Th1, Tfh, and Treg) were little affected. Peripheral CD4+ T cells displayed poor proliferation, but normal cytokine production upon stimulation with mitogens in vitro. Thus, inherited IL-7 deficiency impairs T cell development less severely and in a more subset-specific manner than IL-7R deficiency. These findings suggest that another IL-7R-binding cytokine, possibly thymic stromal lymphopoietin, governs an IL-7-independent pathway of human T cell development.

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BACKGROUND: Aberrant activation of mesenchymal epithelial transition (MET) has been considered to mediate primary and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). However, mechanisms underlying this process are not wholly clear and the effective therapeutic strategy remains to be determined. METHODS: The gefitinib-resistant NSCLC cell lines were induced by concentration increase method in vitro. Western blot and qPCR were used to investigate the relationship between MET and vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway. Double luciferase reporter gene and co-immunoprecipitation were used to further reveal the regulation mechanism between MET and VEGF/VEGFR2. The effect of combined inhibition of MET and VEGF/VEGFR2 signaling pathway on the therapeutic sensitivity of EGFR-TKI in gefitinib resistant cell lines with MET aberration was verified ex vivo and in vivo. RESULTS: We successfully obtained two gefitinib-resistant NSCLC cell lines with EGFR mutation and abnormal activation of MET. We observed that MET formed a positive feedback loop with the VEGF/VEGFR2 signaling, leading to persistent downstream signaling activation. Specifically, MET up-regulated VEGFR2 expression in a MAPK/ERK/ETS1-dependent manner, while VEGF promoted physical interaction between VEGFR2 and MET, thereby facilitating MET phosphorylation. A MET inhibitor, crizotinib, combined with an anti-VEGF antibody, bevacizumab, enhanced the sensitivity of NSCLC cells to gefitinib and synergistically inhibited the activation of downstream signaling in vitro. Dual inhibition of MET and VEGF combined with EGFR TKIs markedly restrained tumor growth in both human NSCLC xenograft models and in an EGFR/MET co-altered case. CONCLUSIONS: Our work reveals a positive feedback loop between MET and VEGF/VEGFR2, resulting in continuous downstream signal activation. Combined inhibition of MET and VEGF/VEGFR2 signaling pathway may be beneficial for reversing EGFR TKIs resistance.

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Background/Aims: Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific proteinase 29 (USP29) plays pivotal roles in hepatic ischemia‒reperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid ß-oxidation (FAO) under metabolic stimulation, directly interacted with Acyl-CoA synthetase long chain family member 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions: USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

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BACKGROUND: S100ß is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100ß and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. METHODS: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100ß levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. RESULTS: A total of 1072 patients were included in the analysis. The highest S100ß levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100ß level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: ß 36.853, 95% confidence interval (CI) 22.659-51.048, P < 0.001; non-dominant: ß 23.645, 95% CI 10.774-36.516, P = 0.007). However, serum S100ß levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: ß 3.470, 95% CI 2.392-4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936-10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: ß 0.326, 95% CI  - 0.735-1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538-1.445, P = 0.619). The association of S100ß levels and HT was not significant in either stroke lateralization group. CONCLUSIONS: Serum S100ß levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100ß in judging the degree of disease and predicting prognosis.

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Extreme climate events have increased in terms of their amplitudes, frequency and severity, greatly affecting ecosystem functions and the balance of the global carbon cycle. However, there are still uncertainties about how extreme climate change will affect tree growth. This study characterized the responses of tree growth to extreme climate on the northeastern Tibetan Plateau from 2000 to 2020. Meanwhile, a back propagation neural network was used to predict tree growth trends under two future emission scenarios from 2020 to 2050. This study revealed that: (1) the tree-ring width index (RWI) showed a decreasing trend (- 0.04/decade) in the eastern region, but the enhanced vegetation index (EVI) showed an increasing trend (0.05/decade) from 2000 to 2020. While both RWI and EVI in the middle and western regions showed increasing trends. (2) The responses of RWI and EVI to extreme climate were regionally asymmetric. In the eastern region, extreme precipitation inhibited tree radial growth, while extreme warm nights promoted tree canopy growth. In two other regions, both extreme precipitation and extreme warm nights promoted tree growth. (3) The model predicts that there was no significant change in RWI and EVI in the western region, but both RWI and EVI showed an increasing trend in the middle and eastern regions under the low emission scenario. Under the high emission scenario, the growth of tree stem and canopy in all three regions shows a general decreasing trend. The results of this study both improved the understanding of the differences in carbon allocation between tree stem (RWI) and canopy (EVI) and identified vulnerability thresholds for tree populations.

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Background: When individuals infected with human immunodeficiency virus (HIV) experience pulmonary infections, they often exhibit severe symptoms and face a grim prognosis. Consequently, early, rapid, and accurate pathogen diagnosis is vital for informing effective treatment strategies. This study aimed to use metagenomic next-generation sequencing (mNGS) and targeted mNGS (tNGS) to elucidate the characteristics of pulmonary infections in HIV and non-HIV individuals. Methods: This study enrolled 90 patients with pulmonary infection at the Department of Infectious Diseases of The First Hospital of Jilin University from June 2022 to May 2023, and they were divided into HIV (n=46) and non-HIV (n=44) infection groups. Their bronchoalveolar lavage fluid (BALF) was collected for mNGS analysis to evaluate the differences in pulmonary infection pathogens, and tNGS detection was performed on BALF samples from 15 HIV-infected patients. Results: A total of 37 pathogens were identified in this study, including 21 bacteria, 5 fungi, 5 viruses, 5 mycobacteria, and 1 mycoplasma. The sensitivity of mNGS was 78.9% (71/90), which is significantly higher than that of conventional methods (CTM) (39/90, P=1.5E-8). The combination of mNGS with CTM can greatly enhance the sensitivity of pathogen detection. The prevalence of Pneumocystis jirovecii (82.6% vs. 9.1%), cytomegalovirus (CMV) (58.7% vs. 0%), and Epstein-Barr virus (EBV) (17.4% vs. 2.3%) was significantly higher in the HIV infection group than in the non-HIV infection group (P<0.05). Although no statistically significant difference was observed, the detection rate of Mycobacteria was higher in HIV-infected patients (17.4%) than in the non-HIV group (6.8%). Furthermore, the tNGS results of BALF from 15 HIV-infected patients were not entirely consistent with the mNGS results., and the concordance rate of tNGS for the detection of main pathogens reached 86.7% (13/15). Conclusion: Next-generation sequencing (NGS) can accurately detect pathogens in the BALF of patients with pulmonary infection. The sensitivity of tNGS is comparable to that of mNGS. Therefore, this technique should be promoted in the clinic for better patient outcomes.

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The development of electrocatalysts with low cost, high efficiency, and long-term durability is crucial for advancing green hydrogen production. Transition metal phosphides (TMPs) have been proved to be efficient electrocatalyst, while the improvement in the performance and durability of the TMPs remains a big challenge. Employing atmospheric pressure chemical vapor deposition (APCVD) and phosphorization, FeP/Ti electrodes are fabricated featuring controllable oxygen ingredients (O-FeP/Ti). This manipulation of oxygen content fine-tunes the electronic structure of the catalyst, resulting in improved surface reaction kinetics and catalytic activity. The optimized O-FeP-400/Ti exhibits outstanding HER activity with overpotentials of 142 and 159 mV at -10 mA cm-2 in 0.5 M H2SO4 and 1 M KOH, respectively. Notably, the obtained O-FeP/Ti cathode also displays remarkable durability of up to 200 h in acidic electrolyte with surface topography remaining intact. For the first time, the low-valence titanium oxide (Ti3O) interlayer is identified in the composite electrode and ascribed for the superior connection between Ti substrate and the surface O-FeP catalyst, as supported by experimental results and density functional theory (DFT) analysis. This work has expanded the potential applications of transition metal phosphides (TMPs) as a cost-effective, highly efficient and durable catalyst for water splitting.

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PURPOSE: Tumor-associated macrophages (TAMs) are important biomarkers of tumor invasion and prognosis in patients with glioblastoma. We combined the imaging and radiomics features of preoperative MRI to predict CD68+ macrophage infiltration. METHODS: Clinical, MRI image, and pathology data of 188 patients with glioblastoma were analyzed. Overall, 143 patients were included in the training (n = 101) and validation (n = 42) sets, whereas 45 patients were included in an independent test set. The optimal cut-off value (14.8%) was based on the minimum p-value formed by the Kaplan-Meier survival analysis and log-rank tests which divided patients into groups with high CD68+ TAMs (≥ 14.8%) and low CD68+ TAMs (< 14.8%). Regions of interest and radiomics features extraction were based on contrast-enhanced T1-weighted images (CE-T1WI) and T2WI. Multi-parameter stepwise regression was used to create the clinical, radiomics, and combined models, each evaluated using the receiver operating characteristic curve. Decision curve analysis was used to assess the clinical applicability of the nomogram. RESULTS: A clinical model based on the minimum apparent diffusion coefficient (ADCmin) revealed an area under the curve (AUC) of 0.768, 0.764, and 0.624 for the training set, validation set, and test set, respectively. The 2D radiomics model, based on two features, revealed an AUC of 0.783, 0.724, and 0.789 for the training, validation, and test sets, respectively. The 3D radiomics model, based on three features, revealed AUCs of 0.823, 0.811, and 0.787 for the training, validation, and test sets, respectively. The combined model, with ADCmin and radiomics features, showed the best performance, with AUCs of 0.865, 0.822, and 0.776 for the training, validation, and test sets, respectively. The calibration curve of the combined model nomogram showed good agreement between the estimated and actual probabilities. CONCLUSION: The combined model constructed using ADCmin, a quantitative imaging parameter, combined with five key radiomics features can be used to evaluate the extent of CD68+ macrophages before surgery.

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Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24-30 Fr while maintaining a balloon pressure of 25-35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16-165) with median estimated blood loss of 2 ml (range 0-150). The median postoperative hospital stay was 3 d (range 1-15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3-100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

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The forensic characteristics and genetic relationships of Hainan Han population are still not fully understood. The aim of this study was to investigate the forensic features and genetic variations of 23 short tandem repeat (STR) included in the HuaxiaTM Platinum system in Hainan Han and analyze the population genetic relationships between Hainan Han and other adjacent Chinese populations. The genetic polymorphisms of 23 STR loci included in the HuaxiaTM Platinum kit were evaluated from 2971 Hainan Han individuals. Comprehensive comparisons were conducted based on genetic distance, phylogenetic tree, multidimensional scaling and principal component analysis (PCA) to explore inter-population genetic relationship. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) of the 23 STR loci was 0.999 999 999 999 999 999 999 999 999 819 and 0.999 999 999 625 408, respectively. The investigated Hainan Han population has high genetic similarity with geographically close Han populations, while great genetic difference with other ethnic minorities, prominently in Yunnan Miao, Xinjiang Uygurs, Xinjiang Kazakh, and Tibetans. Our study found the 23 STR loci were highly polymorphic and suitable for forensic personal identification and paternity testing in Hainan Han population. Genetic similarity widely existed among Han populations from different regions, and significant genetic divergence existed between Han populations and some ethnic minorities. The populations genetic diversity and similarity were closely associated with ethnic origin and geographical distribution.

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Increasing air pollution could undermine human health, but the causal link between air pollution and eye and ear health has not been well-studied. Based on four-week-level records of eye and ear health over 1991-2015 provided by the China Health and Nutrition Survey, we estimate the causal effect of air pollution on eye and ear health. Using two-stage least squares estimation, we find that eye or ear disease possibility rises 1.48% for a 10 µg/m3 increase in four-week average PM2.5 concentration. The impacts can last about 28 weeks and will be insignificant afterward. Females, individuals aged 60 years and over, with high exposure environments, relatively poor economic foundations, and low knowledge levels are more vulnerable to such negative influences. Behavioral channels like more smoking activities and less sleeping activities could partly explain this detrimental effect. Our findings enlighten how to minimize the impact of air pollution and protect public health.

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Lung cancer, one of the most prevalent cancers worldwide, stands as the primary cause of cancer-related deaths. As is well-known, the utmost crucial risk factor contributing to lung cancer is smoking. In recent years, remarkable progress has been made in treating lung cancer, particularly non-small cell lung cancer (NSCLC). Nevertheless, the absence of effective and accurate biomarkers for diagnosing and treating lung cancer remains a pressing issue. Interleukin 22 (IL-22) is a member of the IL-10 cytokine family. It exerts biological functions (including induction of proliferation and anti-apoptotic signaling pathways, enhancement of tissue regeneration and immunity defense) by binding to heterodimeric receptors containing type 1 receptor chain (R1) and type 2 receptor chain (R2). IL-22 has been identified as a pro-cancer factor since dysregulation of the IL-22-IL-22R system has been implicated in the development of different cancers, including lung, breast, gastric, pancreatic, and colon cancers. In this review, we discuss the differential expression, regulatory role, and potential clinical significance of IL-22 in lung cancer, while shedding light on innovative approaches for the future.

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To identify modifier loci underlying variation in body mass index (BMI) in persons with cystic fibrosis (pwCF), we performed a genome-wide association study (GWAS). Utilizing longitudinal height and weight data, along with demographic information and covariates from 4,393 pwCF, we calculated AvgBMIz representing the average of per-quarter BMI Z scores. The GWAS incorporated 9.8M single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) > 0.005 extracted from whole-genome sequencing (WGS) of each study subject. We observed genome-wide significant association with a variant in FTO (FaT mass and Obesity-associated gene; rs28567725; p value = 1.21e-08; MAF = 0.41, ß = 0.106; n = 4,393 individuals) and a variant within ADAMTS5 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 5; rs162500; p value = 2.11e-10; MAF = 0.005, ß = -0.768; n = 4,085 pancreatic-insufficient individuals). Notably, BMI-associated variants in ADAMTS5 occur on a haplotype that is much more common in African (AFR, MAF = 0.183) than European (EUR, MAF = 0.006) populations (1000 Genomes project). A polygenic risk score (PRS) calculated using 924 SNPs (excluding 17 in FTO) showed significant association with AvgBMIz (p value = 2.2e-16; r2 = 0.03). Association between variants in FTO and the PRS correlation reveals similarities in the genetic architecture of BMI in CF and the general population. Inclusion of Black individuals in whom the single-gene disorder CF is much less common but genomic diversity is greater facilitated detection of association with variants that are in LD with functional SNPs in ADAMTS5. Our results illustrate the importance of population diversity, particularly when attempting to identify variants that manifest only under certain physiologic conditions.

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Clinical trials on innovative drugs in China have witnessed a stage of rapid development in recent years. The introduction of a number of government policies has stimulated enthusiasm for research and development in the pharmaceutical industry. We analyzed the data of the early-phase clinical trials registered in the Chinese Center for Drug Evaluation (CDE) from September 6, 2013, to December 31, 2022. All related registration information disclosed on the CDE website, including posted time, drug classification, dosing formula, indications, trial design, and trial status, were summarized and analyzed. A total of 5336 early-phase clinical trials were identified. The quantity and growth rate of early-phase clinical trials have increased substantially each year. Chemical drugs accounted for the largest proportion of early-phase clinical trials, although it dropped from 85.7% in 2013 to 59.5% in 2022. Moreover, the number of oncology drugs has increased yearly, accounting for 49.2% of all early-phase clinical trials in 2022. We can conclude that during 2013-2022, the development of early-phase clinical trials has progressed due to government support and advanced development techniques. To enhance the efficiency and success rate of early-phase clinical trials in the future, it is necessary to acquire advanced technical support and improve standardized supervision systems.

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Achelura yunnanensis is a destructive pest of forests, causing substantial damage on tree growth and severe economic losses. Additionally, as a daytime-active moth, this species also holds important scientific value for investigating the genetic mechanisms governing day-night activity patterns of Lepidoptera. To facilitate effective pest control and deepen our understanding of the diurnal behavior's genetic basis of moths, genomic data for this species are crucial. In this study, we present a chromosome-level reference genome of A. yunnanensis (368.15 Mb in 32 chromosomes; scaffold N50 = 12.61 Mb; BUSCO completeness = 98.0%). Genome annotation shows that the new assembly comprises 37.10% (136.55 Mb) repetitive elements, 1,828 non-coding RNAs, and 15,523 protein-coding genes. Genes involved in lipid metabolism and xenobiotics biodegradation and metabolism, such as cytochrome P450 families, experienced significant expansion in the A. yunnanensis genome. The chromosome-level genome of A. yunnanensis provides a valuable genomic resource for devising novel pest control strategies, and will also help to study the genetic mechanism of the shift of diurnal behavior in Lepidoptera.

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