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Humid heatwaves, characterized by high temperature and humidity combinations, challenge tropical societies. Extreme wet-bulb temperatures (TW) over tropical land are coupled to the warmest sea surface temperatures by atmospheric convection and wave dynamics. Here, we harness this coupling for seasonal forecasts of the annual maximum of daily maximum TW (TWmax). We develop a multiple linear regression model that explains 80% of variance in tropical mean TWmax and significant regional TWmax variances. The model considers warming trends and El Niño and Southern Oscillation indices. Looking ahead, the strong-to-very-strong El Niño at the end of 2023, with an Oceanic Niño Index of ∼2.0, suggests a 2024 tropical land mean TWmax of 26.2°C (25.9–26.4°C), and a 68% chance (24%–94%) of breaking existing records. This method also predicts regional TWmax in specific areas.

In this work, we investigate the worldvolume fermion on the flavor brane in the D0-D4/D8 model which is holographically equivalent to the four-dimensional QCD with instantons, or equivalently with a theta angle. The action for the worldvolume fermion is obtained by the T-duality rules in string theory and we accordingly derive its effectively five-dimensional, canonical four-dimensional forms by using the systematical dimensional reduction and decomposition of spinor. Afterwards, we employ the AdS/CFT dictionary in order to evaluate the two-point correlation function as the spectral function for the worldvolume fermion and interpret the fermion as baryon by analyzing its quantum number with the baryon vertex in holography. In this sense, the interacted action involving the worldvolume fermion and gauge field on the flavor brane are finally derived in holography which describes the various interaction of meson and baryon with instantons in large-N limit. Therefore, this work provides a holographic picture to describe baryon and its interactions based on string theory, in particular, in the presence of instantons or a theta angle., Comment: 34 pages, 2 tables, 6 figures, fix some typos in this version

As the out-of-time-order correlator (OTOC) is a measure of quantum chaos and an important observable in the context of AdS/CFT, we investigate the OTOC of holographic Skyrmion which is described by an analytical quantum mechanical system from the D4/D8 model (as the holographic QCD). By employing the OTOC defined in quantum mechanics, we derive the formulas and demonstrate the numerical calculations of the OTOC explicitly which is also available for the general case with central force field. Our numerical evaluation illustrates the behaviors of the OTOC with large $N_{c}$, however the expected exponential growth of OTOC is not obtained. Besides, we also take a look at the classical limit of the OTOC and analyze the associated behaviors. At the end of this work, we additionally study the OTOC with three-dimensional Coulomb potential, as another example for the central force field, to support our analyses of the general properties of quantum OTOC., Comment: 30 pages, 8 figures

Hao Du,1 Wentao Li,1 Xueyi Li,2 Zhiyuan Qiu,1 Jie Ding,2 Yi Zhang1 1Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Cultivation and Construction Site of the State Key Laboratory of Intelligent Imaging and Interventional Medicine, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Jie Ding; Yi Zhang, Email dingjie711@seu.edu.cn; yizhangcir@126.comBackground: Poly-L-lactic acid (PLLA) stents have broad application prospects in the treatment of cardiovascular diseases due to their excellent mechanical properties and biodegradability. However, foreign body reactions caused by stent implantation remain a bottleneck that limits the clinical application of PLLA stents. To solve this problem, the biocompatibility of PLLA stents must be urgently improved. Albumin, the most abundant inert protein in the blood, possesses the ability to modify the surface of biomaterials, mitigating foreign body reactions—a phenomenon described as the “stealth effect”. In recent years, a strategy based on albumin camouflage has become a focal point in nanomedicine delivery and tissue engineering research. Therefore, albumin surface modification is anticipated to enhance the surface biological characteristics required for vascular stents. However, the therapeutic applicability of this modification has not been fully explored.Methods: Herein, a bionic albumin (PDA-BSA) coating was constructed on the surface of PLLA by a mussel-inspired surface modification technique using polydopamine (PDA) to enhance the immobilization of bovine serum albumin (BSA).Results: Surface characterization revealed that the PDA-BSA coating was successfully constructed on the surface of PLLA m

Yi Zhang,1 Dang Liu,2 Bin Qiao,3 Yuanli Luo,3 Liang Zhang,3 Yang Cao,3 Haitao Ran,3,* Chao Yang4,* 1Department of Ultrasound, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Radiology, Jiulongpo District People’s Hospital, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haitao Ran, Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Tel +86 13512373563, Email ranhaitao@cqmu.edu.cn Chao Yang, Department of Radiology, Jiulongpo District People’s Hospital, Chongqing, People’s Republic of China, Tel +86 13883095836, Email ychaof737@163.comPurpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers.Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity.Results: The PIBD nanoparticles exhibited str

Assessing the levels of motivation in the learning process are pivotal in the daily life of college students, for the learning motivation profoundly impacts their overall academic performance. Yet, the prevailing methods to measure learning motivation levels still predominantly depend on expert evaluation and self-report, advancements in passive smartphone sensing have not been fully utilized in measuring motivation levels in learning process. In this study, we investigate and analyze behaviors and behavioral changes associated with their levels of learning motivation of N=118 undergraduate college students integrating passive smartphone sensing with self-report survey. We collect a dataset regarding the students' daily behaviors and self-report responses using a mobile application and questionnaire. Subsequently, we identify a variety of behaviors based on behavioral features captured from passive sensing data, followed by an exploration of the correlations between levels of learning motivation and the identified behaviors. Moreover, we analyze differences in behavioral changes among groups characterized by varying levels of learning motivation. Our study contributes to enhancing psychological assessment approaches by introducing a novel integrated method for more quantified and multidimensional measurement of learning motivation, providing valuable perspectives for assessing and intervening learning motivation in future research endeavors.

Zhiliang Li,1,2,* Jiali Yang,1,3,* Yang Sun,1 Shuo Han,1 Jietao Gong,1 Yi Zhang,1,3 Zhiyuan Feng,1 Hong Yao,4 Peiying Shi1,5 1College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 2College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 3College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 4Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 5State and Local Joint Engineering Laboratory of Natural Biotoxins, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Yao, Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email hongyao@mail.fjmu.edu.cn Peiying Shi, College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China, Email peiyshi@126.comPurpose: Bee pollen possesses favorable anticancer activities. As a medicinal plant source, Schisandra chinensis bee pollen (SCBP) possesses potential pharmacological properties, such as reducing cisplatin-induced liver injury, but its anti–liver cancer effect is still rarely reported. This paper aims to investigate the effect and mechanism of SCBP extract (SCBPE) on hepatocellular carcinoma HepG2 cells.Methods: The effect of SCBPE on cell proliferation and migration of HepG2 cells was evaluated based on MTT assay, morphology observation, or scratching assay. Furthermore, tandem mass tag-based quantitative proteomics was used to study the effect mechanisms. The mRNA expression levels of identified proteins were verified by RT-qPCR.Results: Tandem mass tag-based quantitative proteomic

Mengnan Li,1,2,* Xifeng Yang,1,2,* Ru Li,1,2 Baofeng Wu,1,2 Jinxuan Hao,1,2 Yijie Qi,1,2 Tao Bai,1 Luyang Yang,1 Yi Zhang,3 Yunfeng Liu1,4 1Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Clinical Research Center of Endocrine and Metabolic Diseases in Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email yizhang313@163.comPurpose: There is evidence that long-term vascular risk remains increased in patients with hyperthyroidism even after normalization of thyroid function, and the mechanisms that regulate this risk are unclear. The aim of this study was to assess how visceral fat area and subcutaneous fat area change after hyperthyroidism treatment, and to further explore the relationship between thyroid hormones, abdominal fat area (visceral fat area and subcutaneous fat area), and lipids.Patients and Methods: 50 patients with newly diagnosed Graves’ disease were selected. Anthropometric parameters (weight, height, body mass index, waist circumference, neck circumference), laboratory parameters (thyroid hormones, lipid metabolism indices), abdominal fat area (visceral fat area and subcutaneous fat area), and drug dose were collected. Measurements were made at baseline, 6 and 12 months after treatment. We used linear mixed-effects models for analysis.Results: The results showed that the following indexes changed significantly at different time

Minmin Han,1,2,* Xiaoming Cao,3,* Jian Zhang,1,2 Xifeng Yang,1,2 Yi Zhang,4,5 Yunfeng Liu1,2 1Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 2First Clinical Medical College, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 3Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 4Department of Pharmacology, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 5Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, No. 85, Jiefang Nan Road, Taiyuan, 030000, People’s Republic of China, Tel +86-18703416196, Fax +86-351-4639756, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan, 030000, People’s Republic of China, Tel +86-18835102847, Fax +86-351-4135971, Email yizhang313@163.comPurpose: This study aimed to investigate the glycometabolism, fat mass, and lean mass in primary aldosteronism (PA) during disease progression.Patients and Methods: Patients diagnosed with PA and healthy controls (HCs) were enrolled. A flash glucose monitoring system (FGMS) and dual-energy X-ray absorptiometry (DEXA) were used to measure glucose variability and glucose target rate along with fat mass and lean mass. Comparative analysis of FGMS- or DEXA-derived parameters along with correlation analyses between these parameters and PA progression were performed.Results: Increased glucose variability and poor glucose target rate, along with an increased proportion of truncal fat mass, and decreased proportion of appendicular lean mass, were identified in PA group comp

Yi Zhang,* Yiqing Guo,* Chao Gong, Junzuo Fu, Lianhua Chen Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junzuo Fu; Lianhua Chen, Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, No. 100 Haining Road, Shanghai, 200080, People’s Republic of China, Tel +86-21-63240090, Email Fujunzuo021@163.com; emily19941010@126.comBackground: The positive roles of deep muscle relaxation in abdominal surgeries and transversus abdominis plane block (TAPB) in the postoperative analgesia. This study aimed to discuss the effects of TAPB on abdominal muscle relaxation, the intraoperative diaphragmatic, and the respiratory functions.Methods: The patients were randomly divided into the TAPB group who received single-shot TAPB bilaterally (n=30), and the control group who did not receive TAPB (n=30). Both groups keep the same steps for other procedures in the surgeries and anesthesia. Four time points for monitoring were defined: The moment when pneumoperitoneum pressure stabilized following endotracheal intubation and anesthetic induction (T0), appearance of the first incisure in the pressure-volume (P-V) loop (T1), appearance of the second incisure in the P-V loop (T2), and the moment with single stimulation (SS) =20% (T3). Primary observation parameters were SS1 measured by muscle relaxation monitoring at T1, and SS2 at T2. Secondary observation parameters included surgeon’s satisfaction with surgical field and respiratory dynamics at the four time points.Results: The two groups were comparable in age, gender, BMI, ASA grade, and operation time. The TAPB group had a dramatic reduction in the total dose of intraoperative sufentanil (0.73± 0.21 ug/kg) compared with the control group (0.87± 0.18 ug/kg) (P=0.023); Other use of drug did not differ between the two groups. The two

Yi Zhang,1,* Kefan Bi,2,* Linfu Zhou,3 Jie Wang,2 Lingtong Huang,4 Yan Sun,5 Guoping Peng,5 Wei Wu2 1Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Critical Care Units, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Neurology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Wu; Guoping Peng, Email zjuwuwei@zju.edu.cn; guopingpeng@zju.edu.cnAbstract: Alzheimer’s disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as a continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis and interventions aimed at delaying the decline in mental function. Despite the proven efficacy of cerebrospinal fluid and positron emission tomography in diagnosing AD, their broader utility is constrained by significant costs and the invasive nature of these procedures. Consequently, the innovation of blood biomarkers such as Amyloid-beta, phosphorylated-tau, total-tau et al, distinguished by their high sensitivity, minimal invasiveness, accessibility, and cost-efficiency, emerges as a promising avenue for AD diagno

Luyang Gao,* Sicheng Zhang,* Zhihui Zhao, Qing Zhao, Tao Yang, Qixian Zeng, Yi Zhang, Xin Li, Zhihua Huang, Anqi Duan, Qin Luo, Zhihong Liu Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhihong Liu; Qin Luo, Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Tel/Fax +86-010-88396589, Email zhihongliufuwai@163.com; luoqin2009@163.comIntroduction: Mounting evidence indicates a possible connection between the systemic inflammatory response index (SIRI) and the prognosis of heart failure, but its role in idiopathic pulmonary arterial hypertension (IPAH) is not well understood. This study aimed to investigate the relationship between SIRI and variables such as functional ability, echocardiography results, hemodynamic measurements, and long-term outcomes in patients with IPAH.Methods: The study included 426 consecutive IPAH patients who underwent right heart catheterization at Fuwai Hospital from January 2013 to December 2020. SIRI was calculated using composite inflammation indicators from routine blood tests. The main outcome measure was clinical deterioration. Spearman correlation coefficients were used to assess associations between SIRI and indicators of IPAH severity. Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal SIRI threshold and predictive ability. Kaplan-Meier analysis and Cox proportional hazard models were use

BACKGROUND: Swamp-type buffaloes with varying degrees of white spotting are found exclusively in Tana Toraja, South Sulawesi, Indonesia, where spotted buffalo bulls are highly valued in accordance with the Torajan customs. The white spotting depigmentation is caused by the absence of melanocytes. However, the genetic variants that cause this phenotype have not been fully characterized. The objective of this study was to identify the genomic regions and variants responsible for this unique coat-color pattern.RESULTS: Genome-wide association study (GWAS) and selection signature analysis identified MITF as a key gene based on the whole-genome sequencing data of 28 solid and 39 spotted buffaloes, while KIT was also found to be involved in the development of this phenotype by a candidate gene approach. Alternative candidate mutations included, in addition to the previously reported nonsense mutation c.649 C > T (p.Arg217*) and splice donor mutation c.1179 + 2T > A in MITF, a nonsense mutation c.2028T > A (p.Tyr676*) in KIT. All these three mutations were located in the genomic regions that were highly conserved exclusively in Indonesian swamp buffaloes and they accounted largely (95%) for the manifestation of white spotting. Last but not the least, ADAMTS20 and TWIST2 may also contribute to the diversification of this coat-color pattern.CONCLUSIONS: The alternative mutations identified in this study affect, at least partially and independently, the development of melanocytes. The presence and persistence of such mutations may be explained by significant financial and social value of spotted buffaloes used in historical Rambu Solo ceremony in Tana Toraja, Indonesia. Several de novo spontaneous mutations have therefore been favored by traditional breeding for the spotted buffaloes.

The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.

Resistance welding technology is an effective solution for connecting thermoplastic composites. However, limited research on non -uniform distribution of interfacial temperature and complex evolution mechanism of phase-change molding hinders its application. This reliance on traditional experimental and trial-and-error methods severely impedes its development. Therefore, this study employed a novel cross-scale numerical simulation method, being applied for the first time in the field of resistance welding for elucidating the underlying mechanism of joint formation through multi-component phase transformation. The constructed model accurately represented the transient heat transfer of a realistic wire mesh structure in three dimensions, while incorporating complex gradient effects arising from both spatial and temporal variations in heating element temperature due to air interference. Further, melting, flow, and consolidation behavior of the resin matrix in resistance welding of carbon fiber/polyetheretherketone (CF/PEEK) thermoplastic composite was investigated herein at a mesoscopic scale. To accomplish this objective, a three-phase flow spatial forming and evolution model for resistance welding was developed at the mesoscopic scale by integrating principles from fluid dynamics. Interestingly, introduction of an air phase reinstated the spatial voids formation and flow in resistance welding, providing robust evidence for the initiation mechanism of internal defects. Moreover, this study revealed variations in the melting mode of PEEK resin across different regions within the weld and highlighted distinct distributions of voids resulting from uneven heat transfer. The interfacial phenomenon and flow diffusion mechanism between components in resistance welding tests were further verified and discussed through analyzing scanning electron microscopy and energy dispersive spectroscopy results. Temporal and spatial correlation in void distribution within the welding zone

Combinatorial optimization (CO) has a broad range of applications in various fields, including operations research, computer science, and artificial intelligence. However, many of these problems are classified as nondeterministic polynomial-time (NP)-complete or NP-hard problems, which are known for their computational complexity and cannot be solved in polynomial time on traditional digital computers. To address this challenge, continuous-time Ising machine solvers have been developed, utilizing different physical principles to map CO problems to ground state finding. However, most Ising machine prototypes operate at speeds comparable to digital hardware and rely on binarizing node states, resulting in increased system complexity and further limiting operating speed. To tackle these issues, a novel device-algorithm co-design method is proposed for fast sub-optimal solution finding with low hardware complexity. On the device side, a piezoelectric lithium niobate (LiNbO3) microelectromechanical system (MEMS) oscillator network-based Ising machine without second-harmonic injection locking (SHIL) is devised to solve Max-cut and graph coloring problems. The LiNbO3 oscillator operates at speeds greater than 9 GHz, making it one of the fastest oscillatory Ising machines. System-wise, an innovative grouping method is used that achieves a performance guarantee of 0.878 for Max-cut and 0.658 for graph coloring problems, which is comparable to Ising machines that utilize binarization. © 2024 The Authors. Advanced Science published by Wiley-VCH GmbH.

Objective: This study aims to evaluate the feasibility and applicability of an online cervical cancer screening program using a website as the public platform and self-collected HPV testing as the primary screening method. Methods: A website (mcareu.com) was developed to facilitate the online cervical cancer screening program by Peking University Shenzhen Hospital (PUSH). Women in Shenzhen could register for participation on the website by providing essential demographic data. Sampling kits and specimens were delivered through regular logistics. Eligible women collected vaginal samples by themselves using the provided kits and in referring of the graphic guidance. The specimens were tested for HPV at PUSH or a reference lab, and the results were accessible on the website through participants' personal accounts. Participants who tested positive for high-risk HPV were scheduled for colposcopy and biopsies. The demographic and social background data of the eligible participants were analyzed to evaluate the feasibility and applicability of the online screening approach. Results: A total of 1712 applicants registered for participation, with 99.9% (1710/1712) completing registration with full data. The analysis included 1560 applicants aged 30–59, with an average age of 41.1 (± 7.6) years. Among them, 83.3% (1299/1560) provided self-collected samples for testing. Age-group analysis revealed an overall sample provision rate (SPR) exceeded 80% in all age groups. A significant difference in SPR was observed only between the 30–34 and 45–49 age groups (p < 0.05), while no significant differences were found among other age groups. 99.7% of the samples were tested qualified, and there was no significant difference in sampling failure rate among age groups. Analysis of demographic and social elements showed no significant impact on the rates of sample provision among groups in most of the social elements but the medical insurance and the monthly family-incomes. Conclusion: The

Single-cell chromatin accessibility sequencing (scATAC-seq) reconstructs developmental trajectory by phenotypic similarity. However, inferring the exact developmental trajectory is challenging. Previous studies showed age-associated DNA methylation (DNAm) changes in specific genomic regions, termed clock-like differential methylation loci (ClockDML). Age-associated DNAm could either result from or result in chromatin accessibility changes at ClockDML. As cells undergo mitosis, the heterogeneity of chromatin accessibility on clock-like loci is reduced, providing a measure of mitotic age. In this study, we developed a method, called EpiTrace, that counts the fraction of opened clock-like loci from scATAC-seq data to determine cell age and perform lineage tracing in various cell lineages and animal species. It shows concordance with known developmental hierarchies, correlates well with DNAm-based clocks and is complementary with mutation-based lineage tracing, RNA velocity and stemness predictions. Applying EpiTrace to scATAC-seq data reveals biological insights with clinically relevant implications, ranging from hematopoiesis, organ development, tumor biology and immunity to cortical gyrification. © The Author(s) 2024.

Using the gauge-gravity duality, we investigate the fermionic correlation function in the D(-1)-D3 brane system which describes the instantonic plasma in holography. In this system, the charge of the D(-1) brane as the D-instanton gives the gluon condensate. To simplify the holographic setup, we first reduce briefly the ten-dimensional supergravity background produced by D(-1)-D3-branes to an equivalently five-dimensional background. Then using the standard method for computing the Green function in the AdS/CFT dictionary, we derive the equations for the fermionic correlation functions and solve them numerically with the infalling boundary condition. Our numerical results illustrate that the fermionic correlation function as spectral function includes two branches of the dispersion curves whose behavior is very close to the results obtained from the method of hard thermal loop. And the effective mass generated by the medium effect of fermion splits into two values due to the spin-dependent interactions induced by instantons. Therefore, this work in holography demonstrates the instantonic configuration is very influential to the fermionic plasmino in plasma., Comment: 19 pages, 5 figures

We revisit anomalies of $(4,0)$ and $(3,1)$ maximally supersymmetric tensor theories in $d=6$. A $(4,0)$ on-shell tensor multiplet descends to that of the $d=5$ maximal supergravity upon a dimensional reduction, hypothesized to offer a strong-coupled UV completion of the latter in the same sense of $(2,0)$ theories as the UV completion of $d=5$ $\mathcal{N}=2$ pure Yang-Mills. The gravitational anomalies, found to be nonvanishing, had been computed, although its relevance in the absence of the $d=6$ metric is not obvious. We perform a comprehensive anomaly computation for $(4,0)$ and $(3,1)$ tensor supermultiplets, respectively, for $Sp(4)$ and $Sp(3)\times Sp(1)$ $R$-symmetry anomalies and the mixed $R$-gravitational anomaly thereof, and find that anomalies involving $R$-symmetries cancel out identically. We close with questions on how to address the anomaly in this class of theories with no general covariance., Comment: 16 pages + appendix + bibliography

We explore new aspects of internal fermionic shifting symmetries, present in physical systems such as free Dirac spinors and p-form tensor-spinor fields. We propose a novel procedure to gauge these global symmetries, which also introduces a new St\"uckelberg mechanism to give a mass to free fermionic fields. Furthermore, we find new magnetic fermionic symmetries in these physical systems whose charged objects are disorder operators. For the case of a Dirac spinor, we discuss an dual description, where the magnetic symmetry acts on the holonomies of a dual 2-form tensor-spinor. Further generalizations such as higher-group-like structures are also discussed., Comment: 5 pages plus 2 appendices

We study the out-of-time-order correlators (OTOC) of Skyrmion as baryon in the D0-D4/D8 model which is expected to be holographically dual to QCD with instantons as D0-branes or with a non-zero theta angle. Baryon states are identified to the excitations of the Skyrmion which are described by a holographic quantum mechanical system in this model. By employing the definition of OTOC in quantum mechanics, we derive the formulas and demonstrate explicitly the numerical calculations of the OTOC. Our calculation illustrates the quantum OTOC with imaginary Lyapunov coefficient indicates the possibly metastable baryonic status in the presence of the instanton while the classical OTOC can not, thus it reveals the instantonic or theta-dependent features of QCD are dominated basically by its quantum properties. Furthermore, the OTOC also implies the baryonic phase becomes really chaotic with real Lyapunov exponent if the instanton charge increases sufficiently which agrees with the unstable baryon spectrum presented in this model. In this sense, we believe the OTOC may be treated as a tool to detect the baryonic phase structure of QCD., Comment: 20 pages, 5 Figures

The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.

The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.

The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.

Human mixed lineage leukemia 4 (MLL4), also known as KMT2D, regulates cell type specific transcriptional programs through enhancer activation. Along with the catalytic methyltransferase domain, MLL4 contains seven less characterized plant homeodomain (PHD) fingers. Here, we report that the sixth PHD finger MLL4 (MLL4 PHD6 ) binds to the hydrophobic motif of ten -eleven translocation 3 (TET3), a dioxygenase converts methylated cytosine into oxidized derivatives. The solution NMR structure of the TET3-MLL4 complex and binding assays show that, like histone H4 tail, TET3 occupies the hydrophobic site MLL 4 PHD6 , and that this interaction is conserved in the seventh PHD finger of homologous MLL3 (MLL3 PHD7 Analysis of genomic localization of endogenous MLL4 and ectopically expressed TET3 in mouse embryonic stem cells reveals a high degree overlap on active enhancers and suggests a potential functional relationship of MLL4 and TET3.

The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.

Natural Language to SQL systems (NL-to-SQL) have recently shown improved accuracy (exceeding 80%) for natural language to SQL query translation due to the emergence of transformer-based language models, and the popularity of the Spider benchmark. However, Spider mainly contains simple databases with few tables, columns, and entries, which do not reflect a realistic setting. Moreover, complex real-world databases with domain-specific content have little to no training data available in the form of NL/SQL-pairs leading to poor performance of existing NL-to-SQL systems. In this paper, we introduce ScienceBenchmark, a new complex NL-to-SQL benchmark for three real-world, highly domain-specific databases. For this new benchmark, SQL experts and domain experts created high-quality NL/SQL-pairs for each domain. To garner more data, we extended the small amount of human-generated data with synthetic data generated using GPT-3. We show that our benchmark is highly challenging, as the top performing systems on Spider achieve a very low performance on our benchmark. Thus, the challenge is many-fold: creating NL-to-SQL systems for highly complex domains with a small amount of hand-made training data augmented with synthetic data. To our knowledge, ScienceBenchmark is the first NL-to-SQL benchmark designed with complex real-world scientific databases, containing challenging training and test data carefully validated by domain experts.

BACKGROUND: Predictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from the Anti-PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled the assessment of predictive models by using data from two randomized controlled clinical trials (RCTs) of ICIs in first-line metastatic NSCLC.METHODS: Participants developed and trained models using public resources. These were evaluated with data from the CheckMate 026 trial (NCT02041533), according to the model-to-data paradigm to maintain patient confidentiality. The generalizability of the models with the best predictive performance was assessed using data from the CheckMate 227 trial (NCT02477826). Both trials were phase III RCTs with a chemotherapy control arm, which supported the differentiation between predictive and prognostic models. Isolated model containers were evaluated using a bespoke strategy that considered the challenges of handling transcriptome data from clinical trials.RESULTS: A total of 59 teams participated, with 417 models submitted. Multiple predictive models, as opposed to a prognostic model, were generated for predicting overall survival, progression-free survival, and progressive disease status with ICIs. Variables within the models submitted by participants included tumor mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, and gene-expression-based signatures. The best-performing models showed improved predictive power over reference variables, including TMB or PD-L1.CONCLUSIONS: This DREAM Challenge is the first successful attempt to use protected phase III clinical data for a crowdsourced effort towards generating predictive models for ICI clinical outcomes and could serve as a blueprint for similar efforts in other tumor types and disease states, setting a benchmark for future studies aiming to identify biomarkers predictive of

Ru Li,1,2,&ast; Baofeng Wu,1,2,&ast; Minmin Han,1,2 Mengnan Li,1,2 Xifeng Yang,1,2 Jian Zhang,1,2 Yi Zhang,3 Yunfeng Liu1 1Department of Endocrinology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2The First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, The First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan, People’s Republic of China, Tel +86 18703416196, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email yizhang313@163.comAbstract: Uric acid (UA) is the end product of purine metabolism in the human, and the imbalance between production and excretion results in the disturbance of serum uric acid (SUA). There is evidence suggesting that pituitary-target gland hormones can affect UA metabolism through regulating the activity of xanthine oxidase and UA transporters. Related endocrine diseases including thyroid dysfunction, polycystic ovary syndrome, acromegaly and Cushing’s syndrome are often accompanied by elevated UA levels. In addition to the direct influence of abnormal hormones, obesity and insulin resistant play a pivotal role. Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion also present with abnormal SUA levels due to the action of antidiuretic hormone. However, certain evidence within the population is disputed. This review summarized the effects of pituitary-target gland hormones on UA metabolism, and preliminarily described the related mechanisms, offering a theoretical foundation for assessing SUA in endocrine disorders as well as guiding its management.Keywords: uric acid, hyperuricemia, pituitary-target gland, en

Pijun Yan,1– 5 Jia Li,1– 5 Yi Zhang,1– 5 Xiaofang Dan,1– 5 Xian Wu,1– 5 Xing Zhang,1– 5 Yuxia Yang,1– 5 Xiping Chen,6 Shengxi Li,6 Pan Chen,1– 5 Qin Wan,1– 5 Yong Xu1– 5 1Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China; 3Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, People’s Republic of China; 4Sichuan Clinical Research Center for Nephropathy, Luzhou, People’s Republic of China; 5Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 6Clinical medical College, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Pijun Yan, Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86-830-3165361, Email peter2007110361@126.comObjective: Very few and conflicting data are available regarding the correlation between circulating carbohydrate antigen 19-9 (CA19-9) levels and diabetic kidney disease (DKD) and its components including albuminuria and a low estimated glomerular filtration rate (eGFR). This study aimed to examine the association of circulating CA19-9 and DKD in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: A total of 402 hospitalized T2DM patients between September 2017 and December 2021 were included in this cross-sectional study. There were 224 and 178 subjects in non-DKD and DKD groups, respectively. Serum CA19-9 was measured by chemiluminescence method, and its potential relationship with DKD was evaluated by multivariate logistic regression and correlation analyses, and receiver operating characteristic (ROC) curve analysis.Results: T2DM patients with DKD had significantly higher serum CA19-9 levels than those without, and

Guangxin Zhou,1,2 Wei Zhao,2 Yi Zhang,2 Wenli Zhou,2 Haizhou Yan,2 Yongli Wei,1 Yuming Tang,1 Zijing Zeng,2 Hanrong Cheng1 1Department of Sleep Medicine, Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 2OPPO Health, Guangdong OPPO Mobile Telecommunications Co. Ltd., Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Hanrong Cheng, Department of Sleep Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China, Email cheng.hanrong@szhospital.comObjective: To evaluate the clinical performance of the OPPO Watch (OW) Sleep Analyzer (OWSA) on OSA screening with polysomnography reference.Methods: We recruited 350 participants using OWSA and PSG simultaneously in a sleep laboratory. The respiratory event index (REI) derived from OWSA and the apnea-hypopnea index (AHI) provided by PSG were compared. SHapley Additive exPlanation (SHAP) values were calculated to explain the model of OWSA.Results: The OWSA-REI (26.5± 18.5 events/h) correlated well with PSG-AHI (33.2± 25.7 events/h; r = 0.91, p < 0.001), with an intraclass correlation coefficient (ICC) of 0.83. Using a threshold of AHI ≥ 15 events/h, the sensitivity, specificity, accuracy, and area under the curve (AUC) were 86.1%, 86.7%, 86.3%, and 0.94, respectively. Bland-Altman analysis showed that OWSA-REI and PSG-AHI were in good agreement (Mean Difference: − 6.7, 95% CI:16.0 to − 29.3 events/h). In addition, the effectiveness of the models in OWSA were also explained by visualizing SHAP values.Conclusion: The OWSA demonstrated a reasonable performance for OSA screening in the clinical setting. In light of this, it is possible for s

On-surface reactions of terminal alkynes in ultrahigh vacuum have attracted widespread attention due to their high technological promise. However, employing different precursors and substrate materials often intricate reaction schemes appear far from being well-understood. Thus, recent investigations of alkyne coupling on noble metal surfaces suggest non-dehydrogenative scenarios, contradicting earlier reports. Herein, the study employs noncontact atomic force microscopy (nc-AFM) with high spatial resolution to conclusively characterize exemplary alkyne coupling products. Contrary to initial interpretations proposing dehydrogenative homocoupling on Ag(111), bond-resolved AFM imaging reveals the expression of enyne motifs. Based on complementary, extensive density functional theory calculations, the pertaining reaction mechanisms are explored. It is proposed that enyne formation initiates with a direct carbon-carbon coupling between two alkyne groups, followed by surface-assisted dehydrogenation-hydrogenation processes. Thereby consecutive steps of atomic hydrogen cleavage, surface migration and recombination to a different carbon atom enable bridging via carbon-carbon double bonding. The new results shed light on subtle, but crucial surface-mediated hydrogen transfer processes involved in the chemical bond formation, which are suggested to be of general relevance in on-surface synthesis. Terminal alkyne coupling on Ag(111) in ultrahigh vacuum is conclusively examined by bond-resolved atomic force microscopy and density functional theory modeling. The prevailing bonding motif is the enyne moiety, originating from a distinct surface-mediated dehydrogenation-hydrogenation reaction pathway. The findings highlight the important role of hydrogen transfer in the course of on-surface synthesis procedures. image, Funding Agencies|National Natural Science Foundation of China [12174431, 1192780039]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDB30000000]; Swedish Research Council [2022-06725]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoeping University (Faculty Grant SFO-Mat-LiU) [2009-00971]; German Research Foundation (DFG); European Union [847471]; DFG Excellence Cluster e-conversion; Munich Quantum Center

Global potent greenhouse gas nitrous oxide (N2O) emissions from soil are accelerating, with increases in the proportion of reactive nitrogen emitted as N2O, i.e., N2O emission factor (EF). Yet, the primary controls and underlying mechanisms of EFs remain unresolved. Based on two independent but complementary global syntheses, and three field studies determining effects of acidity on N2O EFs and soil denitrifying microorganisms, we show that soil pH predominantly controls N2O EFs and emissions by affecting the denitrifier community composition. Analysis of 5438 paired data points of N2O emission fluxes revealed a hump-shaped relationship between soil pH and EFs, with the highest EFs occurring in moderately acidic soils that favored N2O-producing over N2O-consuming microorganisms, and induced high N2O emissions. Our results illustrate that soil pH has a unimodal relationship with soil denitrifiers and EFs, and the net N2O emission depends on both the N2O/(N2O + N2) ratio and overall denitrification rate. These findings can inform strategies to predict and mitigate soil N2O emissions under future nitrogen input scenarios.

Yulin Chen,1 Yi Zhang,2 Jianjun Wang,3 Xiong Cai,1 Junzhang Chen,1 Xiaobo Min,1 Yunjie Xu,1 Qi Qin,1 Chidan Wan1 1Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Engineering Research Center of Tumor-Targeted Biochemotherapy, Wuhan, 430030, People’s Republic of China; 3Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of ChinaCorrespondence: Qi Qin; Chidan Wan, Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Email qinqi8441@163.com; wcdwhxhgdwk@163.comBackground: Hepatocellular Carcinoma (HCC) poses significant challenges due to limited effective treatments and high recurrence rates. Immunotherapy, a promising approach, faces obstacles in HCC patients due to T-cell exhaustion and immunosuppression within the tumor microenvironment.Methods: Using doxorubicin-loaded tumor-derived microparticles (Dox-TMPs), the mice with H22 ascites model and subcutaneous tumors model were treated. Following the treatment, mice were re-challenged with H22 cells to compare the therapeutic effects and recurrence among different groups of mice, alongside examining the changes in the proportions of immune cells within the tumor microenvironment. Furthermore, Dox-TMPs were combined with anti-PD-1 to further validate their anti-tumor efficacy. In vitro studies using various liver cancer cell lines were conducted to verify the tumor-killing effects of Dox-TMPs. Additionally, CD8+ T cells from the abdominal cavity of tumor-free mice were co-cultured with H22 cells to confirm their specific tumor-killing abilities.Results: Dox-TMPs demonstrate effective anti-tumor effects both in vitro and in viv

Peng Luo,1,&ast; Yi Zhang,2,3,&ast; Maodi Huang,1 Guochen Luo,1 Yaping Ma,1,4 Xin Wang1,4 1Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, People’s Republic of China; 2Department of Hygiene Toxicology, School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 3Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4Guizhou Provincial Key Laboratory of Medicinal Biotechnology in Colleges and Universities, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Wang, Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, People’s Republic of China, Tel +86 136 3928 8558, Fax +86-851-2860 8903, Email xin.wang@zmu.edu.cnIntroduction: Osteoporotic-related fractures remains a significant public health concern, thus imposing substantial burdens on our society. Excessive activation of osteoclastic activity is one of the main contributing factors for osteoporosis-related fractures. While polylactic acid (PLA) is frequently employed as a biodegradable scaffold in tissue engineering, it lacks sufficient biological activity. Microdroplets (MDs) have been explored as an ultrasound-responsive drug delivery method, and mesenchymal stem cell (MSC)-derived exosomes have shown therapeutic effects in diverse preclinical investigations. Thus, this study aimed to develop a novel bioactive hybrid PLA scaffold by integrating MDs-NFATc1-silencing siRNA to target osteoclast formation and MSCs-exosomes (MSC-Exo) to influence osteogenic differentiation (MDs-NFATc1/PLA-Exo).Methods: Human bone marrow-derived mesenchymal stromal cells (hBMSCs) were used for exosome isolation. Transmission electron mic

KM2A is one of the main sub-arrays of LHAASO, working on gamma ray astronomy and cosmic ray physics at energies above 10 TeV. Detector simulation is the important foundation for estimating detector performance and data analysis. It is a big challenge to simulate the KM2A detector in the framework of Geant4 due to the need to track numerous photons from a large number of detector units (>6000) with large altitude difference (30 m) and huge coverage (1.3 km^2). In this paper, the design of the KM2A simulation code G4KM2A based on Geant4 is introduced. The process of G4KM2A is optimized mainly in memory consumption to avoid memory overffow. Some simpliffcations are used to signiffcantly speed up the execution of G4KM2A. The running time is reduced by at least 30 times compared to full detector simulation. The particle distributions and the core/angle resolution comparison between simulation and experimental data of the full KM2A array are also presented, which show good agreement.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at $3.67 \pm 0.05 \pm 0.15$ PeV. Below the knee, the spectral index is found to be -$2.7413 \pm 0.0004 \pm 0.0050$, while above the knee, it is -$3.128 \pm 0.005 \pm 0.027$, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -$0.1200 \pm 0.0003 \pm 0.0341$. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components., Comment: 8 pages, 3 figures

Understanding how the hot circum-galactic medium (CGM) properties relate to the galaxy's properties can constrain galaxy evolution models. We aim to measure the scaling relations between the X-ray luminosity of the hot CGM and the fundamental properties of a galaxy, i.e., its stellar mass and halo mass. We calculate the X-ray luminosity of the hot CGM based on the surface brightness profiles of central galaxy samples measured in Zhang et al. (2024a, submitted) from Spectrum Roentgen Gamma (SRG)/eROSITA all-sky survey data. We relate the X-ray luminosity to the galaxies' stellar and halo mass. We compare the observed relations to the TNG, EAGLE, and SIMBA simulations. The hot CGM X-ray luminosity correlates with the galaxy's stellar mass ($M_*$). It increases from $2.1 \pm 1.3\times10^{39} \rm erg/s$ to $2.0 \pm 0.1\times10^{41} \rm erg/s$, when $\log(M_*)$ increases from 10.0 to 11.5. A double power law describes the correlation, with a break at $\log(M_*)=11.28\pm 0.03$ and a power-law index or $1.9\pm 0.2$ ($4.2\pm0.1$) below (above) the break. The hot CGM X-ray luminosity as a function of halo mass is measured within $\log(M_{\rm 500c})=11.3-13.7$, extending our knowledge of the scaling relation by more than two orders of magnitude. $L_{\rm X,CGM}$ increases with $M_{\rm 500c}$ from $2.7 \pm 0.9\times10^{39}\ \rm erg/s$ at $\log(M_{\rm 500c})=11.3$ to $9.2 \pm 0.4\times10^{41}\ \rm erg/s$ at $\log(M_{\rm 500c})=13.7$. The relation follows a power law of $\log(L_{\rm X,CGM})= (1.35\pm 0.04)\times \log(M_{\rm 500c})+(23.8\pm0.5)$. We find a general agreement between simulations and observation. We explore, at the low mass end, the average scaling relations between the CGM X-ray luminosity and the galaxy's stellar mass or halo mass, which constitutes a new benchmark for galaxy evolution models and feedback processes., Comment: 8 pages, 4 figures, submitted to A&A

We apply a stacking technique to gain enough statistics to detect the hot CGM around galaxies. We use the X-ray data from the first four SRG/eROSITA all-sky surveys (eRASS:4). We discuss how the satellite galaxies could bias the stacking and carefully build the central galaxy samples based on the SDSS spectroscopic survey and halo-based group finder algorithm and isolated galaxy sample from the ninth data release of the DESI Legacy survey (LS DR9, photometric). We mask the detected X-ray point sources and carefully model the X-ray emission from the unresolved active galactic nuclei (AGN) and X-ray binaries (XRB) to obtain the X-ray emission from the hot CGM. The X-ray surface brightness profiles are measured for $\log(M_*)>10.0$ or $\log(M_{\rm 200m})>11.5$ central galaxies, and $\log(M_*)>9.5$ isolated galaxies. We detect the X-ray emission around MW-mass ($\log(M_*)=10.5-11.0$) and more massive central galaxies extending up to the virial radius ($R_{\rm vir}$). The signal-to-noise ratio of the extended emission around the MW-mass galaxy is about $8.1\sigma$ within $R_{\rm vir}$. We use the $\beta$ model to describe the X-ray surface brightness profiles of the hot CGM. We obtain a central surface brightness of $S_{\rm X,0}\approx 3.1\times10^{35}\rm erg/s/kpc^2$ and $\beta \approx0.42$ for MW-mass galaxy. We estimate the baryon budget of the hot CGM and obtain a value lower than the $\Lambda CDM$ cosmology predicted. Our results set a firm footing for the presence of a hot CGM around MW-mass and more massive central galaxies. These measurements constitute a new benchmark for galaxy evolution models and possible implementations of feedback processes therein., Comment: 21 pages, 12 figures, submitted to A&A

Massive black holes (MBHs) are typically hosted in the centres of massive galaxies but they appear to become rarer in lower mass galaxies, where nuclear star clusters (NSCs) frequently appear instead. The transition region, where both an MBH and NSC can co-exist, has been poorly studied to date and only a few dozen galaxies are known to host them. One avenue for detecting new galaxies with both an MBH and NSC is to look for accretion signatures of MBHs. Here, we use new SRG/eROSITA all-sky survey eRASS:4 data to search for X-ray signatures of accreting MBHs in NSCs, while also investigating their combined occupation fraction. We find significant detections for 18 galaxies (~8.3%), including one ultra-luminous X-ray source; however, only three galaxies (NGC2903, 4212, and 4639) have X-ray luminosities that are higher than the expected value from X-ray binaries, indicative of the presence of an MBH. In addition, the X-ray luminosity of six galaxies (NGC2903, 3384, 4321, 4365, 4639, and 4701) differs from previous studies and could indicate the presence of a variable active galactic nucleus. The combined occupation fraction of accreting MBHs and NSCs becomes non-zero for galaxy masses above ~10^7.5 M_sun and this result is slightly elevated as compared to the literature data. Our data extend, for the first time, towards the dwarf elliptical galaxy regime and identify promising MBH candidates for higher resolution follow-up observations. At most galaxy masses (and with the exception of three cases), the X-ray constraints are consistent with the expected emission from binary systems or an Eddington fraction of at most 0.01%, assuming a black holes mass of 10^6.5 M_sun. This work confirms the known complexities in similar-type of studies, while providing the appealing alternative of using X-ray survey data of in-depth observations of individual targets with higher resolution instruments., Comment: 12 pages, 9 figures, 1 table. Accepted for publication by A&A. Abstract was abriged to meet arXiv requirements

The detection of GW170817/GRB170817A implied the strong association between short gamma-ray bursts (SGRBs) and binary neutron star (BNS) mergers which produce gravitational waves (GWs). More evidence is needed to confirm the association and reveal the physical processes of BNS mergers. The upcoming High Altitude Detection of Astronomical Radiation (HADAR) experiment, excelling in a wide field of view (FOV) and a large effective area above tens of GeV, is a hope for the prompt detection of very-high-energy (VHE; > 10 GeV) SGRBs. The aim of this paper is to simulate and analyse GW/SGRB joint detections by future GW detector networks in synergy with HADAR, including the second generation LIGO, Virgo and KAGRA and the third generation ET and CE. We provide a brief introduction of the HADAR experiment for SGRB simulations and its expected SGRB detections. For GW simulations, we adopt a phenomenological model to describe GWs produced by BNS mergers and introduce the signal-noise ratios (SNRs) as detector responses. Following a theoretical analysis we compute the redshift-dependent efficiency functions of GW detector networks. We then construct the simulation of GW detection by Monte Carlo sampling. We compare the simulated results of LIGO-Virgo O2 and O3 runs with their actual detections as a check. The combination of GW and SGRB models is then discussed for joint detection, including parameter correlations, triggered SNRs and efficiency skymaps. The estimated joint detection rates are 0.09-2.52 per year for LHVK network with HADAR under different possible configurations, and approximately 0.27-7.89 per year for ET+CE network with HADAR.

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) with lower (sparsely-branched; SB-) and higher (overly-branched; OB-) numbers of methylated branches relative to the “regular” brGDGTs (B-GDGTs) are abundant in anoxic waters in the Black Sea. Observed changes in abundances and numbers of methylated branches of the entire series OB-GDGTs, B-GDGTs, and SB-GDGTs relative to dissolved oxygen (DO) levels in anoxic waters suggest that these compounds can potentially track changes in oceanic DO levels through time. To explore this, we determine the entire brGDGT series in surface or near-surface sediments from sites with different DO distributions in marine waters and sediments, extending the limited core-top collection of these lipids. We propose a modified methylation index based on only OB-GDGTs, called MOB, to avoid the potential impacts of terrestrial-derived B-GDGTs. Interestingly, MOB values in our extended core-top collection are strongly related to changes in bottom-water DO concentrations rather than the site-specific minimum DO values, i.e. usually within mid-depth oxygen minimum zones (OMZs). This suggests that sedimentary lipids are likely derived from heterotrophic bacteria living at the sediment-water boundary in sediments while lipids produced within mid-depth OMZs are not effectively exported to deep oceans. Analysis of MOB values in ancient sediments in the East Equatorial Pacific shows a gradual decline in bottom water DO, correlating with the progressive increase in global export productivity, organic carbon burial, and elevated level of deep-water nutrient contents since the middle Miocene. These findings highlight the potential of MOB as a tool for reconstructing past oceanic (de)oxygenation events.

Cun Zhang,1,&ast; Lei Jiang,2,3,&ast; Ke Hu,2,&ast; Liang Chen,2 Yi-Jia Zhang,2 Hao-Zhe Shi,2 Su-Mei He,4 Xiao Chen,5 Dong-Dong Wang2 1Department of Pharmacy, Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Department of Pharmacy, Taixing People’s Hospital, Taixing, Jiangsu, 225400, People’s Republic of China; 4Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu, 215153, People’s Republic of China; 5School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Su-Mei He, Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 1 Lijiang Road, Suzhou, Jiangsu, 215153, People’s Republic of China, Email hehe8204@163.com Dong-Dong Wang, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy & School of Pharmacy, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Email 13852029591@163.comObjective: Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug–drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients.Methods: In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database. In addition, related medical information, such as physiological, biochemical indexes, and concomitant drugs was acquired using medical log. Sixty-five sch

Jian-Jun Wu,1 Ping-An Zhang,1 Ming-Zhe Chen,2 Yi Zhang,1 Wei-Sha Du,1 Xiao-Ning Li,1 Guo-Chao Ji,1 Liang-Duo Jiang,3 Yang Jiao,4,&ast; Xin Li5,&ast; 1Respiratory Department, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Infectious Disease Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 3Respiratory Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Respiratory Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Glaucoma Department, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Li, Glaucoma Department, Eye Hospital, China academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email doudou8295@163.comBackground: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear.Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained.Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regu

Min Wu,1,2,&ast; Sining Zeng,3,&ast; Yi Zhang,1,2,&ast; Yanru Liu,1,2 Bingbing Li,1,2 Xuemei Yi,1,2 Yuling Shi,1,2 Xiaoping Zhu3 1Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, People’s Republic of China; 2Institute of Psoriasis, Tongji University School of Medicine, Shanghai, 200443, People’s Republic of China; 3Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhu, Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86-021-66300588, Fax +86-021-66307542, Email xiaopingzhu0424@163.com Yuling Shi, Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Baode Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86-021-36803020, Fax +86-021-36803021, Email shiyuling1973@tongji.edu.cnBackground: Psoriasis is a chronic autoimmune inflammatory skin condition characterized by erythema, papules, and scales. It imposes a heavy psychological and social strain on both patients and their families. Surprisingly, there’s limited research delving into the disease burden and coping strategies of spouses contending with psoriasis.Objective: The objective is to explore the disease burden faced and coping strategies utilized by spouses of individuals living with psoriasis. This exploration aims to offer insights crucial for devising mental health support and intervention strategies.Methods: The research methodology employed in this study was phenomenological, a qualitative approach. A total of fifteen spouses of patients with psoriasis were selected using an objective sampling method for in-depth, semi-structured interviews. Thematic analy

Shu Jiao Zhang,1,2,&ast; Yi Fei Zhang,1,2,&ast; Xue Hui Bai,1,2 Meng Qi Zhou,1,2 Ze Yu Zhang,1,2 Shuai Xing Zhang,1,2 Zi Jing Cao,1,2 Lin Wang,1,2 Shao Wei Ding,1,2 Hui Juan Zheng,1,2 Yu Ning Liu,1– 3 Guo Yong Yu,1 Wei Jing Liu1– 3 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Renal Research Institution of Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo Yong Yu, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 Haiyuncang, Beijing, Dongcheng District, 100700, People’s Republic of China, Email 18901133535@163.com Wei Jing Liu, Renal Research Institution of Beijing University of Chinese Medicine, and Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Tel/Fax +86-010-84013190, Email 1977@hotmail.comBackground: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically.Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molec

Yue Zhang,&ast; Yafan Bai,&ast; Yi Zhang, Yingjie Du, Min Liu, Jiayu Zhu, Guyan Wang Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomingxiang, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Fax +86-10-58268017, Email guyanwang2006@163.comPurpose: Despite the implementation of various insulation measures, the incidence of hypothermia during thyroid surgery remains high. This randomized controlled study aimed to evaluate the effects of aggressive thermal management combined with resistive heating mattresses to prevent perioperative hypothermia in patients undergoing thyroid surgery.Patients and Methods: 142 consecutive patients scheduled for elective thyroid surgery were enrolled in the study. They were randomly and equally allocated to the aggressive warming or routine care groups (n = 71). The patients’ body temperature was monitored before the induction of anesthesia until they returned to the ward. The primary outcome was the incidence of perioperative hypothermia. Secondary outcomes included postoperative complications, such as mortality, cardiovascular complications, wound infection, shivering, postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, fever, headache and hospital length of stay (LOS).Results: In our study, the results showed that a significantly higher rate of hypothermia was observed in the routine care group compared with the aggressive warming group. The incidence of perioperative hypothermia was 19.72% (14/71) in the aggressive warming group and 35.21% (25/71) in the routine care group (P < 0.05). The incidence of shivering in the aggressive warming group (1.41%) was significantly lower than that in the routine care group (11.27%) (P &

Background: Intracranial plasmacytomas are rare tumors arising from plasma cells with approximately half of the cases progressing to multiple myeloma (MM). However, there is a lack of comprehensive clinical cohort analysis on the clinical and pathological features, progression, and outcomes of intracranial plasmacytomas. Methods: A retrospective analysis of 190 cases was conducted, combining data from 38 cases in a single institution and 152 cases from the literature. Patient demographics, clinical presentations, tumor locations, imaging features, surgical treatments, and follow-up outcomes were collected and analyzed. Survival analysis and Cox regression analysis were performed to identify prognostic factors. Results: A total of 190 intracranial plasmacytoma patients with an average age of 55.4 years were included in the study. The preoperative misdiagnosis ratio was high at 55.3%, and 59.7% of the tumors affected the calvaria convexity, compared to 40.3% located at the skull base. Resection and biopsy were achieved in 72.4% and 27.6% patients, respectively. Among them, 34.2% (65/190) of patients were initially diagnosed with MM with intracranial plasmacytoma as their first presentation (MM-IPFP), while 63.2% (120/190) of patients were diagnosed with solitary intracranial plasmacytoma (SIP), including 61 extramedullary plasmacytomas and 59 solitary bone plasmacytomas. In the SIP group, 22.4% (24/107) of patients experienced disease progression leading to the development of MM during a median follow-up time of 42.6 months (range 1-230 months). Multivariate analysis unveiled that radiotherapy (HR, 0.05; 95% CI, 0.00-0.87; p = 0.04), not surgery, was a protective prognostic factor for overall survival in MM-IPFP patients. Comparison between the SIP progression group and non-progression group revealed a significant difference of Ki-67 index (non-progression vs. SIP progression, 8.82% +/- 7.03 vs. 16.5% +/- 10.5, p < 0.05). AUC analysis determined that a cutoff value of