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Ying-Jie Ma,1,* Meng-Yao Li,1,2,* Jing-Yan Song,1,3 Zhen-Gao Sun1,3 1The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Reproductive and Genetic Center of Integrative Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen-Gao Sun; Jing-Yan Song, Tel +8653182950414, Email sunzhengao77@126.com; hanlingjuzei91@126.comRationale: Idiopathic hypogonadotropic hypogonadism (IHH) is a prevalent congenital genetic disorder with multiple inheritance patterns. IHH can manifest as normal hypogonadotrophic sexual hypofunction (nIHH) or with an abnormal sense of smell, known as Kallmann. It primarily affects the production and effectiveness of gonadotropin-releasing-hormone (GnRh), leading to reduced follicle-stimulating hormone and luteinizing hormone levels. This results in infertility and underdeveloped secondary sexual characteristics.Patient Concerns: A 29-year-old female presented with infertility.Diagnosis: IHH diagnosis was confirmed through magnetic resonance (MR) scan, endocrine tests, physical examination, and B ultrasonic inspection. Additionally, genetic studies, including chromosome analysis, were conducted for the patient. The results confirmed no genetic abnormalities or concerns.Interventions: The patient underwent multiple ovulation induction programs.Outcome: After several ovulation induction cycles, the patient conceived and delivered a live baby.Lessons: For IHH patients, a tailored human menopausal gonadotropin (HMG) dose is recommended. High-dose HMG can benefit those with poor follicular response. The addition of letrozole (5– 7.5mg) may enhance follicular response during stimulation. Our approach, which emphasizes the combined use of high-dose HMG, letrozole, and the adjustment of FSH and LH ratios, offers a unique perspective compared to traditional treatments. If HMG treatment is ineffective, alternative ovulation induction methods, such as r-fsh combined with r-lh or HMG combined with rLH, can be considered. Adjusting the FSH and LH ratio and varying rFSH and rLH additions might help achieve dominant follicles and live birth in resistant cases. This case report underscores the potential benefits of our regimen, suggesting its consideration for future research and clinical applications.Keywords: HMG, IHH, infertility, rLH

Yue-Ling Peng,1 Yan Zhang,1 Lin Pang,2 Ya-Fang Dong,3 Mu-Ye Li,4 Hui Liao,5 Rong-Shan Li1 1Department of Nephrology, Shanxi Provincial People’s Hospital (Fifth Hospital of Shanxi Medical University), Taiyuan, People’s Republic of China; 2Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pathology and Pathophysiology, School of Basic Medicine, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Department of Ocular Fundus Diseases, Shanxi Eye Hospital, Shanxi Medical University, Taiyuan, People’s Republic of China; 5Drug Clinical Trial Institution, Shanxi Provincial People’s Hospital (Fifth Hospital of Shanxi Medical University), Taiyuan, People’s Republic of ChinaCorrespondence: Rong-Shan Li, Department of Nephrology, Shanxi Provincial People’s Hospital (Fifth Hospital of Shanxi Medical University), Taiyuan, People’s Republic of China, Email rongshanli@126.comBackground: Increasing evidence suggests that immune modulation contributes to the pathogenesis and progression of diabetic nephropathy (DN). However, the role of immune modulation in DN has not been elucidated. The purpose of this study was to search for potential immune-related therapeutic targets and molecular mechanisms of DN.Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. A total of 1793 immune-related genes were acquired from the Immunology Database and Analysis Portal (ImmPort). Weighted gene co-expression network analysis (WGCNA) was performed for GSE142025, and the red and turquoise co-expression modules were found to be key for DN progression. We utilized four machine learning algorithms, namely, random forest (RF), support vector machine (SVM), adaptive boosting (AdaBoost), and k-nearest neighbor (KNN), to evaluate the diagnostic value of hub genes. Immune infiltration patterns were analyzed using the CIBERSORT algorithm, and the correlation between immune cell type abundance and hub gene expression was also investigated.Results: A total of 77 immune-related genes of advanced DN were selected for subsequent analyzes. Functional enrichment analysis showed that the regulation of cytokine–cytokine receptor interactions and immune cell function play a corresponding role in the progression of DN. The final 10 hub genes were identified through multiple datasets. In addition, the expression levels of the identified hub genes were corroborated through a rat model. The RF model exhibited the highest AUC. CIBERSORT analysis and single-cell sequencing analysis revealed changes in immune infiltration patterns between control subjects and DN patients. Several potential drugs to reverse the altered hub genes were identified through the Drug-Gene Interaction database (DGIdb).Conclusion: This pioneering work provided a novel immunological perspective on the progression of DN, identifying key immune-related genes and potential drug targets, thus stimulating future mechanistic research and therapeutic target identification for DN.Keywords: diabetic nephropathy, machine learning, single cell, cell-to-cell communication, immune therapy

Ying-Jie Ma,1,* Meng-Yao Li,1,* Jing-Yan Song,1,2 Zhen-Gao Sun1,2 1The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250011, People’s Republic of China; 2Reproductive and Genetic Center of Integrative Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250014, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen-Gao Sun; Jing-Yan Song, Reproductive and Genetic Center of Integrative Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42, Wenhua Road (W), Lixia District, Jinan, Shandong, 250014, People’s Republic of China, Email sunzhengao77@126.com; hanlingjuzei91@126.comBackground: Gonadotropin-releasing hormone antagonists (GnRH-ant) are widely used in current in vitro fertilization-embryo transfer (IVF-ET), however, whether the lowest daily dose of GnRH-ant is individualized remains unknown. Due to the negative effect of GnRH-ant on endometrial receptivity, lessening the amount of GnRH-antagonists used during controlled ovarian stimulation may be helpful for embryo implantation. As such, a randomized controlled study is essential to validate the feasibility and efficacy of daily GnRH-ant dose reduction to 0.125 mg geared towards providing scientific evidence for guidance in clinical practice.Methods: In total, 620 infertile women undergoing in vitro fertilization will be enrolled in the multicentered, randomized, parallel controlled trial. Based on a computer-generated random list, they will be randomly and equally subdivided into half-dose GnRH-ant group or conventional-dose GnRH-ant group. The primary outcome is ongoing pregnancy ie, intrauterine pregnancy diagnosed by pelvic ultrasonography at more than 12 weeks of gestation accompanied by normal fetal heartbeats. Secondary outcomes include cycle cancellation, premature luteinizing hormone surge, positive pregnancy, embryo implantation rate, clinical pregnancy, early spontaneous abortion, and live birth. The intention-to-treat and per protocol analyses will be used to initially analyze the difference in ongoing pregnancy rate between the two groups, while the multiple imputation method was used to handle missing values in the data.Discussion: At present, no randomized controlled trials (RCTs) have been performed on the use of the half-dose GnRH-ant protocol (0.125mg/d) to improve reproductive outcomes of IVF-ET in predicted normal responder, compared to conventional-dose GnRH-ant protocol (0.25mg/d). Half-dose GnRH-ant protocol might provide a suitable clinical solution for predicted normal responder undergoing IVF treatment. Thus, it is critical to conduct a well-designed RCT to evaluate the impact of a half-dose GnRH-ant protocol on the reproductive outcomes of IVF-ET in predicted normal responder.Trial Registration: This study was registered in the Chinese Clinical Trials Registry Platform on August 29, 2020. (chictr.org.cn; identifier: ChiCTR2000037629). This trial is version 1.3.Keywords: gonadotropin-releasing hormone antagonist, in vitro fertilization-embryo transfer, half-dose GnRH-ant protocol, predicted normal responder, randomized controlled trial

Xiao Lu,1,* Quan-Xing Liu,1,* Jiao Zhang,1 Dong Zhou,1 Gui-Xue Yang,1 Man-Yuan Li,1 Yuan Qiu,2 Qian Chen,3 Hong Zheng,1 Ji-Gang Dai1 1Department of Thoracic Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, People’s Republic of China; 2Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, People’s Republic of China; 3Cancer Center of Daping Hospital, Army Medical University, Chongqing 400042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ji-Gang Dai; Hong Zheng Email daijigang@tmmu.edu.cn; ziecoe@163.comBackground: Lung cancer remains the leading cause of cancer-related death worldwide. The human PINK1 gene (PTEN induced kinase 1, Park6), an important gene for Parkinson’s disease, was found to be associated with tumor development although the molecular mechanisms underlying this relationship remain largely unknown.Objective: To analyze the clinical value and molecular mechanism of PINK1 in non-small cell lung cancer (NSCLC).Materials and Methods: Western blot, qRT-PCR and Immunohistochemistry were employed to determine the levels of PINK1 in 87 paired NSCLC tissues, Oncomine and TCGA databases were also used for the evaluation of expression and prognosis of PINK1. The mitophagy, proliferation, migration, invasion, and apoptosis abilities of A549 and H1975 cells were detected, and the autophagy-related proteins in the cells were also determined.Results: Immunohistochemical staining revealed higher PINK1 expression in tumor tissues, which was strongly linked to the tumor-node-metastasis classification. Survival analysis of 1085 NSCLC patients also revealed that low PINK1 expression levels were associated with significantly longer overall survival. Univariate and multivariate analyses indicated that PINK1 expression was an independent predictor of overall survival among patients with NSCLC. We also evaluated the influence of PINK1 deficiency in NSCLC cell lines (A549 and H1975), which revealed significant suppression of migration capability and cell viability, as well as a significantly elevated apoptosis ratio. In cells with stable interference of PINK1 expression, dysfunctional mitochondria accumulated while autophagy was inhibited, which indicated that cell activity suppression was mediated by the accumulation of dysfunctional mitochondria. The suppression of migration and autophagy was reversed in cells that overexpressed PINK1.Conclusion: Our results suggest that PINK1 may be a potential therapeutic target and prognostic biomarker in NSCLC.Keywords: PINK1, NSCLC, mitochondria, autophagy, migration, proliferation

Xiaojun Huang,1,2 Zhaomin Deng,1 Qiang Zhang,1 Wanyi Li,1 Baoning Wang,1 Mingyuan Li1,3 1Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 2Department of Microbiology, School of Medicine, Hubei University for Nationalities, Enshi, People’s Republic of China; 3State Key Laboratory of Oral Diseases, Chengdu, People’s Republic of China Background: The complex pathogenesis of Helicobacter pylori (H. pylori) and the features of the host influence the diverse clinical outcomes. A mass of studies about virulence genes have accelerated the exploration of pathogenesis of H. pylori infection. Induced by contact with epithelium gene A (iceA) is one of the biggest concerned virulence genes. In this study, we explored the relationship between iceA and the magnitude of the risk for clinical outcomes and the prevalence of iceA-positive H. pylori in People’s Republic of China and other countries.Methods: We searched the electronic databases of PubMed, Embase, CNKI, VIP, and Wanfang by literature search strategy. The studies conforming to the inclusion criteria were assessed. With these data, we systematically analyzed the relationship between the iceA gene of H. pylori and clinical outcomes.Results: Nineteen articles with 22 studies, a total of 2,657 cases, were involved in the study. The iceA1 gene was significantly associated with peptic ulcer disease (odds ratio =1.28, 95% confidence interval =1.03–1.60; P=0.03), especially in People’s Republic of China (odds ratio =1.40, 95% confidence interval =1.07–1.83; P=0.01). Moreover, the prevalence of iceA1 was significantly higher than iceA2 in People’s Republic of China (P

Chirality characterizes an object that is not identical to its mirror image. In condensed matter physics, Fermions have been demonstrated to obtain chirality through structural and time-reversal symmetry breaking. These systems display unconventional electronic transport phenomena such as the quantum Hall effect and Weyl semimetals. However, for bosonic collective excitations in atomic lattices, chirality was only theoretically predicted and has never been observed. We experimentally show that phonons can exhibit intrinsic chirality in monolayer tungsten diselenide, whose lattice breaks the inversion symmetry and enables inequivalent electronic K and -K valley states. The time-reversal symmetry is also broken when we selectively excite the valley polarized holes by circularly polarized light. Brillouin-zone-boundary phonons are then optically created by the indirect infrared absorption through the hole-phonon interactions. The unidirectional intervalley transfer of holes ensures that only the phonon modes in one valley are excited. We found that such photons are chiral through the transient infrared circular dichroism, which proves the valley phonons responsible to the indirect absorption has non-zero pseudo-angular momentum. From the spectrum we further deduce the energy transferred to the phonons that agrees with both the first principle calculation and the double-resonance Raman spectroscopy. The chiral phonons have significant implications for electron-phonon coupling in solids, lattice-driven topological states, and energy efficient information processing.

© 2017, National Academy of Sciences. All rights reserved. Human schistosomiasis, caused by Schistosoma species, is a major public health problem affecting more than 700 million people in 78 countries, with over 40 mammalian host reservoir species complicating the transmission ecosystem. The primary cause of morbidity is considered to be granulomas induced by fertilized eggs of schistosomes in the liver and intestines. Some host species, like rats (Rattus norvegicus), are naturally intolerant to Schistosoma japonicum infection, and do not produce granulomas or pose a threat to transmission, while others, like mice and hamsters, are highly susceptible. The reasons behind these differences are still a mystery. Using inducible nitric oxide synthase knockout (iNOS−/−) Sprague–Dawley rats, we found that inherent high expression levels of iNOS in wild-type (WT) rats play an important role in blocking growth, reproductive organ formation, and egg development in S. japonicum, resulting in production of nonfertilized eggs. Granuloma formation, induced by fertilized eggs in the liver, was considerably exacerbated in the iNOS−/−rats compared with the WT rats. This inhibition by nitric oxide acts by affecting mitochondrial respiration and energy production in the parasite. Our work not only elucidates the innate mechanism that blocks the development and production of fertilized eggs in S. japonicum but also offers insights into a better understanding of host–parasite interactions and drug development strategies against schistosomiasis.

YEuBaCuO(x = 0, 0.1, 0.3, 0.5) thin films were prepared on buffered substrates by trifluoroacetate metal organic deposition (TFA-MOD). The europium-doped film showed better out- and in-plane texture than the pure YBaCuO thin film and special topography. In the meantime, the superconducting transition temperature T was improved with the increase of europium content and spanned a small range when x= 0.5 doping levels. Besides, the J value was obviously enhanced with europium addition, and YEuBaCuO showed the best superconducting properties under self-field. Furthermore, the J value was obviously improved under magnetic field, and the enhanced flux-pinning properties was also observed in europium-substituted samples which may be attributed to the good grain connections and the effective flux pinning centers introduced by europium addition. The thickness of prepared film samples were approximately 400 nm. The structure of samples were characterized by x-ray diffraction (XRD), Raman spectrum was used to investigate the crystallization and growth orientation, and the surface morphology of films were got by field-emission scanning electronic microscopy (FE-SEM). Moreover, energydispersive spectroscopy (EDS) was utilized to determine element composition. Spatial distribution of J of the film was obtained by mapping analysis of inductive measurement at 77 K. And the superconducting properties under magnetic fields were measured by magnetic property measurement system with a SQUID magnetometer. [ABSTRACT FROM AUTHOR]

Contents Small RNA represents several unique non-coding RNA classes that have important function in a wide range of biological processes including development of germ cells and early embryonic, cell differentiation, cell proliferation and apoptosis in diverse organisms. However, little is known about their expression profiles and effects in yak oocytes maturation and early development. To investigate the function of small RNAs in the maturation process of yak oocyte and early development, two small RNA libraries of oocytes were constructed from germinal vesicle stage ( GV) and maturation in vitro to metaphase II-arrested stage (M II) and then sequenced using small RNA high-throughput sequencing technology. A total of 9,742,592 and 12,168,523 clean reads were obtained from GV and M II oocytes, respectively. In total, 801 and 1,018 known mi RNAs were acquired from GV and M II oocytes, and 75 mi RNAs were found to be significantly differentially expressed: 47 mi RNAs were upregulated and 28 mi RNAs were downregulated in the M II oocytes compared to the GV stage. Among the upregulated mi RNAs, miR-342 has the largest fold change (9.25-fold). Six highly expressed mi RNAs (let-7i, miR-10b, miR-10c, miR-143, miR-146b and miR-148) were validated by real-time quantitative PCR ( RT- qPCR) and consistent with the sequencing results. Furthermore, the expression patterns of two mi RNAs and their potential targets were analysed in different developmental stages of oocytes and early embryos. This study provides the first mi RNA profile in the mature process of yak oocyte. Seventy-five mi RNAs are expressed differentially in GV and M II oocytes as well as among different development stages of early embryos, suggesting mi RNAs involved in regulating oocyte maturation and early development of yak. These results showed specific mi RNAs in yak oocytes had dynamic changes during meiosis. Further functional and mechanistic studies on the mi RNAs during meiosis may beneficial to understanding the role of mi RNAs on meiotic division. [ABSTRACT FROM AUTHOR]

Background and Purpose: The lung adenocarcinoma cell line, A549, undergoes epithelial-mesenchymal cell transition (EMT) in response to TGF-β. Glucocorticoids do not prevent the EMT response, but TGF-β induced resistance to the cytokine-regulatory action of glucocorticoids. We sought to characterize the impairment of glucocorticoid response in A549 cells.Experimental Approach: A549 cells were exposed to TGF-β for up to 96 h before glucocorticoid treatment and challenge with IL-1α to assess glucocorticoid regulation of IL-6 and CXCL8 production. Nuclear localization of the glucocorticoid receptor α (GRα) was ascertained by immunofluorescence and Western blotting. Transactivation of the glucocorticoid response element (GRE) was measured with a transfected GRE-secreted human placental alkaline phosphatase reporter.Key Results: TGF-β (40-400 pM) reduced the maximum inhibitory effect of dexamethasone on IL-1α-induced IL-6 and CXCL8 production. The impaired glucocorticoid response was detected with 4 h of TGF-β (40 pM) exposure (and 4 h IL-1α to induce CXCL8 expression) and therefore was not secondary to EMT, a process that requires longer incubation periods and higher concentrations of TGF-β. TGF-β also impaired dexamethasone regulation of granulocyte-macrophage colony-stimulating factor in thrombin-stimulated BEAS-2B epithelial cells. Impaired regulation of CXCL8 was associated with markedly reduced GRE transactivation and reduced induction of mRNA for IκBα, the glucocorticoid-inducible leucine zipper and the epithelial sodium channel (SCNN1A). The expression, cellular levels and nuclear localization of GRα were reduced by TGF-β.Conclusions and Implications: We have identified mechanisms underlying the impairment of responses to glucocorticoids by TGF-β in the A549 and BEAS-2B cell lines. [ABSTRACT FROM AUTHOR]

The stroma surrounding cancer cell population is increasingly recognized as playing an important role in cancer proliferation, invasion, and metastasis. To identify the stromal proteins involved in nasopharyngeal carcinoma (NPC) carcinogenesis, differences in protein expression of the stroma from NPC and normal nasopharyngeal epithelium tissues (NNET) were assessed using a comparative proteomic approach combined with laser capture microdissection (LCM). LCM was performed to purify stromal cells from NPC and NNET, respectively. Proteins between the pooled microdissected tumor and normal stroma were separated by two-dimensional electrophoresis (2-DE) and differential proteins were identified by mass spectrometry (MS). Sixty differential proteins between normal stroma (NS) and tumor stroma (TS) were identified, and the expression of CapG protein was further confirmed by western blotting and immunohistochemical analysis. Our results will be helpful to study the role of stroma in the NPC carcinogenesis and may provide helpful clues for pathogenesis, early diagnosis, and progression of NPC. [ABSTRACT FROM AUTHOR]

Aims: To screen for differentially tyrosine-phosphorylated proteins between nasopharyngeal carcinoma (NPC) and normal nasopharyngeal epithelial tissues (NNET) to provide a basis for elucidate the molecular mechanisms of NPC carcinogenesis.Methods: Two-dimensional (2-D) electrophoresis was applied to separate proteins from NPC and NNET, respectively, and 2-D Western blotting was performed to detect tyrosine-phosphorylated proteins using antiphosphotyrosine antibody. Differentially tyrosine-phosphorylated proteins were identified by electrospray ionization-quadrupole time-of-flight MS (ESI-Q-TOF MS). NetPhos software was used to predict the tyrosine-phosphorylation sites of the identified proteins, and Western blotting was used to detect the tyrosine-phosphorylated levels of RKIP in NPC and NNET.Results: Twenty-five differentially tyrosine-phosphorylated proteins in the two types of tissues were found, 13 of which were identified by ESI-Q-TOF MS. Among the 13 identified proteins, tyrosine-phosphorylated levels of 7 proteins were increased, and those of 6 proteins were decreased in NPC compared with NNET. NetPhos software prediction showed that all the 13 identified proteins contained tyrosine phosphorylation sites, and the differentially tyrosine-phosphorylated level of RKIP in NPC and NNET was confirmed.Conclusion: The 13 differentially tyrosine-phosphorylated proteins may be involved in the development and progression of NPC. [ABSTRACT FROM AUTHOR]

Эффективная и длительная терапия остеопороза не возможна без активного, правильного участия пациента в этом процессе, который требуется проведения образовательных программ. Цель. Оценить эффективность проведения образовательных мероприятий для больных ОП. Материал и методы. 48 пациентов с ОП основной группы прошли обучение в школе (5 занятий в течение года), 40 пациентов составили контрольную группу, которые только приходили на консультацию ревматолога 4-5 раз за год. Группы были сопоставимы по полу, возрасту, структуре (первичный и вторичный) и тяжести ОП, наличию переломов, получаемой терапии. Исходно и через 6 месяцев определялись интенсивность болевого синдрома в спине по ВАШ, приверженность к лечению. Исходно и через 12 месяцев проведена денситометрия. Результаты. Через 6 месяцев от начала обучения интенсивность боли в спине достоверно (р

This study evaluates the survival outcomes of segmental ureterectomy (SU) combined with chemotherapy in patients with high-grade non-metastatic ureteral cancer (UC) using data from the SEER database. A total of 1757 patients with Grade III-IV non-metastatic UC were analyzed. Overall survival (OS) was assessed through Kaplan-Meier analysis, and independent prognostic factors were identified via Cox regression. A Nomogram model was developed and evaluated using the concordance index, area under the time-dependent ROC curve, calibration curves, and decision curve analysis. The 1-, 3-, and 5-year OS rates were 82.8%, 55.6%, and 42.8%, respectively. Age, treatment protocol, T stage, and N stage were significant prognostic factors. Both SU + chemotherapy and radical nephroureterectomy (RNU) + chemotherapy demonstrated comparable survival outcomes, outperforming surgery alone, particularly in patients aged 70 and older. The Nomogram demonstrated high predictive accuracy and clinical utility. These findings suggest that SU + chemotherapy offers survival benefits similar to RNU + chemotherapy, making it a viable option, especially for elderly patients or those with impaired renal function., (© 2024. The Author(s).)

In recent years, metal-organic framework (MOF) materials with long persistent luminescence (LPL) have inspired extensive attention and presented various applications in security systems, information anticounterfeiting, and biological imaging fields. However, obtaining LPL materials with ultralong lifetime remains challenging. Halogen atoms, as nonmetallic elements existing in the frameworks, can not only induce the heavy-atom effect, effectively enhancing spin-orbit coupling and promoting intersystem crossing (ISC) processes, but also suppress non-radiative transition of the triplet states through the intra- and intermolecular interactions. Specifically, fluorine atoms with the strongest electronegativity may form intermolecular aggregate interlockings through halogen-bonding interactions that restrict molecular motions and vibrations, thereby improving phosphorescent lifetime. With the aforementioned considerations, two distinct types of MOFs with/without fluorine atoms (namely, Ca-MOF and 5FCa-MOF) were synthesized. Notably, by introducing fluorine atoms into MOFs, fluorine-induced intermolecular aggregate interlockings effectively enhanced the phosphorescent lifetime of 5FCa-MOF exceeding 264 ms compared to that of Ca-MOF (103.94 ms). Remarkably, both MOFs displayed bright LPL to the naked eye after removal of the irradiation source, especially 5FCa-MOF which can last for about 2 s. By introducing fluorine atoms, 5FCa-MOF exhibits greatly enhanced ISC with a rate constant up to 4.1 × 10 6 s -1 and suppressed non-radiative decay down to 3.73 s -1 , thereby extending the LPL time. The thus obtained LPL provides potential in information encryption, security systems, optical anticounterfeiting, and so on.

An ingenious microstructure of electromagnetic microwave absorption materials is crucial to achieve strong absorption and a broad bandwidth. Herein, one-dimensional (1D) carbon fibers with implantation of zero-dimensional (0D) ZIF-8-derived carbon frameworks and construction of a three-dimensional (3D) microcosmic multichannel porous structure are fabricated by electro-blown spinning, solvent-thermal reaction, and high-temperature pyrolysis techniques. The 1D carbon fiber skeleton with a multichannel structure provides a direct axial conductive pathway for charge transport, which plays an important role in dielectric loss. The 0D surface carbon frameworks offer plenty of heterogeneous interfaces to trigger intensive interfacial polarization loss and act as dihedral angles for microwave scattering. The 3D microcosmic multichannel pores can not only generate multiple reflections as much as possible to dissipate electromagnetic microwave energy but also supply huge interior cavities to improve impedance matching. Thanks to the synergistic effect of a strong electrically conductive pathway for enhancing the conductive loss, a plenteous heterogeneous interface for triggering intensive interfacial polarization loss, microcosmic multichannel pores for generating multiple reflections and improving impedance matching, and N and O atom doping for inducing dipole polarization, the optimal sample with an ingenious microstructure delivers an excellent absorption performance of a minimum reflection loss of -35.5 dB at a thickness of 5.0 mm and an effective absorption bandwidth of 6.72 GHz (10.96-17.68 GHz) at a thickness of 2.0 mm. Such a well-designed multichannel porous carbon fiber may pave the way for the exploitation of high-performance microwave absorbing materials.

Terrestrial runoff is a key pathway for the transmission of the terrestrial pathogen Toxoplasma gondii from land to sea, posing a significant threat to marine ecosystems. Understanding the mechanisms by which T. gondii is transported from terrestrial to marine environment is crucial for developing effective prevention and control strategies for toxoplasmosis in marine organisms. This study investigates the transport of T. gondii through terrestrial runoff in the Sow River, a representative watershed in Weihai, China. Surface water, bottom water and sediment samples were collected and analyzed for T. gondii DNA using PCR methods. Out of 5328 samples, the prevalence of T. gondii was found to be 8.61 % in surface water, 9.80 % in bottom water and 16.61 % in sediment, with sediment identified as a significant reservoir. Additionally, estuarine zones showed a higher prevalence of T. gondii (16.80 %) compared to riverine areas (9.00 %). The study further revealed that seasonal climate variations, such as temperature and precipitation, had no significant impact on the distribution of T. gondii. However, there was significant spatial variability, with estuarine conditions facilitating increased pathogen transmission. These findings highlight the importance of estuaries and sediments as key conduits for T. gondii entry in marine food webs. The results provide a theoretical basis for designing infection prevention and control strategies aimed at protecting marine ecosystems., 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 B.V. All rights reserved.)

Abnormalities in thalamocortical crosstalk can lead to neuropsychiatric disorders. Variants in CACNA1G, which encodes the α1G subunit of the thalamus-enriched T-type calcium channel, are associated with absence seizures, intellectual disability, and schizophrenia, but the cellular and circuit consequences of these genetic variants in humans remain unknown. Here, we developed a human assembloid model of the thalamocortical pathway to dissect the contribution of genetic variants in T-type calcium channels. We discovered that the M1531V CACNA1G variant associated with seizures led to changes in T-type currents in thalamic neurons, as well as correlated hyperactivity of thalamic and cortical neurons in assembloids. By contrast, CACNA1G loss, which has been associated with risk of schizophrenia, resulted in abnormal thalamocortical connectivity that was related to both increased spontaneous thalamic activity and aberrant axonal projections. These results illustrate the utility of multi-cellular systems for interrogating human genetic disease risk variants at both cellular and circuit level., Competing Interests: Declaration of interests Stanford University has filed a provisional patent application covering the generation of multi-region assembloids. M.H.P. is on the Board of Directors and holds equity in Graphite Bio. M.H.P. serves on the SAB of Allogene Tx and is an advisor to Versant Ventures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti-osteoporotic mechanism are still unclear, restricting its development and application., Methods: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti-osteoporosis targets and mechanism were predicted using network pharmacology., Results: A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan-ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K-Akt signaling pathway, estrogen signaling pathway, and so on., Conclusions: This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti-osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis., (© 2024 John Wiley & Sons Ltd.)

The transition of stem cells from a quiescent state to an active state is a finely tuned process that requires the dismantling of the quiescence program and the establishment of a cell cycle-promoting transcriptional landscape. Whether epigenetic processes control stem cell states to promote the regeneration of adult tissues remains elusive. In this study, we show that a repressive histone modification, H2AK119ub, is dynamic between quiescent and active hair follicle stem cells (HFSCs) in the adult murine skin. Ablation of H2AK119ub in HFSCs leads to impaired quiescence leading to premature activation and an eventual exhaustion of HFSC pool. Transcriptional and chromatin studies revealed that H2AK119ub directly represses a proliferation promoting transcriptional program in the HFSCs to preserve quiescence. Lastly, we identify that the inhibitory FGF signaling produced by the hair follicle niche keratinocytes maintains H2AK119ub in quiescent HFSCs. Together, these findings reveal that a repressive histone mark, H2AK119ub, is under the dynamic regulation of inhibitory niche signaling to prevent the untimely establishment of an activated state to preserve SC function and longevity.

Aims: As aging is a major risk factor for chronic diseases, strategies to promote healthy aging are essential. Dietary diversity has been reported to be beneficial for human health, however, the role in the biological aging process remains underexplored. Our aim was to analyse the potential link between diet diversity and aging., Methods: Twenty-two thousand six hundred participants from the National Health and Nutrition Examination Survey (NHANES) were included in this study. Dietary diversity was assessed by the dietary diversity score (DDS), which aggregated data on participants' self-reported dietary categories for the 5 major food groups (18 subgroups) over 2 rounds. Biological age was determined using the phenotypic age, with the residual between biological age and chronological age, phenotypic age acceleration, representing biological aging advance. Weighted multivariate regressions analysis were used to examine the relationship between DDS and phenotypic age acceleration. Sensitivity, subgroup interaction and mediation analyses were employed for further analysis., Results: Higher DDS was consistently associated with slower phenotypic age acceleration ( β  < 0, p  < 0.001). Subgroup analyses revealed that the inverse relationship persisted across categories, with minimal interaction effects. Sensitivity analyses confirmed the robustness of results. The oxidative stress indicator glutamyltransferase partially mediated the relationship between DDS and aging [4.9% (3.6, 6.0%), p  < 0.001]., Conclusion: Dietary diversity is associated with a slower rate of biological aging, which may be due in part to reduced oxidative stress. These findings underscore the potential of a rich, broad-spectrum diet to promote healthy aging and reduce the burden of age-related diseases., 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 Liao and Li.)

Heavy metal pollution from informal e-waste recycling may adversely affect child growth. However, the potential toxic mechanisms from a population perspective remain unknown. Herein, 18 hair heavy metals, urinary metabolomics, and three child growth indices [i.e., weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), and BMI Z-score (BMIZ)] were measured in children from e-waste recycling (ER, N = 426) and control areas (CR, N = 247). We examined longitudinal changes in heavy metal exposure and child growth after e-waste control to further elucidate causal relationships. Results showed that children in regulated ER site were still exposed to higher levels of several heavy metals and experienced poorer growth compared to those in control areas. Elevated exposure to heavy metals like tin, antimony, lead, cadmium, and cobalt correlated with poor child growth, particularly affecting girls and younger children. Tin, rather than traditionally concerning heavy metals, exhibited the most crucial role in driving the adverse effects of metal mixtures on child growth. Reducing heavy metal exposure through e-waste control could notably improve child growth, confirming the causal relationship between heavy metal exposure and poor child growth and underscoring the health benefits of e-waste regulation. Our research identified the roles of steroid biosynthesis, folate biosynthesis, amino acid metabolism, and purine metabolism in mediating the effects of metal exposure on child growth. Testosterone glucuronide, riboflavin, folic acid, xanthosine, and xanthine emerged as key mediators, potentially serving as metabolic signatures of heavy metal exposure. These findings illuminate the toxic mechanisms underlying poor child growth resulted from heavy metal exposure, offering important insights from a population-based perspective. In addition to lead and cadmium, monitoring and regulating tin and antimony are crucial to mitigate their negative impact on child growth in e-waste recycling areas., 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 Ltd. All rights reserved.)

Although the strigolactone (SL) signaling pathway and SL-mediated anthocyanin biosynthesis have been reported, the molecular association between SL signaling and anthocyanin biosynthesis remains unclear. In this study, we identified the SL signal transduction pathway associated with anthocyanin biosynthesis and the crosstalk between gibberellin (GA) and SL signaling in apple (Malus × domestica). ELONGATED HYPOCOTYL5 (HY5) acts as a key node integrating SL signaling and anthocyanin biosynthesis, and the SL-response factor AGAMOUS-LIKE MADS-BOX9 (AGL9) promotes anthocyanin biosynthesis by activating HY5 transcription. The SL signaling repressor SUPPRESSOR OF MAX2 1-LIKE8 (SMXL8) interacts with AGL9 to form a complex that inhibits anthocyanin biosynthesis by downregulating HY5 expression. Moreover, the E3 ubiquitin ligase PROTEOLYSIS1 (PRT1) mediates the ubiquitination-mediated degradation of SMXL8, which is a key part of the SL signal transduction pathway associated with anthocyanin biosynthesis. In addition, the GA signaling repressor REPRESSOR-of-ga1-3-LIKE2a (RGL2a) mediates the crosstalk between GA and SL by disrupting the SMXL8-AGL9 interaction that represses HY5 transcription. Taken together, our study reveals the regulatory mechanism of SL-mediated anthocyanin biosynthesis and uncovers the role of SL-GA crosstalk in regulating anthocyanin biosynthesis in apple., Competing Interests: Conflict of interest statement. None declared., (© 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.)

Ucp1 promoter-driven Cre transgenic mice are useful in the manipulation of gene expression specifically in thermogenic adipose tissues. However, the wildly used Ucp1-Cre line was generated by random insertion into the genome and showed ectopic activity in some tissues beyond adipose tissues. Here, we characterized a knockin mouse line Ucp1-iCre generated by targeting IRES-Cre cassette immediately downstream the stop codon of the Ucp1 gene. The Cre insertion had little to no effect on uncoupling protein 1 (UCP1) levels in brown adipose tissue. Ucp1-iCre mice of both genders exhibited normal thermogenesis and cold tolerance. When crossed with Rosa-tdTomato reporter mice, Ucp1-iCre mice showed robust Cre activity in thermogenic adipose tissues. In addition, limited Cre activity was sparsely present in the ventromedial hypothalamus (VMH), choroid plexus, kidney, adrenal glands, ovary, and testis in Ucp1-iCre mice, albeit to a much lesser extent and with reduced intensity compared with the conventional Ucp1-Cre line. Single-cell transcriptome analysis revealed Ucp1 mRNA expression in male spermatocytes. Moreover, male Ucp1-iCre mice displayed a high frequency of Cre-mediated recombination in the germline, whereas no such effect was observed in female Ucp1-iCre mice. These findings suggest that Ucp1-iCre mice offer promising utility in the context of conditional gene manipulation in thermogenic adipose tissues, while also highlighting the need for caution in mouse mating and genotyping procedures. NEW & NOTEWORTHY Ucp1 promoter-driven Cre transgenic mice are useful in the manipulation of gene expression specifically in thermogenic adipose tissues. The widely used Ucp1-Cre mouse line (Ucp1-Cre Evdr ), which was generated using the bacterial artificial chromosome (BAC) strategy, exhibits major brown and white fat transcriptomic dysregulation and ectopic activity beyond adipose tissues. Here, we comprehensively validate Ucp1-iCre knockin mice, which serve as another optional model besides Ucp1-Cre Evdr mice for specific genetic manipulation in thermogenic tissue.

Under the guidance of MS/MS-based molecular networking, five new clerodane diterpenoid glucosides, tinosinesides R-V (1-5), along with 15 known diterpenoids (6-20), were isolated from the stems of Tinospora sinensis. Compound 1 represents the first example of diterpenoid bearing a thio sugar and compound 5 is the first 18,19-dinor-clerodane with cis-fused A/B ring. The structures of the new compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation and chemical methods. Selected compounds were evaluated for their immunomodulatory effect and several compounds could enhance the proliferation of B lymphocytes. Preliminary mechanistic studies disclosed that 3 could promote B cell generation and inhibit B cell differentiation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) is a well-established treatment modality, typically conducted with single-wavelength irradiation, which may not always be optimal for varying tumor locations and sizes. To address this, photosensitizers with absorption wavelengths ranging from 550 to 760 nm are being explored. Herein, a series of 5,15-diaryltetrabenzoporphyrins (Ar 2 TBPs) were synthesized. All compounds displayed obvious absorption at 550-700 nm (especially at ∼668 nm), intense fluorescence, efficient generation of singlet oxygen and good photodynamic antitumor effects. Notably, compound I 3 (5,15-bis[(4-carboxymethoxy)phenyl]tetrabenzoporphyrin) showed excellent cytotoxicity against Eca-109 cell line upon red light irradiation, with an IC 50 value of 0.45 μM, and phototherapeutic index of 25.8. Flow cytometry revealed that I 3 could induce distinct cell apoptosis. In vivo studies revealed that compound I 3 selectively accumulated at tumor site and exhibited outstanding PDT effect with antitumor activity under single-time administration and light irradiation, and revealed more efficiency than the clinical photosensitizer Verteporfin. These findings underscore the considerable promise of I 3 as a robust theranostic agent, offering capabilities in real-time fluorescence imaging and serving as a potent photosensitizer for personalized and precise photodynamic therapy of tumors., 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.)

The spine grapes (Vitis davidii Foëx.) are wild grape species that grow in southern China, and can be used for table grapes, juicing and winemaking. To systematically investigate the flavor profiles of spine grapes, flavonoids and volatile compounds were detected in five spine grape varieties (Seputao, Ziqiu, Miputao, Tianputao and Baiputao) using HPLC-QqQ-MS/MS and GC-MS. The content of flavonoids highly depended on the variety, such as the total concentrations of anthocyanins (91.43-328.85 mg/kg FW) and flavonols (33.90 to 83.16 mg/kg FW). The volatile compounds with higher odor active value were selected to describe the aroma of spine grapes. Hexanal, (E)-2-hexenal and (E, Z)-2,6-nonadienal contributed to the higher herbaceous flavor to Baiputao and Ziqiu. β-Damascenone and (E)-2-nonenal gave Baiputao a flavor with more floral, fruity and earthy. Their characteristic flavor compounds were subsequently revealed using multivariate statistical analysis. The results helped producers to further develop and utilize the spine grapes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Perioperative hypothermia is a common anesthesia-related complication that can result in negative outcomes. Intraoperative active heating can positively impact these outcomes. Therefore this study aimed to investigate the effectiveness of three common heating devices for controlling hypothermia, improving thermal comfort, and reducing anesthesia recovery time., Design: Systematic review and meta-analysis., Methods: Seven electronic literature databases were searched from the inception date of the databases to March 18, 2022. RevMan 5.4 and Stata 15.1 were used to perform meta-analyses on the obtained data, and the Cochrane Evaluation Manual was used for quality risk assessment of the included studies., Findings: A total of 18 studies involving 1,511 patients undergoing surgery using heating devices were included. In this meta-analysis, a ranking method known as the Surface Under the Cumulative Ranking Curve (SUCRA) was used. SUCRA provides a numerical measure of the effectiveness of treatments, with higher values indicating superior efficacy. Findings demonstrated that the concurrent use of three heating devices led to an elevation in core body temperatures (SUCRA = 69.2%) and enhanced delayed recovery (SUCRA = 88.6%) as compared to the application of a single device. Furthermore, for thermal comfort, the employment of heating blankets proved to be the most effective (SUCRA = 87.8%)., Conclusions: This study showed the core body temperatures and reductions in delayed recovery were greater when three heating devices were used together as compared to use one of them alone. Heating blankets was the most effective option for improving the thermal comfort of patients. Thus, clinicians should opt for appropriate heating equipment according to the type of surgery and the characteristics and needs of patients. The choice of appropriate heating equipment will ensure surgical safety, improve patient comfort, and reduce surgical risks., Competing Interests: Declaration of Competing Interest We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agreed with submission to the International Journal of Nursing Practice. The study has no financial support and the authors have no conflicts of interest to declare. Prof. Xiao-ying Yan and Prof. Xiao-hong Huang will be responsible for the paper’s pre-publication., (Copyright © 2024 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)