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In order to discuss theoretically the effects of surface roughness on gearing contact fatigue stress,a mixed Elastohydrodynamic Lubrication（ EHL） model for heavy-duty gear transmission was established based on the transverse roughness features simulated by the fractal function,which were superimposed to the film equation. Applied the multi-grid method,40 groups of numerical calculations were completed. The results show that the average film thickness is almost linearly increased with an increment of the roughness value. But it is not simply the case that the less the roughness value,the better. When the roughness is less than a critical value,however,increasing roughness value is found to reduce the maximum principal shear stress on pinion subsurface. At the end,the quantitative relation between the maximum principal shear stress and the roughness is acquired based on the regression analysis of the calculation results.

The surface roughness data of a disc with longitudinal roughness texture is measured by a roughness profile measuring analyzer firstly. With the help of the nonlinear Fourier transform,the measured data is used to form a roughness function which is then added to the oil film thickness equation and a model of mixed Elastohydrodynamic lubrication for a pair of mechanical parts in higher pair contact is established. Based on this model,45 groups numerical calculations are carried through changing lubricant viscosities. The computing results show that the average oil film thickness for rough surfaces is smaller than the corresponding value for smooth surface. But the two tend to consistent when the film ratio exceeds a specific value. As the viscosity increases,the maximum value of contact stress on rough surface decreases gradually,but it is always greater than the corresponding value for smooth surface contact. However,the both are less than the corresponding Hertz stress regardless of rough or smooth surface contact,which indicates once again that a scientific lubrication is very helpful for increasing the contact fatigue life of mechanical parts.

Crystal TaS2nanobelt arrays were fabricated on Ta wafers by a two-step method. Field-emission measurements show that the nanobelt arrays are decent field emitters with a turn-on field of ∼0.7 V μm−1, a threshold field of ∼2.1 V μm−1, and a field enhancement factor of ∼4.33 × 104. [ABSTRACT FROM AUTHOR]

Iodine-doped TaS2 hierarchical nanostructures, for which nanorod arrays are vertically grown on the edge of nanosheets, were prepared and showed superconductivity below 5 K. [ABSTRACT FROM AUTHOR]

Iodine-doped TaS2hierarchical nanostructures, for which nanorod arrays are vertically grown on the edge of nanosheets, were prepared and showed superconductivity below 5 K. [ABSTRACT FROM AUTHOR]

Abstract Three new ent-kaurane diterpenoids, silvaticusins A–C (1–3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC50 values spanning from 1.27 ± 0.08 to 7.52 ± 0.33 μM. Graphical Abstract

Intratumor heterogeneity and divergent clonal lineages within and among primary and recurrent hepatocellular carcinomas (HCCs) produce challenges to patient management. We investigated genetic and epigenetic variations within liver tumors, among hepatic lesions, and between primary and relapsing tumors. Tumor and matched nontumor liver specimens were collected from 113 patients who underwent partial hepatectomy for primary or recurrent HCC at 2 hospitals in Hong Kong. We performed whole-genome, whole-exome, or targeted capture sequencing analyses of 356 HCC specimens collected from multiple tumor regions and matched initial and recurrent tumors. We performed parallel DNA methylation profiling analyses of 95 specimens. Genomes and epigenomes of nontumor tissues that contained areas of cirrhosis or fibrosis were analyzed. We developed liver cancer cell lines that endogenously expressed a mutant form of TP53 (R249S) or overexpressed mutant forms of STAT3 (D170Y, K348E, and Y640F) or JAK1 (S703I and L910P) and tested the abilities of pharmacologic agents to reduce activity. Cells were analyzed by immunoblotting and chromatin immunoprecipitation with quantitative polymerase chain reaction. We determined the monoclonal origins of individual tumors using a single sample collection approach that captured more than 90% of mutations that are detected in all regions of tumors. Phylogenetic and phylo-epigenetic analyses revealed interactions and codependence between the genomic and epigenomic features of HCCs. Methylation analysis revealed a field effect in cirrhotic liver tissues that predisposes them to tumor development. Comparisons of genetic features revealed that 52% of recurrent HCCs derive from the clonal lineage of the initial tumor. The clonal origin if recurrent HCCs allowed construction of a temporal map of genetic alterations that associated with tumor recurrence. Activation of JAK signaling to STAT was a characteristic of HCC progression via mutations that associate with response to drug sensitivity. The combination of a mutation that increases the function of TP53 and the 17p chromosome deletion might provide liver cancer cells with a replicative advantage. Chromatin immunoprecipitation analysis of TP53 with the R249S substitution revealed its interaction with genes that encode chromatin regulators (MLL1 and MLL2). We validated MLL1 and MLL2 as direct targets of TP53R249S and affirmed their association in the Cancer Genome Atlas dataset. The MLL-complex antagonists MI-2-2 (inhibitor of protein interaction) and OICR-9492 (inhibitor of activity) specifically inhibited proliferation of HCC cells that express TP53R249S at nanomolar concentrations. We performed a systematic evaluation of intra- and intertumor genetic heterogeneity in HCC samples and identified genetic and epigenetic changes that associate with tumor progression and recurrence. We identified chromatin regulators that are upregulated by mutant TP53 in HCC cells and inhibitors that reduce proliferation of these cells. DNA methylation patterns in cirrhotic or fibrotic liver tissues might be used to identify those at risk of HCC development. [ABSTRACT FROM AUTHOR]

A hot corona is suggested to be above the standard thin disk. The anisotropy of hard X-ray emission in radio-quiet active galactic nuclei implies that the corona is not static and probably moves outwards like winds. We perform two-dimensional magnetohydrodynamical simulations to study the outflowing corona driven by magnetic field and radiation force. In our simulations, as the initial state and the boundary condition at the disk surface, the corona temperature is set to 109 K inside a 10 Schwarzschild radius (rs), while the corona temperature is set to 107 K outside 10 rs. We employ a weak poloidal magnetic field as the initial magnetic field. A collimated outflow and a wide-angle ordered outflow are observed in our simulations. The collimated outflow is around the rotational axis and has a bulk velocity of ∼0.03–0.3c (c is speed of light) at 90 rs, while their mass outflow rate is very low. The collimated outflow is a weak jet. The wide-angle ordered outflow is distributed at middle and high latitudes and moves outwards with a velocity of 102–104 km s−1. The outflow velocity depends on the disk luminosity. The gas around the disk surface is turbulent, especially outside of 10 rs. The other properties of outflows are discussed in detail. [ABSTRACT FROM AUTHOR]

Absorption lines with high blueshifted velocities are frequently found in the ultraviolet (UV) and X-ray spectra of luminous active galactic nuclei (AGNs). This implies that high-velocity winds/outflows are common in AGNs. In order to study the formation of high-velocity winds, especially ultrafast outflows (UFOs), we perform two-dimensional magnetohydrodynamic (MHD) simulations. Initially, a magnetic field is set to be weaker than the gas pressure at the disk surface. In our simulations, line force operates on the region like filaments because the X-ray radiation from corona is shielded by dense gas in the inner region at some angle. The location of filaments changes with time and then the line-driven winds are exposed to X-rays and become highly ionized. The line force at the UV bands does not directly drive the highly ionized winds. In the sense of time average, the properties of high-velocity winds meet the formation condition of UFOs. Compared with line force, the function of magnetic field is negligible in directly driving winds. In the MHD model, the region around the rotational axis becomes magnetic-pressure dominated, which prevents gases from spreading to higher latitudes and then enhances the gas column density at middle and low latitudes (20°–70°). Higher column density is helpful to shield X-ray photons, which causes the line force to be more effective in the MHD model than in the hydrodynamic model. Higher-velocity winds with a broader opening angle are produced in the MHD model. [ABSTRACT FROM AUTHOR]

Observations show that winds can be driven from the innermost region (inside a 50 Schwarschild radius) of a thin disk. It is interesting to study the winds launched from the innermost region. A hot corona above the black hole (BH) thin disk is irradiated by the disk. We perform two-dimensional hydrodynamical simulations to study the winds driven by radiation force from the corona in the innermost regions. The hard X-ray spectrum from active galactic nuclei (AGNs) suggests that the corona temperature is about 109 K, so that we mainly analyze the properties of winds (or outflows) from the 109 K corona. The disk luminosity plays an important role in driving the outflows. The more luminous the disk, the stronger the outflows. Mass outflow rate () at a 90 Schwarschild radius depends on disk luminosity, which can be described as (Γ is the ratio of the disk luminosity to the Eddington luminosity). In the case of high luminosity (e.g., Γ = 0.75), the supersonic outflows with maximum speed 1.0 × 104 Km s−1 are launched at ∼17°–30° and ∼50°–80° away from the pole axis. The Bernoulli parameter keeps increasing with the outward propagation of outflows. The radiation force keeps accelerating the outflows when outflows move outward. Therefore, we can expect the outflows to escape from the BH gravity and go to the galactic scale. The interaction between outflows and interstellar medium may be an important AGN feedback process. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent malignant tumor among women globally, posing a serious threat to women's health. With the establishment of staging and typing principles for breast cancer diagnosis and treatment, and the development and application of novel antitumor drugs, the survival and quality of life of breast cancer patients have been continuously improving. In China, the large base of breast cancer patients possesses unique incidence characteristics, necessitating ongoing exploration of more appropriate treatment strategies; the volume and level of clinical research are also continuously advancing. In 2023, significant clinical research results were reported for different subtypes of breast cancer. In surgical treatment, clinical trials on targeted axillary lymph node dissection and the establishment of a predictive model BRCA-CRisk for contralateral breast cancer risk provide more evidence for de-escalation in surgical treatment. In the area of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, pyrotinib has shown significant efficacy in advanced breast cancer treatment. In triple-negative breast cancer, precision subtype treatment and immunotherapy continue to improve patient survival. For hormone receptor-positive breast cancer, significant research results were obtained in exempting low-risk patients from chemotherapy and exploring alternative options after resistance to endocrine therapy. In the aspect of BRCA mutations, BGB-290-201 further confirmed the therapeutic efficacy and safety of poly(ADP-ribose) polymerase (PARP) inhibitors for the Chinese population. For advanced HER2-negative patients carrying germline BRCA (gBRCA)1/2 mutations, pamiparib will be an ideal treatment choice. This article reviews the important clinical research in the field of breast cancer in China in 2023, summarizes key results, and aims to provide reference ideas for future clinical research.

Seventeen undescribed sesquiterpene-alkaloid hybrids (liriogerphines E–U, 1 – 17) were isolated and identified during a further phytochemical investigation on the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. These unique heterodimers are conjugates of germacranolide-type sesquiterpenoids with structurally diverse alkaloids [i.e., aporphine- (1 – 15), proaporphine- (16), and benzyltetrahydroisoquinoline-type (17)] via the formation of a C–N bond. The previously undescribed structures were elucidated by comprehensive spectroscopic data analyses and electronic circular dichroism calculations. Such a class of sesquiterpene-alkaloid hybrids presumably biosynthesized via an aza-Michael addition is quite rare from terrestrial plants. In particular, the sesquiterpene-benzyltetrahydroisoquinoline hybrid skeleton has never been reported until the present study. All the isolates were evaluated for their cytotoxic effects against a small panel of leukemia cell lines (Raji, Jeko-1, Daudi, Jurkat, MV-4-11 and HL-60), and some of them exhibited considerable activities. Seventeen previously undescribed hybrids (liriogerphines E–U, 1 – 17), conjugating by germacranolide-type sesquiterpenoids and structurally diverse alkaloids, were isolated and identified during a further phytochemical investigation on the brunches and leaves of Chinese tulip tree (Liriodendron chinense). These sesquiterpene-alkaloid hybrids were quite rare in terrestrial plants and some of them exhibited significant anti-leukemia activities. [Display omitted] • 17 undescribed sesquiterpene-alkaloid hybrids were isolated from Chinese tulip tree. • The structures were established by spectroscopic analysis and chemical calculations. • The hybrids presumably formed by aza-Michael addition were quite rare in nature. • Liriogerphine U is the first example of sesquiterpene-benzylisoquinoline hybrid. • Some isolates exhibited considerable cytotoxicities against six leukemia cell lines. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to help with determination of optimal raw materials for squid surimi products. Methods: The differences in gel strength, water-holding capacity, cooking loss, rheological properties and chemical interaction force of surimi gels, obtained from three species of squid, were evaluated. Results: The gel strength and water-holding capacity of the three species of surimi gel were in descending order as follows: Illex argentinus>Dosidicus gigas>Ommastephes bartrami, while the cooking loss was the opposite. The dynamic rheological temperature scan showed that the energy storage modulus(G′) of the three kinds of surimi decreased with temperature to a minimum value of 45 ℃, then increased to a maximum value of 75 ℃ and decreased again. The G′ of Illex argentinus surimi was higher than the other two kinds of squids when the second stage heating at 90 ℃.The ionic bonding, hydrogen bonding, and hydrophobic interactions of Illex argentinus surimi gel were significantly stronger than the other two kinds of squids. Conclusion: Illex argentinus surimi is the best raw material for squid surimi products; and the production needs to use auxiliary means to improve the gel quality according to the different characteristics of the three kinds of squid surimi.

Fermentation technology was used to prepare the acaí (Euterpe oleracea) fermentation liquid. The optimal fermentation parameters included a strain ratio of Lactobacillus paracasei: Leuconostoc mesenteroides: Lactobacillus plantarum = 0.5:1:1.5, a fermentation time of 6 days, and a nitrogen source supplemental level of 2.5%. In optimal conditions, the ORAC value of the fermentation liquid reached the highest value of 273.28 ± 6.55 μmol/L Trolox, which was 55.85% higher than the raw liquid. In addition, the FRAP value of the acaí, as well as its scavenging ability of DPPH, hydroxyl, and ABTS free radicals, increased after fermentation. Furthermore, after fermentation treatment, the microstructure, basic physicochemical composition, amino acid composition, γ‐aminobutyric acid, a variety of volatile components, and so on have changed. Therefore, fermentation treatment can significantly improve the nutritional value and flavor of the acaí. This provides a theoretical basis for the comprehensive utilization of acaí. [ABSTRACT FROM AUTHOR]

The bark of Streblus indicus, a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF-α, IL-6, IL-1β, IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus, and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF-α, IL-1β, and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF-kB signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus, but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents.

An abstract of the article "Using Two-Component Systems and Other Bacterial Regulatory Factors for the Fabrication of Synthetic Genetic Devices," by Alexander J. Ninfa and colleagues is presented.

Two new benzophenanthridine alkaloids enantiomers (±)-zanthonitidumines A (1) and B (2), along with seven known analogues (3 – 9), were isolated from Zanthoxylum nitidium. Their structures were elucidated on the basis of extensive spectroscopic techniques and ECD data. Compound 2 exhibited the most significant inhibition of IL-6 generation as well as TNF- α release which suggest that it may be a potential anti-inflammatory agent. [Display omitted] • Two new benzophenanthridine alkaloids enantiomers, (±)-Zanthonitidumine A (1) and B (2), were isolated from Zanthoxylum nitidium. • Absolute configuration of the new compounds was established by extensive spectroscopic and ECD analysis. • Compound 2 exhibited potent anti-inflammatory activity comparable to that of the positive control. [ABSTRACT FROM AUTHOR]

The hepatic manifestation of the metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), can lead to the development of hepatocellular carcinoma (HCC). Despite a strong causative link, NAFLD-HCC is often underrepresented in systematic genome explorations. Herein, tumor-normal pairs from 100 patients diagnosed with NAFLD-HCC were subject to next-generation sequencing. Bioinformatic analyses were performed to identify key genomic, epigenomic and transcriptomic events associated with the pathogenesis of NAFLD-HCC. Establishment of primary patient-derived NAFLD-HCC culture was used as a representative human model for downstream in vitro investigations of the underlying CTNNB1 S45P driver mutation. A syngeneic immunocompetent mouse model was used to further test the involvement of CTNNB1 mut and TNFRSF19 in reshaping the tumor microenvironment. Mutational processes operative in the livers of patients with NAFLD inferred susceptibility to tumor formation through defective DNA repair pathways. Dense promoter mutations and dysregulated transcription factors accentuated activated transcriptional regulation in NAFLD-HCC, in particular the enrichment of MAZ-MYC activities. Somatic events common in HCCs arising from NAFLD and viral hepatitis B infection underscore similar driver pathways, although an incidence shift highlights CTNNB1 mut dominance in NAFLD-HCC (33%). Immune exclusion correlated evidently with CTNNB1 mut. Chromatin immunoprecipitation-sequencing integrated with transcriptome and immune profiling revealed a unique transcriptional axis, wherein CTNNB1 mut leads to an upregulation of TNFRSF19 which subsequently represses senescence-associated secretory phenotype-like cytokines (including IL6 and CXCL8). This phenomenon could be reverted by the Wnt-modulator ICG001. The unique mutational processes in the livers of patients with NAFLD and NAFLD-HCC allude to a "field effect" involving a gain-of-function role of CTNNB1 mutations in immune exclusion. The increasing prevalence of metabolic syndrome in adult populations means that NAFLD is poised to be the major cause of liver cancer in the 21st century. We showed a strong "field effect" in the livers of patients with NAFLD, wherein activated β-catenin was involved in reshaping the tumor-immune microenvironment. [Display omitted] • Unique mutational processes in NAFLD-liver and NAFLD-HCC allude to a field effect. • Distinct aberrations and a driver shift to activating CTNNB1 mutations were observed in NAFLD-HCC. • CTNNB1 mutations lead to immune exclusion via the upregulation of TNFRSF19 and subsequent inhibition of SASP-like features. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) formula Wenjing Decoction (WJD) longstanding efficacy in enhancing blood circulation, resolving blood stasis, and mitigating dysmenorrhea symptoms. Despite its prevalent application, the specific mechanism underlying effect of WJD remains elusive. The purpose of this study is to examine the material basis of Wenjing Decoction and explore the effect of WJD on rat models of dysmenorrhea with blood stasis syndrome and elucidate its mechanism. In this study, we initially identified the chemical constituents of WJD using liquid chromatography-mass spectrometry (LC-MS). Subsequently, we employed network pharmacology to predict the mechanism of WJD in treating acute blood stasis dysmenorrhea. To further investigate the role of WJD, we established a rat model of acute blood stasis. We monitored changes in blood coagulation indexes, IL-6, TNF- α , NO, and COX-2 in rats before and after administration to confirm the successful establishment of the rat model and evaluate the therapeutic effect of WJD on dysmenorrhea and acute blood stasis. Finally, real-time fluorescence quantitative PCR (qPCR) and Western blot (WB) were utilized to investigate its mechanism. Through LC-MS analysis, 69 chemical substances were identified in WJD. Network pharmacology study revealed that the mechanism of WJD in treating BSS may be associated with the PI3K/AKT/NF- κ B pathway. Following administration, the WJD group showed gradual recovery of physical signs and coagulation index to a healthy level. Additionally, the levels of IL-6, TNF- α , and COX-2 decreased in a dose-dependent manner, whereas NO levels increased. Results from QPCR and WB detection indicated increased expression levels of p-PI3K, p-AKT, Bcl-2, and eNOS, and decreased expression levels of Bax, NF κ Bp65, ICAM1, and VCAM1. The results show that WJD significantly improves the characterization, dysmenorrhea index, and coagulation-related factors in BSS rats. Through network pharmacological prediction, real-time fluorescence quantitative PCR, and Western blot analysis, it is postulated that the beneficial effects of WJD on dysmenorrhea may be linked to the PI3K/AKT/NF- κ B signaling pathway. These findings offer a theoretical foundation for the advancement and utilization of WJD. [Display omitted] • UPLC-Q-TOF-MS analysis identified a total of 69 compounds within Wenjing Decoction (WJD). • The rat model of acute blood stasis was established by subcutaneous injection of epinephrine hydrochloride combined with ice bath. • The effects of WJD on dysmenorrhea may be related to PI3K/AKT/NF- κ B signaling pathway through network pharmacological prediction, real-time fluorescence quantitative PCR and western blot. [ABSTRACT FROM AUTHOR]

A Rh-catalyzed aryl migratory/decarbonylation of unstrained ketones has been developed. This viable transformation provides a complementary decarbonylative method using diaryl ketones to afford a variety of alkenylated heterocycles in good yields with moderate to good stereoselectivity and broad substrate scope. The synthetic utility of this protocol is also demonstrated by the conversion of the alkenylated heterocycles to tetrahydrocarbazole derivatives. [ABSTRACT FROM AUTHOR]

Objective. To assess the effect of embryonic age on the pregnancy outcomes of blastocyst graded as CC in single frozen-thawed blastocyst transfer cycles. Methods. A total of 565 patients undergoing single frozen-thawed blastocyst transfer at Shanghai TOWAKO Hospital from April 2017 to December 2019 were included in this study, and they were divided into high-quality blastocyst group (grade AA, AB, and BA; n=189), medium-quality blastocyst group (grade BB, AC, and CA; n=114), low-quality blastocyst group (grade CB and BC; n=140) and CC grade blastocyst group (n=122). And the CC grade blastocysts were further divided into CC grade blastocysts of Day 5 (D5 subgroup, n=26), Day 6 (D6 subgroup, n=81) and Day 7 (D7 subgroup, n=15) according to the embryonic age. Thereafter, the cycle characteristics and pregnancy outcomes of the four groups and the three embryonic age subgroups of CC grade blastocysts were compared. Results. The clinical pregnancy rate (58.7% vs 54.4% vs 47.1% vs 25.4%, P=0.000) and live birth rate (46.2% vs 43.2% vs 36.2% vs 17.6%, P=0.000) of the high-quality, medium-quality, low-quality, and CC grade blastocyst groups decreased sequentially. Multivariate analysis showed that embryo quality was significantly correlated with clinical pregnancy rate. Compared with high-quality blastocyst group, CC grade blastocyst group had a lower clinical pregnancy rate (aOR=0.81, 95%CI 0.71 - 0.93, P=0.003). The analysis of CC grade blastocyst embryonic age subgroups showed that the clinical pregnancy rate (42.3% vs 23.5% vs 6.7%, P=0.040) and live birth rate (31.6% vs 15.6% vs 0, P=0.133) of the D5, D6 and D7 subgroups also decreased sequentially. Multivariate analysis showed that the embryonic age had a significant impact on the clinical pregnancy rate of CC grade blastocyst transfer. Compared with the D5 subgroup, the D7 subgroup had a lower clinical pregnancy rate (aOR= 0.69, 95%CI 0.49-0.96, P=0.032). Conclusion. D5 CC grade blastocysts predict good pregnancy outcome. Although the clinical pregnancy rate of D6 CC grade blastocysts is low, they are still useable. However, D7 CC grade blastocysts are of little clinical value. [ABSTRACT FROM AUTHOR]

Background: The bimodal balance-recovery model predicts that corticospinal tract (CST) integrity in the affected hemisphere influences the partterns of brain recovery after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been used to promote functional recovery of stroke patients by modulating motor cortical excitability and inducing reorganization of neural networks. This study aimed to explore how to optimize the efficiency of repetitive transcranial magnetic stimulation to promote upper limb functional recovery after stroke according to bimodal balance-recovery model. Methods: 60 patients who met the inclusion criteria were enrolled to high CST integrity group (n = 30) or low CST integrity group (n = 30), and further assigned randomly to receive high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS) or sham rTMS in addition to routine rehabilitation, with 10 patients in each group. Outcome measures included Fugl-Meyer scale for upper extremity (FMA-UE), Wolf Motor Function (WMFT) scale and Modified Barthel Index (MBI) scale which were evaluated at baseline and after 21 days of treatment. Results: For patients with high CST integrity, the LF group achieved higher FMA-UE, WMFT and MBI scores improvements after treatment when compared to the HF group and sham group. For patients with low CST integrity, after 21 days treatment, only the HF group showed significant improvements in FMA-UE and WMFT scores. For MBI assessment, the HF group revealed significantly better improvements than the LF group and sham group. Conclusions: For stroke patients with high CST integrity, low-frequency rTMS is superior to high-frequency rTMS in promoting upper limb motor function recovery. However, only high-frequency rTMS can improve upper limb motor function of stroke patients with low CST integrity.

We study the dynamics of dipolar gas in deep lattices described by a nonlocal nonlinear discrete Gross-Pitaevskii equation. The stabilities and the propagation properties of traveling plane waves in the system with defects are discussed in detail. For a clean lattice, both energetic and dynamical stabilities of the traveling plane waves are studied. It is shown that the system with attractive local interaction can preserve the stabilities, i.e., the dipoles can stabilize the gas because of repulsive nonlocal dipole-dipole interactions. For a lattice with defects, within a two-mode approximation, the propagation properties of traveling plane waves in the system map onto a nonrigid pendulum Hamiltonian with quasimomentum-dependent nonlinearity (induced by the nonlocal interactions). Competition between defects, quasimomentum of the gas, and nonlocal interactions determines the propagation properties of the traveling plane waves. Critical conditions for crossing from a superfluid regime with propagation preserved to a normal regime with defect-induced damping are obtained analytically and confirmed numerically. In particular, the critical conditions for supporting the superfluidity strongly depend on the defect type and the quasimomentum of the plane waves. The nonlocal interaction can significantly enhance the superfluidity of the system. [ABSTRACT FROM AUTHOR]

Lactoferrin (Lf) is a multifunctional protein in the transferrin family. It is involved in many physiological functions, including the regulation of iron absorption and immune response. It also has antibacterial, antiviral, anti-inflammatory, anticancer and antioxidant capabilities under pathophysiological conditions. The mammalian lactoferrin receptor (LfR) plays a key role in mediating multiple functions of Lf. Studies have shown that Lf/LfR is abnormally expressed in the brain of Parkinson's disease, and the excessive accumulation of iron in the brain caused by the overexpression of Lf and LfR is considered to be one of the initial causes of the degeneration of dopaminergic neurons in Parkinson's disease. On the other hand, a number of recent studies have reported that Lf/LfR has a significant neuroprotective effect on Parkinson's disease. In other words, it seems paradoxical that Lf/LfR has both neurodegenerative and neuroprotective effects in Parkinson's disease. This article focuses on recent advances in the possible mechanisms of the neurodegenerative and neuroprotective effects of Lf/LfR in Parkinson's disease and discusses why Lf/LfR has a seemingly contradictory role in the development of Parkinson's disease. Based on the evidence obtained so far, we believed that Lf/LfR has a neuroprotective effect on Parkinson's disease, while as to whether the overexpressed Lf/LfR is the cause of the development of Parkinson's disease, the current evidence is insufficient and further investigation needed., 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.)

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNA Cys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture., (© 2024. The Author(s).)

Background: Cardiovascular diseases present a significant challenge in clinical practice due to their sudden onset and rapid progression. The management of these conditions necessitates cardiologists to possess strong clinical reasoning and individual competencies. The internship phase is crucial for medical students to transition from theory to practical application, with an emphasis on developing clinical thinking and skills. Despite the critical need for education on cardiovascular diseases, there is a noticeable gap in research regarding the utilization of artificial intelligence in clinical simulation teaching., Objective: This study aims to evaluate the effect and influence of AI-empowered scenario-based simulation teaching mode in the teaching of cardiovascular diseases., Methods: The study utilized a quasi-experimental research design and mixed-methods. The control group comprised 32 students using traditional teaching mode, while the experimental group included 34 students who were instructed on cardiovascular diseases using the AI-empowered scenario-based simulation teaching mode. Data collection included post-class tests, "Mini-CEX" assessments, Clinical critical thinking scale from both groups, and satisfaction surveys from experimental group. Qualitative data were gathered through semi-structured interviews., Results: Research shows that compared with traditional teaching models, AI-empowered scenario-based simulation teaching mode significantly improve students' performance in many aspects. The theoretical knowledge scores(P < 0.001), clinical operation skills(P = 0.0416) and clinical critical thinking abilities of students(P < 0.001) in the experimental group were significantly improved. The satisfaction survey showed that students in the experimental group were more satisfied with the teaching scene(P = 0.008), Individual participation(P = 0.006) and teaching content(P = 0.009). There is no significant difference in course discussion, group cooperation and teaching style of teachers(P > 0.05). Additionally, the qualitative data from the interviews highlighted three themes: (1) Positive new learning experience, (2) Improved clinical critical thinking skills, and (3) Valuable suggestions and concerns for further improvement., Conclusion: The AI-empowered scenario simulation teaching Mode plays an important role in the improvement of clinical thinking and skills of medical undergraduates. This study believes that the AI-empowered scenario simulation teaching mode is an effective and feasible teaching model, which is worthy of promotion in other courses., (© 2024. The Author(s).)

Three new ent-kaurane diterpenoids, silvaticusins A-C (1-3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC 50 values spanning from 1.27 ± 0.08 to 7.52 ± 0.33 μM., (© 2024. The Author(s).)