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The silver-lipped pearl oyster ( Pinctada maxima ) is the largest and most commercially valuable pearl-producing oyster, renowned for its ability to generate large, lustrous pearls. This species is a sequential hermaphrodite, with pearl production displaying notable sexual dimorphism. Consequently, understanding the molecular mechanisms governing sex determination and differentiation is crucial for advancing breeding strategies in the pearl oyster industry. To elucidate these mechanisms, this study conducted integrative transcriptomic analyses of P. maxima gonadal tissues using isoform sequencing (Iso-seq) and RNA sequencing (RNA-seq). Comparative analysis of ovarian and testicular tissues identified 2 768 differentially expressed genes (DEGs). Gene co-expression network analysis delineated four key modules, including three sex-specific modules and one shared module. Key genes implicated in sex determination and maintenance were identified, including FOXL2 , NANOS1 , and β-catenin , important for ovarian maintenance, and DMRT , SOX30 , FEM1 , and FOXJ1 , crucial for testicular maintenance. These genes, widely studied in other taxa, were confirmed as hub genes in the sex-related modules of P. maxima . Interestingly, genes within the shared module were significantly enriched in the spliceosome pathway. Alternative splicing analysis highlighted its extensive role in gonadal tissues, with more pronounced activity observed in the testis compared to the ovary. Nearly half (47.83%, 375) of the identified genes undergoing differential alternative splicing (DASGs) also exhibited differential transcript usage (DTUGs), while only 17% of DTUGs overlapped with DEGs. Genes associated with sex differentiation, such as DMRT , β-catenin , and U2AF2 , displayed sex-specific and/or sex-biased isoforms. These findings offer novel insights into the molecular basis of sex differentiation in P. maxima , which could inform the development of targeted breeding strategies aimed at sex control, thereby enhancing pearl quality and yield in aquaculture. This study offers a robust molecular foundation for advancing breeding programs and optimizing production in the pearl oyster industry.

This study aimed to investigate the effects of adding Qiamagu polysaccharides to feed on the growth performance, immunity and gut health of yellow-feathered broilers. A total of 240 healthy, day-old, male yellow-feathered broiler chickens with similar body weights were randomly divided into four groups, each with six replicates and 10 chickens per replicate. The groups consisted of a control group (CON) and three treatment groups: TP1 (250 mg/kg), TP2 (500 mg/kg), and TP3 (1000 mg/kg) of Qiamagu polysaccharide in the diet, with a feeding period of 64 days. The average daily weight gain of all experimental groups were significantly higher than those of the CON group (P < 0.05) in 1-21 days. The average daily gain of TP1 and TP2 groups was increased (P < 0.05), and the ratio of feed to gain was decreased (P < 0.05), at 43-63 days. The levels of IgM, IgA, IgG, IL-1β, IL-2 and TNF-α in the serum of broilers in the TP1 and TP2 groups exhibited a consistent increase at 21,42 and 63 day (P < 0.05). At 22-42 days, the villus length of duodenum and ileum and the ratio of Villus height to crypt depth ratio were increased in TP2 group (P < 0.05). The ileal mucosa IL-1β and IL-2 mRNA levels of broilers in TP3 group were down-regulated in 1-42 days (P < 0.05). The mRNA levels of MUC2, ZO-1 and Occluding in ileum mucosa of broilers in TP3 group were up-regulated in 1-63days (P < 0.05). The total number of cecal flora species in TP1, TP2 and TP3 groups was higher than that in control group (P < 0.05). The relative abundance of Lactobacillus in TP2 group was increased (P < 0.05). In conclusion, this study showed that the addition of Qiamagu polysaccharide improved the growth performance, enhanced the immune response and had better impact on intestinal health of yellow-feathered broilers., Competing Interests: Declarations. Institutional Review Board Statement: All procedures in this study were approved by the Animal Experiment Ethics Committee of Animal Science and Technology of Shihezi University China, approval number: 2023-031. Informed consent: Informed consent was obtained from all subjects involved in the study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Acute promyelocytic leukemia (APL) is marked by a block at the promyelocyte stage. Treatments like ATRA and ATO face resistance and relapse issues. Plastrum testudinis , a traditional Chinese medicine, may offer therapeutic potential. This study investigated xtr-miR-22-3p from P. testudinis for treating APL. High expression of xtr-miR-22-3p was confirmed, with target prediction indicating interactions with key genes, including PML. xtr-miR-22-3p reduced HL-60 leukemia cell growth, altered the cell cycle, and selectively inhibited HL-60 proliferation while promoting BMSC growth, suggesting its potential as a targeted APL therapy.

As a novel protein source, the black soldier fly (Hermetia illucens) possesses the potential to enhance fish health due to its high protein content, essential amino acids, and bioactive compounds, but the mechanisms by which defatted black soldier fly meal affects fish health remain unclear. This study aimed to evaluate the effects of partially replacing soybean meal (SM) with defatted black soldier fly larvae meal on the pathogen resistance of juvenile Nile tilapia (Oreochromis niloticus) and to explore the underlying mechanisms. Defatted black soldier fly (Hermetia illucens) meal was used to replace 0 % (CON), 15 % (H15), 30 % (H30), 45 % (H45), and 60 % (H60) of soybean meal in the diets, which were fed to Nile tilapia for 8 weeks. At the second week of the experiment, an unexpected infection was observed in the Nile tilapia, with subsequent isolation and identification confirming the pathogen as Aeromonas veronii. The results showed that defatted black soldier fly meal improved the survival rate and reduced the intestinal inflammation of Nile tilapia in H60 group compared to CON group (P < 0.05). Periodic acid-Schiff (PAS) staining of the gut indicated that a 60 % replacement of soybean meal with defatted black soldier fly meal significantly increased the number of goblet cells in the intestine (P < 0.05) and upregulated the expression level of mucin 2 (muc2) (P < 0.05). Throughout the experiment period, the survival rate in the defatted black soldier fly meal groups was higher than that in the soybean meal group, with the H60 group exhibiting the most significant improvement. In addition, defatted black soldier fly meal exhibited a promotion effect on goblet cell numbers, mucin production and mucin secretion with a dose dependent manner (P < 0.05). To identify the possible mechanism by which defatted black soldier fly meal enhanced goblet cell numbers, gut microbiome and metabolomics were conducted. The results showed that the defatted black soldier fly meal altered the composition of intestinal microbiota and increased the content of L-tyrosine in the H60 group. The effects of L-tyrosine were further identified in LS174T cells, and the results showed that L-tyrosine upregulated the expression levels of muc2 and SAM pointed domain-containing Ets transcription factor (spdef) (P < 0.05). In conclusion, the defatted black soldier fly meal improves gut health and enhances pathogen resistance, ultimately leading to the increased survival rates of Nile tilapia when exposed to A. veronii., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of Interest., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Municipal solid waste incinerators (MSWIs) are deemed important sources of polychlorinated and polybrominated dibenzo-p-dioxin/furans (PCDD/Fs and PBDD/Fs). However, compared to PCDD/Fs, the emission characteristics of MSWI-derived PBDD/Fs have been rarely studied. Here we selected a long-term operating MSWI, investigated the generation of PBDD/Fs under varying incineration conditions within the normal range, and compared them to those of PCDD/Fs. Generally, PBDD/Fs exhibited mass-based emission factors (mass-EFs) one order of magnitude higher than those of PCDD/Fs and were predominantly released via slag, as were PCDD/Fs, though at lower percentages. Both PBDD/Fs and PCDD/Fs showed significant changes in emissions with the variations in waste load, O 2 content, and waste composition, particularly PBDD/Fs. Comparatively, furnace-derived PBDD/Fs demonstrated heightened sensitivity to waste load and composition, whereas PCDD/Fs were primarily influenced by O 2 levels, followed by waste composition; PCDD/Fs consistently exhibited increasing mass-EFs under unconventional conditions and PCDD/Fs in filtered fly ash were highly sensitive to all the three variables, while filtered PBDD/Fs remained insensitive to these conditions. Data comparison between raw flue gas and filtered fly ash indicated secondary generation of PBDD/Fs and PCDD/Fs during gas purification, as well as the insufficient dioxin-trapping efficiency of bag filters, particularly for PBDD/Fs. Therefore, MSWI-derived PBDD/Fs and dioxins in slag and other MSWI-derived wastes warrant significant attention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Senecavirus A (SVA) infection causes vesicular disease in pigs and acute death of newborn piglets. Frequent gene mutation and recombination events lead to difficulties for SVA prevention and eradication, especially impeding the development of effective vaccine or treatment drug. SVA nonstructural 3 A protein plays an important role in viral replication and various immune evasion pathways, which makes it a potential therapeutic target. In this study, prokaryotic 3 A protein was successfully expressed in Escherichia.coli BL21 (DE3) system and purified with Ni-affinity chromatography. Western blotting results showed 3 A protein specifically reacted with serum of SVA infected pig, indicating that nonstructural 3 A protein was a potential diagnostic maker for SVA serological testing, especially for differentiating infected from vaccinated animals. In addition, specific monoclonal antibody (mAb) 5A7 against 3 A protein was also prepared. Indirect immunofluorescence assay and Western blotting assay showed mAb 5A7 specifically reacted with SVA cultured in IBRS-2 cells. To characterize the epitope of mAb 5A7, serial truncated peptides of 3 A protein were prepared. Western blotting assay showed the epitope of mAb 5A7 was 5 NDDTPVDEALGR 16 . Bioinformatic studies revealed that the epitopes are located on the extrinsic membrane domain of 3 A protein with good antigenicity. To sum up, SVA 3 A protein and its specific mAb 5A7 were successfully prepared in this study, which will contribute to biological function study of 3 A protein and the pathogenic mechanism of SVA, as well as the diagnosis and prevention of this disease., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Purpose: This study aims to compare side-to-side anastomosis (SSA) and end-to-side anastomosis (ESA) in laparoscopic right hemicolectomy from multiple perspectives to guide the selection of the optimal anastomotic technique., Methods: This review was pre-registered with PROSPERO (CRD42024614418). A comprehensive literature search was performed using Embase, PubMed, Cochrane Library, and China Biology Medicine (CBM). The primary outcome was anastomotic complications, and secondary outcomes included non-anastomotic complications, short-term prognosis, and surgical parameters., Results: A total of 18 articles involving 14,555 participants were included in this systematic review and meta-analysis. No significant difference was found between SSA and ESA regarding overall anastomotic complications (OR = 1.14, 95% CI = 0.81 to 1.62, P = 0.45). However, SSA showed advantages in reducing postoperative anastomotic bleeding (OR = 0.64, 95% CI = 0.45 to 0.90, P = 0.01), while ESA appeared more favorable for reducing anastomotic leakage (AL) (OR = 1.29, 95% CI = 0.97 to 1.73, P = 0.08) and intestinal obstruction (OR = 1.20, 95% CI = 0.99 to 1.47, P = 0.07), though these differences were not statistically significant. No significant differences were found in non-anastomotic complications, short-term prognosis, or surgical parameters., Conclusion: Current clinical evidence suggests that SSA is more effective than ESA in reducing postoperative anastomotic bleeding during right hemicolectomy for cancer. However, no significant differences were observed between the two techniques regarding overall anastomotic., Competing Interests: Declarations. Ethics approval and consent to participate: Not appliance. Consent for publication: Not appliance. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

By a carbon nanotube (CNT) spatially confined metal-catalyzed structural reconstruction, carbon nanofibers (CNFs) with a hollow, hollow-solid, solid graphite core, and CNT shell are prepared using nitrogen heterocycle (NHC) and polycyclic aromatic hydrocarbon (PAH) as carbon sources. The formation mechanism of CNFs with oriented graphene layers and enlarged intergraphene spacing is studied by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and selected area electron diffraction analysis. It revealed that this one-dimensional nanoconfined metal-catalyzed carbon rearrangement is totally different from the reported spatially localized metal-catalyzed graphitization of electrospun polymer and nanocasted carbohydrate nanofibers, as the graphene orientation, cavity volume, and interlayer distance of CNFs can be controlled by the carbon concentration-related competitive metal-catalyzed tip growth of latitudinal and longitudinal graphene layers from NHC and PAH. The unique CNF structure renders good electronic/ionic conductivity, abundant Li + storage interlayer gaps, and robust mechanical durability, resulting in outstanding electrochemical properties as anodes in lithium-ion batteries. The optimum CNF anode delivers a stable discharge capacity of 475 mA h g -1 at 0.1 C, an extraordinary rate capability of 303 mA h g -1 at 5 C, and a remarkable long-term cycling stability of 378 mA h g -1 after 600 cycles at 1 C. This 1D nanoconfined metal catalysis synthesis could be useful for the development of efficient CNF anodes in many electrochemical reactions with a potential for industrial applications.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide. Its primary risk factors are chronic liver diseases such as metabolic fatty liver disease, non-alcoholic steatohepatitis, and hepatitis B and C viral infections. These conditions contribute to a specific microenvironment in liver tumors which affects mitochondrial function. Mitochondria are energy producers in cells and are responsible for maintaining normal functions by controlling mitochondrial redox homeostasis, metabolism, bioenergetics, and cell death pathways. HCC involves abnormal mitochondrial functions, such as accumulation of reactive oxygen species, oxidative stress, hypoxia, impairment of the mitochondrial unfolded protein response, irregularities in mitochondrial dynamic fusion/fission mechanisms, and mitophagy. Cell death mechanisms, such as necroptosis, pyroptosis, ferroptosis, and cuproptosis, contribute to hepatocarcinogenesis and play a significant role in chemoresistance. The relationship between mitochondrial dynamics and HCC is thus noteworthy. In this review, we summarize the recent advances in mitochondrial alterations and signatures in HCC and attempt to elucidate its molecular biology. Here, we provide an overview of the mitochondrial processes involved in hepatocarcinogenesis and offer new insights into the molecular pathology of the disease. This may help guide future research focused on improving patient outcomes using innovative therapies., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

With the rapid advancement of agricultural modernization, biodegradable mulch （BDM） in farmland has become increasingly prevalent. However, little is known about the effects of BDM buried in soil on bacterial communities. In this study, a burial experiment was conducted on farmland using BDM （PBAT+PLA）. The bacterial communities on the surface of the BDM （H8） at different burial stages were analyzed through Illumina NovaSeq high-throughput sequencing technology. The landfill experiment was carried out for a total of 75 days. The results revealed that the bacterial α -diversity in BDM was significantly lower than that in the control soil, with a notable decrease in soil bacterial α -diversity on the BDM surface in the later stages of burial compared to that in the early stages （ P &lt;0.05）. The bacterial community of control soil was significantly different from that of BDM （ P &lt;0.01）. The relative abundance of the Proteobacteria phylum in the BDM was significantly higher than that in the control soil （ P &lt;0.05）. LEfSe analysis revealed significant differences in taxa between the buried BDM and the control group across burial stages. During the early stage, Pseudarthrobacter and Acidovorax showed significant differences. Variovorax and Mycobacterium exhibited differences in the mid-stage, whereas Hydrogenophaga and Chryseolinea differed significantly in the late stage. These taxa served as indicator species for their corresponding burial stages. Functional analysis of bacterial communities revealed an enhancement of carbon metabolism-related functions in the bacterial community on the BDM surface during the early and middle stages. Moreover, network analysis revealed that, compared to that in the control soil, BDM exhibited a simpler network structure of the bacterial community, higher modularity values, and more negative correlation connections. These findings collectively provide a scientific foundation for a comprehensive understanding of the impact of BDM on the soil microecological environment.

Background: The efficacy of adjuvant chemotherapy for T1N0M0 triple-negative breast cancer (TNBC) has not been clearly elucidated. Thus, we aimed to evaluate the efficacy of adjuvant chemotherapy for patients with T1a-cN0M0 TNBC., Patients and Methods: Patients newly diagnosed with TNBC between 2011 and 2015 were identified and followed up until the end of 2020 using the Taiwan Cancer Registry. Univariate and multivariate Cox proportional hazards regression analyses were performed to compare the recurrence-free survival (RFS) and OS between patients who received and those who did not receive adjuvant chemotherapy., Results: Of the 62 483 patients registered during 2011-2015, 1074 patients with T1N0M0 TNBC (T1a, n = 103; T1b, n = 167; and T1c, n = 804) who underwent definitive breast surgery were included. Overall, 850 (79%) patients received adjuvant chemotherapy; these comprised 24.3%, 67.7%, and 88.6% of the patients with T1a, T1b, and T1c disease, respectively. Over a median follow-up of 7.18 years, a significant RFS and OS benefit from adjuvant chemotherapy was observed in the T1c subgroup but not in the T1a and T1b subgroups. However, subgroup analysis of T1b disease indicated that adjuvant chemotherapy yielded an OS benefit to patients with histological grade III disease (adjusted hazard ratio = 0.08, 95% CI, 0.01-0.77; P = .03)., Conclusions: Adjuvant chemotherapy improved the RFS and OS in patients with T1cN0M0 TNBC and improved the OS in patients with histological grade III T1bN0M0 disease. Our study advocates for the utilization of adjuvant chemotherapy in patients diagnosed with T1cN0M0 and histological grade III T1bN0M0 TNBC., (© The Author(s) 2025. Published by Oxford University Press.)

Direct sampling mass spectrometry (MS) has rapidly advanced with the development of ambient ionization MS techniques. Swab touch-spray (TS)-MS has shown promise for rapid clinical diagnostics. However, commercially available swabs are notorious for their high background signals, particularly in the positive ionization mode. Although changes to MS methods or precleaning of the swabs can serve as workarounds, this inherent issue still limits the clinical application of swab TS-MS. In this study, we report the use of the sterile-packaged OmniSwab as an alternative material for untargeted swab TS-MS analysis. As a proof of concept, breast surgical margins were swabbed in vivo during surgeries and analyzed using a compact mass spectrometer within the hospital. Subsequently, various machine learning algorithms were applied to the acquired MS spectra to determine the optimal model for classifying margins as normal or tumor. The Least Absolute Shrinkage and Selection Operator (LASSO) model yielded the highest prediction performance, with accuracies exceeding 90% in both testing and validation data sets. Notably, three out of four surgical margins involved with cancer cells were accurately identified. The entire workflow, from swab TS-MS analysis to margin prediction, can be completed within 5 min with high accuracy, demonstrating the feasibility of swab TS-MS to assist intraoperative decision-making.

Suppressing non-radiative energy loss (ΔE 3 ) mediated by the triplet charge transfer state is crucial for high-performance organic solar cells (OSCs). Here, we decode the energy inversion through multi-scale theoretical simulations, which inhibit the formation of non-emissive triplet (T 1 ) state. However, it is mystified by the system dependence. We first demonstrate a direct relationship of "the probability of Face-on orientation (P Face-on ) is proportional to the probability of energy inversion (P EI )", which is related to the function of terminal fluorination. Through Pearson's correlation coefficient and machine learning model, the useful stacking structural parameters were obtained to clarify the effect of π-bridge group on the function of terminal fluorination. Based on the molecular descriptors established, we explain that the fluorination effect is beneficial to Face-on orientation and thus energy inversion due to the enhanced intermolecular coupling. But the π-bridge inhibits this coupling with the interfacial stacking configuration appearing more "TT&#95;IC". This work provides a directional standard for promoting energy inversion to reduce ΔE 3 for the high-performance OSCs., (© 2024 Wiley-VCH GmbH.)

GPR20, an orphan G protein-coupled receptor (GPCR), shows significant expression in intestinal tissue and represents a potential therapeutic target to treat gastrointestinal stromal tumors. GPR20 performs high constitutive activity when coupling with G i . Despite the pharmacological importance of GPCR constitutive activation, determining the mechanism has long remained unclear. In this study, we explored the constitutive activation mechanism of GPR20 through large-scale unbiased molecular dynamics simulations. Our results unveil the allosteric nature of constitutively activated GPCR signal transduction involving extracellular and intracellular domains. Moreover, the constitutively active state of the GPR20 requires both the N-terminal cap and G i protein. The N-terminal cap of GPR20 functions like an agonist and mediates long-range activated conformational shift. Together with the previous study, this study enhances our knowledge of the self-activation mechanism of the orphan receptor, facilitates the drug discovery efforts that target GPR20., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: The bare area is defined as a transverse region within the trochlear notch, serving as an optimal entry point for olecranon osteotomy due to the absence of articular cartilage coverage. However, there is limited research on the morphology and location of the bare area, and there is a lack of intuitive visual description. Thus, the purpose of this study is to delineate anatomical features of the bare area and visualize its morphology and refine the olecranon osteotomy approach., Method: Thirty-six cadaveric elbow joints (comprising 18 pairs) were meticulously dissected. Measurements encompassed the lateral (radial side) and medial (ulnar side) widths, proximal and distal lengths, and the distance from the corresponding dorsal cortical point of the bare area to the triceps insertion. Post-dissection, the humeral ulnar joint was realigned, followed by randomized transverse or chevron osteotomy. Subsequent CT scans were conducted pre- and post-osteotomy to delineate the shape of the bare area and osteotomy fracture line, facilitating the generation of superimposed and heat maps for visualization., Results: The bare area was present in all specimens, exhibiting a lateral (radial) width of 7.09 ± 4.86 mm, a medial (ulnar) width of 12.08 ± 3.66 mm, a proximal length of 15.70 ± 8.06 mm, and a distal length of 16.49 ± 7.06 mm. The distance from the triceps insertion to the corresponding dorsal cortical point of the bare area averaged 18.12 ± 3.21 mm. Notably, considerable variability was observed in both the position and shape of the bare area. Visualization through superimposed and heat maps revealed a bow-tie configuration, with the medial side wider than the lateral side, situated at the narrowest segment of the proximal ulna in the coronal plane, analogous to its waist. The superimposed map of fracture lines reveals that the fracture lines from transverse osteotomies are more concentrated than those from chevron osteotomies., Conclusion: The position and shape of the bare area demonstrates notable diversity, manifesting not as a strictly transverse shape nor a consistently contiguous region. Rather, the bare area generally assumes a bow-tie configuration, rendering the conventional definition of its width along the sagittal plane inadequate and potentially misleading. Based on the typical position of the bare area, we can propose that when the precise morphology and position of a patient's bare area are unknown, targeting this region via an osteotomy from the proximal ulna's narrowest segment provides an effective approach., (Copyright © 2025. Published by Elsevier Inc.)

This study examined the effects of different fatigue types on action anticipation and physical performance in high-level volleyball players. Twenty-four participants underwent four counterbalanced conditions: 60-min cycling at 60% peak power output, 60-min Stroop task, 60-min cycling at 60% peak power output with Stroop task and 60-min neutral documentary to induce physical fatigue (PF), mental fatigue (MF), dual fatigue (DF) and control group (CG), respectively. Action anticipation (anticipation test and visual search test) and physical performance (countermovement jump, T-test, and spike test) were conducted at baseline, immediately after (Post1), and after 10-min rest (Post2). DF and PF led to significantly lower jump height, T-test completion time, and spiking speed at Post1 and Post2 compared with CG and MF. Compared with PF, DF led to a significant decline in jumping, agility, and spiking performance at Post1 and decreased jumping performance at Post2. MF significantly decreased the reaction time of anticipation test at Post1 compared with CG. Reaction times of visual search test were significantly lower in DF and MF at Post2 compared with CG. It is suggested that PF decreased physical performance, and this is exacerbated in DF. Anticipation performance was affected by MF but not by DF and PF.

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.e., 64.3%) is achieved. Moreover, 5 of the 14 evaluable subjects exhibited partial responses (overall response rate = 35.7%). The combination of anti-PD1 antibody and anti-hormone therapy is associated with an enhanced immunoreactive microenvironment influencing treatment efficacy, as observed in pre- and post-treatment tumor samples through NanoString analysis. Post-treatment tumors are associated with increased immune response and immune cells. The findings indicate that combining HT with anti-PD1 antibody is a promising treatment strategy for patients with premenopausal ER+/HER2- MBC. This study was registered at ClinicalTrials.gov (NCT02990845)., Competing Interests: Declaration of interests I.-C.C. received honoraria from AstraZeneca, Daiichi Sankyo, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, and Sanofi and received research grants from AstraZeneca, Merck Sharp & Dohme, and Novartis. D.-Y.C. received honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, MSD, Novartis, ONO Pharma, Pierre Faber, Pfizer, Roche, Sanofi, and TTY Biopharm. T.W.-W.C. received honoraria from Roche, Novartis, Eli Lilly, Eisai, Pfizer, Daiichi Sankyo, and AstraZeneca. Y.-S.L. received honoraria from Merck Sharp & Dohme and Pfizer and received research grants from Merck Sharp & Dohme and Pfizer., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Transition metal phosphides (TMPs) show promise in water electrolysis due to their electronic structures, which activate hydrogen/oxygen reaction intermediates. However, TMPs face limitations in catalytic efficiency due to insufficient active sites, poor conductivity, and multiple intermediate steps in water electrolysis. Here, we synthesize a highly efficient bifunctional self-supported electrocatalyst, which consists of an N-doped carbon shell anchored on Fe-doped CoP/Co 2 P arrays on nickel foam (NC@Fe-Co x P/NF) using hydrothermal and phosphorization techniques. Experimental and theoretical results indicate that the modified morphology, with increased active site density and a tunable electronic structure induced by Fe doping in the CoP/Co 2 P heterostructure, leads to superior water electrolysis performance. The resulting NC@Fe 0.1 -CoP/Co 2 P/NF catalyst exhibits overpotentials of 122 mV for the hydrogen evolution reaction (HER) and 270 mV for the oxygen evolution reaction (OER) at 100 mA cm -2 . Furthermore, using NC@Fe 0.1 -CoP/Co 2 P/NF as both the cathode and anode in an alkaline electrolyzer enables the cell system to achieve 100 mA cm -2 at a voltage of 1.70 V, while maintaining long-term catalytic durability. This work may pave the way for designing self-supported, highly efficient electrocatalysts for practical water electrolysis applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cardiac fibrosis characterized by aberrant activation of cardiac fibroblasts impairs cardiac contractile and diastolic functions, inducing the progression of the disease towards its terminal phase, resulting in the onset of heart failure. Therefore, the inhibition of cardiac fibrosis has become a promising treatment for cardiac diseases. The ovarian follicle-stimulating hormone folliculin (FLCN) plays a significant role in various biological processes, such as lysosome function, mitochondrial synthesis, angiogenesis, ciliogenesis and autophagy. Severe heart failure was observed in FLCN knockout mice. In this study, we investigated the role of FLCN in cardiac fibrosis and its potential mechanisms. The mice were subjected to transverse aortic constriction (TAC) surgery. Myocardial fibrosis developed in the mice 8 weeks after surgery. We showed that the protein and mRNA expression levels of FLCN were significantly decreased in TAC mice. Similar results were observed in primary mouse cardiac fibroblasts treated with Ang-II, an in vitro cardiac fibrosis model, suggesting that FLCN is involved in the pathological process of cardiac fibrosis. We demonstrated that overexpression of FLCN inhibited lysosome function in cardiac fibroblasts. Furthermore, overexpression of FLCN protected the heart from TAC-induced pathological cardiac fibrosis. We revealed that FLCN bound to the cPLA2 protein, increased its activity, regulated lysosomal function, and promoted membrane permeabilisation in cardiac fibroblasts during cardiac fibrosis. Knockdown of cPLA2 blocked the antifibrotic effect of FLCN in cardiac fibrosis. In addition, we found that the reduced expression of FLCN in cardiac fibrosis resulted from the modulation of YTHDF3-regulated m 6 A methylation of FLCN mRNA. The overexpression of YTHDF3 alleviated the production of collagens and improved cardiac structure and function in TAC mice. YTHDF3 inhibited proliferation and differentiation and regulated lysosomal function in mouse cardiac fibroblasts, whereas these effects were abolished by FLCN knockdown. We conclude that FLCN undergoes YTHDF3-regulated m 6 A modification and interacts with cPLA2 to improve lysosomal function in cardiac fibroblasts, highlighting its role in myocardial fibrosis therapy. These results suggest that FLCN and YTHDF3 could serve as potential therapeutic targets for cardiac fibroblast treatment., Competing Interests: Competing interests: The authors declare no competing interests. Ethics: This study was carried out in accordance with the recommendations of regulations of the experimental animal ethics committee of Guangdong Pharmaceutical University. The protocol was approved by the experimental animal ethics committee of Guangdong Pharmaceutical University., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Recent studies suggest that the anterior limb of the internal capsule may be an area of convergence for multiple compulsion loops. In this study, the role of different dopaminergic compulsion loops in the mechanism of obsessive-compulsive disorder (OCD) was investigated by selectively damaging dopaminergic neurons or fibers in the corresponding targets with 6-hydroxydopamine (6-OHDA) and depicting the anatomical map of various compulsion loops located in the anterior limb of the internal capsule., Methods: A total of 52 male Sprague Dawley (SD) rats were exposed to either saline (1 mL/kg, NS group, n = 6) or quinpirole (QNP, dopamine D2-agonist, 0.5 mg/kg, n = 46) twice weekly for 5 weeks. After each injection, the rats were placed on an open field to analyze aspects of their behaviour, including the number of home base visits (NOH), average time between each home base visit (ATBO), and total distance travelled (TDM). After model setup, 46 QNP rats were divided randomly into five groups: 6-OHDA anterior limb of internal capsule (AC) stereotactic injection group (QNP+AC group, n = 10), 6-OHDA mediodorsal thalamic nucleus (MD) stereotactic injection group (QNP+MD group, n = 10), 6-OHDA nucleus accumbens (NAC) stereotactic injection group (QNP+NAC group, n = 10), saline stereotactic injection group (QNP+NS-S group, n = 10), and non-surgical group (QNP+Non-S group, n = 6). In the NS group, rats simultaneously received a 6-OHDA stereotactic injection (NS+6-OHDA-S group, n = 6: AC2, MD2, NAC2). All QNP-treated rats were then continued to be given QNP twice a week for 4 weeks, and their behaviour was observed after each infusion. After 4 weeks, immunofluorescence staining was used to monitor the distribution of dopamine neurons and nerve fibers in different areas of the intervention nerve loops, and quantitative analysis was performed., Results: Compulsive behaviour declined gradually in the QNP+AC and QNP+NAC groups 3 and 4 weeks after surgery, with the QNP+AC group decreasing more rapidly. The QNP+MD group had decreased by 3 weeks after surgery but increased to almost the same level as pre-surgery at 4 weeks post-surgery. Postoperative fluorescence staining and quantitative analysis suggested the number of dopamine (DA) neurons or nerve fibers in the corresponding target area of the 6-OHDA injection were significantly reduced compared with the QNP+Non-S group., Conclusions: 6-OHDA selectively damages the targets of dopaminergic neurons or nerve fibers within the OCD loop, which somewhat alleviates compulsive behaviours. The results suggest that the AC might be the best target for therapeutic interventions for OCD., (© 2025 The Author(s). Published by IMR Press.)

Purpose: To analyze dynamic and static changes in the disc-condyle relationship in patients with skeletal Class III malocclusion after orthognathic surgery., Methods: The surgical group comprised 30 patients with skeletal Class III malocclusion, and the magnetic resonance imaging and mandibular movement data were obtained at T0 (preoperatively), T1 (3 months postoperatively), and T2 (at the end of orthodontic treatment). The control group included 20 patients with normal occlusion, and the mandibular movement data were recorded., Results: The maximum mouth opening at T1 decreased compared with that at T0 and recovered close to the preoperative level at T2. The marginal movement of the mandible at T1 decreased compared with that at T0 (P > 0.05), among which the movement distances of the condyles during mouth opening and closing decreased significantly compared with those at T0(P < 0.05). Following postoperative orthodontics in patients with skeletal Class III malocclusion, RET-L was significantly lower than that in the control group(P < 0.05).Regarding the temporomandibular joint of ADDwR, the CPL at T1 decreased significantly compared with that at T0(P < 0.05). At T2, the LPM, LLM, and CPL increased significantly compared with those at T1(P < 0.05), and the LPM and LLM levels at T2 exceeded those at T0 significantly (P < 0.05)., Conclusions: In the short term, after orthognathic surgery, the marginal movement of the mandible showed a certain degree of decline; however, in the long term, it recovered or even exceeded the preoperative level. Orthognathic surgery results in a particularly significant improvement in the functional movement of the ADDwR joint. In addition, it improves TMD in patients with skeletal Class III malocclusion and has a positive effect on improving the position of the joint disc position., Competing Interests: Declaration of competing interest All authors report no conflicts of interest., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO&#95;4·2H&#95;2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO&#95;4·2H&#95;2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO&#95;4·2H&#95;2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO&#95;4·2H&#95;2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO&#95;4·2H&#95;2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO&#95;4·2H&#95;2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO&#95;4·2H&#95;2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO&#95;4·2H&#95;2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO&#95;4·2H&#95;2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO&#95;4·2H&#95;2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO&#95;4·2H&#95;2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO&#95;4·2H&#95;2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO&#95;4·2H&#95;2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.

Fabricating transition metal selenide (TMSe) anode materials with rapid K + diffusion and high-rate performance is crucial for the advancement of potassium-ion batteries (PIBs), yet it remains a challenge. In this study, a Cu 2+ -doped Co 0.85 Se@N-doped carbon anode with an optimal concentration of Cu 2+ -doped and yolk-shell structure (denoted as Cu-Co 0.85 Se@NC-2) is developed to enhance the reaction kinetics and cycling life. The Cu 2+ -doped modulates the electronic structure of the Co 0.85 Se interface, improves the diffusion and adsorption of K + , and further promotes the charge transport efficiency, as demonstrated by theoretical calculations and experimental results. In addition, an optimal Cu 2+ -doped content is identified that is conducive to achieving the best structure and electrochemical performance. Moreover, the N-doped carbon shell effectively enhances the conductivity of the electrode and alleviates the volume change of Co 0.85 Se yolk during cycling. Benefiting from the above advantages, the obtained Cu-Co 0.85 Se@NC-2 anode exhibits excellent rate performance (208.1 mA h g -1 at 10 A g -1 ) and cycling stability (239.7 mA h g -1 at 2 A g -1 after 500 cycles, the capacity retention rate is up to 80.4%). This work integrates nanostructure engineering and ion-doped to provide a straightforward and effective strategy for designing advanced high-rate TMSe anodes for next-generation PIBs., (© 2024 Wiley‐VCH GmbH.)

The photocatalytic reduction of CO 2 into valuable chemicals and fuels has become a significant research focus in recent years due to its environmental sustainability and energy efficiency. Metal halide perovskites (MHPs), renowned for their remarkable optoelectronic properties and tunable structures, are regarded as promising photocatalysts. Yet, their practical uses are constrained by inherent instability, severe electron-hole recombination, and a scarcity of active sites, prompting substantial research efforts to optimize MHP-based photocatalysts. This review summarizes the latest advancements in MHP-based photocatalysis. First the fundamental principles of photocatalysis are outlined and the structural and optical characteristics of MHPs are evaluated. Then key strategies for enhancing MHP photocatalysts, including morphology and surface modification, encapsulation, metal cation doping, heterojunction engineering, and molecular immobilization are highlighted. Finally, considering recent research progress and the needs for industrial application, challenges and future prospects are explored. This review aims to support researchers in the development of more efficient and stable MHP-based photocatalysts., (© 2024 Wiley‐VCH GmbH.)

The vascularized iliac crest flap has garnered widespread acclaim within the field of mandibular reconstruction attributable to its sufficient bone mass and congruent curved morphology. However, when the precise orientation of the iliac crest is imperative during mandibular reconstruction and there exists an accompanying defect within the oral soft tissue, the indispensability of an additional flap to facilitate concurrent defect repair becomes evident. In such instances, the submental island flap emerges as an exemplary candidate., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Carbonates are ideal birefringent materials because their π-conjugated [CO 3 ] groups are beneficial for large anisotropy. How to maximize the birefringence and maintain a wide transmittance simultaneously in carbonates is a great challenge. Adopting a multiple-functional group synergy strategy by combining alkaline-earth metal Ba 2+ with large ion radius, PbO 6 F distorted hexagonal pyramid, and paralleled π-conjugated CO 3 triangles together, we synthesized a new metal carbonate crystal, BaPb 2 (CO 3 ) 2 F 2 . BaPb 2 (CO 3 ) 2 F 2 features a typical two-dimensional layered structure, which consists of a PbCO 3 F monolayer parallel to the ab plane and Ba 2+ cations filled between the monolayers. BaPb 2 (CO 3 ) 2 F 2 exhibits a large experimental birefringence of approximately 0.245@546 nm and a short ultraviolet absorption edge down to 264 nm (Eg = 4.70 eV), indicating that it is a promising ultraviolet birefringent material. The reported highest experimental birefringence index among carbonate crystals is surpassed by BaPb 2 (CO 3 ) 2 F 2 . The theoretical calculation shows that the contribution percentages for total birefringence are 57 and 43% for the CO 3 group and PbO 3 F group, respectively. Our work offers a new route for designing new birefringent materials with excellent comprehensive performance.

Oral diseases not only greatly impact patients' daily lives, but also pose a severe threat to their overall health. Due to the constant exposure of saliva to oral diseases, the former plays a vital role in their diagnosis and monitoring. Exosomes, nanosized bilayer lipid encapsulated nanovesicles, are widely present in saliva and can be released by any type of cell. Exosomes inherit features from their mother cells in both physiological and pathological conditions. The molecular characteristics and expression levels of exosomes depend on their cellular origin, and they can directly reflect the physiological state of the body and cells. This makes salivary exosomes a promising source for early detection and monitoring of oral diseases. As a result, researchers have been exploring the potential use of exosomes as biomarkers for diagnosing and predicting various oral diseases. This review provides an overview of the composition, separation and function of salivary exosomes. It also discusses their potential as diagnostic and prognostic markers for several oral diseases, including periodontitis, primary Sjögren's syndrome, oral mucosal diseases, hand-foot-mouth disease and oral squamous cell carcinoma. By studying salivary exosomes, researchers hope to improve the early detection and monitoring of oral diseases, leading to better outcomes for patients.

This study provides a practical route to synthesize tetrasubstituted alkenes that involves Co(III)-catalyzed C-H bond activation and regioselective insertion of the alkyne, followed by chelation of the substrate hydroxyl to Co and migration of the pyridine group. Density functional theory studies revealed the origin of regioselectivity and elucidated the crucial role of the hydroxyl group for the migration of pyridine. The method can be conducted on a gram scale, is compatible with a wide range of substrates, and has a high functional group tolerance. To demonstrate its significance, the method was used for the late-stage modification of Fasudil. Furthermore, the synthetic significance of the method was demonstrated by the various derivatizations of the products, many of which exhibit intriguing fluorescence characteristics.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen in pigs. This study aimed to investigate the impact of PRRSV infection on cellular metabolism, particularly focusing on lipid metabolism to understand its role in promoting viral replication. We conducted a metabolic analysis on MARC-145 cells before and after PRRSV infection. Our results demonstrated that the most significant alterations in cellular metabolism, accounting for 40.8 % of total changes, were related to lipid metabolism. These changes were primarily driven by the activation of sterol regulatory-element binding proteins (SREBPs), critical regulators of lipid biosynthesis. To understand the mechanisms behind SREBPs activation by PRRSV, we investigated the involvement of upstream effectors, specifically protein kinase B (AKT) and phosphoenolpyruvate carboxykinase 1 (PCK1). Our findings indicated that PRRSV infection triggered AKT activation, leading to the subsequent activation of PCK1. Activated PCK1 then phosphorylated insulin-induced genes (INSIGs), resulting in their degradation. This degradation facilitated the translocation of SREBPs from the endoplasmic reticulum to the nucleus. Additionally, we observed that PRRSV infection stimulated the production of reactive oxygen species (ROS), which played a critical role in activating AKT. Collectively, our findings demonstrate that PRRSV enhances lipid synthesis through a ROS-dependent AKT/PCK1/INSIG/SREBPs signaling axis, which provides new insights into the metabolic strategies employed by PRRSV., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Apparently, the genomes of many organisms are pervasively transcribed, and long noncoding RNAs (lncRNAs) make up the majority of cellular transcripts. LncRNAs have been reported to play important roles in many biological processes; however, their effects on locomotion are poorly understood. Here, we presented a novel lncRNA, Locomotion Regulatory Gene (LRG), which participates in locomotion by sequestering Synaptotagmin 1 (SYT1). LRG deficiency resulted in higher locomotion speed which could be rescued by pan-neuronal overexpression but not by limited ellipsoid body, motoneuron or muscle-expression of LRG. At the molecular level, the synaptic vesicles (SVs) release and movement-related SYT1 protein was recognized as LRG-interacting protein candidate. Furthermore, LRG had no effects on SYT1 expression. Genetically, the behavioral defects in LRG mutant could be rescued by pan-neuronal knock-down of Syt1. Taken together, all the results suggested LRG exerts regulatory effects on locomotion via sequestering SYT1 thereby blocking its function without affecting its expression. Our work displays a new function of lncRNA and provides insights for revealing the pathogenesis of neurological diseases with motor disorders., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Background: Emergence delirium (ED) is a common postoperative cognitive dysfunction in children. ED may cause distress to patients and their families in the early post-anesthesia period and have long-term adverse effects on children. THE PRIMARY PURPOSE: was to verify whether dexmedetomidine can reduce the occurrence of ED in children., Research Type: Systematic review and meta-analysis of RCTs., Data Acquisition: A search was conducted on Web of Science, WHO Trials, Cochrane Library, Clinical Trials.gov, and PubMed for all published studies from inception to 23 Oct. 2022., Eligibility Criteria: Randomized clinical trials that met the following criteria: patients aged 1-18 years, study site in the PACU (Post-anesthesia care unit), incidence of ED as the primary outcome, and prophylactic use of dexmedetomidine defined as injected before admission to the PACU., Results: A total of 7 randomized trials were included (6 studies during eye and neck surgery, 1 during hernia surgery), involving 512 patients (257 (50.1%) with dexmedetomidine, and 250 (49.9%) with control. ED was observed in 17.51% of the patients treated with dexmedetomidine and in 43.14% of those receiving control (risk ratio (RR) = 0.40, 95 % confidence interval [CI] [0.30-0.55], P < 0.00001). Additionally, the prophylactic application of dexmedetomidine also reduced the occurrence of Post-Operating Nausea and Vomiting (RR = 0.24, 95%CI [0.12-0.49], P = 0.0001) and PACU stay time after extubation (mean difference (MD) = -1.57, 95%CI [-3.07 to -0.07], P = 0.04). However, sensitivity analysis of RCTs showed that our effect estimates were not stable (MD = -1.78, 95%CI [-4.18-0.62], P = 0.15)., Conclusion: The prophylactic use of dexmedetomidine was associated with a reduction of ED. However, our findings only apply to eye and neck surgery., Trial Registration: PROSPERO: CRD42022371840., (Copyright © 2024. Published by Elsevier Masson SAS.)

The exploration of chemical space holds promise for developing influential chemical entities. Molecular representations, which reflect features of molecular structure in silico, assist in navigating chemical space appropriately. Unlike atom-level molecular representations, such as SMILES and atom graph, which can sometimes lead to confusing interpretations about chemical substructures, substructure-level molecular representations encode important substructures into molecular features; they not only provide more information for predicting molecular properties and drug‒drug interactions but also help to interpret the correlations between molecular properties and substructures. However, it remains challenging to represent the entire molecular structure both intactly and simply with substructure-level molecular representations. In this study, we developed a novel substructure-level molecular representation and named it a group graph. The group graph offers three advantages: (a) the substructure of the group graph reflects the diversity and consistency of different molecular datasets; (b) the group graph retains molecular structural features with minimal information loss because the graph isomorphism network (GIN) of the group graph performs well in molecular properties and drug‒drug interactions prediction, showing higher accuracy and efficiency than the model of other molecular graphs, even without any pretraining; and (c) the molecular property may change when the substructure is substituted with another of differing importance in group graph, facilitating the detection of activity cliffs. In addition, we successfully predicted structural modifications to improve blood‒brain barrier permeability (BBBP) via the GIN of group graph. Therefore, the group graph takes advantages for simultaneously representing molecular local characteristics and global features.Scientific contribution The group graph, as a substructure-level molecular representation, has the ability to retain molecular structural features with minimal information loss. As a result, it shows superior performance in predicting molecular properties and drug‒drug interactions with enhanced efficiency and interpretability., Competing Interests: Declarations. Ethics, consent to participate, and consent to publish declarations: Not applicable. Competing interests: The author declares no competing interests., (© 2024. The Author(s).)

Background: Past research has highlighted that bipolar I disorder is associated with significant changes in brain structure and function. Notably, the manifestation and progression of bipolar I disorder have been known to differ between males and females. However, the relationship between sex-related differences and bipolar I disorder diagnosis affecting these changes was not fully understood. This study aimed to investigate the sex-by-diagnosis interactions concerning the structural and functional features of the brain in individuals with bipolar I disorder., Methods: Both structural and functional MRI data were obtained from 105 individuals with bipolar I disorder (36 males and 69 females) and 210 healthy controls (72 males and 138 females). Voxel-wise analyses of gray matter volume and functional connectivity were conducted using a general linear regression model. This model included age, sex, diagnosis, and a sex-by-diagnosis interaction as predictors to explore potential sex-related differences in the brain features of participants with bipolar I disorder., Results: The gray matter volume analysis revealed significant sex-by-diagnosis interactions in six brain regions: the left caudate (p < 0.001), left thalamus (p < 0.001), right caudate (p = 0.003), right thalamus (p < 0.001), left anterior cingulate gyrus (p = 0.022), and left middle/posterior cingulate gyrus (p = 0.015). Using these regions as seeds, we detected a significant sex-by-diagnosis interaction in the functional connectivity alteration between the left thalamus and right angular gyrus (p = 0.019)., Conclusions: Our findings revealed a noteworthy sex-by-diagnosis interaction, with male individuals with bipolar I disorder displaying larger gray matter volume and altered functional connectivity in the limbic system compared to female individuals with bipolar I disorder and healthy participants. These results hint at potential sex-related differences in the pathophysiology of the limbic system in bipolar I disorder, which may have significant implications for understanding the underlying mechanisms in bipolar I disorder. Our findings could contribute to developing more personalized treatment approaches for individuals with bipolar I disorder., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Taipei Veterans General Hospital and National Yang Ming Chiao Tung University. All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Leptospirosis, a re-emerging zoonotic disease caused by Leptospira spp., poses significant global health and veterinary challenges. Long-term colonization of renal tubules by Leptospira in asymptomatic hosts highlights the need for sensitive detection methods. This study evaluates the chronic or latent Leptospira infections in kidneys using a novel molecular approach to examine individual immune responses differences. Digital PCR strategies employing newly developed primer-probe sets targeting the flagellar fliG gene were used to assess the presence of trace Leptospira in infected murine kidneys and urine samples from laboratory-confirmed leptospirosis patients. RNA-based digital PCR detected leptospires in 58 % (targeting lipl32 ) and 83 % (targeting fliG ) of infected kidneys, demonstrating that the digital PCR strategy targeting the fliG gene offers superior sensitivity. Notably, the newly developed fliG -targeting assay detected as low as 20 fg of Leptospira DNA, offering ten-fold greater sensitivity than traditional qPCR for trace detection. This allows for differential detection of Leptospira species and facilitates monitoring of extremely low bacterial loads with greater sensitivity than conventional methods. We also observed regenerating renal tubules with mitosis and elevated cytokine expression in kidneys with transcriptionally active Leptospira during chronic infection. This approach aids in identifying latent infections and offers insights into individual variations. Our research provides a powerful molecular tool for epidemiological studies and public health surveillance, contributing valuable insights into the prevalence and transmission dynamics of this pervasive zoonotic disease., Competing Interests: L.-F. C., P.-Y. H. and C.-W. Y. are inventors (Kidney Research Center, Chang Gung Memorial Hospital) on a patent for “Innovative method for nucleic acid detection tracking minute quantities of Leptospira spp. in biological tissues and environmental samples” (US Provisional Patent Application 63/605,750, filed 4 December 2023). The remaining authors declare no competing interests., (© 2024 The Author(s).)

Obsessional slowness (OS) is characterized by a syndrome of extreme slowness in doing ordinary, day-to-day activities. Several scholars regarded OS as secondary to obsessive compulsive disorder (OCD). Therefore, it is commonly thought to be the consequence of extensive rituals and has been paid minimal attention in its own right. A combination of behavior therapy and aromatherapy are recommended for treatment of this condition. However, the outcome is often frustrating. Reports of surgical management for OS are limited., Patient Concerns: She had symptoms characterized by repeated checking and progressive slowness in self-care behavior., Diagnosis: At the age of 19, the patient had the first presentation. The patient was diagnosed with a case of OCD with obsessional slowness according to the International Classification of Diseases and Related Health Problems (ICD-10)., Interventions: Considering the lack of a response to pharmacotherapy and cognitive behavioral therapy (CBT), we treated this case with anterior capsulotomy and accumbensotomy., Outcomes: Moderate somnolence, urticaria, juvenile behavior, mild short-term memory impairment and slight nonsense were noted during the first postoperative days. At 10 months, the patient's OCD symptoms recovered nearly to her preoperative level. The OS symptom also had an obvious rebound at 10 months. Through comprehensive judgment, we decided to choose accumbensotomy. At 9 months after the accumbensotomy, the OCD symptoms started to rebound. Soon after, the OS symptoms also recurred. At the last timepoint of 30 months, the patient's OCD and OS symptoms had completely rebounded. This time, the patient and parents refused any treatment., Conclusion: This case suggests that OCD with OS, as a special category, might not be suitable for stereotactic neurosurgery. Furthermore, multiple surgeries in this kind of OCD patient should be considered with as much caution as much as possible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lai, Pang, Ming, He, Xiong, You, Chen and Gong.)

Multiresonance thermally activated delayed fluorescence (MR-TADF) materials have attracted widespread attention due to ultrahigh definition display standards. However, many MR-TADF materials lack TADF properties in both the solution and solid states. Interestingly, the TADF characteristics appear once these MR-TADF compounds are doped in a suitable host film, but the precise mechanism involved in the host-guest interaction remains uncertain. Herein, we systematically investigated the role of host-guest interactions employing doped films ( DABNA-1@mCBP and DABNA-1@DPEPO ) with opposite phenomena. The results indicate that mCBP with a V-shape and enhanced rigidity could facilitate the formation of an energy spacing layer by employing short-range Coulomb energy through the MR luminescent core, which could offset the sensitivity of the stacking distance, enhancing the coupling between T 1 and T 2 , and thus switch the reverse internal conversion and the higher T 2 reverse intersystem crossing process. This work is a further development of luminescence mechanisms and an update of the host-guest interaction criteria for the targeted design of doped films.

Oxychalcogenides are receiving increasing interest as nonlinear-optical (NLO) materials because of the possible combination of advantages from oxides and chalcogenides. Here, two new pentanary oxythiogermanates Eu 2 MGe 2 OS 6 [M = Zn ( 1 ), Cd ( 2 )] were obtained by the facile metal oxide-boron-sulfur solid-state route. They crystallize with a melilite-type structure and feature {[MGe 2 OS 6 ] 4- } ∞ layers built by Ge 2 OS 6 dimers and MS 4 tetrahedra. Their optical band gaps are 2.37 and 2.38 eV. As the first NLO rare-earth (RE)/d 10 dual-metal oxychalcogenides, they exhibit phase-matchable NLO responses and enhanced laser-induced damage thresholds. Theoretical calculations show that the NLO responses are predominantly contributed by the EuOS 7 motifs. This work provides the potential of RE/d 10 dual-metal-based NLO materials.

The chemistry of the Meisenheimer complexes is of fundamental interest in organic chemistry. While the nitro group has been extensively employed to facilitate the formation and stabilization of Meisenheimer complexes, the analogous application of more user-friendly ester groups has remained an unexplored frontier. Herein, we report ester-stabilized Meisenheimer complexes, which have remarkable air-, moisture-, and thermo-stability. Moreover, the isolable and well-defined Meisenheimer intermediates exhibit divergent reactivity for dearomatization reactions, including modular 1,4-additions, dearomative (2 + 3) cycloadditions, and even higher-order (4 + n ) cycloadditions. These methodologies enabled rapid access to complicated cyclohexane derivatives with multiple all-carbon quaternary centers and interesting structure topologies.

Iron nitrides with the merits of high theoretical capacities, cost-effectiveness, and good electronic/ionic conductivity have been recognized as attractive anode candidates for lithium-ion batteries (LIBs). Carbon compositing, pore engineering, and nanostructure construction have proved to be effective strategies to prepare high-performance metal nitride anodes for LIBs. Herein, we synthesized a series of Fe 3 N-embedded and N-doped carbon nanorods (Fe 3 N@NCNR) with a hierarchical porous system and controllable topography by metal-catalyzed graphitization-nitridization of the Fe(III)-triazole framework (Fe-MOF) and thermal evaporation of the triblock copolymer F127 template assembled in Fe-MOF via hydrogen bonding interaction, followed by the air oxidation and urea-assisted ammonolysis processes. The Fe 3 N@NCNR as anodes for LIBs display extraordinary lithium storage capabilities with a high reversible capacity of 830 mA h g -1 at 0.1 C, a good rate performance of 576 mAh g -1 at 5 C, and a long-term cycling stability of 742 mA h g -1 over 600 cycles at 1 C. Such outstanding performance benefits from the spongy carbon nanorods with rich macropores for rapid electronic/ionic transport and effective accommodation of electrode volume expansion, abundant N-doped meso-/microporous carbon for the additional storage of Li + via capacitive effect, and the efficient utilization of Fe 3 N nanoparticles uniformly distributed through carbon nanorods. Importantly, this work introduces an effective strategy to construct superior performance nitride anodes from MOF surfactants based on hydrogen bonding-driven interface self-assembly and provides insight into the preparation of highly efficient nanoarchitectures for Li + storage.

The chiral recognition and separation of enantiomers are of great importance for biological research and the pharmaceutical industry. Preparing homochiral materials with adjustable size and chiral binding sites is beneficial for achieving an efficient chiral recognition performance. Here, a homochiral covalent organic framework membrane modified with β-cyclodextrin (CD-COF) was constructed, which was subsequently utilized as an electrochemical sensor for the enantioselective sensing of tryptophan (Trp) molecules. The preferential adsorption of l-Trp over d-Trp at the β-CD sites can enhance the surface charge density and hydrophilicity of the CD-COF membrane, resulting in an increased transmembrane ionic current. Trp enantiomers with concentrations down to 0.28 nM can be effectively discriminated. The l-/d-Trp recognition selectivity increases with the Trp concentration and reaches a value of 19.2 at 1 mM. The selective adsorption of l-Trp to the CD-COF membrane will also hinder its transport, resulting in a l-/d-Trp permeation selectivity of 15.3. This study offers a new strategy to construct homochiral porous membranes and achieve efficient chiral sensing and separation.

Thylakoid-free cyanobacteria are thought to preserve ancestral traits of early-evolving organisms capable of oxygenic photosynthesis. However, and until recently, photosynthesis studies in thylakoid-free cyanobacteria were only possible in the model strain Gloeobacter violaceus . Here, we report the isolation, biochemical characterization, cryo-EM structure, and phylogenetic analysis of photosystem I from a newly-discovered thylakoid-free cyanobacterium, Anthocerotibacter panamensis , a distant relative of the genus Gloeobacter . We find that A. panamensis photosystem I exhibits a distinct carotenoid composition and has one conserved low-energy chlorophyll site, which was lost in G. violaceus . These features explain the capacity of A. panamensis to grow under high light intensity, unlike other Gloeobacteria. Furthermore, we find that, while at the sequence level photosystem I in thylakoid-free cyanobacteria has changed to a degree comparable to that of other strains, its subunit composition and oligomeric form might be identical to that of the most recent common ancestor of cyanobacteria., Competing Interests: Competing interests: Authors declare that they have no competing interests.

Vanadium (V)-based oxides have garnered significant attention as cathode materials for aqueous zinc-ion batteries (AZIBs) due to their multiple valences and high theoretical capacity. However, their sluggish kinetics and low conductivity remain major obstacles to practical applications. In this study, Mo-doped V 2 O 3 with oxygen vacancies (OVs, Mo-V 2 O 3-x @NC) is prepared from a Mo-doped V-metal organic framework. Ex situ characterizations reveal that the cathode undergoes an irreversible phase transformation from Mo-V 2 O 3-x to Mo-V 2 O 5-x ·nH 2 O and serves as an active material exhibiting excellent Zn 2+ storage in subsequent charge-discharge cycles. Mo-doped helps to further improve cycling stability and increases with increasing content. More importantly, the synergistic effect of Mo-doped and OVs not only effectively reduces the Zn 2+ migration energy barrier, but also enhances reaction kinetics, and electrochemical performance. Consequently, the cathode demonstrates ultrafast electrochemical kinetics, showing a superior rate performance (190.9 mAh g -1 at 20 A g -1 ) and excellent long-term cycling stability (147.9 mAh g -1 at 20 A g -1 after 10000 cycles). Furthermore, the assembled pouch cell exhibits excellent cycling stability (313.6 mAh g -1 at 1 A g -1 after 1000 cycles), indicating promising application prospects. This work presents an effective strategy for designing and fabricating metal and OVs co-doped cathodes for high-performance AZIBs., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

The aesthetic demand has become an imperative challenge to advance the practical and commercial application of daytime radiative cooling technology toward mitigating climate change. Meanwhile, the application of radiative cooling materials usually focuses on the building surface, related tightly to fire safety. Herein, the absorption and reflection spectra of organic and inorganic colorants are first compared in solar waveband, finding that iron oxides have higher reflectivity in NIR region. Second, three kinds of iron oxides-based colorants are selected to combine porous structure and silicon-modified ammonium polyphosphate (Si-APP) to engineer colored polyurethane-based (PU) coating, thus enhancing the reflectivity and flame retardancy. Together with reflectivity of more than 90% in near-infrared waveband and infrared emissivity of ≈91%, average temperature drops of ≈5.7, ≈7.9, and ≈3.8 °C are achieved in porous PU/Fe 2 O 3 /Si-APP, porous PU/Fe 2 O 3 ·H 2 O/Si-APP, and porous PU/Fe 3 O 4 ·H 2 O/Si-APP, compared with dense control samples. The catalysis effect of iron oxides in the cross-linking reaction of pyrolysis products and dehydration mechanism of Si-APP enable PU coating to produce an intumescent and protective char residue. Consequently, PU composite coatings demonstrate desirable fire safety. The ingenious choice of colorants effectively minimizes the solar heating effect and trades off the daytime radiative cooling and aesthetic appearance requirement., (© 2024 Wiley‐VCH GmbH.)

Purpose: In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk., Methods: We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer., Results: Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1&#95;rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001)., Conclusion: APEX1&#95;rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microprocessor is an essential nuclear complex responsible for the initial RNase-mediated cleavage of primary miRNA, which is a tightly controlled maturation process that requires the proper assembly of Drosha and DGCR8. Unlike previously identified mechanisms directly targeting the enzymatic subunit Drosha, current knowledge about the biological ways of controlling miRNA nuclear maturation through DGCR8 is less addressed. In this study, we unveiled that the microprocessor assembly is governed by a master gene regulator HIF-1α irrespective of its canonical transcriptional activity. First, a widespread protein binding of HIF-1α with DGCR8 instead of Drosha was observed in response to biological stimulations. Similar protein interactions between their corresponding orthologues in model organisms were also observed. After dissecting the essential protein domains, we noticed that HIF-1α suppresses microprocessor assembly via binding to DGCR8. Furthermore, our results showed that HIF-1α hijacks monomeric DGCR8 thus reducing its dimer formation prior to microprocessor assembly, and consequently, the suppressed microprocessor formation and nuclear processing of primary miRNA were demonstrated. In conclusion, here we unveiled the mechanism of how microprocessor assembly is regulated by HIF-1α, which not only demonstrates a non-transcriptional function of nuclear HIF-1α but also provides new molecular insights into the regulation of microprocessor assembly through DGCR8., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Alkali-activated concrete (AAC), produced from industrial by-products like fly ash and slag, offers a promising alternative to traditional Portland cement concrete by significantly reducing carbon emissions. Yet, the inherent variability in AAC formulations presents a challenge for accurately predicting its compressive strength using conventional approaches. To address this, we leverage machine learning (ML) techniques, which enable more precise strength predictions based on a combination of material properties and cement mix design parameters. In this study, we curated an extensive dataset comprising 1756 unique AAC mixtures to support robust ML-based modeling. Four distinct input variable schemes were devised to identify the optimal predictor set, and a comparative analysis was performed to evaluate their effectiveness. After this, we investigated the performance of several popular ML algorithms, including random forest (RF), adaptive boosting (AdaBoost), gradient boosting regression trees (GBRTs), and extreme gradient boosting (XGBoost). Among these, the XGBoost model consistently outperformed its counterparts. To further enhance the predictive accuracy of the XGBoost model, we applied four state-of-the-art optimization techniques: the Gray Wolf Optimizer (GWO), Whale Optimization Algorithm (WOA), beetle antennae search (BAS), and Bayesian optimization (BO). The optimized XGBoost model delivered superior performance, achieving a remarkable coefficient of determination (R 2 ) of 0.99 on the training set and 0.94 across the entire dataset. Finally, we employed SHapely Additive exPlanations (SHAP) to imbue the optimized model with interpretability, enabling deeper insights into the complex relationships governing AAC formulations. Through the lens of ML, we highlight the benefits of the multi-faceted synergistic approach for AAC strength prediction, which combines careful input parameter selection, optimal hyperparameter tuning, and enhanced model interpretability. This integrated strategy improves both the robustness and scalability of the model, offering a clear and reliable prediction of AAC performance.

Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1β, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-β. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1β signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A 32-year-old male presented with a painless swelling on his nasal dorsum, persisting for over 3 months. He reported a gradual increase in the size of the mass, with no identifiable triggers except occasional skin redness. He denied nosebleeds, rhinorrhea, nasal obstruction, trauma, prior surgery, or spontaneous pain. His medical history revealed gout, managed with colchicine and diclofenac. Despite dietary and pharmaceutical interventions, he continued to have bouts of hyperuricemia, with blood uric acid levels measuring 739 μmol/L. Multiple tophi were evident, especially on the left first metatarsophalangeal joint (Figure 1A). Examination revealed an irregularly shaped, immobile, hard swelling at the nasal radix, measuring 3 cm×2 cm. Computerized tomography (CT) imaging of the nose showed bilateral nasal bone destruction from the lesion. Given its impact on the patient's appearance and his history of gout, the mass was initially diagnosed as unusual gouty tophus. The patient requested surgical removal of the lesion, and the dissection revealed a mass partly encased by a capsule-like connective tissue adherent to the nasal bone. As the lesion damaged the nasal bone, removal of the lesion led to defect of nasal bone. After an extensive rinse of the surgery site, the incision was sutured., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Several life-prolonging therapies for metastatic castration-resistant prostate cancer (mCRPC) are available, including radium-223 dichloride ( 223 Ra), which was approved based on phase 3 data demonstrating improved overall survival (OS) and a favorable safety profile. To date, real-world evidence for 223 Ra use in Taiwan is from three studies of <50 patients. This observational study (NCT04232761) enrolled male patients with histologically/cytologically confirmed mCRPC with bone metastases from centers across Taiwan. 223 Ra was prescribed as part of routine practice by investigators. Patients with prior 223 Ra treatment were excluded. The primary objective was to assess 223 Ra safety; secondary objectives evaluated efficacy parameters, including OS. Overall, 224 patients were enrolled. Most patients had an Eastern Cooperative Oncology Group performance status of 0/1 (79.0%) and ≤20 bone metastases (69.2%); no patients had visceral metastases. 223 Ra was first- or second-line therapy in 23.2% and 47.7% of patients, respectively. The total proportion of patients who received 5-6 223 Ra cycles was 68.8%; this proportion was greater with first-line use (84.3%) than second- (65.7%) or third-/fourth-line use (64.1%). More chemotherapy-naïve patients (61.9%) completed the 6-cycle 223 Ra treatment than chemotherapy-exposed patients (56.7%). Any-grade treatment-emergent adverse events (TEAEs) and serious TEAEs occurred in 54.0% and 28.6% of patients, respectively, while 12% experienced 223 Ra-related adverse events. Median OS was 15.7 months (95% confidence interval 12.13-19.51); patients receiving 5-6 223 Ra injections and earlier 223 Ra use had longer OS than those receiving fewer injections and later 223 Ra use. 223 Ra provides a well-tolerated and effective treatment for Taiwanese patients with mCRPC and bone metastases., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)