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Yi-Zi Zheng,1,* Jia-Ying Li,2,3,* Lv-Wen Ning,3 Ni Xie3 1Department of Thyroid and Breast Surgery, Shenzhen Breast Tumor Research Center for Diagnosis and Treatment, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 2Hengyang Medical School, University of South China, Hengyang, Hunan, People’s Republic of China; 3Biobank, First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ni Xie, Biobank, First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen University, 3002 Sungang West Road, Shenzhen, 518035, Guangdong, People’s Republic of China, Tel +86-13501580802, Fax +86-0755-83003435, Email xn100@szu.edu.cnIntroduction: Tripartite motif-containing protein (TRIM) family members play crucial roles in carcinogenesis and chemotherapy resistance. In this study, we aimed to determine whether TRIM58 protein expression is related to patient responses to neoadjuvant therapy (NAT) and their survival outcome.Methods: Immunohistochemistry was performed on female breast cancer samples from biopsies before NAT in Shenzhen Second People’s Hospital. Univariate and multivariate logistic regression tests were used to analyze the association between TRIM58 protein expression and pathological complete response (pCR). The Cox proportional hazards model was used to calculate the adjusted hazard ratio (HR) with a 95% confidence interval (95% CI). The Kaplan–Meier plotter database was used to analyze the prognostic value of TRIM58.Results: High TRIM58 expression was associated with small tumor size in all the patients (n = 58). Multivariate analysis suggested that low TRIM58 expression was an independent predictive factor for higher pCR (odds ratio = 0.06, 95% CI 0.005– 0.741, P = 0.028). The Kaplan–Meier Plotter dataset suggested that the TRIM58 high-expression group showed a worse 5-year overall survival than the low-expression group (HR = 1.34, 95% CI 1.07– 1.67, P = 0.01). Pathway analysis revealed the potential mechanisms of TRIM58 in chemoresistance.Discussion: Our study suggests that TRIM58 is a promising biomarker for both neoadjuvant chemosensitivity and long-term clinical outcomes in breast cancer. It may also help to identify candidate responders and determine treatment strategies.Keywords: chemosensitivity, pathological complete response, biomarker, patient stratification, predictive diagnostics

Yi-Zi Zheng,1,2 Hong-Bin Qin,1 Zi-Zheng Li,1 He-Sheng Jiang,3 Greg Zhang,4 Shi-Wei Yang,5 Xian-Ming Wang,2 Yang-Chun Xu,1 Zhen-Han Deng,6 Guo-Wen Liu2 1Department of Thyroid and Breast Surgery, The People’s Hospital of Hechi, Hechi, Guangxi, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Shenzhen Breast Tumor Research Center for Diagnosis and Treatment, National Standardization Center for Breast Cancer Diagnosis and Treatment, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Surgery, Oregon Health & Science University, Portland, OR, USA; 4McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA; 5Teaching Office, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 6Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Yang-Chun XuDepartment of Thyroid and Breast Surgery, The People’s Hospital of Hechi, Middle 455 Jinchengjiang Road, Hechi, 547000, Guangxi, People’s Republic of ChinaTel/Fax +86-778-2293900Email xuyangchun2010@163.comYi-Zi ZhengDepartment of Thyroid and Breast Surgery, Shenzhen Breast Tumor Research Center for Diagnosis and Treatment, National Standardization Center for Breast Cancer Diagnosis and Treatment, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, 3002 Sungang West Road, Shenzhen, 518035, Guangdong, People’s Republic of ChinaTel/Fax +86-755-83366388Email 14111230029@fudan.edu.cnPurpose: Ductal carcinoma in situ with microinvasion (DCISM) can be challenging to balance the risks of overtreatment versus undertreatment. We aim to identify prognostic factors in patients with DCISM and construct a nomogram to predict breast cancer-specific survival (BCSS).Materials and Methods: A retrospective cohort study of women diagnosed with DCISM from 1988 to 2015 who were identified in the Surveillance, Epidemiology and End Results database. Clinical variables and tumor characteristics were evaluated, and Cox proportional-hazards regression was performed. A nomogram was constructed from the multivariate logistic regression to combine all the prognostic factors to predict the prognosis of DCISM patients at 5 years, 10 years, and 15 years.Results: We identified 5438 total eligible breast cancer patients with a median and max survival time of 78 and 227 months, respectively. Here, patients with poorer survival outcomes were those diagnosed between 1988 and 2001, African-American race, under 40 years of age, higher tumor N stage, progesterone receptor-negative tumor, and received no surgery. The nomogram was constructed by the seven variables and passed the calibration and validation steps. The area under the receiver operating characteristic (ROC) curve (AUC) of both the training set and the validating set (5-year AUC: 0.77 and 0.88, 10-year AUC: 0.75 and 0.73, 15-year AUC: 0.72 and 0.65). Receiving chemotherapy was associated with a better BCSS (hazard ratio, HR=0.45, 95% confidence interval, 95% CI = 0.23– 0.89), especially in patients with estrogen receptor (ER) negative, progesterone receptor (PR) negative (HR = 0.35, 95% CI = 0.13– 0.97) and ER+PR-/ER-PR+ DCISM (HR = 0.07, 95% CI = 0.01– 0.59).Conclusion: Our current study is the first to construct nomograms of patients with DCISM which could help physicians identify breast cancer patients that more likely to benefit from more intensive treatment and follow-up. Chemotherapy might benefit patients with ER-PR- and ER+PR-/ER-PR+ DCISM.Keywords: breast cancer, ductal carcinoma in situ, microinvasion, nomogram, survival

Li-Yun Lin,1– 3,* Jian Li,4,* Hui-Ying Huang,5,6 Xue-Yan Liang,5,6 Ting-Ting Jiang,4 Jiang-Tao Chen,7,8 Carlos Salas Ehapo,9 Urbano Monsuy Eyi,9 Yu-Zhong Zheng,1 Guang-Cai Zha,1 Dong-De Xie,7,8 Yu-Ling Wang,7,8 Wei-Zhong Chen,5,6 Xiang-Zhi Liu,5,6 Min Lin1,5,6 1School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong Province, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, People’s Republic of China; 4Department of Human Parasitology, School of Basic Medical Sciences; Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, People’s Republic of China; 5Department of Medical Laboratory, Chaozhou People’s Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong Province, People’s Republic of China; 6Department of Medical Genetics, Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 7The Chinese Medical Aid Team to the Republic of Equatorial Guinea, Guangzhou, Guangdong Province, People’s Republic of China; 8Department of Medical Laboratory, Huizhou Central Hospital, Huizhou, Guangdong Province, People’s Republic of China; 9Department of Medical Laboratory, Malabo Regional Hospital, Malabo, Equatorial Guinea*These authors contributed equally to this workCorrespondence: Min LinSchool of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong Province, People’s Republic of ChinaTel/Fax +86 768-2317422Email konfutea@hotmail.comPurpose: Antimalarial drug resistance is one of the major challenges in global efforts to control and eliminate malaria. In 2006, sulfadoxine-pyrimethamine (SP) replaced with artemisinin-based combination therapy (ACT) on Bioko Island, Equatorial Guinea, in response to increasing SP resistance, which is associated with mutations in the dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes.Patients and Methods: To evaluate the trend of molecular markers associated with SP resistance on Bioko Island from 2011 to 2017, 179 samples collected during active case detection were analysed by PCR and DNA sequencing.Results: Pfdhfr and Pfdhps gene sequences were obtained for 90.5% (162/179) and 77.1% (138/179) of the samples, respectively. For Pfdhfr, 97.5% (158/162), 95.7% (155/162) and 98.1% (159/162) of the samples contained N51I, C59R and S108N mutant alleles, respectively. And Pfdhps S436A, A437G, K540E, A581G, and A613S mutations were observed in 25.4% (35/138), 88.4% (122/138), 5.1% (7/138), 1.4% (2/138), and 7.2% (10/138) of the samples, respectively. Two classes of previously described Pfdhfr-Pfdhps haplotypes associated with SP resistance and their frequencies were identified: partial (IRNI-SGKAA, 59.4%) and full (IRNI-SGEAA, 5.5%) resistance. Although no significant difference was observed in different time periods (p> 0.05), our study confirmed a slowly increasing trend of the frequencies of these SP-resistance markers in Bioko parasites over the 7 years investigated.Conclusion: The findings reveal the general existence of SP-resistance markers on Bioko Island even after the replacement of SP as a first-line treatment for uncomplicated malaria. Continuous molecular monitoring and additional control efforts in the region are urgently needed.Keywords: malaria, drug resistance, dihydrofolate reductase, dihydropteroate synthase, sulfadoxine-pyrimethamine

The primary cause of the accelerated battery failure in aqueous zinc-ion batteries (AZIBs) is the uncontrollable evolution of the zinc metal-electrolyte interface. In the present research on the development of multiadditives to ameliorate interfaces, it is challenging to elucidate the mechanisms of the various components. Additionally, the synergy among additive molecules is frequently disregarded, resulting in the combined efficacy of multiadditives that is unlikely to surpass the sum of each component. In this study, the "molecular synergistic effect" is employed, which is generated by two nonhomologous acid ester (NAE) additives in the double electrical layer microspace. Specifically, ethyl methyl carbonate (EMC) is more inclined to induce the oriented deposition of zinc metal by means of targeted adsorption with the zinc (002) crystal plane. Methyl acetate (MA) is more likely to enter the solvated shell of Zn 2+ and will be profoundly reduced to produce SEI that is dominated by organic components under the "molecular synergistic effect" of EMC. Furthermore, MA persists in a spontaneous hydrolysis reaction, which serves to mitigate the pH increase caused by the hydrogen evolution reaction (HER) and further prevents the formation of byproducts. Consequently, the 1E1M electrolyte not only extends the cycle life of the zinc anode to 3140 cycles (1 mA h cm -2 and 1 mA cm -2 ) but also extends the life of the Zn//MnO 2 full battery, with the capacity retention rate still at 89.9% after 700 cycles.

HER2-positive breast cancer is an aggressive subtype that accounts for 15% to 20% of all breast cancers. Recent studies have suggested that HER2-positive breast cancer is a group of heterogeneous diseases with different sensitivities to standard treatment regimens. Revealing the molecular heterogeneity of HER2-positive breast cancer could potentially enable more precise treatment strategies. In this study, we performed multiomics profiling on a HER2-positive breast cancer cohort and identified four transcriptome-based subtypes. The classical HER2 (HER2-CLA) subtype comprised 28.3% of the samples and displayed high ERBB2 activation and significant benefit from anti-HER2 therapy. The immunomodulatory (HER2-IM) subtype (20%) featured an immune-activated microenvironment, potentially suitable for de-escalated treatment and immunotherapy. The luminal-like (HER2-LUM) subtype (30.6%) possessed similar molecular features of hormone receptor-positive HER2-negative breast cancer, suggesting endocrine therapy and CDK4/6 inhibitors as a potential therapeutic strategy. Lastly, the basal/mesenchymal-like (HER2-BM) subtype (21.1%) had a poor response to current dual HER2-targeted therapy and could potentially benefit from tyrosine kinase inhibitors. The molecular characteristics and clinical features of the subtypes were further explored across multiple cohorts, and the feasibility of the proposed treatment strategies was validated in patient-derived organoid and patient-derived tumor fragment models. This study elucidates the molecular heterogeneity of HER2-positive breast cancer and paves the way for a more tailored treatment. Significance: Illumination of the inherent heterogeneity within HER2-positive breast cancers through the delineation of distinct molecular subtypes lays the groundwork for developing more personalized treatment strategies based on specific patient characteristics., (©2024 American Association for Cancer Research.)

Background: The purpose of this study was to investigate the effects of caffeinated chewing gum on female softball pitching and hitting performance in trained female softball fielders and pitchers., Methods: Twenty-four trained female softball players (10 pitchers and 14 fielders) were divided into a caffeine chewing gum trial (CAF) or a placebo trial (PLA) in a single-blind, randomized, crossover experimental design. Two pieces of gum containing 100 mg of caffeine (CAF) or without caffeine (PLA) were chewed for 10 minutes and then spit out, followed by a 15-minute warm-up. The physical tests included grip strength and countermovement jump (CMJ). The softball-specific tests included pitching or hitting. The two trials were separated by seven days., Results: The CAF trial had significantly higher grip strength than the PAL trial in fielder (P=0.032, Cohen's d=0.29) and pitcher (P=0.016, Cohen's d=0.33). The height of CMJ in fielders was significantly higher in the CAF trial than in the PLA trial (P=0.015, Cohen's d=0.65) but not in pitchers (P=0.596, Cohen's d=0.15). The fielder's average and maximum batting exit speeds were significantly higher in the CAF trial than in the PLA trial (P<0.05). The average and max fastball speeds of the CAF trial were significantly higher than that of the PLA trial in pitchers (P<0.05)., Conclusions: The study showed that chewing gum containing two pieces of gum containing 100 mg of caffeine effectively improved female softball fielder's batting performance and pitcher's pitching performance.

Introduction: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD)., Methods: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC., Results: After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference., Discussion: This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Three mononuclear Dy III compounds [DyL 1 (Ph 3 SiO) 2 ][BPh 4 ]·MeCN·2H 2 O ( 1 ), [DyL 2 (Ph 3 SiO) 2 ][BPh 4 ]·C 2 H 5 OH·H 2 O ( 2 ), and [DyL 3 (Ph 3 SiO)(OAc)][BPh 4 ]·CH 3 OH·3H 2 O ( 3 ) and their corresponding Y III diluted analogues [Dy 0.0967 Y 0.9033 L 1 (Ph 3 SiO) 2 ][BPh 4 ]·MeCN·2H 2 O ( 1@Y ), [Dy 0.2668 Y 0.7332 L 2 (Ph 3 SiO) 2 ][BPh 4 ]·C 2 H 5 OH·H 2 O ( 2@Y ), and [Dy 0.1260 Y 0.8740 L 3 (Ph 3 SiO)(OAc)][BPh 4 ]·CH 3 OH·3H 2 O ( 3@Y ) were synthesized with hexaazamacrocyclic Schiff base ligands as an equatorial ligand. The substituents in the equatorial hexaazamacrocyclic Schiff base ligand show a significant effect on the replacement of the axial ligands. Compounds 1 , 2 , and 3 are typical zero dc field single-molecule magnets with effective energy barriers ( U eff ) of 1092(6), 946.1(7), and 150.1(9) K, respectively. Although the effective energy barriers of 1 and 2 are close, the magnetic hysteresis remains open up to 20 K for 1 , twice as large as that of 2 (10 K), which is different from the previously reported compounds, probably due to nonplanarity N6 in the equator. Ab initio calculations indicate that the ground states of compounds 1 and 2 exhibit high anisotropy and pure second and third excited states, while compound 3 exhibits pure ground-state anisotropy and highly mixed excited states, leading to the easy occurrence of quantum tunneling of magnetization between the ground and excited states in compound 3 . This work indicates that the substituents in equatorial hexaazamacrocyclic Schiff base ligands have a significant effect on the construction and magnetic properties of Dy III SIMs with D 6h symmetry.

We described a chiral phosphoric acid (CPA) catalyzed asymmetric [3 + 3] cycloaddition of cinnamaldehyde-derived N -aryl nitrones with 2-indolylmethanols to prepare various indole-fused 1,2-oxazines in high yields (up to 96%) with excellent enantioselectivity (>99% ee). Control experiments indicate that hydrogen bonding plays important roles in controlling the enantioselectivity of products. This strategy provides an efficient pathway to construct enantioenriched indole-fused 1,2-oxazines from N -aryl nitrones with 2-indolylmethanols.

Plants bearing double flowers have long been cultivated as ornamental plants. Hose-in-hose flowers, bearing 2-whorled corolla tubes in whorls 1 and 2, are uncommon but recur in Sinningia (Gesnerioideae, Gesneriaceae). In this study, we selected 15 hose-in-hose cultivars as materials to explore the underlying molecular and genetic mechanisms of this floral architecture. We found that they originated from different hybridization events within the Dircaea clade. Three B-class MADS-box genes were globally expressed in all floral whorls, but only GLOBOSA1 (GLO1) has accumulated a dominant mutation, i.e., the insertion of a hAT-like miniature inverted-repeat transposable element (MITE) into its promoter, that co-segregated with the hose-in-hose phenotype. In addition, all 15 hose-in-hose cultivars contained the same dominant GLO1 allele. Transient gene expression assays confirmed the role of this MITE insertion in up-regulating the promoter activity of GLO1 by providing several cis-regulatory elements. Genetic transformation in heterologous Chirita pumila (Didymocarpoideae, Gesneriaceae) verified that this dominant GLO1 allele is sufficient to confer the hose-in-hose phenotype. We further demonstrated that both the GLO1 allele and the hAT-like MITE descended from wild S. cardinalis with single flowers. This study highlights the significance of wide hybridization in frequent gains of the dominant GLO1 allele and thereafter repeated occurrence of hose-in-hose flowers in Sinningia., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To investigate the clinical features and prognosis of children with fungal bloodstream infection (BSI) following chemotherapy for acute leukemia (AL)., Methods: A retrospective analysis was performed on 23 children with fungal BSI following chemotherapy for AL in three hospitals in Fujian Province, China, from January 2015 to December 2023. Their clinical features and prognosis were analyzed., Results: Among all children following chemotherapy for AL, the incidence rate of fungal BSI was 1.38% (23/1 668). At the time of fungal BSI, 87% (20/23) of the children had neutrophil deficiency for more than one week, and all the children presented with fever, while 22% (5/23) of them experienced septic shock. All 23 children exhibited significant increases in C-reactive protein and procalcitonin levels. A total of 23 fungal isolates were detected in peripheral blood cultures, with Candida tropicalis being the most common isolate (52%, 12/23). Caspofungin or micafungin combined with liposomal amphotericin B had a relatively high response rate (75%, 12/16), and the median duration of antifungal therapy was 3.0 months. The overall mortality rate in the patients with fungal BSI was 35% (8/23), and the attributable death rate was 22% (5/23)., Conclusions: Fungal BSI following chemotherapy in children with AL often occurs in children with persistent neutrophil deficiency and lacks specific clinical manifestations. The children with fungal BSI following chemotherapy for AL experience a prolonged course of antifungal therapy and have a high mortality rate, with Candida tropicalis being the most common pathogen.

Developing highly active and enantioselective ligands for the asymmetric hydrogenation of ketones has consistently attracted significant attention from scientists. A series of novel tetradentate sulfur-containing ligands, termed as f-thiophamidol, were successfully designed and synthesized which exhibited excellent performance in the asymmetric hydrogenation of simple ketones (up to 99% yield, 99% ee) and α-substituted β-keto sulfonamides (up to 99% yield, 99% ee, 99:1 dr). The subsequent successful gram-scale experiments with high TON demonstrated the immense potential application value of this system in synthesizing drug molecules.

Fluoride based lattice is attractive for reducing phonon-induced quenching in rare-earth (RE) based luminescent materials. However, due to the strong affinity between RE and oxygen, the synthesis of fluoride-based complexes has to be protected under anhydrous conditions, and many known fluoride bridged RE clusters are unstable in air. Here, by using the "mixed-ligand" strategy a family of fluoride bridged RE clusters is synthesized, namely RE 16 (μ 4 -F) 6 (μ 3 -F) 12 ( t BuCOO) 18 [N(CH 2 CH 2 O) 3 ] 4 (RE = Eu, EuFC-16; RE = Tb, TbFC-16), which are highly stable in air and decomposed thermally only when heating above 435 °C. Moreover, both clusters exhibit high photoluminescence quantum yields (PLQY EuFC-16 = 87.7%, PLQY TbFC-16 = 99.0%). Upon warming, EuFC-16 and TbFC-16 display excellent structural, thermal, and chroma stability. Thus, EuFC-16 and TbFC-16 have the potential to be used in light-emitting diode (LED) devices, offering many advantages over commercial phosphors. First, both clusters are soluble in UV-curable resin at any mixing rate, and the emission colors can be tuned from magenta, turquoise, willow green, and ivory to pure white if mixing blue phosphor BAM:Eu 2+ . Second, the clusters are hydrophobic, and the LEDs work well after soaking in water, indicating a good quality for outdoor lighting., (© 2024 Wiley‐VCH GmbH.)

Transformation between oxidation states is widespread in transition metal coordination chemistry and biochemistry, typically occurring in solution. However, air-induced oxidation in porous crystalline solids with retention of crystallinity is rare due to the dearth of materials with high structural stability that are inherently redox active. Herein, we report a new family of such materials, four isostructural cobalt-pyrazolate frameworks of face-centered cubic, fcu , topology, fcu-L-Co , that are sustained by Co 8 molecular building blocks (MBBs) and dipyrazolate ligands, L . fcu-L-Co were observed to spontaneously transform from Co(II) 8 to Co(III) 8 MBBs in air with retention of crystallinity, marking the first such instance in metal-organic frameworks (MOFs). This transformation can also be achieved through water vapor sorption cycling, heating, or chemical oxidation. The reverse reactions were conducted by exposure of fcu-L-Co(III) to aqueous hydrazine. fcu-L-Co(II) exhibited high gravimetric water vapor uptakes of 0.55-0.68 g g -1 at 30% relative humidity (RH), while in fcu-L-Co(III) the inflection point shifted to lower RH and framework stability improved. Insight into the transformation between fcu-L-Co(II) and fcu-L-Co(III) was gained from single crystal X-ray diffraction and in situ spectroscopy. Overall, the crystal engineering approach we adopted has afforded a new family of MOFs that exhibit cobalt redox chemistry in a confined space coupled with high porosity.

Objective: To analyze the clinical characteristics and prognosis of children with hypodiploid B-cell precursor acute lymphoblastic leukemia (BCP-ALL)., Methods: The clinical data of 1 287 children with BCP-ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed. According to the results of chromosome karyotype, all the patients were grouped into hypodiploid subgroup and non-hypodiploid subgroup. The clinical characteristics, early treatment response ［minimal residual disease (MRD) on middle stage of induction chemotherapy and end of induction chemotherapy］ and long-term efficacy ［overall survival (OS) and event-free survival (EFS)］ were compared. The prognostic factors of hypodiploid BCP-ALL were further explored., Results: Among 1 287 BCP-ALL patients， 28 patients (2.2%) were hypodiploid BCP-ALL. The proportion of patients with white blood cell count （WBC）≥50×10 9 /L in the hypodiploid subgroup was significantly higher than that in the non-hypodiploid subgroup ( P =0.004), while there was no statistically significant difference in gender ratio, age group at initial diagnosis, and early treatment response between the two groups (all P >0.05). The 5-year EFS and OS rate of the hypodiploid subgroup were 75.0%(95% CI ：66.8%-83.2%) and 77.8%(95% CI ：69.8%-85.8%), respectively, which were lower than those of non-hypodiploid subgroup ［EFS: 79.6%(95% CI ：78.4%-80.8%); OS: 86.4%(95% CI ：85.4%-87.5%)］, but the difference was not statistically significant (all P >0.05). Further subgroup analysis by risk stratification showed that the 5-year EFS and OS rates of the hypodiploid subgroup were significantly lower than those in the low-risk (LR) group ［LR group EFS: 91.4% (95% CI ：88.4%-93.6% ), P < 0.001; OS: 94.7% (95% CI ：92.1%-96.4%), P < 0.001］ ; it was similar to that of BCP-ALL children stratified into intermediate-risk (IR) excluding hypodiploid ［IR group EFS: 79.4%(95% CI ：74.9%-83.2%), P =0.343; OS: 87.3%(95% CI ：83.6%-90.2%), P =0.111］; while was higher than that of EFS in HR group, but the difference was not statistically significant ［HR group EFS: 58.7%(95% CI ：52.6%-64.8%), P =0.178. OS: 69.9%(95% CI ：63.5%-75.4%), P =0.417］. Univariate analysis showed that gender, age, white blood cell count, and MRD on middle stage of induction chemotherapy had no significant impact on OS and EFS; chromosome count< 40 was a risk factor for lower OS ( P =0.026), but has no significant effect on EFS; MRD≥0.01% after induction therapy was a risk factor for lower OS and EFS ( P =0.002, and 0.001, respectively)., Conclusion: Children with hypodiploid BCP-ALL have an intermediate prognosis, and MRD ≥0.01% after induction chemotherapy may be a risk factors for poor prognosis.

Catalytic activation of C aryl -O bonds is considered as a powerful strategy for the production of aromatics from lignin. However, due to the high reduction potentials of diaryl ether 4-O-5 linkage models, their single electron reduction remains a daunting challenge. This study presents the blue light-induced bifunctional N-heterocyclic carbene (NHC)-catalyzed one-electron reduction of diaryl ether 4-O-5 linkage models for the synthesis of trivalent phosphines. The H-bond between the newly devised bifunctional NHC and diaryl ethers is responsible for the success of the single electron transfer. Furthermore, this approach demonstrates selective one-electron reduction of unsymmetric diaryl ethers, oligomeric phenylene oxide, and lignin model., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Identification of compounds to modulate NADPH metabolism is crucial for understanding complex diseases and developing effective therapies. However, the complex nature of NADPH metabolism poses challenges in achieving this goal. In this study, we proposed a novel strategy named NADPHnet to predict key proteins and drug-target interactions related to NADPH metabolism via network-based methods. Different from traditional approaches only focusing on one single protein, NADPHnet could screen compounds to modulate NADPH metabolism from a comprehensive view. Specifically, NADPHnet identified key proteins involved in regulation of NADPH metabolism using network-based methods, and characterized the impact of natural products on NADPH metabolism using a combined score, NADPH-Score. NADPHnet demonstrated a broader applicability domain and improved accuracy in the external validation set. This approach was further employed along with molecular docking to identify 27 compounds from a natural product library, 6 of which exhibited concentration-dependent changes of cellular NADPH level within 100 μM, with Oxyberberine showing promising effects even at 10 μM. Mechanistic and pathological analyses of Oxyberberine suggest potential novel mechanisms to affect diabetes and cancer. Overall, NADPHnet offers a promising method for prediction of NADPH metabolism modulation and advances drug discovery for complex diseases., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: Arthrodesis, usage of metallic implants for internal fixation, is commonly employed as the primary treatment modality for Müller-Weiss disease (MWD). Nevertheless, the efficacy of the current methods of fixation leaves room for improvement. Inadequate fixation strength and the risk of fixation failure are both critical concerns requiring attention. This study explored the clinical effects of implementing a modified fixation technique in talonavicular arthrodesis for the treatment of MWD., Methods: A total of 14 cases diagnosed with MWD undergoing talonavicular (TN) arthrodesis from January 2021 toMarch 2023 were included in the retrospective study. The fixation method for fusion involved the use of screws, with additional support from the shape-memory alloy (SMA) staple. Relevant clinical outcomes and complications were evaluated preoperatively and postoperatively. Paired-samples t-test was used for all data comparisons., Results: Radiographic evidence confirmed solid fusion, and follow-up evaluations showed satisfactory results in all cases. The American Orthopedic Foot and Ankle Society (AOFAS) scores were elevated from 32.21 ± 4.0 (range: 22-38) preoperatively to 86.5 ± 2.7 (range: 81-90) postoperatively (p < 0.001). The visual analog scale (VAS) scores declined from 7.40 ± 0.8 (range: 6-8.5) preoperatively to 1.21 ± 1.1 (range: 0-3) postoperatively (p < 0.001). The lateral Meary's angle changed from 13.50 ± 5.2 (range: 8-24) preoperatively to 4.14 ± 2.9 (range: 1-11) degrees postoperatively (p < 0.001). The calcaneal pitch angle increased from 10.07 ± 4.0 (range: 5-19) preoperatively to 14.35 ± 4.0 (range: 8-21) degrees postoperatively (p < 0.001). The talar-first metatarsal angle decreased from 11.71 ± 3.8 (range: 8-18) preoperatively to 4.28 ± 3.1 (range: 0-9) degrees postoperatively (p < 0.001). One patient was observed to experience delayed wound healing and wound infection. No nerve damage, malunion, pseudoarthrosis, or fixation failure were observed., Conclusion: The results indicated that the fusion of the TN joint using a combination of screws and shape memory alloy staples, could lead to favorable clinical outcomes and significantly enhance the quality of life for patients with MWD. This technique is not only safe and effective but also straightforward to perform., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: The clinical response rate to immune checkpoint blockade (ICB) therapy in melanoma remains low, despite its widespread use. Circular non-coding RNAs (circRNAs) are known to play a crucial role in cancer progression and may be a key factor limiting the effectiveness of ICB treatment., Methods: The circRNAs that were downregulated after coadministration compared with single administration of PD-1 inhibitor administration were identified through RNA-seq and Ribo-seq, and thus the circPIAS1 (mmu&#95;circ&#95;0015773 in mouse, has&#95;circ&#95;0008378 in human) with high protein coding potential was revealed. Fluorescence in situ hybridization (FISH) assays were conducted to determine the localization of circPIAS1 in human and mouse melanoma cells, as well as its presence in tumor and adjacent tissues of patients. Validation through dual-luciferase reporter assay and LC-MS/MS confirmed the ability of circPIAS1 to encode a novel 108 amino acid polypeptide (circPIAS1-108aa). Specific antisense oligonucleotides (ASOs) targeting the junction site of circPIAS1 were developed to reduce its intracellular levels. Proliferation changes in melanoma cells were assessed using CCK8, EdU, and colony formation assays. The impact of circPIAS1-108aa on the ferroptosis process of melanoma cells was studied through GSH, MDA, and C11-BODIPY staining assays. Western Blot, Immunoprecipitation (IP), and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques were employed to investigate the impact of circPIAS1-108aa on the P-STAT1/SLC7A11/GPX4 signaling pathway, as well as its influence on the balance between STAT1 SUMOylation and phosphorylation. Additionally, a melanoma subcutaneous transplanted tumor mouse model was utilized to examine the combined effect of reducing circPIAS1 levels alongside PD-1 inhibitor., Results: Compared with the group treated with PD-1 inhibitor alone, circPIAS1 was significantly down-regulated in the coadministration group and demonstrated higher protein coding potential. CircPIAS1, primarily localized in the nucleus, was notably upregulated in tumor tissues compared to adjacent tissues, where it plays a crucial role in promoting cancer cell proliferation. This circRNA can encode a unique polypeptide consisting of 108 amino acids, through which it exerts its cancer-promoting function and impedes the effectiveness of ICB therapy. Mechanistically, circPIAS1-108aa hinders STAT1 phosphorylation by recruiting SUMO E3 ligase Ranbp2 to enhance STAT1 SUMOylation, thereby reactivating the transduction of the SLC7A11/GPX4 signaling pathway and restricting the immunogenic ferroptosis induced by IFNγ. Furthermore, the combination of ASO-circPIAS1 with PD-1 inhibitor effectively inhibits melanoma growth and significantly enhances the efficacy of immune drugs in vivo., Conclusions: Our study uncovers a novel mechanism regarding immune evasion in melanoma driven by a unique 108aa peptide encoded by circPIAS1 in melanoma that dramatically hinders immunogenic ferroptosis triggered by ICB therapy via modulating the balance between SUMOylation and phosphorylation of STAT1. This work reveals circPIAS1-108aa as a critical factor limiting the immunotherapeutic effects in melanoma and propose a promising strategy for improving ICB treatment outcomes., (© 2024. The Author(s).)

Lanthanide (Ln) based mononuclear single-molecule magnets (SMMs) provide probably the finest ligand regulation model for magnetic property. Recently, the development of such SMMs has witnessed a fast transition from coordination to organometallic complexes because the latter provides a fertile, yet not fully excavated soil for the development of SMMs. Especially those SMMs with heterocyclic ligands have shown the potential to reach higher blocking temperature. In this minireview, we give an overview of the design principle of SMMs and highlight those "shining stars" of heterocyclic organolanthanide SMMs based on the ring sizes of ligands, analysing how the electronic structures of those ligands and the stiffness of subsequently formed molecules affect the dynamic magnetism of SMMs. Finally, we envisaged the future development of heterocyclic Ln-SMMs., (© 2024 Wiley-VCH GmbH.)

Background: Myocardial fibrosis, a hallmark of heart disease, is closely associated with macrophages, yet the genetic pathophysiology remains incompletely understood. In this study, we utilized integrated single-cell transcriptomics and bulk RNA-seq analysis to investigate the relationship between macrophages and myocardial fibrosis across omics integration., Methods: We examined and curated existing single-cell data from dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocardial infarction (MI), and heart failure (HF), and analyzed the integrated data using cell communication, transcription factor identification, high dimensional weighted gene co-expression network analysis (hdWGCNA), and functional enrichment to elucidate the drivers of macrophage polarization and the macrophage-to-myofibroblast transition (MMT). Additionally, we assessed the accuracy of single-cell data from the perspective of driving factors, cell typing, anti-fibrosis performance of left ventricular assist device (LVAD). Candidate drugs were screened using L1000FWD., Results: All four heart diseases exhibit myocardial fibrosis, with only MI showing an increase in macrophage proportions. Macrophages participate in myocardial fibrosis through various fibrogenic molecules, especially evident in DCM and MI. Abnormal RNA metabolism and dysregulated transcription are significant drivers of macrophage-mediated fibrosis. Furthermore, profibrotic macrophages exhibit M1 polarization and increased MMT. In HF patients, those responding to LVAD therapy showed a significant decrease in driver gene expression, M1 polarization, and MMT. Drug repurposing identified cinobufagin as a potential therapeutic agent., Conclusion: Using integrated single-cell transcriptomics, we identified the drivers of macrophage-mediated myocardial fibrosis in four heart diseases and confirmed the therapeutic effect of LVAD on improving HF with single-cell accuracy, providing novel insights into the diagnosis and treatment of myocardial fibrosis., (© 2024. The Author(s).)

A facile copper-catalyzed [3 + 2] cycloaddition of N -2,2,2-trifluoroethylisatin ketimines with various electron-deficient alkenes to access structurally polyfunctionalized spiro-pyrrolidine-oxindole motifs has been developed. Under the catalytic system, the N -2,2,2-trifluoroethylisatin ketimines could be utilized to react with a series of exocyclic alkenes, including 2-acylamino acrylates, 3-methylene-β-lactams, and sterically hindered cycloalkenes represented by cyclobutenone, to obtain a variety of densely functionalized spiro-pyrrolidine frameworks bearing an α-amino acid ester, β-lactam, and cyclobutanone, respectively, in generally good yields with excellent diastereo- and enantioselectivities.

The human malaria parasite Plasmodium falciparum (P. falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti-P. falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P. falciparum. Our results reveal that ubiquitin carboxyl-terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6' region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P. falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti-malarial agents in the future., (© 2024 Wiley-VCH GmbH.)

Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α-Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α-ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long-standing catalysis challenge. Herein, an unprecedented TBD-switched Pd-catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late-stage modify pharmaceuticals, scalability to large-scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd-catalyzed double isocyanide insertion process, thereby selectively providing the desired α-ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α-ketoimine amide are successfully isolated and determined by X-ray analysis, confirming that they are probable intermediates in the catalytic pathway., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: To investigate the mechanism of the CXCL10/CXCR3 axis regulating Th1 cell differentiation and migration through the PI3K/AKT pathway in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)., Methods: Experimental autoimmune prostatitis (EAP) model, a well-described and validated animal model of CP/CPPS, was used in our study. After treatment with CXCL10, the severity of EAP and Th1 cell proportion were respectively measured by HE stains, immunohistochemistry, and flow cytometry. Then, the protein expression of the PI3K/AKT pathway in CXCL10/CXCR3-regulated Th1 cell differentiation and migration was evaluated by western blotting. Additionally, by the CXCR3 antagonist AMG487 and the PI3K inhibitor LY294002 applications, the effects of CXCL10/CXCR3 through PI3K/AKT pathway on the Th1 cell differentiation and migration were further assessed., Results: The EAP model was successfully built. CXCL10 increased the proportion of Th1 cells in EAP mice, accompanied by upregulation of the PI3K/AKT pathway. Additionally, the PI3K/AKT pathway was found to be involved in CXCL10/CXCR3 axis-mediated Th1 cell differentiation and migration., Conclusions: Our investigations indicate that the CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in EAP through the PI3K/AKT pathway, which provides a new perspective on the immunological mechanisms of CP/CPPS., (© 2023 American Society of Andrology and European Academy of Andrology.)

Among measures tackling the impacts of the COVID-19 pandemic, the selling of private insurance policies covering individual infection is overlooked by the ethics literature. To record the "COVID Claimania" in Taiwan and to assess its ethical implications, we collected 38 policies from 10 insurers sold between January 2020 and May 2022 and found that their risk calculation of the COVID-19 prevalence ranged from 0.5% to 11.08%. In reality, the prevalence by the end of 2022 was 37% in Taiwan. Selling private insurance policies is ethically problematic in three ways. First, it represents the insurance industry's irresponsible risk-taking profit-seeking behaviors. Second, it would jeopardize the effectiveness of the disease-prevention measures by inducing uncontrollable moral hazards. Third, it would expose the insurance companies to unbearable financial risks and cause substantial negative external impacts. The government should intervene in the private insurance market in preparation for future public health emergencies., (© 2023 John Wiley & Sons Ltd.)

Background: The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development., Results: In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults., Conclusion: Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Introduction: RESLES (Reversible splenial lesion syndrome) can be observed secondary to various diseases, and intramyelinic edema may play a crucial role in the pathogenesis of SCC (Splenium of the corpus callosum). Some studies have suggested that hypoxic-ischaemic encephalopathy may constitute a risk factor for SCC lesions. However, the potential impact of high-altitude environments on SCC, especially during chronic exposure, remain obscure., Methods: Our study included 19 patients who satisfied the diagnostic criteria of RESLES at high altitudes. Ten low-altitude patients with RESLES were included as controls. All participants received MRI (Magnetic resonance imaging) scans twice. Routine blood tests, liver, kidney and thyroid function, coagulation function, electrolytes and vitamins were detected during hospitalization and before discharge. In addition, the patients were followed up in May 2023., Results: Hypoxic environments at high altitudes may increase the risk of RESLES. The two groups showed different clinical symptoms. High-altitude patients had significantly higher CRP levels than low-altitude patients. The lesion size in high-altitude patients showed a positive correlation with SaO 2 levels. However, the patients at low altitudes had positive correlation trends between lesion size and several inflammatory markers (WBC, NEU and CRP). All patients had a benign prognosis that may not be affected by the use of prednisone acetate., Conclusions: Hypoxic environments at high altitudes may play a role in the aetiology of RESLES. Additionally, RESLES is a reversible disease and the administration of glucocorticoids may be dispensable for its treatment.

Carbon emission reduction is an important measure to mitigate the greenhouse effect, which has become a hotspot in global climate change research. To contribute to this, here, we fabricated two Co-based metal-organic frameworks (Co-MOFs), namely, {[Co 3 (NTB) 2 (bib)]·(DMA) 2 ·(H 2 O) 4 } n (DZU-211) and {[Co 3 (NTB) 2 (bmip)]·(DMA) 2 } n (DZU-212) (H 3 NTB = 4,4',4″-nitrilotribenzoic acid, bib = 1,4-bis(imidazol-1-yl)-butane, bmip = 1,3-bis(2-methyl-1 H -imidazol-1-yl)propane) to realize efficient CO 2 /N 2 separation by dividing coordination spaces into suitable pores with narrow windows. DZU-211 reveals a 3D open porous framework, while DZU-212 exhibits a 3D double-fold interpenetrated structure. The two MOFs both possess large coordination spaces and small open pore sizes, via the bib ligand insertion and framework interpenetration, respectively. Comparatively, DZU-211 reveals superior selective CO 2 uptake properties due to its more suitable pore characteristics. Gas sorption experiments show that DZU-211 has a CO 2 uptake of 52.6 cm 3 g -1 with a high simulated CO 2 /N 2 selectivity of 101.7 (298 K, 1 atm) and a moderate initial adsorption heat of 38.1 kJ mol -1 . Moreover, dynamic breakthrough experiments confirm the potential application of DZU-211 as a CO 2 separation material from postcombustion flue gases.

The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated in vitro and in vivo. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC., Competing Interests: Declaration of competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

N -Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access N -acyl/sulfonyl-α-functionalized THIQs. This method features the use of oxygen (from air) as the green oxidant, high atom and step economy, and decent structural diversity. The synthetic applicability of the method was further demonstrated via the facile construction of valuable bioactive molecules. Mechanistic studies indicated that oxidation with singlet oxygen and the acceptor-less dehydrogenation were involved in the photoredox process.

Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a vital role in regulating redox homeostasis and reductive biosynthesis. However, if exogenous NADPH can be transported across the plasma membrane has remained elusive. In this study, we present evidence supporting that NADPH can traverse the plasma membranes of cells through a mechanism mediated by the P2X7 receptor (P2X7R). Notably, we observed an augmentation of intracellular NADPH levels in cultured microglia upon exogenous NADPH supplementation in the presence of ATP. The P2X7R-mediated transmembrane transportation of NADPH was validated with P2X7R antagonists, including OX-ATP, BBG, and A-438079, or through P2X7 knockdown, which impeded NADPH transportation into cells. Conversely, overexpression of P2X7 resulted in an enhanced capacity for NADPH transport. Furthermore, transfection of hP2X7 demonstrated the ability to complement NADPH uptake in native HEK293 cells. Our findings provide evidence for the first time that NADPH is transported across the plasma membrane via a P2X7R-mediated pathway. Additionally, we propose an innovative avenue for modulating intracellular NADPH levels. This discovery holds promise for advancing our understanding of the role of NADPH in redox homeostasis and neuroinflammation., 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. Published by Elsevier Inc.)

Objective: To optimize the technical parameters related to the preparation of novel frozen human platelets and formulate corresponding protocol for its preparation., Methods: Novel frozen human platelets were prepared with O-type bagged platelet-rich plasma (PRP), the key technical parameters (DMSO addition, incubation time, centrifugation conditions, etc.) of the preparation process were optimized, and the quality of the frozen platelets was evaluated by routine blood tests, apoptosis rate, platelet activation rate and surface protein expression level., Results: In the preparation protocol of novel frozen human platelets, the operation of centrifugation to remove supernatant was adjusted to before the procedure of platelets freezing, and the effect of centrifugation on platelets was minimal when the centrifugation condition was 800× g for 8 min. In addition, platelets incubated with DMSO for 30 min before centrifugation exhibited better quality after freezing and thawing. The indexes of novel frozen human platelets prepared with this protocol remained stable after long-term cryopreservation., Conclusion: The preparation technique of novel frozen human platelets was established and the protocol was formulated. It was also confirmed that the quality of frozen platelets could be improved by incubating platelets with DMSO for 30 min and then centrifuging them at 800× g for 8 min in the preparation of novel frozen human platelets.

Photocatalysis has the advantages of practical, sustainable and environmental protection, so it plays a significant role in energy transformation and environmental utilization. CeO 2 has attracted widespread attention for its unique 4 f electrons, rich defect structures, high oxygen storage capacity and great chemical stability. In this paper, we review the structure of CeO 2 and the common methods for the preparation of CeO 2 -based composites in the first part. In particular, we highlight the co-precipitation method, template method, and sol-gel method methods. Then, in the second part, we introduce the application of CeO 2 -based composites in photocatalysis, including photocatalytic CO 2 reduction, hydrogen production, degradation, selective organic reaction, and photocatalytic nitrogen fixation. In addition, we discuss several modification techniques to improve the photocatalytic performance of CeO 2 -based composites, such as elemental doping, defect engineering, constructing heterojunction and morphology regulation. Finally, the challenges faced by CeO 2 -based composites are analyzed and their development prospects are prospected. This review provides a systematic summary of the recent advance of CeO 2 -based composites in the field of photocatalysis, which can provide useful references for the rational design of efficient CeO 2 -based composite photocatalysts for sustainable development., (© 2024 Wiley-VCH GmbH.)

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo . Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation., Competing Interests: 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., (© 2024 The Authors.)

Opioids exert analgesic effects by agonizing opioid receptors and activating signaling pathways coupled to receptors such as G-protein and/or β-arrestin. Concomitant respiratory depression (RD) is a common clinical problem, and improvement of RD is usually achieved with specific antagonists such as naloxone; however, naloxone antagonizes opioid analgesia and may produce more unknown adverse effects. In recent years, researchers have used various methods to isolate opioid receptor-mediated analgesia and RD, with the aim of preserving opioid analgesia while attenuating RD. At present, the focus is mainly on the development of new opioids with weak respiratory inhibition or the use of non-opioid drugs to stimulate breathing. This review reports recent advances in novel opioid agents, such as mixed opioid receptor agonists, peripheral selective opioid receptor agonists, opioid receptor splice variant agonists, biased opioid receptor agonists, and allosteric modulators of opioid receptors, as well as in non-opioid agents, such as AMPA receptor modulators, 5-hydroxytryptamine receptor agonists, phosphodiesterase-4 inhibitors, and nicotinic acetylcholine receptor agonists., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Portal vein injury is an uncommon complication of endoscopic retrograde cholangiopancreatography (ERCP), for which stent malpositioning in the portal vein is very rare and can lead to fatal events. We report a case of biliary stent migration to the portal vein and a novel method for its safe removal under the guidance of portal angiography. Moreover, we reviewed the literature and summarized reports on the identification and management of this condition., Case Summary: A 59-year-old woman with pancreatic cancer presented with abdominal pain and a high fever 20 days after the placement of two plastic biliary stents under the guidance of ERCP. Blood cultures and laboratory tests revealed sepsis, which was treated with antibiotics. A contrast-enhanced computed tomography scan revealed that one of the biliary stents in the main portal vein was malpositioned. To safely remove the stent, portal angiography was performed to visualize the portal vein and to allow the management of any bleeding. The two stents were removed without obvious bleeding, and an uncovered self-expanding metal stent was placed in the common bile duct for drainage. The patient had an uneventful 6-month follow-up period, except for self-resolving portal vein thrombosis., Conclusion: The combination of endoscopic and angiographic techniques allowed uneventful management of stent malposition in the portal vein., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)] 2 ( 1 ), [Ag(3-apy)(mef)] ( 2 ), [Ag 2 (tmpyz)(mef) 2 ] ( 3 ), and {[Ag(4,4'-bipy)(mef)] 2 (CH 3 CN) 1.5 (H 2 O) 2 } n ( 4 ), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.

Background: Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures., Methods: The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture., Results: The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516)., Conclusions: RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD., (© 2024. The Author(s).)

Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C-H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which's an important synthetic intermediate of antifungal drug Ravuconazole., (© 2024. The Author(s).)

Introduction: In immunotherapy, antibodies are activated to block immune checkpoints, resist tumour immunosuppression, shrink tumours and prevent a recurrence. As the science behind tumour immunotherapy continuously develops and improves, neoadjuvant immunotherapy bears more prominent advantages: antigen exposure not only enhances the degree of tumour-specific T-cell response but also prolongs the duration of actions. In this study, we evaluated the efficacy and safety of McKeown minimally invasive oesophagectomy (McKeown MIO) following neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced oesophageal cancer (OC)., Patients and Methods: In this retrospective study, 94 patients underwent either NICT or neoadjuvant chemotherapy (NCT) followed by MIO at our institution from January 2020 to October 2022. We assessed the therapy-related adverse events and perioperative outcomes and compared them between the two groups., Results: After completing at least two cycles of neoadjuvant therapy, all patients underwent McKeown MIO with negative margins within 4-7 weeks. Demographic data of the two cohorts were similar. Regarding perioperative characteristics, the median intraoperative blood loss was 50 ml in the NICT group, lower than that of the NCT group (100 ml, P < 0.05). In addition, the NICT group had significantly more harvested lymph nodes than the NCT group ( P < 0.05). No significant differences were found in post-operative complications. The rate of objective response rate in the NICT group was higher than that in the NCT group (88.3% vs. 58.8%). Regarding tumour regression, the number of patients with TRG Grades 1-3 in the NICT group was more than that in the NCT. Adverse events experienced by the two groups included anaemia and elevated transaminase. We found no difference in the adverse events between the two groups., Conclusions: This study showed the efficacy and feasibility of NICT followed by McKeown MIO in treating locally advanced OC., (Copyright © 2023 Copyright: © 2023 Journal of Minimal Access Surgery.)

2D polarization materials have emerged as promising candidates for meeting the demands of device miniaturization, attributed to their unique electronic configurations and transport characteristics. Although the existing inherent and sliding mechanisms are increasingly investigated in recent years, strategies for inducing 2D polarization with innovative mechanisms remain rare. This study introduces a novel 2D Janus state by modulating the puckered structure. Combining scanning probe microscopy, transmission electron microscopy, and density functional theory calculations, this work realizes force-triggered out-of-plane and in-plane dipoles with distorted smaller warping in GeSe. The Janus state is preserved after removing the external mechanical perturbation, which could be switched by modulating the sliding direction. This work offers a versatile method to break the space inversion symmetry in a 2D system to trigger polarization in the atomic scale, which may open an innovative insight into configuring novel 2D polarization materials., (© 2024 Wiley‐VCH GmbH.)

Microglia-mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21) has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood-brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane-coated PEGylated liposomes (hFGF21@BCM-LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM-LIP specifically targets Aβ 1-42 -induced BV2 cells, with uptake hindered by anti-VCAM-1 antibody, indicating the importance of VCAM-1 and integrin α4/β1 interaction in targeted delivery to BV2 cells. In vivo, following subcutaneous injection near the lymph nodes of the neck, hFGF21@BCM-LIP diffuses into lymph nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid-beta (Aβ 1-42 )-induced mice. Furthermore, the administration of hFGF21@BCM-LIP to activated microglia improves cognitive deficits caused by Aβ 1-42 and reduces levels of tau, p-Tau, and BACE1. It also decreases interleukin-6  (IL-6) and tumor necrosis factor-α (TNF-α) release while increasing interleukin-10 (IL-10) release both in vivo and in vitro. These results indicate that hFGF21@BCM-LIP can be a promising treatment for AD, by effectively crossing the blood-brain barrier and targeting delivery to brain microglia via the neck-meningeal lymphatic vasculature-brain parenchyma pathways., (© 2024 Wiley‐VCH GmbH.)

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Although organic-inorganic hybrid one-dimensional (1D) lead halide postperovskites (LHPPs) have been reported to show white luminescence and tunable photoluminescence quantum yield (PLQY), their structure-property relationships are not fully understood. Here, we used Mn 2+ to test the doping effect on the luminescence of two 1D-LHPPs compounds, namely, {TETA[Pb 2 Br 6 ]} n 1 and {TETA[Pb 2 Cl 6 ]} n 2 , where TETA = triethylenetetrammonium. We found the pristine compounds show yellowish (551 nm) and bluish (447 nm) emission for 1 and 2 , respectively, nanosecond excitation lifetimes (4.17 ns for 1 and 2.29 ns for 2 ) and low PLQYs (4.65 and 3.57% for 1 and 2 , respectively). By fine-doping the Mn 2+ ions to ca. 8% the PLQYs for 1 and 2 are maximized to 24 and 25% for 1 and 2 , respectively. Upon the increasing Mn 2+ dopant, the emission wavelengths can also vary gradually from 551 to 615 nm and from 447 to 660 nm for 1 and 2 , respectively, covering almost the whole visible-light range, and the excitation lifetimes are enhanced to microseconds (0.77 μs for 1 and 0.39 μs for 2 ), owing to the more spin-forbidden d-d transition ( 4 T 1 - 6 A 1 ) component from the Mn 2+ ions present in the photoluminescence spectra. Moreover, these Mn 2+ -doped 1D-LHPPs demonstrate high structural and optical stability in humid and high-temperature environments. Hence, such doped materials can be fabricated into a UV-pumped white light-emitting diode, rendering the potential application for solid-state lighting and display systems.

Study Objectives: In older adults with Alzheimer's disease, slowing of electroencephalographic (EEG) activity during REM sleep has been observed. Few studies have examined EEG slowing during REM in those with mild cognitive impairment (MCI) and none have examined its relationship with cognition in this at-risk population., Methods: Two hundred and ten older adults (mean age = 67.0, SD = 8.2 years) underwent comprehensive neuropsychological, medical, and psychiatric assessment and overnight polysomnography. Participants were classified as subjective cognitive impairment (SCI; n = 75), non-amnestic MCI (naMCI, n = 85), and amnestic MCI (aMCI, n = 50). REM EEG slowing was defined as (δ + θ)/(α + σ + β) power and calculated for frontal, central, parietal, and occipital regions. Analysis of variance compared REM EEG slowing between groups. Correlations between REM EEG slowing and cognition, including learning and memory, visuospatial and executive functions, were examined within each subgroup., Results: The aMCI group had significantly greater REM EEG slowing in the parietal and occipital regions compared to the naMCI and SCI groups (partial η2 = 0.06, p < 0.05 and 0.06, p < 0.05, respectively), and greater EEG slowing in the central region compared to SCI group (partial η2 = 0.03, p < 0.05). Greater REM EEG slowing in parietal (r = -0.49) and occipital regions (r = -0.38 [O1/M2] and -0.33 [O2/M1]) were associated with poorer visuospatial performance in naMCI., Conclusions: REM EEG slowing may differentiate older adults with memory impairment from those without. Longitudinal studies are now warranted to examine the prognostic utility of REM EEG slowing for cognitive and dementia trajectories., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Background/purpose(s): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation., Methods: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples., Results: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA., Conclusion: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies., (© 2024. The Author(s).)

Herein we have pioneered an innovative synthetic strategy for the efficient assembly of various heteroarene-condensed benzofuran derivatives, utilizing benzofuran-derived azadienes (BDAs) and quinolines as the starting materials. This method functions with transition-metal catalysis and uses cost-effective formic acid as the reducing agent. Mechanistic investigations indicate that this transformation would involve a [4 + 2] annulation cascade process. This approach demonstrates a high tolerance to various functional groups and yields excellent results.